Herbal medicines for fatty liver diseases

  • Review
  • Intervention

Authors


Abstract

Background

Fatty liver disease is potentially a reversible condition that may lead to end-stage liver disease. Since herbal medicines such as Crataegus pinnatifida and Salvia miltiorrhiza have increasingly been used in the management of fatty liver disease, a systematic review on herbal medicine for fatty liver disease is needed.

Objectives

To assess the beneficial and harmful effects of herbal medicines for people with alcoholic or non-alcoholic fatty liver disease.

Search methods

We searched The Cochrane Hepato-Biliary Group Controlled Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL) (Issue 3, 2012), MEDLINE, EMBASE, and Science Citation Index Expanded to 1 March 2012. We also searched the Chinese BioMedical Database, Traditional Chinese Medical Literature Analysis and Retrieval System, China National Knowledge Infrastructure, Chinese VIP Information, Chinese Academic Conference Papers Database and Chinese Dissertation Database, and the Allied and Complementary Medicine Database to 2 March 2012.

Selection criteria

We included randomised clinical trials comparing herbal medicines with placebo, no treatment, a pharmacological intervention, or a non-pharmacological intervention such as diet or lifestyle, or Western interventions in participants with fatty liver disease.

Data collection and analysis

Two review authors extracted data independently. We used the 'risk of bias' tool to assess the risk of bias of the included trials. We assessed the following domains: random sequence generation, allocation concealment, blinding, incomplete outcome data, selective outcome reporting, and other sources of bias. We presented the effects estimates as risk ratios (RR) with 95% confidence intervals (CI) or as mean differences (MD) with 95% CI, depending on the variables of the outcome measures.

Main results

We included 77 randomised clinical trials, which included 6753 participants with fatty liver disease. The risks of bias (overestimation of benefits and underestimation of harms) was high in all trials. The mean sample size was 88 participants (ranging from 40 to 200 participants) per trial. Seventy-five different herbal medicine products were tested. Herbal medicines tested in the randomised trials included single-herb products (Gynostemma pentaphyllum, Panax notoginseng, andPrunus armeniaca), proprietary herbal medicines commercially available, and combination formulas prescribed by practitioners. The most commonly used herbs wereCrataegus pinnatifida,Salvia miltiorrhiza,Alisma orientalis,Bupleurum chinense,Cassia obtusifolia, Astragalus membranaceous, and Rheum palmatum. None of the trials reported death, hepatic-related morbidity, quality of life, or costs. A large number of trials reported positive effects on putative surrogate outcomes such as serum aspartate aminotransferase, alanine aminotransferase, glutamyltransferase, alkaline phosphatases, ultrasound, and computed tomography scan. Twenty-seven trials reported adverse effects and found no significant difference between herbal medicines versus control. However, the risk of bias of the included trials was high.

The outcomes were ultrasound findings in 22 trials, liver computed tomography findings in eight trials, aspartate aminotransferase levels in 64 trials, alanine aminotransferase activity in 77 trials, and glutamyltransferase activities in 44 trials. Six herbal medicines showed statistically significant beneficial effects on ultrasound, four on liver computed tomography, 42 on aspartate aminotransferase activity, 49 on alanine aminotransferase activity, three on alkaline phosphatases activity, and 32 on glutamyltransferase activity compared with control interventions.

Authors' conclusions

Some herbal medicines seemed to have positive effects on aspartate aminotransferase, alanine aminotransferase, ultrasound, and computed tomography. We found no significant difference on adverse effects between herbal medicine and control groups. The findings are not conclusive due to the high risk of bias of the included trials and the limited number of trials testing individual herbal medicines. Accordingly, there is also high risk of random errors.

Résumé scientifique

Plantes médicinales pour traiter les stéatoses hépatiques

Contexte

La stéatose hépatique est une maladie potentiellement réversible susceptible d'entraîner une hépatopathie terminale. Puisque les plantes médicinales telles que Crataegus pinnatifida et Salvia miltiorrhiza sont de plus en plus utilisées dans le traitement de la stéatose hépatique, une revue systématique portant sur les plantes médicinales dans le traitement de la stéatose hépatique s'imposait.

Objectifs

Évaluer les effets bénéfiques et néfastes des plantes médicinales sur les patients atteints d'une stéatose hépatique d'origine alcoolique ou non alcoolique.

Stratégie de recherche documentaire

Nous avons effectué une recherche dans le registre spécialisé des essais contrôlés du groupe Cochrane sur les affections hépato-biliaires, le registre Cochrane des essais contrôlés (CENTRAL) (numéro 3, 2012), MEDLINE, EMBASE, et Science Citation Index Expanded jusqu'au 1er mars 2012. Nous avons également consulté les bases de données Chinese BioMedical Database, Traditional Chinese Medical Literature Analysis and Retrieval System, China National Knowledge Infrastructure, Chinese VIP Information, Chinese Academic Conference Papers Database et Chinese Dissertation Database, et la base de données Allied and Complementary Medicine Database jusqu'au 1er mars 2012.

Critères de sélection

Nous avons inclus les essais cliniques randomisés ayant comparé des plantes médicinales à un placebo, l'absence de traitement, une intervention pharmacologique, ou une intervention non pharmacologique telle qu'un régime alimentaire ou un changement du mode de vie, ou des interventions occidentales chez les participants atteints de stéatose hépatique.

Recueil et analyse des données

Deux auteurs de la revue ont extrait les données de façon indépendante. Nous avons utilisé l'outil « Risque de biais » du groupe Cochrane pour évaluer le risque de biais des essais inclus. Les domaines évalués sont les suivants : génération de la séquence de randomisation, assignation secrète, masquage, données de résultats incomplètes, compte-rendu sélectif et autres sources de biais. Nous avons présenté les estimations des effets sous la forme de risques relatifs (RR) avec intervalles de confiance (IC) à 95 % ou de différences moyennes (DM) avec IC à 95 %, en fonction des variables des critères de jugement mesurés.

Résultats principaux

Nous avons inclus 77 essais cliniques randomisés, totalisant 6 753 participants atteints de stéatose hépatique. Le risque de biais (surestimation des effets bénéfiques et sous-estimation des effets néfastes) était élevé dans tous les essais examinés. L'effectif moyen était de 88 participants (allant de 40 à 200 participants) par essai. Soixante-quinze produits à base de plantes médicinales différentes ont été testés. Les plantes médicinales testées dans les essais cliniques randomisés incluaient des produits à base d'une plante unique (Gynostemma pentaphyllum, Panax notoginseng, et Prunus armeniaca), des plantes médicinales de marque commercialisées, et une combinaison de préparations prescrites par les médecins. Les plantes les plus couramment utilisées étaient Crataegus pinnatifida, Salvia miltiorrhiza, Alisma orientalis, Bupleurum chinense, Cassia obtusifolia, Astragalus membranaceous, et Rheum palmatum. Aucun des essais ne rendait compte de la mortalité, de la morbidité hépatique ni de la qualité de vie ou des coûts. Un grand nombre d'essais ont rapporté des effets positifs sur les résultats du critère de substitution putatif tels que les taux d'aspartate aminotransférase, d'alanine aminotransférase, de glutamyltransférase, de phosphatases alcalines sériques, les résultats des examens échographiques, et les résultats de la tomographie informatisée. Vingt-sept essais ont rapporté des effets indésirables et n'ont trouvé aucune différence significative entre les plantes médicinales et l'intervention témoin. Cependant, le risque de biais était élevé dans tous les essais inclus.

Les critères mesurés étaient les résultats de l'échographie dans 22 essais, de la tomographie informatisée hépatique dans huit essais, les taux d'aspartate aminotransférase dans 64 essais, l'activité alanine aminotransférase dans 77 essais, et les activités glutamyltransférase dans 44 essais. Six plantes médicinales ont révélé des effets bénéfiques statistiquement significatifs sur l'échographie, quatre sur la tomographie informatisée hépatique, 42 sur l'activité aspartate aminotransférase, 49 sur l'activité alanine aminotransférase, trois sur l'activité phosphatases alcalines, et 32 sur l'activité glutamyltransférase comparées aux interventions témoins.

Conclusions des auteurs

Certaines plantes médicinales ont semblé avoir des effets positifs sur l'aspartate aminotransférase, l'alanine aminotransférase, l'échographie et la tomographie informatisée. Nous n'avons trouvé aucune différence significative sur les effets indésirables entre les groupes de plantes médicinales et les groupes témoins. Les résultats ne sont pas concluants compte tenu du risque élevé de biais dans tous les essais inclus et du nombre limité d'essais ayant testé des plantes médicinales individuelles. Par conséquent, le risque d'erreurs aléatoires est également élevé.

アブストラクト

脂肪肝疾患に対する生薬

背景

脂肪肝疾患は可逆的な病態であるが、末期肝疾患に至る可能性もある。生薬のたとえばCrataegus pinnatifida(オオミサンザシ)やSalvia miltiorrhiza(タンジン)などを脂肪肝疾患の管理に用いる例が増えているため、脂肪肝疾患への生薬の使用についてのシステマティックレビューが必要である。

目的

アルコール性および非アルコール性脂肪肝疾患の患者に対する生薬の有益な作用と有害な作用を評価すること。

検索戦略

The Cochrane Hepato-Biliary Group Controlled Trials Register、Cochrane Central Register of Controlled Trials (CENTRAL)(2012年第3号)、MEDLINE、EMBASE、Science Citation Index Expanded(~2012年3月1日)を検索した。また、Chinese BioMedical Database、Traditional Chinese Medical Literature Analysis and Retrieval System、China National Knowledge Infrastructure、Chinese VIP Information、Chinese Academic Conference Papers Database and Chinese Dissertation Database、Allied and Complementary Medicine Database(~2012年3月2日)も検索した。

選択基準

脂肪肝疾患の参加者を対象にして、生薬と、プラセボ、無治療、薬理学的介入、または非薬理学的介入(食事療法、生活習慣、通常医療的介入)とを比較するランダム化試験を選択した。

データ収集と分析

2人のレビュー著者が独立してデータを抽出した。「バイアスのリスク」ツールを使用して、対象となった試験のバイアスのリスクを評価した。評価したドメインは、ランダム化順序の作成方法、割りつけのコンシールメント(隠蔵化)、盲検化、不完全なアウトカムデータ、選択的なアウトカムの報告、その他バイアスの原因になるものであった。効果の推定値は、アウトカム指標の変数に応じて、リスク比(RR)(95%信頼区間(CI))または平均差(MD)(95% CI)として示した。

主な結果

77のランダム化試験を選択し、脂肪肝疾患の参加者6753例を対象とした。バイアスのリスク(利益の過大評価と有害性の過小評価)はすべての試験で高かった。試験ごとの平均サンプル・サイズは88例であった(40~200症例)。75種類の生薬製品が試されていた。ランダム化比較試験で試された生薬には、生薬単剤の製剤(Gynostemma pentaphyllum(アマチャズル)、Panax notoginseng(サンシチニンジン)、Prunus armeniaca(アンズ))、市販の生薬専売薬、開業医が処方する配合剤があった。 多く使用されている生薬は、Crataegus pinnatifida(オオミサンザシ)、Salvia miltiorrhiza(タンジン)、Alisma orientalis(サジオモダカ)、Bupleurum chinense(ミシマサイコ)、Cassia obtusifolia(エビスグサ)、Astragalus membranaceous(キバナオウギ)、Rheum palmatum(ショウヨウダイオウ)であった。 死亡、肝疾患の罹患率、QOL、費用を報告している試験はなかった。多くの試験で、血清アスパラギン酸アミノトランスフェラーゼ、アラニンアミノトランスフェラーゼ、グルタミルトランスフェラーゼ、アルカリホスファターゼ、超音波検査、CTスキャンなど、推定される代替アウトカムに対する明確な効果を報告していた。27試験で有害作用を報告していたが、生薬群と対照群の間に有意差はなかった。ただし、選択された試験のバイアスのリスクは高かった。

アウトカムを超音波検査所見としていたのが22試験、肝臓CT所見が8試験、アスパラギン酸アミノトランスフェラーゼ値が64試験、アラニンアミノトランスフェラーゼ活性値が77試験、グルタミルトランスフェラーゼ活性値が44試験であった。対照の介入と比較して統計学的に有意な有益な効果を示した生薬は、超音波検査所見が6種類、肝臓CT所見が4種類、アスパラギン酸アミノトランスフェラーゼ活性値が42種類、アラニンアミノトランスフェラーゼ活性値が49種類、アルカリホスファターゼ活性値が3種類、グルタミルトランスフェラーゼ活性値が32種類であった。

著者の結論

いくつかの生薬は、アスパラギン酸アミノトランスフェラーゼ、アラニンアミノトランスフェラーゼ、超音波検査所見、CT所見に明確な効果を示すようである。有害作用については、生薬群と対照群の間に有意差はみられなかった。選択された試験のバイアスのリスクが高く、個々の生薬を試す試験数が限られているため、これらの所見は決定的なものではない。したがって、確率的誤差のリスクも高い。

訳注

《実施組織》厚生労働省「「統合医療」に係る情報発信等推進事業」(eJIM:http://www.ejim.ncgg.go.jp/)[2016.1.9]
《注意》この日本語訳は、臨床医、疫学研究者などによる翻訳のチェックを受けて公開していますが、訳語の間違いなどお気づきの点がございましたら、eJIM事務局までご連絡ください。なお、2013年6月からコクラン・ライブラリーのNew review, Updated reviewとも日単位で更新されています。eJIMでは最新版の日本語訳を掲載するよう努めておりますが、タイム・ラグが生じている場合もあります。ご利用に際しては、最新版(英語版)の内容をご確認ください。

Plain language summary

Herbal medicines for fatty liver diseases

Fatty liver disease is a potentially reversible illness where fat builds up within the cells of the liver. It may lead to the liver no longer being able to function properly; this is called end-stage liver disease. This systematic review evaluated the effects and safety of herbal medicines (single herbs, branded herbal medicines, and prescribed formulas) for treating fatty liver disease.

We included 77 randomised clinical trials in this review, which tested 75 herbal medicines. All trials had high risk of systematic errors (ie, bias or risk of overestimation of benefits and overestimation of harms) as well as high risks of random errors (ie, play of chance) due to the small number of people in the trials. Herbal medicines tested in the randomised clinical trials included single-herb products (Gynostemma pentaphyllum,Panax notoginseng, andPrunus armeniaca), commercially available branded herbal medicines, and combination formulas prescribed by practitioners. Herbs most commonly included as an ingredient in different products wereCrataegus pinnatifida,Salvia miltiorrhiza,Alisma orientalis,Bupleurum chinense,Cassia obtusifolia,Astragalus membranaceous, andRheum palmatum. We could not combine the results of the trials due to the range of different herbs used. We could not reach any conclusions about the use of herbal medicines for people with fatty liver disease as none of the trials reported results on death, liver-related illnesses, quality of life, or costs. A number of trials showed positive effects of herbal medicines compared with control interventions on enzyme activity (enzymes are proteins that cause chemical reactions in the body; eg, serum aspartate aminotransferase, alanine aminotransferase, glutamyltransferase, alkaline phosphatases), ultrasound scan findings, and computed tomography scan findings. No serious adverse effects were reported for herbal medicines.

However, the methodology of the trials had high risk of systematic errors (bias). Furthermore, the individual herbs were seldomly retested, and all trials had relatively low numbers of people, which increases the risk of random errors (play of chance). Therefore, the findings are inconclusive, and rigorously conducted randomised clinical trials are required to establish the benefits and harms of herbal medicines for fatty liver disease.

Résumé simplifié

Plantes médicinales pour traiter les stéatoses hépatiques

La stéatose hépatique est une maladie potentiellement réversible dans laquelle des triglycérides s'accumulent dans les hépatocyles. Il peut s'en suivre que le foie n'est plus capable de fonctionner normalement ; c'est ce que l'on appelle une hépatopathie terminale. Cette revue systématique a évalué les effets et l'innocuité des plantes médicinales (plantes uniques, plantes médicinales d'une marque et préparations prescrites) pour traiter les stéatoses hépatiques.

Nous avons inclus 77 essais cliniques randomisés dans cette revue, dans laquelle 75 plantes médicinales ont été testées. Tous les essais présentaient un risque élevé d'erreurs systématiques (c'est-à-dire, biais ou risque de surestimation des effets bénéfiques et sous-estimation des effets néfastes) ainsi que des risques élevés d'erreurs aléatoires (c'est-à-dire, fait du hasard) compte tenu du petit nombre de participants inclus dans les essais. Les plantes médicinales testées dans les essais cliniques randomisés incluaient des produits à base d'une plante unique (Gynostemma pentaphyllum, Panax notoginseng, et Prunus armeniaca), des plantes médicinales de marque commercialisées, et une combinaison de préparations prescrites par les médecins. Les plantes les plus couramment incluses à titre d'ingrédient dans les différents produits étaient Crataegus pinnatifida, Salvia miltiorrhiza, Alisma orientalis, Bupleurum chinense, Cassia obtusifolia, Astragalus membranaceous, et Rheum palmatum. Nous n'avons pas été en mesure de combiner les résultats des essais étant donné l'éventail des différentes plantes utilisées. Nous ne sommes pas parvenus à une conclusion quant à l'utilisation des plantes médicinales chez les patients atteints de stéatose hépatique car aucun des essais ne rapportait de résultats sur la mortalité, la morbidité hépatique ni sur la qualité de vie ou les coûts. Un certain nombre d'essais ont démontré des effets positifs des plantes médicinales comparées aux interventions témoins sur l'activité enzymatique (les enzymes sont des protéines qui provoquent des réactions chimiques dans l'organisme ; par exemple aspartate aminotransférase, alanine aminotransférase, glutamyltransférase, phosphatases alcalines sériques), les résultats des examens échographiques, et les résultats de la tomographie informatisée. Aucun effet indésirable grave dû aux plantes médicinales n'avait été signalé.

Toutefois, la méthodologie des essais présentait un risque élevé d'erreurs systématiques (biais). En outre, les plantes individuelles ont été rarement testées plusieurs fois, et tous les essais comptaient un effectif relativement faible de participants, ce qui accroît le risque d'erreurs aléatoires (fait du hasard). Par conséquent, les résultats ne sont pas concluants, et des essais cliniques randomisés conduits avec rigueur sont nécessaires pour établir les effets bénéfiques et néfastes des plantes médicinales dans le traitement de la stéatose hépatique.

Notes de traduction

Traduit par: French Cochrane Centre 16th October, 2013
Traduction financée par: Pour la France : Minist�re de la Sant�. Pour le Canada : Instituts de recherche en sant� du Canada, minist�re de la Sant� du Qu�bec, Fonds de recherche de Qu�bec-Sant� et Institut national d'excellence en sant� et en services sociaux.

Laički sažetak

Biljni lijekovi za liječenje masne jetre

Bolest masne jetre je potencijalno reverzibilna bolest u kojoj se mast stvara između jetrenih stanica. Može dovesti do toga da jetra više ne može funkcionirati normalno; to se naziva završnim stadijem jetrene bolesti. Ovaj Cochrane sustavni pregled ocjenjuje djelotvornost i sigurnost biljnih lijekova (cijelih biljaka, registriranih biljnih lijekova i propisanih formula) za liječenje masne jetre.

U ovaj Cochrane sustavni pregled uključeno je 77 randomiziranih kliničkih pokusa koji su istražili ukupno 75 biljnih lijekova. Svi pokusi su imali visok rizik sustavnih pogrješaka (tj. pristranost ili opasnost od precjenjivanja koristi i precjenjivanja štetnosti) kao i visok rizik slučajnih pogrješaka (tj. utjecaj slučaja) zbog malog broja ispitanika u pokusima. Biljni lijekovi testirani u randomiziranim kliničkim pokusima uključivali su proizvode sačinjene od jedne biljke (Gynostemma pentaphyllum, Panax notoginseng , i Prunus armeniaca), komercijalno dostupne registrirane biljne lijekove i kombinacije formula propisane od strane stručnjaka. Biljke koje su najčešće uključene kao sastojak u različitim proizvodima bile su Crataegus pinnatifida, Salvia miltiorrhiza, Alisma orientalis, Bupleurum chinese, Cassia obtusifolia, Astragalus membranaceous, i Rheum palmatum. Nije bilo moguće objediniti rezultate studija zbog različitih vrsta biljaka koje su korištene. Autori nisu mogli doći ni do kakvog zaključka o primjeni biljnih lijekova za osobe s masnom jetrom jer ni jedno istraživanje nije prijavilo rezultate o smrti, bolestima povezanima s jetrom, kvaliteti života te troškovima. Mnogo istraživanja pokazalo je pozitivne učinke biljnih lijekova u usporedbi s kontrolnim intervencijama, na enzimsku aktivnost (enzimi su bjelančevine koje uzrokuju kemijske reakcije u organizmu; npr. serumske aspartat aminotransferaze, alanin aminotransferaze, glutamiltransferaze, alkalne fosfataze), nalaze ultrazvučnih pregleda i nalaze kompjutorske tomografije. Nikakve ozbiljne nuspojave nisu prijavljene za biljne lijekove.

Međutim, metodologija pokusa je imala visok rizik sustavnih pogrješaka (pristranost). Nadalje, zasebne biljke su malokad bile ponovno testirane te su svi pokusi imali razmjerno mali broj ispitanika što je povećalo rizik slučajnih pogrješaka (igra slučaja). Prema tome, nalazi su neuvjerljivi te su potrebni strogo provedeni randomizirani kontrolni pokusi da bi dokazali koristi i štetnosti biljnih lijekova za bolest masne jetre.

Bilješke prijevoda

Hrvatski Cochrane
Prevela: Marija Radman
Ovaj sažetak preveden je u okviru volonterskog projekta prevođenja Cochrane sažetaka. Uključite se u projekt i pomozite nam u prevođenju brojnih preostalih Cochrane sažetaka koji su još uvijek dostupni samo na engleskom jeziku. Kontakt: cochrane_croatia@mefst.hr

平易な要約

脂肪肝疾患に対する生薬

脂肪肝疾患は可逆的な疾患で、肝臓の細胞内に脂肪が蓄積する。肝臓が正常に機能しなくなる状態、すなわち末期の肝疾患に至る可能性もある。このシステマティックレビューでは、脂肪肝疾患を治療する生薬(単剤の生薬、生薬専売薬、処方薬)の効果と安全性を評価した。

このレビューで選択したランダム化試験は77試験であり、75種類の生薬が試されていた。すべての試験は、システマティックな誤差(バイアス、すなわち利益の過大評価と有害性の過小評価のリスク)のリスクが高く、また試験の参加人数が少ないために確率的誤差(偶然の産物)のリスクも高い。ランダム化試験で試された生薬は、生薬単剤の製剤(Gynostemma pentaphyllum(アマチャズル)、Panax notoginseng(サンシチニンジン)、Prunus armeniaca(アンズ))、市販の生薬専売薬、開業医が処方する配合剤があった。 さまざまな製品で成分として多く使用されている生薬は、Crataegus pinnatifida(オオミサンザシ)、Salvia miltiorrhiza(タンジン)、Alisma orientalis(サジオモダカ)、Bupleurum chinense(ミシマサイコ)、Cassia obtusifolia(エビスグサ)、Astragalus membranaceous(キバナオウギ)、Rheum palmatum(ショウヨウダイオウ)であった。 多くの種類の生薬が使用されていたため、複数の試験の結果を統合することができなかった。脂肪肝疾患の患者への生薬の使用について、いずれの試験も死亡、肝関連の疾患、QOL、費用に関する結果を報告していなかったため、結論を導き出すことはできなかった。多くの試験で、対照の介入と比較して、酵素活性値(酵素とは体内で化学反応を引き起こすタンパク質である。たとえば、血清アスパラギン酸アミノトランスフェラーゼ、アラニンアミノトランスフェラーゼ、グルタミルトランスフェラーゼ、アルカリホスファターゼなど)、超音波検査所見、CTスキャン所見に生薬の明確な効果が示されていた。生薬による重篤な有害作用は報告されていない。

ただし、試験の手法として、システマティックな誤差(バイアス)のリスクが高かった。さらに、個々の生薬はほとんど再試験されていないこと、すべての試験で参加人数が比較的少ないことから、確率的誤差(偶然の産物)のリスクが高くなる。したがって、結果は決定的なものではない。脂肪肝疾患に対する生薬の利益と有害性を確立するには、厳密に実施したランダム化試験が必要である。

訳注

《実施組織》厚生労働省「「統合医療」に係る情報発信等推進事業」(eJIM:http://www.ejim.ncgg.go.jp/)[2016.1.9]
《注意》この日本語訳は、臨床医、疫学研究者などによる翻訳のチェックを受けて公開していますが、訳語の間違いなどお気づきの点がございましたら、eJIM事務局までご連絡ください。なお、2013年6月からコクラン・ライブラリーのNew review, Updated reviewとも日単位で更新されています。eJIMでは最新版の日本語訳を掲載するよう努めておりますが、タイム・ラグが生じている場合もあります。ご利用に際しては、最新版(英語版)の内容をご確認ください。

Streszczenie prostym językiem

Leki ziołowe stosowane w chorobach stłuszczeniowych wątroby

Stłuszczeniowa choroba wątroby jest potencjalnie odwracalną chorobą, w której tłuszcz gromadzi się w komórkach wątroby. Może to uniemożliwić prawidłowe funkcjonowanie tego organu; taki stan nazywany jest schyłkową niewydolnością wątroby. Przedstawiany przegląd systematyczny oceniał skuteczność i bezpieczeństwo leków ziołowych (pojedynczych ziół, markowych leków ziołowych oraz recepturowych leków) służących do leczenia stłuszczeniowej choroby wątroby.

Włączyliśmy 77 badań klinicznych z randomizacją, w których oceniano 75 leków ziołowych. Wszystkie badania charakteryzowały się dużym ryzykiem błędu systematycznego (tj. wypaczenie wyników badania w kierunku przeszacowania lub niedoszacowania korzyści i szkód - przyp. tłum.), jak również dużym ryzykiem błędów przypadkowych ze względu na niewielką liczbę osób biorących udział w badaniach. Leki ziołowe oceniane w badaniach klinicznych z randomizacją obejmowały produkty wytwarzane z pojedynczych ziół (Gynostemma pentaphyllum (tzw. "ziele nieśmiertelności"), Panax notoginseng (żeńszeń amerykański), i Prunus armeniaca (morela pospolita)), dostępne na rynku markowe leki ziołowe oraz preparaty recepturowe przepisane przez lekarzy. Do ziół będących najczęściej składnikami różnych produktów należały: Crataegus pinnatifid (głóg pierzastolistny), Salvia miltiorrhiza (szałwia czerwona), Alisma orientalis (żabiniec babka wodna), Bupleurum chinense (przewiercień chiński), Cassia obtusifolia (strączyniec tępoliściowy), Astragalus membranaceous (traganek błoniasty) i Rheum palmatum (rzewień palczasty). Nie było możliwe połączenie wyników badań ze względu na różnorodność stosowanych ziół. Nie mogliśmy sformułować żadnych wniosków na temat stosowania leków ziołowych u osób z chorobą stłuszczeniową wątroby, gdyż żadne z badań nie raportowało przypadków zgonu, chorób wątroby, jakości życia, lub kosztów. Wiele badań wskazywało na pozytywny wpływ leków ziołowych w porównaniu z interwencjami kontrolnymi na: aktywność enzymów (enzymy są białkami, które przyspieszają reakcje chemiczne w organizmie, np. aminotransferaza asparaginianowa, aminotransferaza alaninowa, glutamylotransferaza, fosfatazy alkaliczne), wyniki USG i wyniki skanów tomografii komputerowej. Nie odnotowano żadnych poważnych działań niepożądanych związanych z przyjmowaniem leków ziołowych.

Metodologia włączonych badań charakteryzowała się dużym ryzykiem błędów systematycznych. Ponadto, poszczególne zioła rzadko były powtórnie testowane, a wszystkie badania obejmowały stosunkowo niewielką liczbę uczestników, co zwiększało ryzyko wystąpienia błędów przypadkowych. W związku z tym otrzymane wyniki są niejednoznaczne, a rygorystycznie przeprowadzone badania kliniczne z randomizacją są niezbędne by ocenić korzyści i szkody leków ziołowych stosowanych w stłuszczeniowej chorobie wątroby.

Uwagi do tłumaczenia

Tłumaczenie: Joanna Zając Redakcja: Magdalena Koperny

Background

Description of the condition

Fatty liver disease is potentially a reversible condition that may lead to end-stage liver disease. Fatty acids, usually in the form of triglycerides, accumulate in the liver cells causing steatosis (Zakim 2003; Yao 2004). It is generally believed that there are four distinct histological states in the natural history of fatty liver disease that indicate the progression of lesions: simple steatosis, steatohepatitis, fibrosis, and cirrhosis (Review 1981; Caldwell 2010). In cirrhosis, the liver is permanently damaged and scarred, and it may not be able to function properly. Fatty liver disease is histologically categorised into alcoholic fatty liver disease (AFLD) and non-alcoholic fatty liver disease (NAFLD) (Reddy 2006).

Most people with fatty liver disease are asymptomatic, but some present with fatigue or fullness, or pain in the right upper quadrant of the abdomen (Adachi 2005; Newton 2010). Usually abnormal biochemistry is the only indication of fatty liver disease. Elevated serum alanine aminotransferase (ALT) and glutamyltransferase (GGT) activities are considered surrogate markers of fat accumulation in the liver, although it is possible for people with fatty liver disease to have normal transaminase activity (Zakim 2003; Yao 2004). Hence, these surrogate markers are neither sufficiently sensitive nor specific for the diagnosis of fatty liver, and are only clinically useful when combined with clinical findings (Preiss 2008). Through identifying fatty acid that has infiltrated the liver, imaging studies may assist in the diagnosis of fatty liver disease. The gold standard for the diagnosis of fatty liver disease is liver biopsy, which is invasive and may even lead to significant complications or death (Sanyal 2002). However, physicians seldom use liver biopsy as an initial diagnosis (Dienstag 2002; Sanyal 2002). AFLD is mainly diagnosed based on the information of excessive alcohol consumption, and it is recommended that people with suspected AFLD or NAFLD be questioned carefully about alcohol use (Sanyal 2002; CSHCMA 2007; Fan 2007). Staging for NAFLD, performed using a combination of radiological and laboratory techniques, is recommended to reduce the requirement for invasive liver biopsy (Dowman 2011).

Fatty liver disease occurs worldwide in people with excessive alcohol intake, in people who are obese, or in people with metabolic syndrome (Browning 2004a; Browning 2004b; Crabb 2004; Rao 2004; Zafrani 2004; Adams 2005; Hamaguchi 2005). Diagnostic differences make estimating the prevalence of fatty liver disease difficult. Population-based studies estimate the prevalence of NAFLD in the general population to be between 2.8% and 46% (Figure 1), depending on the screening test used for liver imaging (eg, ultrasound, computed tomography, or magnetic resonance imaging) (Lazo 2008). The estimated prevalence varies by region: 16.9% in Asian countries, 23.2% in Europe and North America, and 34.7% in the Middle East (Lazo 2008). Another study indicated that the prevalence of liver steatosis on ultrasound was 57% among asymptomatic overweight individuals attending an outpatient clinic (Haentjens 2009). In a study with Chinese people, 63.1% were diagnosed with fatty liver disease on ultrasonography (Wang Y 2010). Most published studies focus on selected subpopulations, particularly on specific subsets within a hospital-based patient population (eg, diabetic or obese individuals) (Denzer 2009; Guajardo-Salinas 2010; Wang Y 2010). Fatty liver disease occurs in all age groups, and there is evidence that the disease is increasing among children, particularly with obesity. One study showed that the prevalence of NAFLD in junior high school students was 4%, which was primarily associated with obesity and reduced daily physical activity (Tsuruta 2010). In an autopsy study of 742 children and adolescents (aged two to 19 years), the prevalence of fatty liver was 38% in obese and 5% in normal-weight children (Schwimmer 2006). Severe disease is more prevalent among adults. People with NAFLD, with or without metabolic syndrome, are at high risk for atherosclerosis (Assy 2010). Fatty liver is an independent predictor of the metabolic syndrome, type 2 diabetes, and cardiovascular disease (Schwimmer 2006).

Figure 1.

Prevalence of nonalcoholic fatty liver disease (NAFLD) in general population. (Adapted from Lazo M, Clark JM. The epidemiology of non-alcoholic fatty liver disease: a global perspective. Seminars in Liver Disease 2008;28:339-50.)

Current treatment of NAFLD focuses primarily on risk factors, such as treating insulin resistance, decreasing delivery of fatty acids to the liver, and using drugs with potentially hepato-protective effects. The current recommended approach for treating NAFLD is to apply lifestyle modification to all participants. People with morbid obesity may also benefit from bariatric surgery, while those who are obese or overweight may benefit from pharmacological therapy (Ahmed 2009). In general, the prognosis of fatty liver disease depends on the extent of liver damage. Steatosis alone generally has a benign course. Data on progression to cirrhosis and the precise risk of mortality are limited (Sanyal 2002).

Description of the intervention

Currently, the only effective treatment for NAFLD is calorie restriction and weight loss (Ahmed 2009). Weight loss may be associated with regression of fat within the liver (Ueno 1997; Dixon 2004). Pharmacological interventions that have been used for fatty liver disease include drugs that improve insulin resistance (eg, metformin), antioxidants (eg, vitamin C, vitamin E), the so-called 'hepato-protective agents' (such as ursodeoxycholic acid, and lipid-lowering drugs (eg, statin and gemfibrozil)), most of which aim to treat the associated abnormal metabolic conditions (Adams 2006). Several of these interventions have been associated with improvement in liver enzyme activity and liver histology (Harrison 2003; Dixon 2004; Promrat 2004; Rallidis 2004; Abdelmalek 2009). Western drugs are generally well tolerated; however, adverse effects, including manifestations due to hepatotoxicity, increased risk of death, heart failure, or pro-arrhythmic potential, may occur in some people (Menon 2001; Sanyal 2004; Guallar 2005; Beltowski 2009; Jacobson 2009). Treatment of AFLD encompasses stop or reduction of alcohol consumption.

An increasing number of people use herbal products, including Chinese herbs, to manage or treat their disease (Eisenberg 1998). Herbal medicines are defined in this review as a product derived from medicinal plants or parts of the plants used for the treatment of a disease, and herbal medicines include the use of plant, animal, and mineral substances in preparations administered as capsules, tablets, teas, injections, decoctions, and powders.

Herbal medicines have been widely used for the management of fatty liver disease. According to the pathological mechanism of traditional Chinese medicine (TCM), fatty liver is characterised by deficiency of three Zang viscera, such as liver, spleen, and kidney, and manifests as spleen Qi deficiency, and liver and kidney deficiency, resulting in phlegm and dampness retaining, Qi stagnation, and blood stasis. Based on the disorder differentiation, the treatment methods for fatty liver are to nourish Qi, using herbs such as Astragalus membranaceous, to strengthen the liver using herbs such as Bupleurum chinense, to strengthen the spleen using herbs such as Crataegus pinnatifida, to clear heat using herbs such as Rheum officinalis and Cassia obtusifolia, to discharge phlegm using herbs such as Alisma orientalis, and to rejuvenate the blood using herbs such as Salvia miltiorrhiza (Xu 2003).

Clinical trials of single herbs, such as Crataegus pinnatifida and Salvia miltiorrhiza, are effective in treating fatty liver disease (Ji 2005; Gu 2007a; Li 2009; Xie 2009; Zhang 2009). One clinical trial of Tiaozhi Yanggan (a herbal formula) decoction showed improvements in the symptoms, signs, liver function, blood lipids, and iconographic indices with no serious adverse reactions in people with NAFLD (Gu 2007a). Danning tablets, a Chinese medicinal herb, showed more beneficial effects than ursodeoxycholic acid in improving body mass index and distress in the hepatic region in people with NAFLD (Ji 2005). All medicinal agents potentially have adverse effects and toxicity, and herbs are no different. Adverse effects of herbal medicines may be intrinsic such as predictable or idiopathic (allergy, anaphylaxis, etc). Some general adverse effects may include low appetite, nausea, stomach-ache, abdominal distension, and diarrhoea.

How the intervention might work

Animal studies indicate that the mechanisms of action vary depending on the medicinal herb used. One animal study showed that TCM could produce a marked effect via relieving lipopolysaccharide-induced liver injury (Gao 2008). The cardiotonic tablets tested for the prevention of AFLD acted via enhanced expression of the peroxisome proliferator-activated receptor alpha (PPAR-alpha) (Horie 2009). The mechanism of action of Xuezhikang (Chinese medicinal herb) on fatty liver disease is likely to involve inhibition of the hepatic expression of tumour necrosis factor-alpha (Hong 2007). The single medicinal herb, Crataegus pinnatifida, contains lipase, which promotes the hydrolysis of fat, and a variety of organic acids, which can increase protease activity (Sha 2009). While some active ingredients from herbal medicines have been identified, the mechanisms of most herbal medicines for the treatment of fatty liver disease are still not clear.

Why it is important to do this review

With a global increase in fatty liver disease, there is considerable merit in investigating therapeutic options that may be used in addition to lifestyle modification, or where lifestyle modification or pharmacological intervention have not worked or are not appropriate. The evidence from randomised clinical trials on the effects of herbal medicines such as Crataegus pinnatifida,Salvia miltiorrhiza,and Yiqi Huoxue formula for fatty liver disease are promising, but the evidence is not conclusive (Ji 2005; Gu 2007a; Li 2009; Zhang 2009). To our knowledge, there are no meta-analyses or systematic reviews of herbal medicines for fatty liver disease. A systematic review that critically appraises the available evidence on the potential benefits and adverse effects of herbal medicines for fatty liver disease is needed to update the body of evidence, to identify areas in need of further research, and also to help people make practical decisions. We wanted to study both AFLD and NAFLD in one review to increase the precision and power of our analyses. However, we are aware that the two major types of fatty liver disease have pathogenetic differences, and we therefore also wanted to test the effects of the individual herbal medicines on AFLD and NAFLD separately, but we also wanted to test their overall effects on fatty liver disease.

Objectives

To assess the beneficial and harmful effects of single-herb products, commercially available proprietary medicines, and combination formulas prescribed by practitioners for people with AFLDor NAFLD.

Methods

Criteria for considering studies for this review

Types of studies

We included randomised clinical trials irrespective of blinding, publication status, or language. We did not include quasi-randomised and observational studies.

Types of participants

Participants of any age, sex, or ethnic origin with AFLD or NAFLD.

Fatty liver disease was diagnosed based on the following criteria (Fan 2007; Dowman 2011):

  1. Imaging techniques showing evidence of hepatic steatosis or steatofibrosis with or without liver biopsy showing histological alterations including simple steatosis, steatohepatitis, and fibrosis.

  2. Exclusion of other causes of hepatic steatosis or steatofibrosis including hepatitis B, hepatitis C, autoimmune hepatitis, and genetic liver diseases such as Wilson's disease and haemochromatosis. We also excluded participants presenting with one or more causes commonly associated with secondary NAFLD (drugs and miscellaneous disorders such as hyper-alpha or hypo-beta-lipoproteinaemia (or both), partial lipodystrophy, environmental toxins, or total parenteral nutrition).

People with NAFLD met the following criteria:

  1. Daily alcohol intake was less than 20 g per day for women and less than 30 g per day for men (Bayard 2006).

  2. Liver biopsy (where available) or other diagnostic criteria (see above) supported the diagnosis of NAFLD.

People with AFLD met the following criteria:

  1. Daily alcohol intake was more than 20 g per day for women and more than 30 g per day for men (Bayard 2006).

  2. Liver biopsy (where available) or other diagnostic criteria (see above) supported the diagnosis of AFLD.

We also accepted diagnosis by national or regional standards.

Types of interventions

Intervention

Medicinal herb refers to using a plant's seeds, berries, roots, leaves, bark, or flowers, or extractions of herbs for medicinal purposes. For inclusion, we considered trials that compared a medicinal herb consisting of a single herb, commercially available proprietary medicines, or prescribed formulas versus placebo, no treatment, a pharmacological intervention, or a non-pharmacological intervention such as diet or exercise.

We considered any pharmacological intervention that might have been administered in addition to the medicinal herb for inclusion as long as all trial comparison groups received it. We included all available interventions under this category regardless of potential mechanisms of action.

For analyses, we grouped the herbal interventions as single herbs, proprietary herbal medicine, or prescribed formulas.

Types of outcome measures

Primary outcomes
  1. Death from any cause.

  2. Hepatic-related mortality.

  3. Hepatic-related morbidity (cirrhosis, variceal bleeding, hepatic encephalopathy, hepato-renal failure, carcinoma).

  4. Adverse events. We defined these as any untoward medical occurrence that may not necessarily have a causal relationship with the treatment, but resulted in a dose reduction or discontinuation of treatment (ICH-GCP 1997). We defined severe adverse events as any event that would increase mortality; was life threatening; required hospitalisation; resulted in a persistent or significant disability; or any important medical event that may jeopardise the participant or require intervention to prevent it.

  5. Health-related quality of life (evaluated by a validated instrument).

Secondary outcomes
  1. Radiological response (degree of fatty liver infiltration assessed by ultrasound, computed tomography , nuclear magnetic resonance, or other imaging techniques).

  2. Biochemical response (serum activities of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatases (ALP), gamma-glutamyl-transpeptidase (GGT), serum total bilirubin, and ferritin).

  3. Histological response (number of people without histological improvement in the degree of fatty liver infiltration, inflammation, and fibrosis).

  4. Costs.

Search methods for identification of studies

Electronic searches

We searched The Cochrane Hepato-Biliary Group Controlled Trials Register (Gluud 2013), the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, Science Citation Index Expanded (Royle 2003), and Allied and Complementary Medicine Database (AMED). The search strategies with the time spans of the searches are given in Appendix 1. The listed English databases were searched to 1 March 2012.

We also searched the Chinese BioMedical Database, Traditional Chinese Medical Literature Analysis and Retrieval System, China National Knowledge Infrastructure, Chinese VIP Information, Chinese Academic Conference Papers Database, and Chinese Dissertation Database. The strategies for these databases were in Chinese and are available from the review authors on request. We searched all Chinese databases to 2 March 2012.

We identified additional key words of relevance during electronic or other searches and modified the search strategies for the electronic databases to incorporate these terms. We included studies published in any language.

Searching other resources

We tried to identify additional trials by searching the reference lists of the included trials.

Data collection and analysis

Selection of studies

Two review authors (ZJ or XLZ and LZL) independently selected the trials to be included in the review according to the prespecified selection criteria. We resolved any disagreements by discussion. We included an adapted preferred reporting Items for systematic reviews and meta-analyses (PRISMA) flow chart of study selection was included (Liberati 2009).

Data extraction and management

For trials that fulfilled the inclusion criteria, two review authors (ZJ or XLZ, and LZL) independently abstracted data on relevant population and intervention characteristics using standard data extraction templates. We resolved any disagreements by discussion, or, if required, by a third review author (JPL).

We tabulated and assessed adverse events with descriptive or statistical analyses between the experimental and control interventions.

Dealing with duplicates and co-publications

If we identified more than one publication of the same randomised clinical trial, we extracted data from the most recent or most explicit publication. We then listed these multiple publications under the original publication.

Assessment of risk of bias in included studies

Two review authors (XLZ and LZL) assessed the methodological quality of each trial independently, using risk of bias domains. We based the definitions on recommendations from the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011), the Cochrane Hepato-Biliary Group Module (Gluud 2013), and publications by Schulz 1995; Moher 1998; Kjaergard 2001; Egger 2003; Wood 2008; Lundh 2012; Savović 2012a; and Savović 2012b.

Sequence generation
  • Low risk of bias: the method used was considered either adequate (eg, computer-generated random numbers, table of random numbers) or unlikely to introduce confounding.

  • Uncertain risk of bias: there was insufficient information to assess whether the method used was likely to introduce confounding.

  • High risk of bias: the method used (eg, quasi-randomised trials) was inadequate and likely to introduce confounding.

Allocation concealment
  • Low risk of bias: the method used (eg, central allocation) was unlikely to induce bias on the final observed effect.

  • Uncertain risk of bias: there was insufficient information to assess whether the method used was likely to induce bias on the estimate of effect.

  • High risk of bias: the method used (eg, open random allocation schedule) was likely to induce bias on the final observed effect.

Blinding
  • Low risk of bias: the trial was described as blinded, the parties that were blinded, and the method of blinding was described, so that knowledge of allocation was adequately prevented during the trial. 

  • Uncertain risk of bias: the trial was described as blind, but the method of blinding was not described, so that knowledge of allocation was possible during the trial.

  • High risk of bias, the trial was not blinded, so that the allocation was known during the trial.

Incomplete outcome data
  • Low risk of bias: the numbers and reasons for dropouts and withdrawals in all intervention groups were described or if it was specified that there were no dropouts or withdrawals. 

  • Uncertain risk of bias: the report gave the impression that there had been no dropouts or withdrawals, but this was not specifically stated. 

  • High risk of bias: the number or reasons for dropouts and withdrawals were not described.

Selective outcome reporting
  • Low risk of bias: predefined, or clinically relevant and reasonably expected outcomes were reported.

  • Uncertain risk of bias: not all predefined, or clinically relevant and reasonably expected outcomes were reported or were not reported fully, or it was unclear whether data on these outcomes were recorded or not.

  • High risk of bias: one or more clinically relevant and reasonably expected outcomes were not reported; data on these outcomes were likely to have been recorded.

Other bias

In addition to the above-mentioned biases, we used the following pattern for industry bias, academic bias, or other bias that could be detected.

  • Low risk of other bias: the trial appeared to be free of other components that could put it at risk of bias.

  • Uncertain risk of bias: the trial may or may not have been free of other components that could put it at risk of bias.

  • High risk of other bias: there were other factors in the trial that could put it at risk of bias; for example, for-profit involvement, authors have conducted trials on the same topic, etc.

Following the evaluation of the above domains, we judged an included trial as a trial with a low risk of bias if the risk of bias was evaluated as 'low' in all the above domains. If we judged the risk of bias as 'uncertain' or 'high', then we listed the trial under the group of trials with 'high risk of bias' trials.

We resolved disagreements by consensus or by consultation with a third review author (JPL).

Measures of treatment effect

Dichotomous data

Dichotomous data (eg, death - yes/no) were expressed as risk ratios (RR) with their 95% confidence interval (CI). We calculated the risk difference (RD) and number needed to treat for an additional beneficial outcome (NNTB) in the analysis, whenever relevant. When adverse events were reported and data could be analysed, we calculated the number needed to treat for an additional harmful outcome (NNTH). We calculated RD, NNTB, and NNTH according to the guidelines in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011).

Continuous data

Continuous outcomes (eg, scores of quality of life) were expressed as mean difference with 95% CI.

Time-to-event data

Whenever time-to-event data (eg, time until death) were available, the treatment effects were expressed as hazard ratios.

Unit of analysis issues

Data from intervention groups in randomised clinical trials, the first period of cross-over trials, and cluster-randomised trials.

Dealing with missing data

We obtained relevant missing data from authors of the included trials. We performed intention-to-treat (ITT) analysis on all data that we obtained from the trial authors. We investigated attrition proportions such as dropouts, losses to follow-up, and withdrawals, and we critically appraised issues of missing data as advised in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011).

Assessment of heterogeneity

In the event of substantial clinical, methodological, or statistical heterogeneity, we only presented the effect estimates for each comparison. We reviewed the trial components, such as participants, diseases, interventions, comparisons, and outcomes, in the included trials to decide if the heterogeneity was substantially large. We identified heterogeneity by visual inspection of the forest plots, by using a standard Chi2 test and a significance level of α = 0.1, in view of the low power of such tests. We specifically examined heterogeneity with the I2 statistic, quantifying inconsistency across studies to assess the impact of heterogeneity on the meta-analysis (Higgins 2002; Higgins 2003). An I2 statistic of 50% and more indicated a substantial level of inconsistency (Higgins 2011). When we found heterogeneity, we attempted to determine potential reasons for it by examining individual trial and subgroup characteristics.

Assessment of biases

We used funnel plots to assess potential existence of bias. There are a number of explanations for the asymmetry of a funnel plot (Sterne 2001). Therefore, we interpreted the results with care (Lau 2006).

Data synthesis

We summarised data statistically whenever they were available, sufficiently similar, and of sufficient quality. We performed statistical analyses using Review Manager 5.1 (RevMan 2011) following the statistical guidelines in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011).

We performed meta-analyses of data, using both random-effects models and fixed-effect models. When significant heterogeneity existed, we reported the results from both models, but when there was no significant heterogeneity, we presented the results from the fixed-effect model only. However, when heterogeneity was substantial, we did not perform a meta-analysis because the effect estimate did not reliably reflect the 'true' value, and we performed a narrative, qualitative summary instead. In order to contrast absolute and relative measures, we also expressed results as NNTB or NNTH. NNTB and NNTH depended, among other things, on the time of follow-up and the baseline risk. Therefore, we tried to adjust for time of follow-up by analysing NNTH and NNTB (Mayne 2006). For discrete data, we adjusted for the baseline risk by analysing change in event proportions. For continuous data, when groups were not matched at baseline, we reported discrete data descriptively.

Trial sequential analysis

Trial sequential analyses (CTU 2011; Thorlund 2011) could reduce the risk of random errors and prevent premature statements of superiority of the experimental or control intervention (Wetterslev 2008). We had planned to perform a trial sequential analysis for our primary outcome with a type I error of 5%, type II error of 20% (80% power), and adjusted for heterogeneity and diversity among included trials (Brok 2008; Wetterslev 2008; Brok 2009; Thorlund 2009; Wetterslev 2009; Thorlund 2010). As it was not possible to perform meta-analyses in this review, we could not perform trial sequential analyses.

Subgroup analysis and investigation of heterogeneity

We mainly carried out subgroup analyses when one of the primary outcome measures demonstrated statistically significant differences between the intervention groups. In any other case, subgroup analyses were clearly marked as a hypothesis-generating exercise.

We planned the following subgroup analyses:

  • NAFLD compared to AFLD.

  • Different durations of intervention.

  • Trials with low risk of bias compared to trials with high risk of bias.

Sensitivity analysis

We performed sensitivity analyses in order to explore the influence of the following factors on intervention effect size.

  • Repeating the analysis excluding any unpublished trials in order to establish how much they dominated the results.

  • Repeating the analysis excluding the trials using the following filters: diagnostic criteria, source of funding (commercially funded compared with non-(commercially) funded), and country.

We also tested the robustness of the results by repeating the analysis using different statistical models (fixed-effect and random-effects models).

Results

Description of studies

Results of the search

Our initial searches identified 8382 citations. All were from electronic searches. After we removed duplicates from different databases, we retained 4810 potentially relevant articles for further assessment. After reading titles and abstracts, we excluded 4719 of these articles because they were duplicates, non-clinical studies, or had study objectives that were different from this review. Ninety-one articles published in Chinese or English were retrieved for further assessment. After screening the full text, we included 76 randomised clinical trials of the 91 trials and we found another trial through reading reference lists of other references. Therefore, we included 77 randomised clinical trials. We excluded 15 studies after reviewing the full papers, and listed the reasons for exclusion in the Characteristics of excluded studies table. We prepared a PRISMA flow diagram to describe the publications found through our searches (Figure 2).

Figure 2.

PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) flow-chart of study selection.

Included studies

We included 77 randomised clinical trials from 77 publications in this review. Further details are given in the Characteristics of included studies table. Seventy-four of the included trials were published in Chinese. The remaining three trials were published in English (Chou 2006; Gu 2007a; Zhang 2008). All of the 77 trials were conducted in China, and all of them used herbal medicines from China. All of the trials employed a parallel two-arm design. We found no unpublished trials.

Participants

We included 6753 participants with fatty liver disease in the 77 trials and only 45 of the 6753 were lost at follow-up. All of the 6753 participants were recruited from Chinese populations. The mean sample size of the trials was 88 participants (range 40 to 200 participants) per trial. Twelve trials did not report the age range of the participants and the ages from the remaining 65 trials ranged from nine to 70 years. Ten trials did not report the mean age of the participants and the mean age (± standard deviation) of the participants from the remaining 67 trials was 42.29 ± 5.87 years. Seven trials did not report the numbers of male and female participants (Huang 2005; Li 2006a; Wu 2006; Ma 2010; Wang 2010; Xu 2010; Wang 2011b). Among the 6210 participants in 70 trials, the proportion of males to females was almost 2:1 (4104 males: 2106 females). Nine trials included inpatients, 40 trials included outpatients, 22 trials included both inpatients and outpatients, and six trials did not specify trial settings.

Diagnosis

Five trials enrolled people with AFLD, 56 trials enrolled people with NAFLD, three trials enrolled people with AFLD or NAFLD, and 13 trials did not specify the type of fatty liver disease. Among the 77 included trials, six trials did not specify diagnostic criteria (Table 1), 64 trials followed the fatty liver disease diagnostic criteria issued by the Fatty Liver and Alcoholic Liver Diseases Group, Society of Hepatology, Chinese Medical Association (see Table 1). Seven trials specified the diagnostic criteria but did not give citations for diagnostic criteria.

Interventions

There were large variations in the formulations, dosages, routes of administration, durations of treatment, and control interventions in the included trials among the herbal medicines tested (Table 2 and Characteristics of included studies).

Table 2. Herbal medicines and adverse effects in the included studies
  1. -: not reported on this item.

Study ID Chinese Name Botanical Name of Ingredient Adverse events (n / %)
Cao 2011Huazhuo Xiaozhi decoction Bupleurum chinensis,Paeonia albiflora Pallas,var,trichocarpa,Atractylodes ovata,Poria cocos,Curcuma aromatica,Saliva miltiorrhiza,Alisma plantago var. viglomum,Crataegus cuneata,Rheum palmatum,Glycyrrhiza glabra var. glandulifera.Not reported.
Chen 2010Huatan Huoxuefang decoction Bupleurum chinense (with vinegar), Salvia miltiorrhiza, Poria cocos, Alisma orientalis, Pinellia ternate, Hordeum vulgare (fried), Crataegus pinnatifida, Nelumbo nucifera, dialectical to add and subtract: Astragalus membranaceous, Atractylodes macrocephala, Melia toosendan, Citrus aurtantium (fried), Codonopsis pilosula, Atractylodes macrocephala, Polygonum multiflorum, Lycium barbarum, Polygonum cuspidatum, Sedum sarmentosum.Not reported.
Chen 2007aZini Zhigan decoction Atractylodes ovata,Cassia obtusifolia.2 cases of dry mouth in the control group.
Chen 2007bJiangzhi Baogan decoction Astragalus membranaceous,Saliva miltiorrhiza,Atractylodes japonica,Atractylodes ovata,Abrus cantoniensis,Crataegus cuneata,Citrus reticulata,Curcuma aromatica,Bupleurum chinensis,Typha latifolia.Not reported.
Cheng 2006Zhiyan Xiao decoction Astragalus membranaceous,Curcuma zedoaria,Nelumbo nucifera,Polygonum multiflorum,Alisma plantago,Saliva miltiorrhiza,Schizandra chinensis.Not reported.
Chou 2006Jiaogulan Cha Gynostemma pentaphyllum.Not observed.
Dai 2009Shuli Qingzhi power Polygonum cuspidatum,Artemisia capillaris,Onioselinum unvittatum,Paeonia albiflora,Curcuma aromatica,Cyperus rotundus,Trichosanthis kirilowii ,Allium macrostemon,Dioscorea batatas,Aquilaria agallocha,Perichaeta communissma,Auricularia auricula,Astragalus membranaceous,Angelica sinensis,Atractylodes pinnatifida,Poria cocos,Schizandra chinensis,Indigo naturalis.Not reported.
Dang 2007Shiweizhigankang  capsule Lysimachia christinae,Citrus reticulate,Curcuma longa,Rheum palmatum.1 case of diarrhoea.
Deng 2003aHuanglong Ganzhixiao decoction Astragalus membranaceous, Polygonatum chinense,Epimedium sagittatum,Crataegus pinnatifida,Alisma plantago.Not reported.
Deng 2010Xiaoyao tabletIngredients not reported.Not reported.
Fei 2009Yuqin granules Curcuma wenyujin,Panax notoginseng,Bupleurum chinense,Glycyrrhiza uralensis,Carthamus tinctorius,Polyporus umbellatus.Not reported.
Gu 2007aTiaozhi Yanggan decoction Bupleurum chinense, Curcuma longa, Paeonia lactiflora, Crataegus pinnatifida, Alisma orientalis, Cassia obtusifolia, Polygonum cuspidata, Rheum palmatum, Prunus armeniaca, Salvia miltiorrhiza, Raphanus sativus, Citrus reticulata.21 cases of diarrhoea, 22 of gastric discomfort or light pain, 15 of abdominal discomfort or dull pain and 11 cases of nausea.
Guan 2010Wild apricot decoction Prunus armeniaca.3 cases of gastric discomfort in the intervention group.
Guo 2007Hegan Yin decoction Amygdalus davidiana,Pinella ternata,Poria cocos,Citrus reticulata,Achyranthes bidentata,Saliva miltiorrhiza, Bupleurum chinensis,Glycyrrhiza glabra.Not reported.
Guo 2010Xiaogan Jiangzhifang formula Crataegus cuneata,Saliva miltiorrhiza,Panax notoginseng,Atractylodes ovata,Poria cocos,Alisma plantago,Cassia obtusifolia,Rheum palmatum.Not reported.
Hu 2010Tangganjian decoction

Paeonia albiflora,var. trichocarpa,Angelica sinensis,

Bupleurum chinensis,Poria cocos,Artemisia capillaris,Schizandra chinensis.

Not reported.
Huang 2005Shugan Lipi San

Bupleurum chinensis,Paeonia albiflora,

Atractylodes ovata,Panax notoginseng,

Alisma plantago var. viglomum,Cassia obtusifolia,

Pueraria lobata,Gynostemma pentaphyllum.

Not observed.
Huang 2011Quyu Huazhuo decoction

Alisma plantago var. viglomum,Sargassum siliquastrum,

Saliva miltiorrhiza,Crataegus cuneata,Silybum marianum,Gallus-gallus domesticus,Cassia obtusifolia,

Bupleurum chinensis,Curcuma aromatica,Phyllostachys nigra var. henonis, Coix lacrym-jobi var. frumenttacea,  Ostrea cucullata,Trionyx sinensis,Rehmannia glutinosa,

Polygonum multiflorum,Polygonatum chinense.

Not reported.
Huo 2008Kezhi capsuleIngredients not reported.Several people increased stool frequency and had mid abdominal pain.
Ji 2005Danning tablet Rheum palmatum,Polygonum cuspidatum,Citrus reticulate,Curcuma wenyujin,Crataegus pinnatifida, Imperata cylindrica var.Rash (1), nausea (3), defecate number increase for many participants, but tolerant and normal after some days.
Jia 2003Juge Yigan decoction Hovenia acerba,Pueraria lobata,Taraxacum albidum,Forsythia supensa,Artemisia capillaris,Patrinia scabiosaefolia,Polygonum cuspidatum,Bupleurum chinensis,Curcuma longa,Alisma plantago var. viglomum,Angelica sinensis,Saliva miltiorrhiza,Glycyrrhiza glabra.Not reported.
Jia 2009Shengqing Jiangzhuo granules Campanumaea pilosula,Pueraria lobata,Crataegus pinnatifida,Bupleurum chinensis,Alisma plantago var. viglomum,Atractylodes japonica,Saliva miltiorrhiza,Nelumbo nucifera.45 cases (72.5%) in the intervention group and 47 cases (75.8%) in the control group; but there were no serious adverse events; frequency of fatigue in the control group was higher and frequency of dry throat and flatulence in the intervention group was higher.
Jiang 2009Zhishi Xiaopi decoction

Citrus aurantium,Campanumaea pilosula,Zingiber offcinale,Glycyrrhiza glabra,Hordeum sativum,Medicata Fermentita Fujianensis Massa,Poria cocos,Atractylodes macrocephala,Pinella ternata, Magnolia  officinalis  

Coptis chinensis.

Not observed.
Kong 2010Lipid-lowering granules Bupleurum chinense, Paeonia lactiflora, Citrus aurantium, Crataegus pinnatifida (charred), Panax notoginseng, Poria cocos, Cyperus rotundus, Arisaema heterophyllum (bile prepared), Pinellia ternate (prepared).Not reported.
Li 2005Huoxue Qinggan decoction Saliva miltiorrhiza,Paeonia albiflora, Imperata arundinacea,Artemisia capillaris,Poria cocos,Pueraria lobata,Glycyrrhiza glabra.Not observed.
Li 2007Shuanghu Qinggan granule Polygonum cuspidatum,Saliva miltiorrhiza,Lonicera japonica,Coptis chinensis,Pinella ternata.Not reported.
Li 2008Shenling Baizhu powder with Erchen decoction Codonopsis pilosula, Atractylodes macrocephala (fried), Poria cocos, Alisma orientalis, Citrus reticulata, Pinellia ternate (prepared with ginger), Artemisia capillaris, Polygonum multiflorum, Crataegus pinnatifida, Salvia miltiorrhiza, Nelumbo nucifera, Glycyrrhiza uralensis.Not reported.
Li 2009Qinggan decoction Bupleurum chinense, Salvia miltiorrhiza, Oldenlandia diffusa, Astragalus membranaceous, Polygonum cuspidatum, Lycium barbarum, Crataegus pinnatifida, Glycyrrhiza uralensis, Rheum palmatum, Alisma orientalis, Artemisia capillaris, Atractylodes macrocephala.Not reported.
Li 2010Xiaotan Jiangzhi formula Pinella ternata,Citrus maxima,Poria cocos,Bupleurum chinensis,Astragalus membranaceous,Glycyrrhiza glabra,Zingiber offcinale,Armeniaca mume,Crataegus pinnatifida,Rheum palmatum, Alisma plantago,Paeonia moutan,Atractylodes macrocephala.Not reported.
Li 2006aBaogan Xiaozhi power Coptis chinensis,Alisma plantago, Cassia tora,Bupleurum chinensis,Pinella ternata,Acorus gramineus,Crataegus pinnatifida,Areca catechu.Not reported.
Li 2006bBaogan Xiaozhi pellet Bupleurum chinensis,Citrus aurantium,Paeonia albiflora,Cassia tora,Crataegus pinnatifida,Alisma plantago, Paeonia albiflora,Conioselinum unvittatum,Fritillaria roylei,Saliva miltiorrhiza,Nelumbo nucifera,Benincasa hispida,Polygonatum chinese,Glycyrrhiza glabra.Not reported.
Liang 2008Herbs mixtures for colon dialysis Atractylodes lancea, Pogostemon cablin, Eupatorium fortunei, Pinellia ternate, Cyperus rotundus, Citrus aurtantium, Cassia obtusifolia, Salvia miltiorrhiza, Crataegus pinnatifida, Rheum palmatum.Not reported.
Liang 2010Jianpi Huashi decoction Codonopsis pilosula,Poria cocos, Atractylodes macrocephala, Coix lacryma-jobi var. ma-yuen, Salvia miltiorrhiza, Crataegus pinnatifidaCurcuma wenyujin, Cassia obtusifolia.Not reported.
Liang 2011Baogan Xiaozhikeli Atractylodes ovata,Curcuma longa,Bupleurum chinensis,Astragalus membranaceous,Alisma plantago,Saliva miltiorrhiza.Not reported.
Lin 2011Yunpi Tongluo formula Atractylodes japonica,Crataegus cuneata,Rheum palmatum,Pinella ternata,Raphanus sativus, Alisma plantago,Plantago major,Cassia obtusifolia.4 cases of fatigue, dizziness, diarrhoea, and abdominal pain.
Lin 2010aXiaozhi Jianpi decoction Panax notoginseng,Paeonia albiflora,Rheum palmatum,Polygonum cuspidatum,Artemisia capillaris,Poria cocos,Bupleurum chinensis.Not reported.
Lin 2010bSelf prescripted Jianpi Huatan formula Astragalus Henryi,Alisma plantago var. viglomum,Torr,Crataegus cuneata,Saliva miltiorrhiza Bge,Atractylodes ovata, Thunb,Pinella ternata,Breitenbach,Citrus reticulata Blanco,Polygonum cuspidatum,Schizandra chinensis (Turcz) Baill,Poria cocos Wolf,Cassia obtusifolia,Gynostemma pentaphyllum (Thumb) Makino.13 people with increased stool frequency and mid-abdominal pain in the intervention group.
Liu 2008Qiyin Chongji decoction Astragalus membranaceous,Artemisia capillaris,Crataegus pinnatifida,Psorales corylifolial,Alisma orientalis,Cassia obtusifolia.Not reported.
Liu 2009Xiaoyu Huatan decoction Alisma orientalis, Pinellia ternate, Sargassum pallidum, Salvia miltiorrhiza, Curcuma wenyujin, Bupleurum chinense, Cassia obtusifoliaRheum palmatum, Astragalus membranaceous, Atractylodes macrocephala. Dialectical to add and subtract: Amomun kravanh, Amomum villosum, Citrus reticulata, Raphanus sativus, Gentiana manshurica, Gardenia jasminoidesCurcuma wenyujin, Trogopterus xanthipes (dung), Codonopsis pilosula, Epimedium brevicornum, Cuscuta chinensis.Not reported.
Lou 2008Yiqi Sanju granule Astragalus membranaceous,Coptis chinensis3 cased of mild diarrhoea, gastric discomfort, and reduced appetite.
Ma 2009Zhigan Qing granule Astragalus membranaceous,Euonymus ulmoides,Cornus officinalis,Angelica sinensis,Bupleurum chinensis,Citrus reticulata,Blanco,Typha latifolia,Crataegus pinnatifida.Not reported.
Ma 2010Qinggan Xiaozhi decoction Bupleurum chinenseCurcuma wenyujin, Polygonum cuspidatum, Artemisia capillaris, Rheum palmatum, Crataegus pinnatifida, Alisma orientalis, Poria cocos, Cassia obtusifolia, Pinellia ternate, Citrus reticulata, Astragalus membranaceous, Salvia miltiorrhiza.Not reported.
Mi 2010Jiangan Jiangzhi tablet Poria cocos, Salvia miltiorrhiza, Cassia obtusifolia, Crataegus pinnatifida, Polygonum multiflorum, Curcuma wenyujin, Citrus aurtantium.1 case of diarrhoea.
Pu 2009Modified Wendan decoction Pinella ternata,Citrus aurantium,Alisma plantago,Poria cocos,Citrus reticulata,Crataegus pinnatifida,Areca catechu,Phyllostachys nigra,Medicata Fermentita Fujianensis Massa,Saliva miltiorrhiza,Glycyrrhiza glabra,Zingiber offcinale,Zizyphus vulgaris,Astragalus membranaceous,Atractylodes ovata, Melia toosendan,Corydalis bulbosa,Magnolia officinalis,Cyperus rotundus.Not reported.
Song 2006Panax Notoginseng powder Panax Notoginseng.Not reported.
Wang 2006Chuige Jiugan decoction Lycopodium cernum,Pueraria lobata,Saliva miltiorrhiza,Curcuma aromatica,Cassia tora, Alisma plantago,Atractylodes ovata, Crataegus pinnatifida,Bupleurum chinensis,Paeonia albiflora,Polygonum cuspidatum,Atractylodes ovata,Rheum palmatum,Cyperus rotundus,Scutellaria baicalensis,Gentiana scabra. Not reported.
Wang 2010Chaihu Shugan decoction Bupleurum chinensis,Citrus aurantium,Citrus reticulata Blanco, Cyperus rotundus,Melia toosendan,Crataegus pinnatifida,Saliva miltiorrhiza,Paeonia albiflora,Rheum palmatum,Alisma plantago,Polygonum multiflorum,Artemisia capillaris,Paeonia moutan,Gardenia florida,Curcuma longa,Curcuma aromatica,Trionyx sinensis,Cornus officinalis,Ligustrum lucidum,Rehmannia glutinosa.Not reported.
Wang 2011aTiaogan Lizhong decoction Dryobalanops aromatica,Citrus maxima,Angelica sinensis,Paeonia albiflora,Paeonia  moutan,Lycopus lucidus,Polygonum cuspidatum, Cassia tora,Crataegus pinnatifida,Campanumaea pilosula, Atractylodes ovata, Amygdalus davidiana,Poria cocos,Hovenia acerba,Indigo naturalis,Curcuma aromatica,Pueraria lobata,Phaseolus radiatus,Rheum palmatum.Not observed.
Wang 2008aSisheng Jiangzhi decoction Astragalus membranaceous, Crataegus pinnatifida, Cassia obtusifolia,Nelumbo nucifera,Coix lacryma-jobi var. ma-yuen, Massa Fermenata, Salvia miltiorrhiza. Dialectical to add and subtract: Bupleurum chinense,Citrus aurtantium, Curcuma wenyujin, Scutellaria baicalensis, Plantago asiatica, Clematis armandi, Prunus persica, Carthamus tinctorius, Angelica sinensis.Not observed.
Wang 2008bJiangzhi Ligan decoction Sargassum Pallidum, Salvia miltiorrhiza, Cassia obtusifolia, Alisma orientalis, Nelumbo nucifera, Curcuma wenyujin, Curcuma longa, Hirude nipponica, Bupleurum chinense. Dialectical to add and subtract: Corydalis yanhusuo, Rheum palmatum, Aloe vera var. chinesis, Sedum sarmentosum, Gentiana manshurica, Panax ginseng, Astragalus membranaceous, Pseudostellaia heterophylla, Epimedium brevicornum.Not reported.
Wang 2011bBushen Yipi formula Lycium chinensel,Rehmannia glutinosa,Polygonum multiflorum,Astragalus membranaceous,Atractylodes macrocephala,Coix lacrym-jobi,Saliva miltiorrhiza,Citrus reticulata,Citrus reticulata.Not reported.
Wu 2006Shan Beimu decoction Crataegus pinnatifida,Fritillaria roylei,Alisma plantago,Trichosanthis kirilowii,Artemisia capillaris,Polygonum cuspidatum.Not reported.
Wu 2008Herbs mixtures Crataegus pinnatifida,Rheum palmatum,Saliva miltiorrhiza, Alisma plantago,Bupleurum chinensis,Cassia obtusifolia,Pinella ternata,Poria cocos,Citrus reticulata,Astragalus membranaceous,Atractylodes ovata, Melia toosendan,Corydalis bulbosa,Magnolia officinalis,Cyperus rotundus.Not reported.
Wu 2010Self prescripted Chailing decoction Bupleurum chinensis,Scutellaria baicalensis,Atractylodes ovata, Polyporus umbellatus,Poria cocos,Alisma plantago,Abrus cantoniensis Hance,Curcuma aromatica,Coix lacrym-jobi,Crataegus pinnatifida,Paeonia albiflora,Glycyrrhiza glabra,Chrysanthemum sinense,Uncaria hirsuta,Cassia tora,Sophora japonica,Eclipta prostrata,Atractylodes macrocephala,Areca catechu,Astragalus membranaceous,Dioscorea opposita.Not reported.
Xin 2005Qingre Huatan Huoxue formula Artemisia capillaris,Trichosanthis kirilowii ,Gynostemma pentaphyllum,Saliva miltiorrhiza,Alisma plantago,Poria cocos,Polygonum multiflorum,Bupleurum chinensis,Curcuma aromatica,Prunella vulgaris,Crataegus pinnatifida.3 cases of mild diarrhoea in the start of treatment.
Xu 2008Huganning tablets Lycopodium cernum,Polygonum cuspidatum,Saliva miltiorrhiza,Ganoderma lucidum.5 cases of mid nausea and decreased appetite in the intervention group and 2 cases of dizziness and decreased appetite in the control group.
Xu 2010Jiejiu Hugan decoction Pueraria lobata,Forsythia suspensa, Acorus tatarinowii,Glycyrrhiza uralensis, Artemisia capillaris, Polygonum cuspidatum, Bupleurum chinense.Not observed.
Yang 2004Xiaozhi Jianggan decoction Crataegus pinnatifida,Polygonum multiflorum,Saliva miltiorrhiza,Chrysanthemum sinense,Nelumbo nucifera,Cassia obtusifolia,Paeonia albiflora,Bupleurum chinensis,Citrus aurantium,Alisma plantago,Lycopus lucidus,Citrus reticulata,Melia toosendan,Curcuma aromatica,Paeonia moutan,Gardenia florida,Angelica sinensis,Lycium chinensel,Rehmannia glutinosa,Pinella ternata,Citrus reticulata,Conioselinum unvittatum, Sparganium stoloniferum,Curcuma zedoaria,Panax ginseng,Astragalus membranaceous.Not reported.
Yang 2005Guben Xiaozhuo decoction Polygonum multiflorum,Epimedium macranthum,Astragalus membranaceous,Polygonum cuspidatum,Alisma plantago v,Ginkgo biloba,Panax notoginseng, Crataegus pinnatifida,Citrus aurantium,Poria cocos,Coix lacrym-jobi,Bupleurum chinensis,Curcuma aromatica,Saliva miltiorrhiza,Paeonia albiflora,Atractylodes macrocephala.Not reported.
Yang 2006Qingzhifugan decoction Astragalus membranaceous,Salvia miltiorrhiza,Poria cocos, Atractylodes macrocephala, Sophora flavescens, Crataegus pinnatifida, Cassia obtusifolia, Polygonum multiflorum. Dialectical to add and subtract: Atractylodes macrocephala, Corydalis yanhusuo, Dolichos lablab, Amomum villosum.Not reported.
Yang 2009Shennong Ganzhining tablet Polygonum multiflorum,Polygonum cuspidatum,Gynostemma pentaphyllum, Nelumbo nucifera,Cassia obtusifolia,Saliva miltiorrhiza.Not reported.
Zeng 2007Xiaozhi decoction Alisma plantago,Saliva miltiorrhiza,Cassia obtusifolia,Crataegus pinnatifida,Bupleurum chinensis,Curcuma zedoaria,Poria cocos,Angelica sinensis,Citrus reticulata,Pinella ternata.1 person increased stool frequency in the intervention group.
Zhang 2002Clearing heat and removing dampness formula Bupleurum chinensis,Artemisia capillaris,Curcuma aromatica,Rheum palmatum,Pueraria lobata,Lysimachia christinae,Polygonum cuspidatum.Not reported.
Zhang 2003Hugan tablet Artemisia capillaris,Bupleurum chinensis,Isatis tinctoria,Schizandra chinensis.Not reported.
Zhang 2005aQugan Zhi decoction Crataegus pinnatifida, Polygonum multiflorum,Saliva miltiorrhiza,Cassia obtusifolia,Paeonia albiflora,Poria cocos,Alisma plantago,Curcuma aromatica,Bupleurum chinensis,Ginkgo biloba, Citrus reticulata,Citrus aurantium,Atractylodes macrocephala, Magnolia officinalis,Scutellaria baicalensis,Angelica sinensis.Not reported.
Zhang 2006aXuezhi Kang capsulePatent medication, ingredients not reported.4 cases of nausea and gastric discomfort in the intervention group.
Zhang 2006bGanzhi Kang capsulePatent medication, ingredients not reported.Not reported.
Zhang 2007Sanyu Huazhuo decoction Bupleurum chinensis,Curcuma aromatica,Artemisia capillaris,Raphanus sativus,Coptis chinensis,Alisma plantago,Cassia tora,Prunella vulgaris,Saliva miltiorrhiza,Crataegus pinnatifida,Lycopus lucidus,Atractylodes ovata, Amomum cardamum,Polygonum multiflorum,Morus multicaulis,Citrus reticulata,Campanumaea pilosula,Polygonatum chinense,Angelica sinensis,Paeonia albiflora.Not reported.
Zhang 2008Quyu Huatan Tongluo decoction Bupleurum chinense, Scutellaria bicalensis, Pinellia ternate, Codonopsis pilosula, Glycyrrhiza uralensis, Ziziphus jujuba, Polygonum cuspidatum, Morinda officinalis, Hedyotis diffusa.Not observed.
Zhang 2011Kangzhi decoction Astragalus membranaceous, Crataegus pinnatifida,Chrysanthemum sinense,Atractylodes ovata, Cassia obtusifolia,Alisma plantago,Nelumbo nucifera,Atractylodes japonica,Lycopodium cernum.Not observed.
Zhao 2009Self prescripted Huoxue Jiangzhi decoction Lycium chinense,Crataegus pinnatifida,Saliva miltiorrhiza,Atractylodes ovata,Astragalus membranaceous,Pinella ternata,Angelica sinensis,Artemisia capillaris,Nelumbo nucifera,Arisaema erubescens,Amygdalus davidiana,Carthamus tinctorius,Paeonia albiflora,Curcuma aromatica,Ligustrum lucidum,Eclipta prostrata,Polygonum multiflorum.Not reported.
Zhao 2010Qiyin Cha Astragalus membranaceous,Artemisia capillaris,Crataegus pinnatifida,Psorales corylifolial,Alisma orientalis,Cassia obtusifolia,Ilex lutifolia,Panax notoginseng,  Rheum palmatum.Not reported.
Zhou 2008Kezhi capsulePatent medication, ingredients not reported.Not reported.
Zhou 2009Lishi Huoxue Tongluo decoction Artemisia scoparia,Alisma orientalis,Crataegus pinnatifida,Rheum palmatum,Carapax trionycis,Saliva miltiorrhiza,Luffa cylindrica.Several cases of mild stomach ache, number of stools increased.
Zhu 2006Zhixiao  capsule Poria cocos, Atractylodes macrocephala,Sinapi alba,Citrus reticulata, Crataegus pinnatifida, Alisma orientalis.Not reported.
Zhu 2010Xiaotan Hugan decoction Astragalus membranaceous, Cassia obtusifolia, Salvia miltiorrhiza, Alisma orientalis, Lysimachia christinae, Curcuma wenyuji, Paeonia lactiflora, Bupleurum chinense.Not observed.

In total, 75 different Chinese herbal medicines were tested, and the compositions of the herbal medicines were single-herb products, commercially available proprietary herbal medicines, and combination formulas prescribed by practitioners (Table 2). The formulations of the herbal medicines were different. The Chinese herbal medicines were prepared in the form of capsules, tablets, granules, herbal teas, and decoctions (beverages that result from the method of decoction). No trial reported the quality standards of the herbal preparations.

The following herbs were most commonly included as an ingredient in different products: Crataegus pinnatifida,Salvia miltiorrhiza,Alisma orientalis,Bupleurum chinense,Cassia obtusifolia,Astragalus membranaceous,Rheum palmatum, Curcuma wenyujin,Citrus reticulata,Poria cocos,Atractylodes macrocephala,Artemisia capillaries,Pinellia ternate,Polygonum cuspidatum,Glycyrrhiza uralensis,Codonopsis pilosula,Citrus aurantium,Nelumbo nucifera,Paeonia lactiflora,Panax notoginseng,and Polygonum multiflorum. They were often used in a formula of multiple ingredients in various combinations. OnlyGynostemma pentaphyllum,Panax notoginseng,and Prunus armeniaca were used as single-herb products. These herbs have the alleged function of nourishing Qi, strengthening the liver and spleen, clearing heat, discharging phlegm, and restores the blood, and the herbs were chosen based on TCM theory. Detailed information is shown in Table 2.

Other herbal ingredients used in the formulas included:Amomum villosum,Carthamus tinctorius,Coix lacryma-jobi var. ma-yuen,Corydalis yanhusuo,Curcuma longa,Cyperus rotundus,Epimedium brevicornum,Gentiana manshurica,Hordeum vulgare,Lysimachia christinae,Psorales corylifolial,Raphanus sativus,Sargassum pallidum. Ilex lutifolia,Acorus tatarinowii,Aloe vera var. chinensis,Amomun kravanh,Angelica sinensis,Arisaema heterophyllum,Clematis armandi,Coptis chinensis,Cuscuta chinensis,Dolichos lablab,Eupatorium fortune,Forsythia suspense,Gardenia jasminoides,Hedyotis diffusa,Imperata cylindrica var. major,Luffa cylindrical,Massa Fermenata,Morinda officinalis,Panax ginseng,Plantago asiatica,Pogostemon cablin,Polyporus umbellatus,Prunus armeniaca,Prunus persica,Pseudostellaia heterophylla,Pueraria lobata,Scutellaria bicalensis,Sedum sarmentosum,Sinapi alba,Sophora flavescens,Trionys sinensis,Trogopterus xanthipes,Ziziphus jujube,Zingiber offcinale,Euonymus ulmoides,Cornus officinalis,Melia toosendan,Chrysanthemum sinense,Uncaria hirsute,Eclipta prostrata,Trichosanthis kirilowii,Isatis tinctoria, and Lycium chinense. Detailed information is shown in Table 2.

The control interventions included placebo, conventional medicine, lifestyle intervention, or lifestyle intervention plus conventional drug(s). The conventional drugs included Essentiale® forte capsules (phosphatidylcholine from soybeans), simvastatin, ethyl polyenoate soft capsules, ursodeoxycholic acid, Essentiale® forte + vitamin, polyene phosphatidyl choline capsules, tiopronin tablets, methionine plus choline bitartrate tablets, silibinin capsules, simvastatin plus diammonium glycyrrihizinate, thiola tablets, reduced glutathione tablets, silybin meglumine tablets or Dongbao Gantai (Ansua Danjia Pian) tablets. Detailed information is shown in the Characteristics of included studies table.

The comparisons were:

  • Herbal medicines versus placebo (one trial).

  • Herbal medicines plus lifestyle intervention versus placebo plus lifestyle intervention (two trials).

  • Herbal medicines plus lifestyle intervention versus lifestyle intervention (five trials).

  • Herbal medicines versus conventional medicine (17 trials).

  • Herbal medicines plus conventional drug versus the same conventional drug (two trials).

  • Herbal medicines plus lifestyle intervention versus conventional drug plus lifestyle intervention (35 trials).

  • Herbal medicines plus lifestyle intervention plus conventional drug(s) versus lifestyle intervention plus the same conventional drug(s) (15 trials).

The durations of treatment were one month in five trials, one and a half months in five trials, two months in 15 trials, three months in 39 trials, six months in 10 trials, 12 months in two trials, and 48 months in one trial (see Characteristics of included studies table). The different treatment durations were not subjected to a sensitivity analysis because there was an insufficient number of homogeneous trials to allow a meta-analysis.

We found no unpublished trials.

Outcomes

None of the trials reported primary outcomes including death from any cause, hepatic-related mortality, hepatic-related morbidity, and health-related quality of life. There were no outcome data in any of the trials on costs. Reported outcomes included serum AST, ALT, GGT, and ALP levels, ultrasound findings, computed tomography (CT) scan findings, and adverse effects. All trials measured outcomes at the end of treatment, and no trial reported follow-up data after the end of treatment. No serious adverse events were reported, but some minor adverse effects occurred (see detailed information in Table 2).

Twenty-seven of the 77 trials reported details on adverse events in the medicinal herb groups. Sixteen trials observed mild adverse events, such as rash, nausea, diarrhoea, gastric discomfort, reduced appetite, light pain, and stomach ache (Table 2). Eleven trials observed no adverse events in the Chinese herbal medicines groups (Table 2). The remaining 50 trials did not report adverse events in the intervention groups.

Excluded studies

We excluded 15 studies as they did not meet the inclusion criteria of this review. The reasons for exclusion are listed in the Characteristics of excluded studies table.

Risk of bias in included studies

Most of the trials provided limited information about study design and methodology. Three multicentre randomised clinical trials were identified (Ji 2005; Li 2008; Wang 2008b). Twenty eight trials had prespecified inclusion criteria, and 32 trials had prespecified exclusion criteria (Characteristics of included studies). None of the trials stated that they had performed an ITT analysis to evaluate the data. Assessment of risk of bias is described for each included trial in the Characteristics of included studies table. Our judgements about each risk of bias domain are presented as percentages across all included trials in Figure 3, and our judgements about each risk of bias domain for each included trial are shown in Figure 4.

Figure 3.

Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.

Figure 4.

Risk of bias summary: review authors' judgements about each risk of bias item for each included study.

Allocation

Sequence generation and allocation concealment

Twenty-eight trials reported detailed information on allocation sequence generation and were regarded as adequate, and 49 trials did not report the specific methods of allocation sequence generation (Characteristics of included studies) (Figure 4). Two of the 77 included trials reported allocation concealment methods, and the methods were assessed as adequate (Ji 2005; Kong 2010). The remaining trials did not provide information on allocation concealment. Detailed information is shown in the Characteristics of included studies table and Figure 4.

Blinding

One trial claimed that it used double-blinding but it did not report who was blinded (Ji 2005). One trial reported that the participants were blinded by using placebo (Chou 2006). One trial reported that the statisticians and outcome assessors were blinded (Kong 2010). The remaining trials did not mention blinding. Detailed information is shown in the Characteristics of included studies table and Figure 4.

Incomplete outcome data

Three trials gave unclear information on withdrawals and loss to follow-up (Wang 2008a; Li 2009; Wang 2011b). Three trials reported participants lost to follow-up without providing the reasons for the loss and were assessed as trials with high risk of bias (Ji 2005; Chou 2006; Lin 2011). The remaining 71 trials reported that no participants were lost to follow-up during the trial or specified the numbers and reasons of withdrawal and loss to follow-up and were assessed as trials with low risk of bias. Detailed information is shown in the Characteristics of included studies table and Figure 4.

Selective reporting

In 24 trials, some prespecified outcome measures were not reported, and the trials were assessed as having high risk of reporting bias (Characteristics of included studies and Figure 4). Fifty-three trials were considered free of selective reporting (Characteristics of included studies and Figure 4).

Other potential sources of bias

Only one of the included trials reported sample size calculations and was assessed as low risk of other bias (Chou 2006). The remaining trials did not report the sample size calculations and were assessed as not free of other potential sources of bias. Detailed information is shown in the Characteristics of included studies table and Figure 4.

Effects of interventions

Reported outcomes included adverse effects, findings from ultrasound scan or computed tomography scan, and serum levels of AST, ALT, GGT, and ALP. No serious adverse events were reported. We could not perform meta-analyses in this review and we only did qualitative synthesis on the included trials due to heterogeneity in the participants, interventions, and controls. We could not do trial sequential analyses to control for risks of random errors because meta-analyses were not performed.

We reported the results according to the outcomes.

Primary outcomes  

Death from any cause

None of the trials reported death.

Hepatic-related mortality

None of the trials reported outcomes on hepatic-related mortality.

Hepatic-related morbidity (cirrhosis, variceal bleeding, hepatic encephalopathy, hepato-renal failure, carcinoma)

None of the trials reported outcomes on hepatic-related morbidity.

Adverse events

Five trials reported adverse events in the intervention and control group (Zhang 2003; Xu 2008; Jia 2009; Guan 2010; Lin 2011). No significant differences were found between the intervention and the control groups (Table 3). We could not perform a meta-analysis as there was only one trial for each medicinal herb.

Table 3. The RevMan results and exact fisher test results of studies that meta-analysis could not be done (categorical variables)
  1. ALT: alanine aminotransferase; AST: aspartate aminotransferase; CI: confidence interval; CT: computed tomography; OR: odds ratio; PPC: polyene phosphatidylcholine; RR: risk ratio; UDCA: ursodeoxycholic acid.

Study ID  Comparison  OutcomeRevMan resultsFisher's test
RR (95% CI)OR (95% CI)P valueOR (95% CI)
Jia 2009Shengqing Jiangzhuo granules + lifestyle intervention versus lifestyle interventionAdverse events1.04 (0.85 to 1.29)1.18 (0.53 to 2.65)0.8381.18 (0.53 to 2.65)
Guan 2010Wild apricot versus vitamin B and C + glucurolactone tabletsAdverse events6.13 (0.33 to 113.50)0.10 (-0.02 to 0.22)0.240-
Lin 2011Yunpi Tongluo formula + lifestyle intervention versus UDCA + lifestyle interventionAdverse events9.28 (0.52 to 165.50)0.13 (0.00 to 0.26)0.053-
Xu 2008Huganning tablets + metformin hydrochloride tablets + lifestyle intervention versus metformin hydrochloride tablets + lifestyle interventionAdverse events0.40 (0.08 to 1.89)0.35 (0.06 to 2.00)0.4220.35 (0.02 to 2.00)
Zhang 2003Hugan tablets + UDCA + lifestyle intervention versus UDCA + lifestyle interventionAdverse events8.90 (0.48 to 166.10)10.02 (0.50 to 202.47)0.079-
Guan 2010Wild apricot versus vitamins B and C + glucurolactone tabletsAbnormal B-ultrasound0.44 (0.24 to 0.80)0.20 (0.07 to 0.62)0.0080.20 (0.07 to 0.62)
Huo 2008Kezhi capsules + PPC capsules + lifestyle intervention versus PPC capsules + lifestyle interventionAbnormal B-ultrasound0.43 (0.18 to 1.00)0.32 (0.11 to 0.96)0.0670.32 (0.11 to 0.96)
Liang 2011Baogan Xiaozhi pellet versus Dongbao gantai tabletsAbnormal B-ultrasound0.73 (0.53 to 1.02)0.41 (0.16 to 1.05)0.1000.41 (0.16 to 1.05)
Wang 2006Chuige Jiugan decoction + tiopronin + lifestyle intervention versus tiopronin + lifestyle interventionAbnormal B-ultrasound0.65 (0.39 to 1.07)0.42 (0.16 to 1.14)0.1370.42 (0.16 to 1.14)
Zhang 2007Sanyu Huazhuo decoction versus EssentialeAbnormal B-ultrasound0.36 (0.19 to 0.67)0.23 (0.10 to 0.53)0.0010.23 (0.10 to 0.53)
Zhang 2008Quyuhua Tan Tongluo decoction versus UDCAAbnormal B-ultrasound0.82 (0.68 to 0.98)0.12 (0.01 to 1.04)0.0540.12 (0.01 to 1.04)
Zhang 2011Kangzhi formula versus tioproninAbnormal B-ultrasound0.79 (0.67 to 0.93)0.33 (0.16 to 0.71)0.0040.33 (0.16 to 0.71)
Mi 2010Jiangan Jiangzhi tablets + lifestyle intervention versus silibinin capsules + lifestyle interventionB-ultrasound: proximal diffuse high echogenic dots1.16 (0.85 to 1.58)1.41 (0.68 to 2.91)0.4601.41 (0.68 to 2.91)
Mi 2010Jiangan Jiangzhi tablets + lifestyle intervention versus silibinin capsules + lifestyle interventionB-ultrasound: distal end echo attenuation1.25 (0.64 to 2.44)1.33 (0.56 to 3.15)0.6621.33 (0.56 to 3.15)
Mi 2010Jiangan Jiangzhi tablets + lifestyle intervention versus silibinin capsules + lifestyle interventionB-ultrasound: reduction of blood flow1.36 (0.94 to 1.97)1.83 (0.89 to 3.78)0.1441.83 (0.89 to 3.78)
Dai 2009Shuai Qingzhi powder + lifestyle intervention versus simvastatin tablets + lifestyle interventionB-ultrasound: unclear hepatic vessel structure0.44 (0.15 to 1.29)0.36 (0.10 to 1.33)0.2090.36 (0.10 to 1.33)
Mi 2010Jiangan Jiangzhi tablets + lifestyle intervention versus silibinin capsules + lifestyle interventionB-ultrasound: unclear hepatic vessel structure1.50 (1.00 to 2.25)2.11 (1.02 to 4.39)0.0662.11 (1.02 to 4.39)
Dai 2009Shuai Qingzhi powder + lifestyle intervention versus simvastatin tablets + lifestyle interventionHepatic B-ultrasound without improvement0.38 (0.11 to 1.28)0.31 (0.07 to 1.29)0.1810.31 (0.07 to 1.29)
Gu 2007aTiaozhi Yanggan decoction + lifestyle intervention versus Thiola tablets + lifestyle interventionB-ultrasound without improvement0.72 (0.24 to 2.12)0.69 (0.20 to 2.38)0.5130.69 (0.20 to 2.38)
Ji 2005Danning tablets + lifestyle intervention versus UDCA capsules + lifestyle interventionB-ultrasound without improvement0.71 (0.27 to 1.90)0.68 (0.22 to 2.11)0.5390.68 (0.22 to 2.11)
Lin 2011Yunpi Tongluo formula + lifestyle intervention versus UDCA + lifestyle interventionB-ultrasound without improvement0.81 (0.66 to 0.98)0.12 (0.01 to 1.03)0.0530.12 (0.01 to 1.03)
Lin 2010aXiaozhi Jiangpi decoction + lifestyle intervention versus PPC capsules + lifestyle interventionHepatic B-ultrasound without improvement0.88 (0.61 to 1.25)0.71 (0.28 to 1.80)0.487-
Liu 2008Qiyin granules + lifestyle intervention versus Essentiale + lifestyle interventionB-ultrasound without improvement1.00 (0.15 to 6.71)1.00 (0.13 to 7.53)1.0001.00 (0.13 to 7.53)
Liu 2009Xiaoyu Huatan decoction + lifestyle intervention versus compound methionine and choline bitartrate tablets + lifestyle interventionB-ultrasound without improvement0.44 (0.26 to 0.75)0.27 (0.12 to 0.63)0.0030.27 (0.12 to 0.63)
Wu 2010Zini Jianpi Huatan formula + lifestyle intervention versus PPC capsules + lifestyle interventionB-ultrasound without improvement0.78 (0.54 to 1.11)0.47 (0.16 to 1.36)0.1950.47 (0.16 to 1.36)
Zhao 2010Qiyin tea + lifestyle intervention versus polyene phosphatidylcholine capsules + lifestyle interventionB-ultrasound without improvement0.80 (0.23 to 2.82)0.78 (0.20 to 3.09)1.0000.78 (0.20 to 3.09)
Zhou 2009Lishi Huoxue Tongluo decoction + lifestyle intervention versus tiopronin tablets + lifestyle interventionB-ultrasound without improvement0.16 (0.07 to 0.35)

0.06 (0.02 to 0.17)

 

< 0.0010.06 (0.02 to 0.17)
Zhu 2010Xiaotan Hugan decoction + Essentiale Forte + vitamin versus Essentiale Forte + vitaminHepatic B-ultrasound without improvement0.60 (0.36 to 1.00)0.33 (0.12 to 0.96)0.0690.33 (0.12 to 0.96)
Gu 2007aTiaozhi Yanggan decoction + lifestyle intervention versus thiola tablets + lifestyle interventionLiver CT without improvement0.29 (0.05 to 1.92)0.27 (0.03 to 2.07)0.2200.27 (0.03 to 2.07)
Ji 2005Danning tablets + lifestyle intervention versus UDCA capsules + lifestyle interventionLiver CT without improvement0.35 (0.05 to 2.28)0.32 (0.04 to 2.46)0.2710.32 (0.04 to 2.46)
Jia 2009Shengqing Jiangzhuo granules + lifestyle intervention versus lifestyle interventionLiver CT without improvement0.80 (0.65 to 0.99)0.36 (0.14 to 0.97)0.0610.36 (0.14 to 0.97)
Yang 2006Qingzhifugan decoction versus EssentialeAbnormal AST (> 50 μ/L)0.28 (0.09 to 0.92)0.21 (0.05 to 0.85)0.0290.21 (0.05 to 0.85)
Yang 2006Qingzhifugan decoction versus EssentialeAbnormal ALT (> 50 μ/L)0.36 (0.15 to 0.87)0.24 (0.07 to 0.78)0.0270.24 (0.07 to 0.78)
Health-related quality of life (evaluated by a validated instrument)

None of the trials reported outcomes on health-related quality of life.

Secondary outcomes  

Radiological response (degree of fatty liver infiltration assessed by ultrasound, computed tomography, nuclear magnetic resonance, or other imaging techniques)
Ultrasound: liver score

Two trials reported ultrasound results, and there were significant differences between the intervention and control groups (Wang 2008b; Wang 2010) (Table 4). Compared with lifestyle intervention, Jiangzhi Ligan decoction plus lifestyle intervention improved the ultrasound results (Wang 2008b) (Table 4). Compared with fenofibrate sustained release capsules plus lifestyle intervention, Chaihu Shugan powder plus lifestyle intervention improved the ultrasound results (Wang 2010) (Table 4). We could not perform a meta-analysis because there was only one trial for each medicinal herb.

Table 4. The RevMan results and t-test results of studies that meta-analysis could not be done (numerical variables)
  1. AST: aspartate aminotransferase; GSH: glutathione; PPC: polyene phosphatidylcholine; UDCA: Ursodeoxycholic acid.

Study IDComparisonOutcomeRevMan resultst test
t-valueP valuet-valueP value
Wang 2008bJiangzhi Ligan decoction + lifestyle intervention versus lifestyle interventionB-ultrasound: liver score-2.280.025-2.280.025
Wang 2010Chaihu Shugan powder + lifestyle intervention versus fenofibrate sustained release capsules + lifestyle interventionB-ultrasound: liver score-3.61< 0.001-3.61< 0.001
Liang 2008Colon herbs dialysis therapy + lifestyle intervention versus PPC + simvastatin + silybin meglumine tablets + lifestyle interventionB-ultrasound: liver echo intensity-1.670.098-1.670.098
Fei 2009Yuqin capsules versus placeboLiver/spleen CT ratio5.65< 0.0015.65< 0.001
Liang 2010Jianpi Huazhuo formula + lifestyle intervention versus PPC capsules + lifestyle interventionLiver/spleen CT ratio8.08< 0.0018.08< 0.001
Ma 2010Qinggan Xiaozhi decoction + reduced glutathione tablets + lifestyle intervention versus reduced glutathione tablets + lifestyle interventionLiver/spleen CT ratio1.480.1441.480.144
Lou 2008Yiqi Sanju formula + lifestyle intervention versus Yiqi Sanju placebo + lifestyle interventionLiver/spleen CT ratio12.11< 0.00112.11< 0.001
Li 2010Xiaotan Jiangzhi formula + polyene phosphatidylcholine capsules + lifestyle intervention versus polyene phosphatidylcholine capsules + lifestyle interventionLiver CT density value3.81< 0.0013.81< 0.001
Cao 2011Huazhuo Xiaozhi decoction + lifestyle intervention versus Baisainuo + lifestyle interventionAST-12.41< 0.001-12.41< 0.001
Chen 2010Huatan Huoxue formula + lifestyle intervention versus Essentiale capsules + lifestyle interventionAST-2.670.009-2.670.009
Chen 2007aZini Zhigan prescription versus liptorAST-0.020.981-0.020.981
Cheng 2006Zhiyan Xiao decoction + lifestyle intervention versus UDCA + lifestyle interventionAST-7.04< 0.001-7.04< 0.001
Chou 2006Gynostemma pentaphyllum + lifestyle intervention versus placebo + lifestyle interventionAST-1.430.159-1.430.159
Dai 2009Shuai Qingzhi powder + lifestyle intervention versus simvastatin tablets + lifestyle interventionAST-3.83< 0.001-3.83< 0.001
Dang 2007Shiwei Ganzhikang capsules versus Dong Bao Gan Tai tabletsAST-1.610.111-1.610.111
Fei 2009Yuqin capsules versus placeboAST-10.12< 0.001-10.12< 0.001
Gu 2007aTiaozhi Yanggan decoction + lifestyle intervention versus thiola tablets + lifestyle interventionAST-3.220.002-3.220.002
Gu 2007bHerbal + lifestyle intervention versus silybininon + lifestyle interventionAST-0.660.512-0.660.512
Guan 2010Wild apricot versus vitamin B and C + glucurolactone tabletsAST0.240.8090.240.809
Guo 2010Xiaogan Jiangzhi formula + lifestyle intervention versus diisopropylamini dichlorocacetas + lifestyle interventionAST-1.140.258-1.140.258
Hu 2010Tangganjian + lifestyle intervention versus metformin hydrochloride tablets + lifestyle interventionAST-7.50< 0.001-7.50< 0.001
Huang 2011Quyu Huazhuo decoction + lifestyle intervention versus PPC capsules + lifestyle interventionAST-2.150.034-2.150.034
Huo 2008Kezhi capsules + PPC capsules + lifestyle intervention versus polyene phosphatidylcholine capsules + lifestyle interventionAST1.600.1141.600.114
Ji 2005Danning tablets + lifestyle intervention versus UDCA capsules + lifestyle interventionAST-1.060.293-1.060.293
Jia 2003Juge Yigan decoction + lifestyle intervention versus vitamin B and folic acid + lifestyle interventionAST-11.42< 0.001-11.42< 0.001
Jiang 2009Zhishi Xiaopi decoction + lifestyle intervention versus PPC capsules lifestyle interventionAST-6.20< 0.001-6.20< 0.001
Li 2005Huoxue Qinggan decoction + PPC capsules + lifestyle intervention versus PPC capsules + lifestyle interventionAST-2.330.022-2.330.022
Li 2008Shengling Baizhu powder with Erchen decoction + lifestyle intervention versus zocor + diammoniium glycyrrihizinate + lifestyle interventionAST-2.530.013-2.530.013
Li 2009Qinggan decoction + lifestyle intervention versus tiopronin tablets + lifestyle interventionAST-6.62< 0.001-6.62< 0.001
Li 2010Xiaotan Jiangzhi formula + PPC capsules + lifestyle intervention versus polyene phosphatidylcholine capsules + lifestyle interventionAST-2.010.049-2.010.049
Li 2006aXiaozhi powder + lifestyle intervention versus lifestyle interventionAST-0.320.749-0.320.749
Li 2006bBaogan Xiaozhi pellet + lifestyle intervention versus vitamin E nicotinicate capsules + lifestyle interventionAST-3.080.003-3.080.003
Liang 2008Colon herbs dialysis therapy + lifestyle intervention versus PPC + simvastatin + silybin meglumine tablets + lifestyle interventionAST-8.65< 0.001-8.65< 0.001
Liang 2010Jianpihuazhuo formula + lifestyle intervention versus PPC capsules + lifestyle interventionAST-0.160.870-0.160.870
Liang 2011Baogan Xiaozhi pellet versus Dongbao gantaiAST-4.16< 0.001-4.16< 0.001
Lin 2011Yunpi Tongluo formula + lifestyle intervention versus UDCA + lifestyle interventionAST-4.00< 0.001-4.00< 0.001
Lin 2010aXiaozhi Jiangpi decoction + lifestyle intervention versus polyene phosphatidylcholine capsules + lifestyle interventionAST-1.990.051-1.990.051
Liu 2008Qiyin granules + lifestyle intervention versus Essentiale + lifestyle interventionAST1.470.1461.470.146
Liu 2009Xiaoyu Huatan decoction + lifestyle intervention versus compound methionine and choline bitartrate tablets + lifestyle interventionAST-12.05< 0.001-12.05< 0.001
Lou 2008Yiqi Sanju formula + lifestyle intervention versus Yiqi Sanju placebo + lifestyle interventionAST-2.810.007-2.810.007
Ma 2009Zhiganqing granules + lifestyle intervention versus tiopronin + lifestyle interventionAST-13.33< 0.001-13.33< 0.001
Ma 2010Qinggan Xiaozhi decoction + reduced glutathione tablets + lifestyle intervention versus reduced glutathione tablets + lifestyle interventionAST0.050.9620.050.962
Mi 2010Jiangan Jiangzhi tablets + lifestyle intervention versus silibinin capsules + lifestyle interventionAST-0.410.680-0.410.680
Pu 2009Modified Wendan decoction + lifestyle intervention versus PPC capsules + lifestyle interventionAST-3.190.002-3.190.002
Song 2006Diammonium glycyrrihizinate capsules with Panax Notoginseng powder + lifestyle intervention versus tiopronin + lifestyle interventionAST-5.12< 0.001-5.12< 0.001
Wang 2006Chuige Jiugan decoction + tiopronin + lifestyle intervention versus tiopronin + lifestyle interventionAST-2.220.030-2.220.030
Wang 2011aBushen Yipi Fa versus PPC capsulesAST1.720.0911.720.091
Wang 2011aTiaogan Lizhong decoction with Qingbai powder + lifestyle intervention versus conventional therapy + lifestyle interventionAST-15.92< 0.001-15.92< 0.001
Wang 2008aSisheng Jiangzhi formula versus simvastatinAST-5.20< 0.001-5.20< 0.001
Wang 2008bJiangzhi Ligan decoction + lifestyle intervention versus lifestyle interventionAST-1.310.194-1.310.194
Wu 2006Shanzha Beimu decoction + lifestyle intervention versus Duoxi Kangzhi capsules + lifestyle interventionAST-6.16< 0.001-6.16< 0.001
Wu 2008Herbal formula versus PPC capsulesAST-0.080.939-0.080.939
Wu 2010Zini Jianpi Huatan formula + lifestyle intervention versus PPC capsules + lifestyle interventionAST-8.15< 0.001-8.15< 0.001
Xu 2008Huganning tablets + metformin hydrochloride tablets + lifestyle intervention versus metformin hydrochloride tablets + lifestyle interventionAST-2.840.006-2.840.006
Xu 2010Jiejiuhugan decoction + polyene phosphatidylcholine capsules + lifestyle intervention versus PPC capsules + lifestyle interventionAST-3.090.003-3.090.003
Yang 2004Zini Xiaozhi Jianggan decoction + lifestyle intervention + diammonium glycyrrihizinate versus lifestyle intervention + diammonium glycyrrihizinateAST-14.01< 0.001-14.01< 0.001
Yang 2005Guben Xiaozhuo decoction + lifestyle intervention versus fenofibrate tablets + lifestyle interventionAST-4.79< 0.001-4.79< 0.001
Yang 2009Shengnong Ganzhi tablets + lifestyle intervention versus lifestyle interventionAST-8.20< 0.001-8.20< 0.001
Zeng 2007Xiaozhi decoction + lifestyle intervention versus Essentiale + lifestyle interventionAST-1.900.063-1.900.063
Zhang 2002Clearing heat and removing dampness + lifestyle intervention versus conventional therapy + lifestyle interventionAST-2.490.017-2.490.017
Zhang 2005aQuganzhi decoction + lifestyle intervention versus Diisopylamini Dichlorovacetas + lifestyle interventionAST-23.68< 0.001-23.68< 0.001
Zhang 2006bGanzhikang capsules versus rosiglitazone hydrochloride tabletsAST-2.570.012-2.570.012
Zhang 2007Sanyu Huazhuo decoction versus EssentialeAST-1.800.075-1.800.075
Zhang 2008Quyuhua Tan Tongluo decoction versus UDCAAST-4.75< 0.001-4.75< 0.001
Zhang 2011Kangzhi formula versus tioproninAST-3.68< 0.001-3.68< 0.001
Zhao 2010Qiyin Tea + lifestyle intervention versus PPC capsules + lifestyle interventionAST-0.260.796-0.260.796
Zhou 2008Kezhi capsule + lifestyle intervention versus lifestyle interventionAST-32.96< 0.001-32.96< 0.001
Zhou 2009Lishi Huoxue Tongluo decoction + lifestyle intervention versus tiopronin tablets + lifestyle interventionAST-27.30< 0.001-27.30< 0.001
Zhu 2006Zhixiao capsules versus ethyl polyenoate soft capsulesAST-1.610.111-1.610.111
Zhu 2010Xiaotan Hugan decoction + Essentiale Forte + vitamin versus Essentiale Forte + vitaminAST-3.490.001-3.490.001
Cao 2011Huazhuo Xiaozhi decoction + lifestyle intervention versus Baisainuo + lifestyle interventionALT-9.13< 0.001-9.13< 0.001
Chen 2010Huatanhuoxue formula + lifestyle intervention versus Essentiale capsules + lifestyle interventionALT-5.42< 0.001-5.42< 0.001
Chen 2007aZini Zhigan prescription versus liptorALT-0.800.427-0.800.427
Chen 2007bJiangzhi Baogan decoction + lifestyle intervention versus placebo + lifestyle interventionALT-26.92< 0.001-26.92< 0.001
Cheng 2006Zhiyan Xiao decoction + lifestyle versus UDCA + lifestyleALT-9.08< 0.001-9.08< 0.001
Chou 2006Gynostemma pentaphyllum + lifestyle intervention versus placebo + lifestyle interventionALT-0.450.657-0.450.657
Dai 2009Shuai Qingzhi powder + lifestyle intervention versus simvastatin tablets + lifestyle interventionALT-3.94< 0.001-3.94< 0.001
Dang 2007Shiwei Ganzhikang capsules versus Dong Bao Gan Tai tabletsALT-4.59< 0.001-4.59< 0.001
Deng 2003aHuanglong Ganzhixiao decoction versus fenofibrate tabletsALT-19.65< 0.001-19.65< 0.001
Deng 2010Xiaoyao tablets + legalon + lifestyle intervention versus Legalon + lifestyle interventionALT-0.880.381-0.880.381
Fei 2009Yuqin capsules versus placeboALT-9.95< 0.001-9.95< 0.001
Gu 2007aTiaozhi Yanggan decoction + lifestyle intervention versus thiola tablets + lifestyle interventionALT-3.240.002-3.240.002
Gu 2007bHerbal versus silybininonALT-0.220.830-0.220.830
Gu 2007bHerbal + silybininon versus silybininonALT-1.950.056-1.950.056
Gu 2007bHerbal + lifestyle intervention versus silybininon + lifestyle interventionALT-0.220.830-0.220.830
Gu 2007bHerbal + silybininon + lifestyle intervention versus silybininon + lifestyle interventionALT-1.950.056-1.950.056
Guan 2010Wild apricot versus vitamin B and C + glucurolactone tabletsALT1.910.0611.910.061
Guo 2007Hegan Yin + tiopronin + lifestyle intervention versus tiopronin + lifestyle interventionALT-3.82< 0.001-3.82< 0.001
Guo 2010Xiaogan Jiangzhi formula + lifestyle intervention versus diisopropylamini dichlorocacetas + lifestyle interventionALT0.490.6270.490.627
Hu 2010Tangganjian + lifestyle intervention versus metformin hydrochloride tablets + lifestyle interventionALT-17.53< 0.001-17.53< 0.001
Huang 2005Shugan Lipi San + GSH + lifestyle intervention versus GSH + lifestyle interventionALT-1.280.204-1.280.204
Huang 2011Quyu Huazhuo decoction + lifestyle versus PPC capsules + lifestyle interventionALT-5.31< 0.001-5.31< 0.001
Huo 2008Kezhi capsules + PPC capsules + lifestyle intervention versus PPC capsules + lifestyle interventionALT-1.390.169-1.390.169
Ji 2005Danning tablets + lifestyle intervention versus UDCA capsules + lifestyle interventionALT-1.830.070-1.830.070
Jia 2003Juge Yigan decoction + lifestyle intervention versus vitamin B and folic acid + lifestyle interventionALT-14.73< 0.001-14.73< 0.001
Jia 2009Shengqing Jiangzhuo granules + lifestyle intervention versus lifestyle interventionALT-0.330.744-0.330.744
Jiang 2009Zhishi Xiaopi decoction + lifestyle intervention versus polyene phosphatidylcholine capsules lifestyle interventionALT-5.36< 0.001-5.36< 0.001
Kong 2010Tianganjiangzhi granules versus Essentiale capsulesALT-29.52< 0.001-29.52< 0.001
Li 2005Huoxue Qinggan decoction + PPC capsules + lifestyle intervention versus PPC capsules + lifestyle interventionALT-2.310.024-2.310.024
Li 2007Shuanghu Qinggan granules + tiopronin tablets + lifestyle intervention versus tiopronin tablets + lifestyle interventionALT-1.190.238-1.190.238
Li 2008Shenglingbaizhu powder with Erchen decoction + lifestyle intervention versus Zocor + diammoniium glycyrrihizinate + lifestyle interventionALT-2.170.033-2.170.033
Li 2009Qinggan decoction + lifestyle intervention versus tiopronin tablets + lifestyle interventionALT-4.49< 0.001-4.49< 0.001
Li 2010Xiaotan Jiangzhi formula + PPC capsules + lifestyle intervention versus PPC capsules + lifestyle interventionALT-3.150.003-3.150.003
Li 2006aXiaozhi powder + lifestyle intervention versus lifestyle interventionALT-0.210.836-0.210.836
Li 2006bBaogan Xiaozhi pellet + lifestyle intervention versus vitamin E nicotinicate capsules + lifestyle interventionALT-8.02< 0.001-8.02< 0.001
Liang 2008Colon herbs dialysis therapy + lifestyle intervention versus PPC + simvastatin + silybin meglumine tablets + lifestyle interventionALT-9.14< 0.001-9.14< 0.001
Liang 2010Jianpihuazhuo formula + lifestyle intervention versus PPC capsules + lifestyle interventionALT-1.080.282-1.080.282
Liang 2011Baogan Xiaozhi pellet versus Dongbao gantaiALT-2.950.004-2.950.004
Lin 2011Yunpi Tongluo formula + lifestyle intervention versus UDCA + lifestyle interventionALT-6.23< 0.001-6.23< 0.001
Lin 2010aXiaozhi Jiangpi decoction + lifestyle intervention versus PPC capsules + lifestyle interventionALT-1.400.167-1.400.167
Lin 2010bZini Jianpi Huatan formula + lifestyle intervention versus PPC capsules + lifestyle interventionALT-10.85< 0.001-10.85< 0.001
Liu 2008Qiyin granules + lifestyle intervention versus Essentiale + lifestyle interventionALT3.050.0033.050.003
Liu 2009Xiaoyu Huatan decoction + lifestyle intervention versus compound methionine and choline bitartrate tablets + lifestyle interventionALT-30.64< 0.001-30.64< 0.001
Lou 2008Yiqi Sanju formula + lifestyle intervention versus Yiqi Sanju placebo + lifestyle interventionALT-9.61< 0.001-9.61< 0.001
Ma 2009Zhiganqing granules + lifestyle intervention versus tiopronin + lifestyle interventionALT-10.84< 0.001-10.84< 0.001
Ma 2010Qinggan Xiaozhi decoction + reduced glutathione tablets + lifestyle intervention versus reduced glutathione tablets + lifestyle interventionALT-4.64< 0.001-4.64< 0.001
Mi 2010Jiangan Jiangzhi tablets + lifestyle intervention versus silibinin capsules + lifestyle interventionALT-1.510.133-1.510.133
Pu 2009Modified Wendan decoction + lifestyle intervention versus PPC capsules + lifestyle interventionALT-3.78< 0.001-3.78< 0.001
Song 2006Diammonium glycyrrihizinate capsules with Panax Notoginseng powder + lifestyle intervention versus tiopronin + lifestyle interventionALT-4.19< 0.001-4.19< 0.001
Wang 2006Chuige Jiugan decoction + tiopronin + lifestyle intervention versus tiopronin + lifestyle interventionALT-1.290.203-1.290.203
Wang 2011aTiaogan Lizhong decoction with Qingbai powder + lifestyle intervention versus conventional therapy + lifestyle interventionALT-9.11< 0.001-9.11< 0.001
Wang 2008aSisheng Jiangzhi formula versus simvastatinALT-3.91< 0.001-3.91< 0.001
Wang 2008bJiangzhi Ligan decoction + lifestyle intervention versus lifestyle interventionALT-1.790.076-1.790.076
Wang 2011bBushen Yipi Fa versus PPC capsulesALT4.29< 0.0014.29< 0.001
Wu 2006Shanzha Beimu decoction + lifestyle intervention versus Duoxi Kangzhi capsules + lifestyle interventionALT-7.85< 0.001-7.85< 0.001
Wu 2008Herbal formula versus PPC capsulesALT0.830.4120.830.412
Wu 2010Zini Jianpi Huatan formula + lifestyle intervention versus PPC capsules + lifestyle interventionALT-7.41< 0.001-7.41< 0.001
Xin 2005Qingre Huatan Huoxue formula versus tiopronin tabletsALT-1.950.056-1.950.056
Xu 2008Huganning tablets + metformin hydrochloride tablets + lifestyle intervention versus metformin hydrochloride tablets + lifestyle interventionALT-2.410.020-2.410.020
Xu 2010Jiejiu Hugan decoction + PPC capsules + lifestyle intervention versus PPC capsules + lifestyle interventionALT-3.420.001-3.420.001
Yang 2004Zini Xiaozhi Jianggan decoction + lifestyle intervention + diammonium glycyrrihizinate versus lifestyle intervention + diammonium glycyrrihizinateALT-11.98< 0.001-11.98< 0.001
Yang 2006Guben Xiaozhuo decoction + lifestyle intervention versus fenofibrate tablets + lifestyle interventionALT-9.14< 0.001-9.14< 0.001
Yang 2009Shengnong Ganzhi tablets + lifestyle intervention versus lifestyle interventionALT-3.70< 0.001-3.70< 0.001
Zeng 2007Xiaozhi decoction + lifestyle intervention versus Essentiale + lifestyle interventionALT-0.880.383-0.880.383
Zhang 2002Clearing heat and removing dampness + lifestyle intervention versus conventional therapy + lifestyle interventionALT4.49< 0.0014.49< 0.001
Zhang 2003Hugan tablets + UDCA + lifestyle intervention versus UDCA + lifestyle interventionALT-5.12< 0.001-5.12< 0.001
Zhang 2005aQuganzhi decoction + lifestyle intervention versus diisopylamini dichlorovacetas + lifestyle interventionALT4.49< 0.0014.49< 0.001
Zhang 2006bGanzhikang capsules versus rosiglitazone hydrochloride tabletsALT-3.91< 0.001-3.91< 0.001
Zhang 2007Sanyu Huazhuo decoction versus EssentialeALT-8.04< 0.001-8.04< 0.001
Zhang 2008Quyuhua Tan Tongluo decoction versus UDCAALT-6.53< 0.001-6.53< 0.001
Zhang 2011Kangzhi formula versus tioproninALT-2.360.019-2.360.019
Zhao 2009Herbal therapy + lifestyle intervention versus Essentiale + lifestyle interventionALT-19.11< 0.001-19.11< 0.001
Zhao 2010Qiyin tea + lifestyle intervention versus PPC capsules + lifestyle interventionALT-0.430.665-0.430.665
Zhou 2008Kezhi capsules + lifestyle intervention versus lifestyle interventionALT-40.51< 0.001-40.51< 0.001
Zhou 2009Lishi Huoxue Tongluo decoction + lifestyle intervention versus tiopronin tablets + lifestyle interventionALT-15.20< 0.001-15.20< 0.001
Zhu 2006Zhixiao capsules versus ethyl polyenoate soft capsulesALT-4.59< 0.001-4.59< 0.001
Zhu 2010Xiaotan Hugan decoction + Essentiale Forte + vitamin versus Essentiale Forte + vitaminALT-3.560.001-3.560.001
Chou 2006Gynostemma pentaphyllum + lifestyle intervention versus placebo + lifestyle interventionALP-2.600.012-2.600.012
Dang 2007Shiwei Ganzhikang capsules versus Dong Bao Gan Tai tabletsALP-5.85< 0.001-5.85< 0.001
Wang 2011bBushen Yipi Fa versus PPC capsulesALP-1.440.156-1.440.156
Zhang 2011Kangzhi formula versus tioproninALP-0.860.390-0.860.390
Zhu 2006Zhixiao capsules versus ethyl polyenoate soft capsulesALP-5.85< 0.001-5.85< 0.001
Cao 2011Huazhuo Xiaozhi decoction + lifestyle intervention versus Baisainuo + lifestyle interventionGGT-18.55< 0.001-18.55< 0.001
Chen 2007aZini Zhigan prescription versus liptorGGT-1.220.229-1.220.229
Cheng 2006Zhiyan Xiao decoction + lifestyle intervention versus UDCA capsules + lifestyle interventionGGT-3.78< 0.001-3.78< 0.001
Dai 2009Shuli Qingzhi powder + lifestyle intervention versus simvastatin tablets + lifestyle interventionGGT-2.460.017-2.460.017
Dang 2007Shiwei Ganzhikang capsules versus Dong Bao Gan Tai tabletsGGT40.52< 0.00140.52< 0.001
Deng 2010Xiaoyao tablets + Legalon + lifestyle intervention versus Legalon + lifestyle interventionGGT-2.570.012-2.570.012
Gu 2007aTiaozhi Yanggan decoction + lifestyle versus Thiola tablets + lifestyleGGT-2.010.047-2.010.047
Guo 2007Hegan Yin + tiopronin + lifestyle intervention versus tiopronin + lifestyle interventionGGT-2.420.018-2.420.018
Guo 2010Xiaogan Jiangzhi formula + lifestyle intervention versus diisopropylamini dichlorocacetas + lifestyle interventionGGT-4.50< 0.001-4.50< 0.001
Huang 2005Shugan Lipi San + GSH + lifestyle intervention versus GSH + lifestyle interventionGGT-16.55< 0.001-16.55< 0.001
Ji 2005Danning tablets + lifestyle intervention versus UDCA capsules + lifestyle interventionGGT-1.570.118-1.570.118
Jia 2003Juge Yigan decoction + lifestyle intervention versus vitamin B and folic acid + lifestyle interventionGGT-12.30< 0.001-12.30< 0.001
Jiang 2009Zhishi Xiaopi decoction + lifestyle intervention versus PPC capsules + lifestyle interventionGGT-6.66< 0.001-6.66< 0.001
Li 2005Huoxue Qinggan decoction + PPC capsules + lifestyle intervention versus PPC capsules + lifestyle interventionGGT0.470.6420.470.642
Li 2007Shuanghu Qinggan granules + tiopronin tablets + lifestyle intervention versus tiopronin tablets + lifestyle interventionGGT-7.46< 0.001-7.46< 0.001
Li 2008Shenlingbaizhu powder with Erchen decotion + lifestyle intervention versus Zocor + diammonium glycyrrihizinate + lifestyle interventionGGT-1.390.168-1.390.168
Li 2010Xiaotan Jiangzhi formula + PPC capsules + lifestyle intervention versus PPC capsules + lifestyle interventionGGT-1.920.059-1.920.059
Li 2006bBaogan Xiaozhi pellet + lifestyle intervention versus vitamin E nicotinicate capsules + lifestyle interventionGGT-15.10< 0.001-15.10< 0.001
Liang 2008Colon herbs dialysis therapy + lifestyle intervention versus PPC + simvastatin + silybin meglumine tablets + lifestyle interventionGGT-1.220.223-1.220.223
Liang 2010Jianpi Huazhuo formula + lifestyle intervention versus PPC capsules + lifestyle interventionGGT-3.300.002-3.300.002
Liang 2011Baogan Xiaozhi pellet versus Dongbao gantai tabletsGGT-2.080.041-2.080.041
Lin 2011Yunpi Tongluo formula + lifestyle intervention versus UDCA + lifestyle interventionGGT-2.870.006-2.870.006
Lin 2010bZini Jianpi Huatan formula + lifestyle intervention versus PPC capsules + lifestyle interventionGGT-4.92<0.001-4.92<0.001
Ma 2009Zhiganqing granules + lifestyle intervention versus tiopronin + lifestyle interventionGGT-14.70< 0.001-14.70< 0.001
Ma 2010Qinggan Xiaozhi decoction + reduced glutathione tablets + lifestyle intervention versus reduced glutathione tablets + lifestyle interventionGGT-0.390.699-0.390.699
Mi 2010Jiangan Jiangzhi tablets + lifestyle intervention versus silibinin capsules + lifestyle interventionGGT-3.410.001-3.410.001
Wang 2006Chuige Jiugan decoction + tiopronin + lifestyle intervention versus tiopronin + lifestyle interventionGGT-1.480.144-1.480.144
Wang 2011aTiaogan Lizhong decoction with Qingbai powder + lifestyle intervention versus conventional therapy + lifestyle interventionGGT-30.71< 0.001-30.71< 0.001
Wang 2008aSisheng Jiangzhi formula versus simvastatinGGT-5.50< 0.001-5.50< 0.001
Wang 2011bBushen Yipi Fa versus PPC capsulesGGT-0.570.571-0.570.571
Wu 2006Shanzha Beimu decotion + lifestyle intervention versus Duoxi Kangzhi capsules + lifestyle interventionGGT-3.280.002-3.280.002
Xin 2005Qingre Huatan Huoxue formula versus tiopronin tabletsGGT-2.830.006-2.830.006
Xu 2010Jiejiuhugan decoction + PPC capsules + lifestyle intervention versus PPC capsules + lifestyle interventionGGT-2.870.006-2.870.006
Yang 2004Zini Xiaozhi Jianggan decoction + lifestyle + diammonium glycyrrihizinate versus lifestyle + diammonium glycyrrihizinateGGT-13.89< 0.001-13.89< 0.001
Yang 2009Shengnong Ganzhi tablets + lifestyle intervention versus lifestyle interventionGGT-7.25< 0.001-7.25< 0.001
Zhang 2002Clearing heat and removing dampness + lifestyle intervention versus conventional therapy + lifestyle interventionGGT-7.63< 0.001-7.63< 0.001
Zhang 2006bGanzhikang capsules versus rosiglitazone hydrochloride tabletsGGT-0.170.867-0.170.867
Zhang 2007Sanyu Huazhuo decoction versus EssentialeGGT-4.56< 0.001-4.56< 0.001
Zhang 2008Quyuhua Tan Tongluo decoction versus UDCAGGT-2.720.009-2.720.009
Zhang 2011Kangzhi formula versus tioproninGGT-2.560.011-2.560.011
Zhao 2009Herbal therapy + lifestyle intervention versus Essentiale + lifestyle interventionGGT-14.67< 0.001-14.67< 0.001
Zhao 2010Qiyin tea + lifestyle intervention versus PPC capsules + lifestyle interventionGGT0.810.4230.810.423
Zhu 2006Zhixiao capsules versus ethyl polyenoate soft capsulesGGT-40.52< 0.001-40.52< 0.001
Zhu 2010Xiaotan Hugan decoction + Essentiale Forte + vitamin versus Essentiale Forte + vitaminGGT-35.19< 0.001-35.19< 0.001
Ultrasound: liver echo intensity

One trial reported ultrasound results, and there was no significant difference between the colon herbs Dialysis therapy plus lifestyle intervention and the control groups (Liang 2008) (Table 4).

Abnormal ultrasound: number of participants

Seven trials reported the outcome data on abnormal ultrasound (Wang 2006; Zhang 2007; Huo 2008; Zhang 2008; Guan 2010; Liang 2011; Zhang 2011). Significant differences were found in the intervention and control groups in three trials (Zhang 2007; Guan 2010; Zhang 2011). Compared with vitamin B and C plus glucurolactone tablets, Prunus armeniaca (wild apricot) significantly reduced the number of people with abnormal ultrasound (Guan 2010). Compared with Essentiale®, Sanyu Huazhuo decoction significantly reduced the number of people with abnormal ultrasound (Zhang 2007). Comparing tiopronin, Kangzhi formula significantly reduced the number of people with abnormal ultrasound (Zhang 2011). Detailed information is shown in Table 3.

Ultrasound: proximal diffuse high echogenic dots

One trial reported ultrasound results on proximal diffuse high echogenic dots, and found no significant difference between Jiangan Jiangzhi tablets plus lifestyle intervention and control groups (Mi 2010) (Table 3).

Ultrasound: distal end echo attenuation

One trial reported B-ultrasound results on distal end echo attenuation, and found no significant difference between Jiangan Jiangzhi tablets plus lifestyle intervention and control groups (Mi 2010) (Table 3).

Ultrasound: reduction of blood flow

One trial reported B-ultrasound results on reduction of blood flow, and found no significant difference between Jiangan Jiangzhi tablets plus lifestyle intervention and control groups (Mi 2010) (Table 3).

Ultrasound: unclear hepatic vessel structure

Two trials reported B-ultrasound results on unclear hepatic vessel structure, and found no significant differences between Shuai Qingzhi powder plus lifestyle intervention, Jiangan Jiangzhi tablets plus lifestyle intervention and control groups (Dai 2009; Mi 2010) (Table 3). We could not perform a meta-analysis because there was only one trial with each medicinal herb.

Hepatic ultrasound without improvement: number of participants

Eleven trials reported the number of people without improvement on hepatic B-ultrasound (Ji 2005; Gu 2007a; Liu 2008; Dai 2009; Liu 2009; Zhou 2009; Lin 2010a; Wu 2010; Zhao 2010; Zhu 2010; Lin 2011) (Table 3). Two trials showed a significant difference between the intervention and control groups (Liu 2009; Zhou 2009). Compared with compound methionine and choline bitartrate tablets plus lifestyle intervention, Xiaoyu Huatan decoction plus lifestyle intervention significantly reduced the number of people with no improvement on hepatic ultrasound results (Liu 2009). Compared with tiopronin tablets plus lifestyle intervention, Lishi Huoxue Tongluo decoction plus lifestyle intervention significantly reduced the number of people with no improvement on hepatic ultrasound results (Zhou 2009). Detailed information is shown in Table 3. We could not perform a meta-analysis as there was only one trial with each medicinal herb.

Liver computed tomography without improvement: number of participants

Three trials reported the number of people with no improvement on liver computed tomography results. No significant difference was found between the intervention and control groups (Ji 2005; Gu 2007a; Jia 2009) (Table 3).

Liver/spleen computed tomography ratio

Four trials reported the level of liver/spleen computed tomography ratio (Lou 2008; Fei 2009; Liang 2010; Ma 2010) (Table 4). The liver/spleen computed tomography ratio was significantly higher in the intervention group than in the control group in three trials (Lou 2008; Fei 2009; Liang 2010). Yuqin capsules significantly increased the liver/spleen computed tomography ratio compared with placebo (Fei 2009) (Table 4). When polyene phosphatidylcholine capsules plus lifestyle intervention was compared with Jianpi Huazhuo formula plus lifestyle intervention, Jianpi Huazhuo formula plus lifestyle intervention significantly increased the liver/spleen computed tomography ratio (Liang 2010). When Yiqi Sanju placebo plus lifestyle intervention was compared with Yiqi Sanju formula plus lifestyle intervention, Yiqi Sanju formula plus lifestyle intervention significantly increased the liver/spleen computed tomography ratio (Lou 2008). Detailed information is shown in Table 4. We could not perform a meta-analysis because there was only one trial in each medicinal herb.

Liver computed tomography density value

One trial reported liver computed tomography density value (Li 2010) (Table 4). Compared with polyene phosphatidylcholine capsules plus lifestyle intervention, Xiaotan Jiangzhi formula plus polyene phosphatidylcholine capsules plus lifestyle intervention significantly increased the liver computed tomography density value (Li 2010) (Table 4).

Nuclear magnetic resonance

None of the trials reported outcomes on nuclear magnetic resonance.

Other imaging techniques

None of the trials reported outcomes on results of other imaging techniques.

Biochemical response (serum activities of AST, ALT, ALP, GGT, serum total bilirubin, and ferritin)
Abnormal AST (greater than 50 U/L): number of participants

One trial reported the number of people with abnormal AST levels (greater than 50 U/L) (Yang 2006) (Table 3). When compared with Essentiale®, Qingzhifugan decoction significantly reduced the number of people with abnormal AST levels (Yang 2006) (Table 3).

AST levels

Sixty-four trials reported AST levels, and detailed information is shown in Table 4. Forty-two trials had significantly lower AST levels in the intervention group than in the control group (Zhang 2002; Jia 2003; Yang 2004; Li 2005; Yang 2005; Zhang 2005a; Cheng 2006; Li 2006b; Song 2006; Wang 2006; Wu 2006; Zhang 2006b; Gu 2007a; Gu 2007b; Li 2008; Liang 2008; Lou 2008; Wang 2008a; Xu 2008; Zhang 2008; Zhou 2008; Dai 2009; Fei 2009; Jiang 2009; Li 2009; Liu 2009; Ma 2009; Pu 2009; Yang 2009; Zhou 2009; Chen 2010; Hu 2010; Li 2010; Wu 2010; Zhu 2010; Cao 2011; Huang 2011; Liang 2011; Lin 2011; Wang 2011a; Zhang 2011). We could not perform a meta-analysis as there was only one trial with each medicinal herb.

Abnormal ALT (greater than 50 U/L): number of participants

One trial reported the number of people with abnormal AST levels (greater than 50 U/L) (Yang 2006) (Table 3). Compared with Essentiale®, Qingzhifugan decoction significantly reduced the number of people with abnormal ALT levels (Yang 2006) (Table 3).

ALT activity

Seventy-seven trials reported ALT activity and detailed information is shown in Table 4. Forty-nine trials had significantly lower ALT levels in the intervention group than in the control group (Deng 2003a; Jia 2003; Zhang 2003; Yang 2004; Li 2005; Chou 2006; Li 2006b; Song 2006; Wu 2006; Yang 2006; Zhang 2006b; Zhu 2006; Chen 2007b; Dang 2007; Gu 2007a; Guo 2007; Zhang 2007; Li 2008; Liang 2008; Lou 2008; Wang 2008a; Xu 2008; Zhang 2008; Zhou 2008; Dai 2009; Fei 2009; Jiang 2009; Li 2009; Liu 2009; Ma 2009; Pu 2009; Yang 2009; Zhao 2009; Zhou 2009; Chen 2010; Hu 2010; Kong 2010; Li 2010; Lin 2010b; Ma 2010; Wu 2010; Xu 2010; Zhu 2010; Cao 2011; Huang 2011; Liang 2011; Lin 2011; Wang 2011a; Zhang 2011). Four trials had significantly higher ALT levels in the intervention group than in the control group (Zhang 2002; Zhang 2005a; Liu 2008; Wang 2011b). We could not perform a meta-analysis as there was only one trial with each medicinal herb.

ALP activity

Four trials reported ALP activity (Chou 2006; Zhu 2006; Dang 2007; Wang 2011b; Zhang 2011). Three trials had significantly lower ALP levels in the intervention group than in the control group (Chou 2006; Zhu 2006; Dang 2007).

Compared with placebo plus lifestyle intervention, Gynostemma pentaphyllum plus lifestyle intervention significantly reduced ALP levels (Chou 2006). Compared with Dongbao Gantai tablets, Shiwei Ganzhikang capsules significantly reduced ALP levels (Dang 2007). Compared with ethyl polyenoate soft capsules, Zhixiao capsules significantly reduced ALP levels (Zhu 2006). Detailed information is shown in Table 4. We could not perform a meta-analysis as there was only one trial with each medicinal herb.

GGT activity

Forty-four trials reported GGT activity (Zhang 2002; Jia 2003; Yang 2004; Huang 2005; Ji 2005; Li 2005; Xin 2005; Cheng 2006; Li 2006b; Wang 2006; Wu 2006; Zhang 2006b; Zhu 2006; Chen 2007a; Dang 2007; Gu 2007a; Guo 2007; Li 2007; Zhang 2007; Li 2008; Liang 2008; Wang 2008a; Zhang 2008; Dai 2009; Jiang 2009; Ma 2009; Yang 2009; Zhao 2009; Deng 2010; Guo 2010; Li 2010; Liang 2010; Lin 2010b; Ma 2010; Mi 2010; Xu 2010; Zhao 2010; Zhu 2010; Cao 2011; Liang 2011; Lin 2011; Wang 2011a; Wang 2011b; Zhang 2011). Thirty-two trials had significantly lower GGT levels in the intervention group than in the control group (Zhang 2002; Jia 2003; Yang 2004; Huang 2005; Xin 2005; Cheng 2006; Li 2006b; Wu 2006; Zhu 2006; Dang 2007; Gu 2007a; Guo 2007; Li 2007; Zhang 2007; Wang 2008a; Zhang 2008; Dai 2009; Jiang 2009; Ma 2009; Yang 2009; Zhao 2009; Xu 2010; Deng 2010; Guo 2010; Liang 2010; Lin 2010b; Mi 2010; Zhu 2010; Cao 2011; Lin 2011; Wang 2011a; Zhang 2011). One trial had significantly lower GGT levels in the intervention group than in the control group (Dang 2007). Detailed information is shown in Table 4. We could not perform a meta-analysis as there was only one trial with each medicinal herb.

Serum total bilirubin

None of the trials reported outcomes on serum total bilirubin.

Ferritin

None of the trials reported outcomes on ferritin.

Histological response (number of people without histological improvement in the degree of fatty liver infiltration, inflammation, and fibrosis)

None of the trials reported outcomes on histological response.

Costs

None of the trials reported outcomes on cost.

Discussion

Summary of main results

We included 77 randomised clinical trials, which involved 6753 participants with fatty liver disease. The majority of the trials included people with NAFLD, but there was also a number of trials with people having unknown disease aetiology, or including people with AFLD. The mean sample size was 88 participants (range 40 to 200 participants) per trial. Seventy-five different medicinal herb products were tested. Six trials showed a statistically significant effect on hepatic B-ultrasound; four trials showed a significant increase on liver/spleen computed tomography ratio; 42 trials showed a significant reduction on AST levels; 49 trials showed a significant reduction on ALT levels in the herbal group; three trials showed a significant reduction on ALP levels in the herbal group; and 32 trials showed a significant reduction on GGT levels. The present systematic review suggests that herbal medicines such as Jiangzhi Ligan decoction, Chaihu Shugan powder, and Qingzhifugan decoction may have positive effects on fatty liver disease, especially on reducing AST and ALT, and improving B-ultrasound results. However, at present there is no sufficient evidence to recommend any of these herbal medicines for the treatment of fatty liver diseases due to risk of bias and the lack of homogenous data. The methodological approaches of the included trials meant that they were all at high risk of bias. The lack of homogenous trials meant that we could not conduct a meta-analysis. We were unable to find a common or predominant herbal medicine used in treating fatty liver disease because almost every trial included in this systematic review tested one single herbal, or one propriety medicine, or one herbal formula. In the future, large sample, multicentred, high-quality trials should be carried out to give more reliable evidence on the effects of Chinese herbal medicines on fatty liver disease.

Overall completeness and applicability of evidence

The age and sex of participants in the included trials were representative factors of people with fatty liver disease. All of the participants were recruited from Chinese populations, and this may have had an impact on the applicability of the interventions to other populations. No primary outcome data and no data longer than six months on any of the review or single trials outcomes were reported in the included trials. Therefore, the long-term effects and safety of the tested herbal medicines needs to be tested in the future. Some trials only recruited people with certain types of patterns of disharmony according to herbal medicines (Dang 2007). The results of this systematic review can only be used to guide clinical practice for the tested herbal medicines and population that we have evaluated in our review. Many types of herbal medicines with possible effects on fatty liver disease have not been investigated in randomised clinical trials, including the possible toxicity of these herbal medicines (Stedman 2002; Stickel 2005). Therefore, the evaluation of these herbs should be addressed in future trials.

Quality of the evidence

All of the randomised trials included in this review were of high risk of bias in terms of their design, methodology, and reporting. They provided only limited descriptions of study design, allocation concealment, and baseline data. Only one multicentre, large-scale randomised trial was identified (Ji 2005). With regards to methods, poorly designed trials could show larger differences between experimental and control groups than those conducted rigorously (Schulz 1995; Moher 1998; Kjaergard 2001; Wood 2008; Lundh 2012; Savović 2012a). However, the insufficient number of adequate trials prohibited us from performing sensitivity analyses. Moreover, the included trials were heterogeneous with regards to the interventions (75 herbal medicines tested only once), and heterogeneous with regards to the reported outcomes.

There were wide variations among the tested herbal medicines and control interventions. We could not perform sensitivity analysis on treatment duration because there was an insufficient number of trials. There was a lack of information on the quality standards for the development of the herbal preparations or the good manufacturing practice of the manufacture of the herbal products. Future trials should provide information about standardisation including composition, quality control, detailed dose regimen, and duration of treatment.

The primary goal of the treatment for fatty liver disease is to prevent hepatic-related morbidity and hepatic-related mortality. No trial reported primary outcomes including quality of life in people with fatty liver disease. Other outcomes from the included trials are mainly putative surrogate outcomes, that is, AST, ALT, ALP, GGT, B-ultrasound results, and computed tomography results (Gluud 2007).

The toxicity of herbal medicines, especially hepatotoxicity, is increasingly recognised as herbal medicines become more popular (Stedman 2002; Stickel 2005). While, there was inadequate reporting on adverse events in the included trials, and we cannot make to firm conclusions about the safety of herbal medicines. In order to obtain more information on the adverse effects of Chinese herbal medicines, safety needs to be further examined and reported in clinical trials and observational studies such as cohort studies and monitoring studies.

Potential biases in the review process

All of the 77 trials were conducted in China and only three of them were published in English. Most of the trials had small sample sizes. We tried to avoid language bias and location bias, but we could not exclude potential publication bias. Though we did not find unpublished material, we could not exclude the possibility that trials with negative findings may have remained unpublished. Two review authors independently selected trials for inclusion in the review, and two review authors independently extracted data and bias risk in the trials.

Agreements and disagreements with other studies or reviews

Three systematic reviews focusing on traditional Chinese herbal medicines for fatty liver disease have been published in Chinese journals (Li 2002; Liu 2005; He 2010). We found one systematic review of TCMs for fatty liver disease published in 2012 (Shi 2012). This review included randomised clinical trials, non-randomised clinical studies, and clinical experiences on NAFLD and only searched two databases (PubMed and the China National Knowledge Infrastructure). The review by Shi included 62 trials and reached the conclusion that TCM is of modest benefit to the treatment of NAFLD. Of the reviews published in Chinese journals, one review included 11 trials using a TCM in the intervention group and a Western medicine in the control group (He 2010). A second review included 23 trials with a TCM in the intervention group and a Western medicine in the control group (Li 2002). The third review included eight trials with TCM in the intervention group and a Western medicine or blank or supportive therapy in the control group (Liu 2005). Two of the reviews only reported the outcome of curative effect (an integrated outcome, different standard used in different included trials) and combined the odds ratio (OR) irrespective of the interventions and controls (Li 2002; Liu 2005). The review by He 2010 reported outcome on ALT, AST, GGT, ALP, total cholesterol, triglycerides, and high-density lipoprotein and did meta-analyses on different comparisons of interventions and controls. None of the three reviews gave definite conclusions on the effects and safety of TCM on fatty liver disease (Li 2002; Liu 2005; He 2010). Five of the clinical trials included in our review were included in the review by He 2010 (Zhu 2006; Chen 2007a; Dang 2007; Zhang 2007; Wang 2008a). The remaining studies included in the systematic reviews by Li 2002, Liu 2005, and He 2010 were not included in our review because they were retrospective studies, clinical controlled studies, or studies that claimed to be randomised clinical trials that did not provide information on sequence generation, allocation concealment, and blinding; had included ineligible participants; or did not provide results on outcomes. We recommend that systematic reviews should be reported under the guidance from the PRISMA statement (Liberati 2009).

Authors' conclusions

Implications for practice

Based on this systematic review, a large number of randomised clinical trials on herbal medicines have shown positive effects on secondary outcomes including biochemical and radiological responses. However, we cannot be certain of the effectiveness and safety of the studies in our review of herbal medicines for the treatment of fatty liver diseases. The evidence is inconclusive due to the high risk of bias of the included trials and the limited number of trials with each of the Chinese herbs and Chinese herbal formulas, as well as the limited number of included participants and patient-relevant outcomes.

Implications for research

To obtain a high level of evidence on herbal medicines on fatty liver disease and give guidance on clinical practice, international, multicentre, rigorously designed, high-quality trials with large sample sizes are required. Attention should be paid to the sample size estimation, the definition of outcomes, duration of treatment and follow-up, and the reporting of adverse events. In addition, the following methodological issues should be addressed: the trial design should be according to the SPIRIT Statement (www.spirit-statement.org), including the methods of randomisation and blinding with the use of placebo with the same appearance, taste, and smell; registering the trial protocol in one of the World Health Organization Registry Network or an International Committee of Medical Journal Editors approved registry before the start of the trial (www.clinicaltrials.gov; www.who.int/ictrp/network/primary/en/index.html); and reporting trials according to the CONSORT statement (www.consort-statement.org) (Schulz 2010). To improve the quality of future trials, we suggest that all researchers receive the necessary training on clinical trial methodology before designing a trial and register the trial on an internationally recognised public trial registry.

From the results of the present review, rigorous description of the pharmacology of the interventions and clinical outcomes should be emphasised for herbal medicines. Information about species, geographical origin of herbs, season for collecting the herbs, and quality of the preparations should be provided (Gagnier 2006). Standardised monitoring and reporting should be used to assess adverse events.

Acknowledgements

We thank Dimitrinka Nikolova for her revisions of the full review. We thank Sarah Louise Klingenberg from the Cochrane Hepato-Biliary Group and Iris Gordon from the Cochrane Eyes and Vision Group for their help in the development of the search strategies and performing electronic research in English databases for this review. We thank Xinxue Li, Ya Nan Wu, and Xi'e Zhuang for their contribution on study selection and downloading of full-text articles.

Dr Jian Ping Liu thanks the National Institutes of Health, National Center for Complementary and Alternative Medicine (R24 AT001293) for partial funding of the review project.

Zhaolan Liu acknowledges the support from the Australian Endeavour Award Program (Award holder number 2758_2012).

Peer reviewers: Si-Yuan Pan, China; Ming-Hua Zheng, China; Bruna Z Schild, Brazil.
Contact editor: Christian Gluud, Denmark.

Data and analyses

Download statistical data

Comparison 1. Medicinal herbs versus placebo
Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size
1 ALT (U/L)1 Mean Difference (IV, Fixed, 95% CI)Totals not selected
1.1 Yuqin capsules versus placebo1 Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]
2 AST (U/L)1 Mean Difference (IV, Fixed, 95% CI)Totals not selected
2.1 Yuqin capsules versus placebo1 Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]
3 Liver/spleen CT ratio1 Mean Difference (IV, Fixed, 95% CI)Totals not selected
3.1 Yuqin capsules versus placebo1 Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]
Analysis 1.1.

Comparison 1 Medicinal herbs versus placebo, Outcome 1 ALT (U/L).

Analysis 1.2.

Comparison 1 Medicinal herbs versus placebo, Outcome 2 AST (U/L).

Analysis 1.3.

Comparison 1 Medicinal herbs versus placebo, Outcome 3 Liver/spleen CT ratio.

Comparison 2. Herbal medicines plus lifestyle intervention versus placebo plus lifestyle intervention
Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size
1 AST (U/L)2 Mean Difference (IV, Fixed, 95% CI)Totals not selected
1.1 Yiqi Sanju formula + lifestyle versus Yiqi Sanju placebo + lifestyle1 Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]
1.2 Gynostemma pentaphyllum + lifestyle versus placebo + lifestyle1 Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]
2 ALT (U/L)3 Mean Difference (IV, Fixed, 95% CI)Totals not selected
2.1 Yiqi Sanju formula + lifestyle versus Yiqi Sanju placebo + lifestyle1 Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]
2.2 Gynostemma pentaphyllum + lifestyle versus placebo + lifestyle1 Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]
2.3 Jiangzhi Baogan decoction + lifestyle versus placebo + lifestyle1 Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]
3 ALP (U/L)1 Mean Difference (IV, Fixed, 95% CI)Totals not selected
3.1 Gynostemma pentaphyllum + lifestyle versus placebo + lifestyle1 Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]
4 Liver/spleen CT ratio1 Mean Difference (IV, Fixed, 95% CI)Totals not selected
4.1 Yiqi Sanju formula + lifestyle versus Yiqi Sanju placebo + lifestyle1 Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]
Analysis 2.1.

Comparison 2 Herbal medicines plus lifestyle intervention versus placebo plus lifestyle intervention, Outcome 1 AST (U/L).

Analysis 2.2.

Comparison 2 Herbal medicines plus lifestyle intervention versus placebo plus lifestyle intervention, Outcome 2 ALT (U/L).

Analysis 2.3.

Comparison 2 Herbal medicines plus lifestyle intervention versus placebo plus lifestyle intervention, Outcome 3 ALP (U/L).

Analysis 2.4.

Comparison 2 Herbal medicines plus lifestyle intervention versus placebo plus lifestyle intervention, Outcome 4 Liver/spleen CT ratio.

Comparison 3. Herbal medicines plus lifestyle intervention versus lifestyle intervention
Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size
1 ALT (IU/L)5 Mean Difference (IV, Fixed, 95% CI)Totals not selected
1.1 Jiangzhi Ligan decoction + lifestyle versus lifestyle1 Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]
1.2 Shengqing Jiangzhuo granules + lifestyle versus lifestyle1 Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]
1.3 Xiaozhi powder + lifestyle versus lifestyle1 Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]
1.4 Shennong Ganzhi tablets + lifestyle versus lifestyle1 Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]
1.5 Kezhi capsule + lifestyle versus lifestyle1 Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]
2 AST (IU/L)4 Mean Difference (IV, Fixed, 95% CI)Totals not selected
2.1 Jiangzhi Ligan decoction + lifestyle versus lifestyle1 Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]
2.2 Xiaozhi powder + lifestyle versus lifestyle1 Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]
2.3 Shennong Ganzhi tablets + lifestyle versus lifestyle1 Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]
2.4 Kezhi capsule + lifestyle versus lifestyle1 Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]
3 Ultrasound: liver score1 Mean Difference (IV, Fixed, 95% CI)Totals not selected
3.1 Jiangzhi Ligan decoction + lifestyle versus lifestyle1 Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]
4 Liver CT without improvement1 Odds Ratio (M-H, Fixed, 95% CI)Totals not selected
4.1 Shengqing Jiangzhuo granule + lifestyle versus lifestyle1 Odds Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]
5 Adverse events1 Risk Ratio (M-H, Fixed, 95% CI)Totals not selected
5.1 Shengqing Jiangzhuo granule + lifestyle versus lifestyle1 Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]
6 GGT (U/L)1 Mean Difference (IV, Fixed, 95% CI)Totals not selected
6.1 Shennong Ganzhi tablets + lifestyle versus lifestyle1 Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]
Analysis 3.1.

Comparison 3 Herbal medicines plus lifestyle intervention versus lifestyle intervention, Outcome 1 ALT (IU/L).

Analysis 3.2.

Comparison 3 Herbal medicines plus lifestyle intervention versus lifestyle intervention, Outcome 2 AST (IU/L).

Analysis 3.3.

Comparison 3 Herbal medicines plus lifestyle intervention versus lifestyle intervention, Outcome 3 Ultrasound: liver score.

Analysis 3.4.

Comparison 3 Herbal medicines plus lifestyle intervention versus lifestyle intervention, Outcome 4 Liver CT without improvement.

Analysis 3.5.

Comparison 3 Herbal medicines plus lifestyle intervention versus lifestyle intervention, Outcome 5 Adverse events.

Analysis 3.6.

Comparison 3 Herbal medicines plus lifestyle intervention versus lifestyle intervention, Outcome 6 GGT (U/L).

Comparison 4. Herbal medicines versus conventional therapy
Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size
1 ALT (IU/L)15 Mean Difference (IV, Fixed, 95% CI)Totals not selected
1.1 Shiwei Ganzhikang capsules versus Dong Bao Gan Tai tablets1 Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]
1.2 Tiaogan Jiangzhi granules versus Essentiale capsules1 Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]
1.3 Sisheng Jiangzhi formula versus simvastatin1 Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]
1.4 Zhixiao capsules versus ethyl polyenoate soft capsules1 Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]
1.5 Quyuhua Tan Tongluo decoction versus UDCA1 Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]
1.6 Zini Zhigan prescription versus liptor1 Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]
1.7 Shugan Jianpi Huashi Tang versus Yuyou Jiangzhi tablets plus vitamin C0 Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]
1.8 Huanglong Ganzhixiao decoction versus fenofibrate tablets1 Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]
1.9 Wild apricot versus vitamin B and C + glucurolactone tablets1 Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]
1.10 Herbal formula versus polyene phosphatidylcholine capsules1 Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]
1.11 Qingre Huatan Huoxue formula versus tiopronin tablets1 Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]
1.12 Ganzhikang capsule versus rosiglitazone hydrochloride tablets1 Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]
1.13 Sanyu Huazhuo decoction versus Essentiale1 Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]
1.14 Baogan Xiaozhi pellet versus Dongbao gantai1 Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]
1.15 Bushen Yipi Fa versus polyene phosphatidylcholine capsules1 Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]
1.16 Kangzhi formula versus tiopronin1 Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]
2 AST (IU/L)12 Mean Difference (IV, Fixed, 95% CI)Totals not selected
2.1 Shiwei Ganzhikang capsules versus Dong Bao Gan Tai tablets1 Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]
2.2 Zhixiao capsules versus ethyl polyenoate soft capsules1 Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]
2.3 Quyuhua Tan Tongluo decoction versus UDCA1 Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]
2.4 Sisheng Jiangzhi formula versus simvastatin1 Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]
2.5 Zini Zhigan prescription versus liptor1 Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]
2.6 Shugan Jianpi Huashi Tang versus Yuyou Jiangzhi tablets plus vitamin C0 Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]
2.7 Wild apricot versus vitamin B and C + glucurolactone tablets1 Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]
2.8 Herbal formula versus polyene phosphatidylcholine capsules1 Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]
2.9 Ganzhikang capsule versus rosiglitazone hydrochloride tablets1 Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]
2.10 Sanyu Huazhuo decoction versus Essentiale1 Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]
2.11 Baogan Xiaozhi pellet versus Dongbao gantai1 Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]
2.12 Bushen Yipi Fa versus polyene phosphatidylcholine capsules1 Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]
2.13 Kangzhi formula versus tiopronin1 Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]
3 GGT (U/L)11 Mean Difference (IV, Fixed, 95% CI)Totals not selected
3.1 Shiwei Ganzhikang capsules versus Dong Bao Gan Tai tablets1 Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]
3.2 Zhixiao capsules versus ethyl polyenoate soft capsules1 Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]
3.3 Quyuhua Tan Tongluo decoction versus UDCA1 Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]
3.4 Sisheng Jiangzhi formula versus simvastatin1 Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]
3.5 Zini Zhigan prescription versus liptor1 Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]
3.6 Qingre Huatan Huoxue formula versus tiopronin tablets1 Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]
3.7 Ganzhikang capsule versus rosiglitazone hydrochloride tablets1 Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]
3.8 Sanyu Huazhuo decoction versus Essentiale1 Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]
3.9 Baogan Xiaozhi pellet versus Dongbao gantai1 Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]
3.10 Bushen Yipi Fa versus polyene phosphatidylcholine capsules1 Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]
3.11 Kangzhi formula versus tiopronin1 Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]
4 ALP (U/L)4 Mean Difference (IV, Fixed, 95% CI)Totals not selected
4.1 Shiwei Ganzhikang capsules versus Dong Bao Gan Tai tablets1 Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]
4.2 Zhixiao capsules versus ethyl polyenoate soft capsules1 Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]
4.3 Bushen Yipi Fa versus polyene phosphatidylcholine capsules1 Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]
4.4 Kangzhi formula versus tiopronin1 Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]
5 Abnormal ultrasound5 Risk Ratio (M-H, Fixed, 95% CI)Totals not selected
5.1 Quyuhua Tan Tongluo decoction versus UDCA1 Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]
5.2 Wild apricot versus vitamin B and C + glucurolactone tablets1 Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]
5.3 Sanyu Huazhuo decoction versus Essentiale1 Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]
5.4 Baogan Xiaozhi pellet versus Dongbaogantai1 Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]
5.5 Kangzhi formula versus tiopronin1 Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]
6 Abnormal AST (> 50 U/L)1 Risk Ratio (M-H, Fixed, 95% CI)Totals not selected
6.1 Qingzhifugan decoction versus Essentiale1 Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]
7 Abnormal ALT (> 50 U/L)1 Risk Ratio (M-H, Fixed, 95% CI)Totals not selected
7.1 Qingzhifugan decoction versus Essentiale1 Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]
8 Adverse events158Risk Difference (M-H, Fixed, 95% CI)0.10 [-0.02, 0.22]
8.1 Wild apricot versus vitamin B and C + glucurolactone tablets158Risk Difference (M-H, Fixed, 95% CI)0.10 [-0.02, 0.22]
Analysis 4.1.

Comparison 4 Herbal medicines versus conventional therapy, Outcome 1 ALT (IU/L).

Analysis 4.2.

Comparison 4 Herbal medicines versus conventional therapy, Outcome 2 AST (IU/L).

Analysis 4.3.

Comparison 4 Herbal medicines versus conventional therapy, Outcome 3 GGT (U/L).

Analysis 4.4.

Comparison 4 Herbal medicines versus conventional therapy, Outcome 4 ALP (U/L).

Analysis 4.5.

Comparison 4 Herbal medicines versus conventional therapy, Outcome 5 Abnormal ultrasound.

Analysis 4.6.

Comparison 4 Herbal medicines versus conventional therapy, Outcome 6 Abnormal AST (> 50 U/L).

Analysis 4.7.

Comparison 4 Herbal medicines versus conventional therapy, Outcome 7 Abnormal ALT (> 50 U/L).

Analysis 4.8.

Comparison 4 Herbal medicines versus conventional therapy, Outcome 8 Adverse events.

Comparison 5. Herbal medicines plus conventional therapy versus conventional therapy
Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size
1 ALT (IU/L)1 Mean Difference (IV, Fixed, 95% CI)Totals not selected
1.1 Xiaotan Hugan decoction + Essentiale Forte + vitamin versus Essentiale Forte + vitamin1 Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]
1.2 Gegen decoction + UDCA + potassium magnesium aspartate + vitamin C, B6 and K1 + potenline versus ursodeoxycholic acid + potassium magnesium aspartate + vitamin C, B6 and K1 + potenline0 Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]
2 AST (IU/L)1 Mean Difference (IV, Fixed, 95% CI)Subtotals only
2.1 Xiaotan Hugan decoction + Essentiale Forte + vitamin versus Essentiale Forte + vitamin160Mean Difference (IV, Fixed, 95% CI)-12.09 [-18.88, -5.30]
3 GGT (IU/L)1 Mean Difference (IV, Fixed, 95% CI)Subtotals only
3.1 Xiaotan Hugan decoction + Essentiale Forte + vitamin versus Essentiale Forte + vitamin160Mean Difference (IV, Fixed, 95% CI)-45.45 [-47.98, -42.92]
4 Hepatic ultrasound without improvement1 Odds Ratio (M-H, Fixed, 95% CI)Totals not selected
4.1 Xiaotan Hugan decoction + Essentiale Forte + vitamin versus Essentiale Forte + vitamin1 Odds Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]
Analysis 5.1.

Comparison 5 Herbal medicines plus conventional therapy versus conventional therapy, Outcome 1 ALT (IU/L).

Analysis 5.2.

Comparison 5 Herbal medicines plus conventional therapy versus conventional therapy, Outcome 2 AST (IU/L).

Analysis 5.3.

Comparison 5 Herbal medicines plus conventional therapy versus conventional therapy, Outcome 3 GGT (IU/L).

Analysis 5.4.

Comparison 5 Herbal medicines plus conventional therapy versus conventional therapy, Outcome 4 Hepatic ultrasound without improvement.

Comparison 6. Herbal medicines plus lifestyle intervention versus conventional therapy plus lifestyle intervention
Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size
1 ALT (IU/L)35 Mean Difference (IV, Fixed, 95% CI)Totals not selected
1.1 Huatan Huoxue formula + lifestyle versus Essentiale capsules + lifestyle1 Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]
1.2 Jianpi Huazhuo formula + lifestyle versus polyene phosphatidylcholine capsules + lifestyle1 Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]
1.3 Qinggan decoction + lifestyle versus tiopronin tablets + lifestyle1 Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]
1.4 Xiaoyu Huatan decoction + lifestyle versus compound methionine and choline bitartrate tablets + lifestyle1 Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]
1.5 Lishi Huoxue Tongluo decoction + lifestyle versus tiopronin tablets + lifestyle1 Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]
1.6 Qiyin granules + lifestyle versus Essentiale + lifestyle1 Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]
1.7 Jiangan Jiangzhi tablets + lifestyle versus silibinin capsules + lifestyle1 Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]
1.8 Qiyin tea + lifestyle versus polyene phosphatidylcholine capsules + lifestyle1 Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]
1.9 Shenling Baizhu powder with Erchen decoction + lifestyle versus Zocor + diammonium glycyrrihizinate + lifestyle1 Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]
1.10 Danning tablets + lifestyle versus UDCA capsules + lifestyle1 Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]
1.11 Tiaozhi Yanggan decoction + lifestyle versus thiola tablets + lifestyle1 Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]
1.12 Zhiyan Xiao decoction + lifestyle versus UDCA + lifestyle1 Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]
1.13 Shuli Qingzhi powder + lifestyle versus simvastatin tablets + lifestyle1 Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]
1.14 Xiaogan Jiangzhi formula + lifestyle versus Diisopropylamini Dichlorocacetas + lifestyle1 Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]
1.15 Tangganjian + lifestyle versus metformin hydrochloride tablets + lifestyle1 Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]
1.16 Quyu Huazhuo decoction + lifestyle versus polyene phosphatidylcholine capsules + lifestyle1 Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]
1.17 Herbal + lifestyle versus silybininon + lifestyle1 Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]
1.18 Juge Yigan decoction + lifestyle versus vitamin B and folic acid + lifestyle1 Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]
1.19 Zhishi Xiaopi decoction + lifestyle versus polyene phosphatidylcholine capsules + lifestyle1 Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]
1.20 Baogan Xiaozhi pellet + lifestyle versus vitamin E nicotinicate capsules + lifestyle1 Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]
1.21 Xiaozhi Jiangpi decoction + lifestyle versus polyene phosphatidylcholine capsules + lifestyle1 Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]
1.22 Zini Jianpi Huatan formula + lifestyle versus polyene phosphatidylcholine capsules + lifestyle1 Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]
1.23 Zhiganqing granules + lifestyle versus tiopronin + lifestyle1 Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]
1.24 Modified Wendan decoction + lifestyle versus polyene phosphatidylcholine capsules + lifestyle1 Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]
1.25 Diammonium glycyrrihizinate capsules with Panax Notoginseng powder + lifestyle versus tiopronin + lifestyle1 Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]
1.26 Shanzha Beimu decoction + lifestyle versus Duoxi Kangzhi capsules + lifestyle1 Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]
1.27 Zini Chailing decoction + lifestyle versus polyene phosphatidylcholine capsules + lifestyle1 Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]
1.28 Guben Xiaozhuo decoction + lifestyle versus fenofibrate tablets + lifestyle1 Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]
1.29 Xiaozhi decoction + lifestyle versus Essentiale + lifestyle1 Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]
1.30 Clearing heat and removing dampness + lifestyle versus conventional therapy + lifestyle1 Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]
1.31 Quganzhi decoction + lifestyle versus diisopropylamini dichlorovacetas + lifestyle1 Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]
1.32 Herbal therapy + lifestyle versus Essentiale + lifestyle1 Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]
1.33 Huazhuo Xiaozhi decoction + lifestyle versus Baisainuo + lifestyle1 Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]
1.34 Yunpi Tongluo formula + lifestyle versus UDCA + lifestyle1 Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]
1.35 Tiaogan Lizhong decoction with Qingbai powder + lifestyle versus conventional therapy + lifestyle1 Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]
2 AST (IU/L)33 Mean Difference (IV, Fixed, 95% CI)Subtotals only
2.1 Huatan Huoxue formula + lifestyle versus Essentiale capsules + lifestyle186Mean Difference (IV, Fixed, 95% CI)-6.30 [-10.90, -1.70]
2.2 Jianpi Huazhuo formula + lifestyle versus polyene phosphatidylcholine capsules + lifestyle175Mean Difference (IV, Fixed, 95% CI)-0.30 [-3.98, 3.38]
2.3 Qinggan decoction + lifestyle versus tiopronin tablets + lifestyle140Mean Difference (IV, Fixed, 95% CI)-34.8 [-45.11, -24.49]
2.4 Xiaoyu Huatan decoction + lifestyle versus compound methionine and choline bitartrate tablets + lifestyle1105Mean Difference (IV, Fixed, 95% CI)-12.2 [-14.70, -9.70]
2.5 Lishi Huoxue Tongluo decoction + lifestyle versus tiopronin tablets + lifestyle1120Mean Difference (IV, Fixed, 95% CI)-19.00 [-20.36, -17.64]
2.6 Qiyin granules + lifestyle versus Essentiale + lifestyle170Mean Difference (IV, Fixed, 95% CI)3.40 [-1.13, 7.93]
2.7 Jiangan Jiangzhi tablets + lifestyle versus silibinin capsules + lifestyle1120Mean Difference (IV, Fixed, 95% CI)-0.60 [-3.44, 2.24]
2.8 Qiyin tea + lifestyle versus polyene phosphatidylcholine capsules + lifestyle1112Mean Difference (IV, Fixed, 95% CI)-0.51 [-4.37, 3.35]
2.9 Shenling Baizhu powder with Erchen decoction + lifestyle versus Zocor + diammonium glycyrrihizinate + lifestyle189Mean Difference (IV, Fixed, 95% CI)-5.60 [-9.97, -1.23]
2.10 Danning tablets + lifestyle versus UDCA capsules + lifestyle1135Mean Difference (IV, Fixed, 95% CI)-2.78 [-8.84, 3.28]
2.11 Tiaozhi Yanggan decoction + lifestyle versus thiola tablets + lifestyle1130Mean Difference (IV, Fixed, 95% CI)-13.55 [-23.47, -3.63]
2.12 Zhiyan Xiao decoction + lifestyle versus UDCA + lifestyle1100Mean Difference (IV, Fixed, 95% CI)-16.20 [-20.71, -11.69]
2.13 Shuli Qingzhi powder + lifestyle versus simvastatin tablets + lifestyle160Mean Difference (IV, Fixed, 95% CI)-11.09 [-16.76, -5.42]
2.14 Xiaogan Jiangzhi formula + lifestyle versus diisopropylamini dichlorocacetas + lifestyle162Mean Difference (IV, Fixed, 95% CI)-1.5 [-4.06, 1.06]
2.15 Tangganjian + lifestyle versus metformin hydrochloride tablets + lifestyle1110Mean Difference (IV, Fixed, 95% CI)-36.57 [-46.15, -26.99]
2.16 Quyu Huazhuo decoction + lifestyle versus polyene phosphatidylcholine1120Mean Difference (IV, Fixed, 95% CI)-3.29 [-6.29, -0.29]
2.17 Herbal + lifestyle versus silybininon + lifestyle140Mean Difference (IV, Fixed, 95% CI)-10.04 [-39.77, 19.69]
2.18 Juge Yigan decoction + lifestyle versus vitamin B + folic acid + lifestyle1200Mean Difference (IV, Fixed, 95% CI)-9.20 [-10.78, -7.62]
2.19 Zhishi Xiaopi decoction + lifestyle versus polyene phosphatidylcholine capsules + lifestyle158Mean Difference (IV, Fixed, 95% CI)-23.56 [-31.08, -16.04]
2.20 Baogan Xiaozhi pellet + lifestyle versus vitamin E nicotinicate capsules + lifestyle180Mean Difference (IV, Fixed, 95% CI)-5.0 [-8.19, -1.81]
2.21 Xiaozhi Jiangpi decoction + lifestyle versus polyene phosphatidylcholine capsules + lifestyle175Mean Difference (IV, Fixed, 95% CI)-3.0 [-6.12, 0.12]
2.22 Zhiganqing granules + lifestyle versus tiopronin + lifestyle160Mean Difference (IV, Fixed, 95% CI)-21.25 [-24.38, -18.12]
2.23 Modified Wendan decoction + lifestyle versus polyene phosphatidylcholine capsules + lifestyle196Mean Difference (IV, Fixed, 95% CI)-15.0 [-24.50, -5.50]
2.24 Diammonium glycyrrihizinate capsules with Panax Notoginseng powder + lifestyle versus tiopronin + lifestyle173Mean Difference (IV, Fixed, 95% CI)-21.1 [-30.21, -11.99]
2.25 Shanzha Beimu decoction + lifestyle versus Duoxi Kangzhi capsules + lifestyle174Mean Difference (IV, Fixed, 95% CI)-16.20 [-21.56, -10.84]
2.26 Zini Chailing decoction + lifestyle versus polyene phosphatidylcholine capsules + lifestyle164Mean Difference (IV, Fixed, 95% CI)-11.8 [-14.64, -8.96]
2.27 Guben Xiaozhuo decoction + lifestyle versus fenofibrate tablets + lifestyle190Mean Difference (IV, Fixed, 95% CI)-16.9 [-23.82, -9.98]
2.28 Xiaozhi decoction + lifestyle versus Essentiale + lifestyle160Mean Difference (IV, Fixed, 95% CI)-7.79 [-15.83, 0.25]
2.29 Clearing heat and removing dampness + lifestyle versus conventional therapy + lifestyle145Mean Difference (IV, Fixed, 95% CI)-4.10 [-7.14, -1.06]
2.30 Quganzhi decoction + lifestyle versus diisopropylamini dichlorovacetas + lifestyle1125Mean Difference (IV, Fixed, 95% CI)-13.23 [-14.36, -12.10]
2.31 Huazhuo Xiaozhi decoction + lifestyle versus Baisainuo + lifestyle190Mean Difference (IV, Fixed, 95% CI)-44.30 [-51.30, -37.30]
2.32 Yunpi Tongluo formula + lifestyle versus UDCA + lifestyle163Mean Difference (IV, Fixed, 95% CI)-9.08 [-13.53, -4.63]
2.33 Tiaogan Lizhong decoction with Qingbai powder + lifestyle versus conventional therapy + lifestyle1112Mean Difference (IV, Fixed, 95% CI)-34.64 [-38.91, -30.37]
3 GGT (IU/L)20 Mean Difference (IV, Fixed, 95% CI)Subtotals only
3.1 Jianpi Huazhuo formula + lifestyle versus polyene phosphatidylcholine capsules + lifestyle175Mean Difference (IV, Fixed, 95% CI)-14.5 [-23.41, -5.59]
3.2 Jiangan Jiangzhi tablets + lifestyle versus silibinin capsules + lifestyle1120Mean Difference (IV, Fixed, 95% CI)-12.60 [-19.84, -5.36]
3.3 Qiyin tea + lifestyle versus polyene phosphatidylcholine capsules + lifestyle1112Mean Difference (IV, Fixed, 95% CI)1.77 [-2.54, 6.08]
3.4 Shenling Baizhu powder with Erchen decoction + lifestyle versus Zocor + diammonium glycyrrihizinate + lifestyle189Mean Difference (IV, Fixed, 95% CI)-4.80 [-11.47, 1.87]
3.5 Danning tablets lifestyle versus UDCA capsules + lifestyle1135Mean Difference (IV, Fixed, 95% CI)-9.63 [-23.76, 4.50]
3.6 Tiaozhi Yanggan decoction + lifestyle versus thiola tablets + lifestyle1130Mean Difference (IV, Fixed, 95% CI)-12.74 [-25.90, 0.42]
3.7 Zhiyan Xiao decoction + lifestyle versus UDCA + lifestyle1100Mean Difference (IV, Fixed, 95% CI)-16.30 [-24.75, -7.85]
3.8 Shuli Qingzhi powder + lifestyle versus simvastatin tablets + lifestyle160Mean Difference (IV, Fixed, 95% CI)-11.88 [-21.36, -2.40]
3.9 Xiaogan Jiangzhi formula + lifestyle versus diisopropylamini dichlorocacetas + lifestyle162Mean Difference (IV, Fixed, 95% CI)-11.60 [-16.54, -6.66]
3.10 Juge Yigan decoction + lifestyle versus vitamin B + folic acid + lifestyle1200Mean Difference (IV, Fixed, 95% CI)-12.30 [-14.26, -10.34]
3.11 Zhishi Xiaopi decoction + lifestyle versus polyene phosphatidylcholine capsules + lifestyle158Mean Difference (IV, Fixed, 95% CI)-28.99 [-37.66, -20.32]
3.12 Baogan Xiaozhi pellet + lifestyle versus vitamin E nicotinicate capsules + lifestyle180Mean Difference (IV, Fixed, 95% CI)-19.6 [-22.14, -17.06]
3.13 Zini Jianpi Huatan formula + lifestyle versus polyene phosphatidylcholine capsules + lifestyle1112Mean Difference (IV, Fixed, 95% CI)-13.30 [-18.62, -7.98]
3.14 Zhiganqing granules + lifestyle versus tiopronin + lifestyle160Mean Difference (IV, Fixed, 95% CI)-35.0 [-39.67, -30.33]
3.15 Shanzha Beimu decoction + lifestyle versus Duoxi Kangzhi capsules + lifestyle174Mean Difference (IV, Fixed, 95% CI)-16.30 [-26.26, -6.34]
3.16 Clearing heat and removing dampness + lifestyle versus conventional therapy + lifestyle145Mean Difference (IV, Fixed, 95% CI)-15.23 [-18.84, -11.62]
3.17 Herbal therapy + lifestyle versus Essentiale + lifestyle197Mean Difference (IV, Fixed, 95% CI)-22.13 [-25.07, -19.19]
3.18 Huazhuo Xiaozhi decoction + lifestyle versus Baisainuo + lifestyle190Mean Difference (IV, Fixed, 95% CI)-13.94 [-15.41, -12.47]
3.19 Yunpi Tongluo formula + lifestyle versus UDCA + lifestyle163Mean Difference (IV, Fixed, 95% CI)-7.35 [-12.39, -2.31]
3.20 Tiaogan Lizhong decoction with Qingbai powder + lifestyle versus conventional therapy + lifestyle1112Mean Difference (IV, Fixed, 95% CI)-34.39 [-36.58, -32.20]
4 L/S CT ratio1 Mean Difference (IV, Fixed, 95% CI)Subtotals only
4.1 Jianpi Huazhuo formula + lifestyle versus polyene phosphatidylcholine capsules + lifestyle175Mean Difference (IV, Fixed, 95% CI)0.49 [0.37, 0.61]
5 Ultrasound without improvement10 Risk Ratio (M-H, Fixed, 95% CI)Totals not selected
5.1 Xiaoyu Huatan decoction + lifestyle versus compound methionine and choline bitartrate tablets + lifestyle1 Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]
5.2 Lishi Huoxue Tongluo decoction + lifestyle versus tiopronin tablets + lifestyle1 Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]
5.3 Qiyin granules + lifestyle versus Essentiale + lifestyle1 Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]
5.4 Qiyin tea + lifestyle versus polyene phosphatidylcholine capsules + lifestyle1 Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]
5.5 Danning tablets + lifestyle versus UDCA capsules + lifestyle1 Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]
5.6 Tiaozhi Yanggan decoction + lifestyle versus thiola tablets + lifestyle1 Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]
5.7 Shuli Qingzhi powder + lifestyle versus simvastatin tablets + lifestyle1 Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]
5.8 Zini Chailing decoction + lifestyle versus polyene phosphatidylcholine capsules + lifestyle1 Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]
5.9 Yunpi Tongluo formula + lifestyle versus UDCA + lifestyle1 Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]
5.10 Xiaozhi Jiangpi decoction + lifestyle versus polyene phosphatidylcholine capsules + lifestyle1 Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]
6 Ultrasound: proximal diffuse high echogenic dots1 Odds Ratio (M-H, Fixed, 95% CI)Totals not selected
6.1 Jiangan Jiangzhi tablets + lifestyle versus silibinin capsules + lifestyle1 Odds Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]
7 Ultrasound: distal end echo attenuation1 Risk Ratio (M-H, Fixed, 95% CI)Totals not selected
7.1 Jiangan Jiangzhi tablets + lifestyle versus silibinin capsules + lifestyle1 Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]
8 Ultrasound: unclear hepatic vessel structure2 Risk Ratio (M-H, Fixed, 95% CI)Totals not selected
8.1 Jiangan Jiangzhi tablets + lifestyle versus silibinin capsules + lifestyle1 Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]
8.2 Shuli Qingzhi powder + lifestyle versus simvastatin tablets + lifestyle1 Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]
9 Ultrasound: reduction of blood flow1 Risk Ratio (M-H, Fixed, 95% CI)Totals not selected
9.1 Jiangan Jiangzhi tablets + lifestyle versus silibinin capsules + lifestyle1 Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]
10 Liver CT without improvement2 Risk Ratio (M-H, Fixed, 95% CI)Totals not selected
10.1 Danning tablets + lifestyle versus UDCA capsules + lifestyle1 Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]
10.2 Tiaozhi Yanggan decoction + lifestyle versus thiola tablets + lifestyle1 Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]
11 Adverse events1 Risk Ratio (M-H, Fixed, 95% CI)Totals not selected
11.1 Yunpi Tongluo formula + lifestyle versus UDCA + lifestyle1 Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]
12 Ultrasound: liver score1 Mean Difference (IV, Fixed, 95% CI)Totals not selected
12.1 Chaihu Shugan powder + lifestyle versus fenofibrate sustained release capsules + lifestyle1 Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]
Analysis 6.1.

Comparison 6 Herbal medicines plus lifestyle intervention versus conventional therapy plus lifestyle intervention, Outcome 1 ALT (IU/L).

Analysis 6.2.

Comparison 6 Herbal medicines plus lifestyle intervention versus conventional therapy plus lifestyle intervention, Outcome 2 AST (IU/L).

Analysis 6.3.

Comparison 6 Herbal medicines plus lifestyle intervention versus conventional therapy plus lifestyle intervention, Outcome 3 GGT (IU/L).

Analysis 6.4.

Comparison 6 Herbal medicines plus lifestyle intervention versus conventional therapy plus lifestyle intervention, Outcome 4 L/S CT ratio.

Analysis 6.5.

Comparison 6 Herbal medicines plus lifestyle intervention versus conventional therapy plus lifestyle intervention, Outcome 5 Ultrasound without improvement.

Analysis 6.6.

Comparison 6 Herbal medicines plus lifestyle intervention versus conventional therapy plus lifestyle intervention, Outcome 6 Ultrasound: proximal diffuse high echogenic dots.

Analysis 6.7.

Comparison 6 Herbal medicines plus lifestyle intervention versus conventional therapy plus lifestyle intervention, Outcome 7 Ultrasound: distal end echo attenuation.

Analysis 6.8.

Comparison 6 Herbal medicines plus lifestyle intervention versus conventional therapy plus lifestyle intervention, Outcome 8 Ultrasound: unclear hepatic vessel structure.

Analysis 6.9.

Comparison 6 Herbal medicines plus lifestyle intervention versus conventional therapy plus lifestyle intervention, Outcome 9 Ultrasound: reduction of blood flow.

Analysis 6.10.

Comparison 6 Herbal medicines plus lifestyle intervention versus conventional therapy plus lifestyle intervention, Outcome 10 Liver CT without improvement.

Analysis 6.11.

Comparison 6 Herbal medicines plus lifestyle intervention versus conventional therapy plus lifestyle intervention, Outcome 11 Adverse events.

Analysis 6.12.

Comparison 6 Herbal medicines plus lifestyle intervention versus conventional therapy plus lifestyle intervention, Outcome 12 Ultrasound: liver score.

Comparison 7. Herbal medicines plus lifestyle intervention plus conventional therapy versus lifestyle intervention plus conventional therapy
Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size
1 Liver/spleen CT ratio1 Mean Difference (IV, Fixed, 95% CI)Totals not selected
1.1 Qinggan Xiaozhi decoction + reduced glutathione tablets + lifestyle versus reduced glutathione tablets + lifestyle1 Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]
2 ALT (U/L)15 Mean Difference (IV, Fixed, 95% CI)Totals not selected
2.1 Colon herbs dialysis therapy + lifestyle + polyene phosphatidylcholine + simvastatin + silybin meglumine tablets versus lifestyle + polyene phosphatidylcholine + simvastatin + silybin meglumine tablets1 Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]
2.2 Qinggan Xiaozhi decoction + reduced glutathione tablets + lifestyle versus reduced glutathione tablets + lifestyle1 Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]
2.3 Jiejiuhugan decoction + polyene phosphatidylcholine capsules + lifestyle versus polyene phosphatidylcholine capsules + lifestyle1 Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]
2.4 Xiaoyao tablets + legalon + lifestyle versus legalon + lifestyle1 Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]
2.5 Hegan Yin + tiopronin + lifestyle versus tiopronin + lifestyle1 Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]
2.6 Shugan Lipi San + GSH + lifestyle versus GSH + lifestyle1 Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]
2.7 Kezhi capsules + polyene phosphatidylcholine capsules + lifestyle versus polyene phosphatidylcholine capsules + lifestyle1 Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]
2.8 Herbal + silybininon + lifestyle versus silybininon + lifestyle1 Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]
2.9 Huoxue Qinggan decoction + polyene phosphatidylcholine capsules + lifestyle versus polyene phosphatidylcholine capsules + lifestyle1 Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]
2.10 Shuanghu Qinggan granules + tiopronin tablets + lifestyle versus tiopronin tablets + lifestyle1 Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]
2.11 Xiaotan Jiangzhi formula + polyene phosphatidylcholine + lifestyle versus polyene phosphatidylcholine + lifestyle1 Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]
2.12 Chuige Jiugan decoction + lifestyle + tiopronin versus tiopronin + lifestyle1 Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]
2.13 Huganning tablets + metformin hydrochloride tablets + lifestyle versus metformin hydrochloride tablets + lifestyle1 Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]
2.14 Zini Xiaozhi Jianggan decoction + lifestyle + diammonium glycyrrihizinate versus lifestyle + diammonium glycyrrihizinate1 Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]
2.15 Hugan tablets + UDCA + lifestyle versus UDCA + lifestyle1 Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]
3 AST (U/L)9 Mean Difference (IV, Fixed, 95% CI)Totals not selected
3.1 Colon herbs dialysis therapy + lifestyle + polyene phosphatidylcholine + simvastatin + silybin meglumine tablets versus lifestyle + polyene phosphatidylcholine + simvastatin + silybin meglumine tablets1 Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]
3.2 Qinggan Xiaozhi decoction + reduced glutathione tablets + lifestyle versus reduced glutathione tablets + lifestyle1 Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]
3.3 Jiejiuhugan decoction + polyene phosphatidylcholine capsules + lifestyle versus polyene phosphatidylcholine capsules + lifestyle1 Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]
3.4 Kezhi capsules + polyene phosphatidylcholine capsules + lifestyle versus polyene phosphatidylcholine capsules + lifestyle1 Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]
3.5 Huoxue Qinggan decoction + polyene phosphatidylcholine capsules + lifestyle versus polyene phosphatidylcholine capsules + lifestyle1 Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]
3.6 Xiaotan Jiangzhi formula + polyene phosphatidylcholine + lifestyle versus polyene phosphatidylcholine + lifestyle1 Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]
3.7 Chuige Jiugan decoction + lifestyle + tiopronin versus tiopronin + lifestyle1 Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]
3.8 Huganning tablets + metformin hydrochloride tablets + lifestyle versus metformin hydrochloride tablets + lifestyle1 Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]
3.9 Zini Xiaozhi Jianggan decoction + lifestyle + diammonium glycyrrihizinate versus lifestyle + diammonium glycyrrihizinate1 Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]
4 GGT (U/L)11 Mean Difference (IV, Fixed, 95% CI)Totals not selected
4.1 Colon herbs dialysis therapy + lifestyle + polyene phosphatidylcholine + simvastatin + silybin meglumine tablets versus lifestyle + polyene phosphatidylcholine + simvastatin + silybin meglumine tablets1 Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]
4.2 Qinggan Xiaozhi decoction + reduced glutathione tablets + lifestyle versus reduced glutathione tablets + lifestyle1 Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]
4.3 Jiejiuhugan decoction + polyene phosphatidylcholine capsules + lifestyle versus polyene phosphatidylcholine capsules + lifestyle1 Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]
4.4 Xiaoyao tablets + legalon + lifestyle versus legalon + lifestyle1 Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]
4.5 Hegan decoction + tiopronin + lifestyle versus tiopronin + lifestyle1 Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]
4.6 Shugan Lipi San + GSH + lifestyle versus GSH + lifestyle1 Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]
4.7 Huoxue Qinggan decoction + polyene phosphatidylcholine capsules + lifestyle versus polyene phosphatidylcholine capsules + lifestyle1 Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]
4.8 Shuanghu Qinggan granules + tiopronin tablets + lifestyle versus tiopronin tablets + lifestyle1 Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]
4.9 Xiaotan Jiangzhi formula + polyene phosphatidylcholine + lifestyle versus polyene phosphatidylcholine + lifestyle1 Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]
4.10 Chuige Jiugan decoction + lifestyle + tiopronin versus tiopronin + lifestyle1 Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]
4.11 Zini Xiaozhi Jianggan decoction + lifestyle + diammonium glycyrrihizinate versus lifestyle + diammonium glycyrrihizinate1 Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]
5 Ultrasound: liver echo intensity1 Mean Difference (IV, Fixed, 95% CI)Totals not selected
5.1 Colon herbs dialysis therapy + lifestyle + polyene phosphatidylcholine + simvastatin + silybin meglumine tablets versus lifestyle + polyene phosphatidylcholine + simvastatin + silybin meglumine tablets1 Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]
6 Abnormal ultrasound2 Risk Ratio (M-H, Fixed, 95% CI)Totals not selected
6.1 Kezhi capsules + polyene phosphatidylcholine capsules + lifestyle1 Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]
6.2 Chuige Jiugan decoction + lifestyle + tiopronin versus tiopronin + lifestyle1 Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]
7 Liver CT value1 Mean Difference (IV, Fixed, 95% CI)Totals not selected
7.1 Xiaotan Jiangzhi formula + polyene phosphatidylcholine + lifestyle versus polyene phosphatidylcholine + lifestyle1 Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]
8 Adverse events2 Risk Ratio (M-H, Fixed, 95% CI)Totals not selected
8.1 Huganning tablets + metformin hydrochloride tablets + lifestyle versus metformin hydrochloride tablets + lifestyle1 Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]
8.2 Hugan tablets + UDCA + lifestyle versus UDCA + lifestyle1 Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]
Analysis 7.1.

Comparison 7 Herbal medicines plus lifestyle intervention plus conventional therapy versus lifestyle intervention plus conventional therapy, Outcome 1 Liver/spleen CT ratio.

Analysis 7.2.

Comparison 7 Herbal medicines plus lifestyle intervention plus conventional therapy versus lifestyle intervention plus conventional therapy, Outcome 2 ALT (U/L).

Analysis 7.3.

Comparison 7 Herbal medicines plus lifestyle intervention plus conventional therapy versus lifestyle intervention plus conventional therapy, Outcome 3 AST (U/L).

Analysis 7.4.

Comparison 7 Herbal medicines plus lifestyle intervention plus conventional therapy versus lifestyle intervention plus conventional therapy, Outcome 4 GGT (U/L).

Analysis 7.5.

Comparison 7 Herbal medicines plus lifestyle intervention plus conventional therapy versus lifestyle intervention plus conventional therapy, Outcome 5 Ultrasound: liver echo intensity.

Analysis 7.6.

Comparison 7 Herbal medicines plus lifestyle intervention plus conventional therapy versus lifestyle intervention plus conventional therapy, Outcome 6 Abnormal ultrasound.

Analysis 7.7.

Comparison 7 Herbal medicines plus lifestyle intervention plus conventional therapy versus lifestyle intervention plus conventional therapy, Outcome 7 Liver CT value.

Analysis 7.8.

Comparison 7 Herbal medicines plus lifestyle intervention plus conventional therapy versus lifestyle intervention plus conventional therapy, Outcome 8 Adverse events.

Appendices

Appendix 1. Search strategies

DatabaseTime spanSearch strategy
The Cochrane Hepato-Biliary Group Controlled Trials RegisterMarch 2012.(((traditional OR Chinese OR oriental OR alternative OR complementary) AND medicine*) OR herb* OR plant*) AND ('fatty liver' OR steatosis OR steatohepatitis OR fibrosis OR cirrhosis)
The Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane LibraryIssue 3 of 12, 2012.#1 MeSH descriptor fatty liver explode all trees
#2 (fatty liver in All Text)
#3 (steatosis in All Text)
#4 (steatohepatitis in All Text)
#5 (fibrosis in All Text)
#6 (cirrhosis in All Text)
#7 (#1 or #2 or #3 or #4 or #5 or #6)
#8 MeSH descriptor Phytotherapy explode all trees
#9 MeSH descriptor Medicine, traditional explode all trees
#10 MeSH descriptor Medicine, Chinese traditional explode all trees
#11 MeSH descriptor Plants, medicinal explode all trees with qualifiers: TH,TU
#12 MeSH descriptor Herbal medicine explode all trees
#13 MeSH descriptor Plant preparations explode all trees with qualifiers: TH,TU
#14 MeSH descriptor Drugs, Chinese herbal explode all trees
#15 (Chinese in All Text near/3 medic* in All Text)
#16 (Chinese in All Text near/3 herb* in All Text)
#17 (Chinese in All Text near/3 drug* in All Text)
#18 (Chinese in All Text near/3 formul* in All Text)
#19 (Chinese in All Text near/3 plant* in All Text)
#20 (Chinese in All Text near/3 prescri* in All Text)
#21 (phyto in All Text near/6 drug* in All Text)
#22 (phyto in All Text near/6 therap* in All Text)
#23 (phyto in All Text near/6 treatment* in All Text)
#24 (phyto in All Text near/6 medicin* in All Text)
#25 (complementary in All Text near/3 therap* in All Text)
#26 (complementary in All Text near/3 medicin* in All Text)
#27 (complementary in All Text near/3 treatment* in All Text)
#28 (alternativ* in All Text near/3 therap* in All Text)
#29 (alternativ* in All Text near/3 medicin* in All Text)
#30 (alternativ* in All Text near/3 treatment* in All Text)
#31 (#8 or #9 or #10 or #11 or #12 or #13 or #14 or #15 or #16 or #17 or #18 or #19 or #20 or #21 or #22 or #23 or #24 or #25 or #26 or #27 or #28 or #29 or #30)
#32 (#7 and #31)
MEDLINE (Ovid SP)1946 to March 2012.1. exp fatty liver/
2. fatty liver.tw,ot.
3. steatosis.tw,ot.
4. steatohepatitis.tw,ot.
5. cirrhosis.tw,ot.
6. or/1-5
7. exp Phytotherapy/
8. exp Medicine, traditional/
9. exp Medicine, Chinese Traditional/
10. exp Plants, Medicinal/th, tu [Therapy, Therapeutic Use]
11. exp Herbal Medicine/
12. exp Plant Preparations/tu [Therapeutic Use]
13. exp Drugs, Chinese herbal/
14. (chines* adj6 traditional medicin*).tw,ot.
15. (Chinese adj3 (medic* or herb* or drug* or formul* or plant* or prescri*)).tw,ot.
16. (phyto adj6 (drug* or pharmaceutical* or therap* or treatment* or medicin*)).tw,ot.
17. ((complementary or alternativ*) adj3 (therap* or medicine*)).tw,ot.
18. or/7-17
19. randomised controlled trial.pt.
20. controlled clinical trial.pt.
21. randomi?ed.ab.
22. placebo.ab.
23. drug therapy.fs.
24. randomly.ab.
25. trial.ab.
26. groups.ab.
27. or/19-26
28. Meta-analysis.pt.
29. exp Technology Assessment, Biomedical/
30. exp Meta-analysis/
31. exp Meta-analysis as topic/
32. hta.tw,ot.
33. (health technology adj6 assessment$).tw,ot.
34. (meta analy$ or metaanaly$ or meta?analy$).tw,ot.
35. ((review$ or search$) adj10 (literature$ or medical database$ or medline or pubmed or embase or cochrane or cinahl or psycinfo or psyclit or healthstar or biosis or current content$ or systemat$)).tw,ot.
36. or/28-35
37. (comment or editorial or historical-article).pt.
38. 36 not 37
39. 27 or 38
40. 6 and 18 and 39
41. (animals not (animals and humans)).sh.
42. 40 not 41
EMBASE (Ovid SP)1974 to until March 2012.1. exp fatty liver/
2. fatty liver.tw,ot.
3. steatosis.tw,ot.
4. steatohepatitis.tw,ot.
5. cirrhosis.tw,ot.
6. or/1-5
7. exp phytotherapy/
8. traditional medicine/
9. exp Chinese medicine/
10. exp medicinal plant/
11. exp herbal medicine/
12. exp plant medicinal product/dt [Drug Therapy]
13. exp herbaceous agent/
14. (chines* adj3 (medicin* or herb* or drug* or plant* or formula* or prescri*)).tw,ot.
15. (phyto adj3 (drug* or pharmaceutical* or therap* or treatment* or medicin*)).tw,ot.
16. ((complementary or alternativ*) adj2 (therap* or treatment* or medicin*)).tw,ot.
17. or/7-16
18. 6 and 17
19. exp Randomized Controlled Trial/
20. exp Controlled Clinical Trial/
21. exp Comparative Study/
22. exp Drug comparison/
23. exp Randomization/
24. exp Crossover procedure/
25. exp Double blind procedure/
26. exp Single blind procedure/
27. exp Placebo/
28. exp Prospective Study/
29. ((comparativ$ or prospectiv$ or randomi?ed) adj3 (trial$ or stud$)).ab,ti.
30. (random$ adj6 (allocat$ or assign$ or basis or order$)).ab,ti.
31. ((singl$ or doubl$ or trebl$ or tripl$) adj6 (blind$ or mask$)).ab,ti.
32. (cross over or crossover).ab,ti.
33. or/19-32
34. exp meta analysis/
35. (metaanaly$ or meta analy$ or meta?analy$).ab,ti,ot.
36. ((review$ or search$) adj10 (literature$ or medical database$ or medline or pubmed or embase or cochrane or cinahl or psycinfo or psyclit or healthstar or biosis or current content$ or systematic$)).ab,ti,ot.
37. exp Literature/
38. exp Biomedical Technology Assessment/
39. hta.tw,ot.
40. (health technology adj6 assessment$).tw,ot.
41. or/34-40
42. (comment or editorial or historical-article).pt.
43. 41 not 42
44. 33 or 43
45. 18 and 44
46. limit 45 to human
Science Citation Index Expanded (www.webofknowledge.com/?DestApp=WOS)1900 to March 2012.#1 TS=(((traditional or chinese or oriental or alternative or complementary) and medicine*) or herb* or plant*)
#2 TS =('fatty liver' OR steatosis OR steatohepatitis OR fibrosis OR cirrhosis)
#3 #1 AND #2
#4 TS=(random* OR blind* OR placebo* OR meta-analysis)
#5 #3 AND #4
AMED (Allied and Complementary Medicine; on Ovid)Until March 2012.1 exp Traditional Medicine Chinese/ (4874)
2 exp plants medicinal/ (16,877)
3 exp plant extracts/ (18,576)
4 exp herbal drugs/ (6740)
5 phytotherapy/ (1474)
6 (((traditional or Chinese or oriental or alternative or complementary) and medicine*) or herb* or plant*).tw. (36,434)
7 or/1-6 (37,507)
8 exp liver disease/ (1093)
9 (fatty liver or steatosis or steatohepatitis or fibrosis or cirrhosis).tw. (734)
10 or/8-9 (1711)
11 7 and 10 (799)
12 humans/ (58,310)
13 11 and 12 (112)
Chinese Biomedical CD Database (CBM)
(sinomed.imicams.ac.cn/)
1978 to March 2012.

Search strategy in Chinese.

1 MeSH ==" fatty liver/all subtitles/all trees"
2 fatty liver

3 steatosis

4 steatohepatitis

5 fibrosis

6 cirrhosis

7 MeSH=="medicine, eastern tradition/all subtitles/all trees"
8 MeSH=="complementary medicine/"
9 MeSH=="plant extracts/all subtitles/all trees"
10 MeSH=="Plant, Therapeutic Use /All subtitles"
11 MeSH=="drugs, over the counter"
12 MeSH=="Phytotherapy/All subtitles/all trees"
13 Herbs or herbal or herb
14 Alternative medicine*
15 Complementary medicine*
16 Traditional medicine*
17 plant or plants
18 (China or The East) with medicine*
19 Plant medicinal product * or medicinal materials or herbal medicine
20 Chinese herbal drugs * or Chinese medicine*
21 Traditional Chinese Medicine *
22 Traditional Chinese Medicine and Western Medicine*
23 MeSH=="animals/all trees"
24 not #23
25 MeSH="Chinese herbal drugs/all subtitles"
26 #6 or #5 or #4 or #3 or #2 or #1
27 #25 or #22 or #21 or #20 or #19 or #18 or #17 or #16 or #15 or #14 or #13 or #12 or #11 or #10 or #9 or #8 or #7
28 #27 and #26 and #24
29 Title: rats or rabbits
30 (not #29) and #28
31 #30 and (summary in MH or summary in PT)
32 (not #31) and #30

China Network Knowledge Information (CNKI)
(www.cnki.net/)
1994 to until March 2012.Search strategy in Chinese.
#1 fatty liver or steatosis or steatohepatitis or fibrosis or cirrhosis
#2 liver disease
#3 Chinese herbal medicine or Chinese medicine or Chinese and western or plants or herbs
#4 #1 OR #2
#5 #3 AND #4
Chinese Science Journal Database (VIP)
(www.cqvip.com/)
1989 to until March 2012.Search strategy in Chinese.
#1 fatty liver or steatosis or steatohepatitis or fibrosis or cirrhosis
#2 liver disease
#3 Chinese herbal medicine or Chinese medicine or Chinese and western or plants or herbs
#4 #1 OR #2
#5 #3 AND #4
Traditional Chinese Medical Literature Analysis and Retrieval System1984 to until March 2012.Search strategy in Chinese.
#1 fatty liver or steatosis or steatohepatitis or fibrosis or cirrhosis
#2 liver disease
#3 Chinese herbal medicine or Chinese medicine or Chinese and western or plants or herbs
#4 #1 OR #2
#5 #3 AND #4
Wanfang Database (www.wanfangdata.com.cn/)1982 to until March 2012.Search strategy in Chinese.
#1 fatty liver or steatosis or steatohepatitis or fibrosis or cirrhosis
#2 liver disease
#3 Chinese herbal medicine or Chinese medicine or Chinese and western or plants or herbs
#4 #1 OR #2
#5 #3 AND #4

Contributions of authors

Zhaolan Liu: title conception, protocol development, developed the search strategy, data abstraction, data analysis, and full review writing.
Liangzhen Xie: literature selection, data extraction, and risk of bias assessment.
Jiang Zhu: protocol development, study selection, data abstraction, and risk of bias assessment.
George Li: full review writing on herbal medicines and full review revision.
Suzanne Grant: full review revision and language improving.
Jian Ping Liu: title conception, protocol development, and full review revision.

Declarations of interest

None known.

Sources of support

Internal sources

  • Centre for Evidence-Based Chinese Medicine, Beijing University of Chinese Medicine, China.

  • Beijing University of Chinese Medicine (2011-CXTD-09), Beijing, China.

  • National Research Centre in Complementary and Alternative Medicine (NAFKAM), University of Tromso, Norway.

External sources

  • Beijing Nova Programme (Number: xx2013031), China.

  • Grant number CSO-51 from Global fund for HIV, China, China.

  • Grant number 2011ZX09302-006 from the Ministry of Science and Technology, China.

  • The Project for Standard Operation Procedure of Clinical Appraisal in the Program for Significant New Drugs Development (2011ZX09302-006-01-03(5), China.

  • Grant number JYBZZ-JS006 from Beijing University of Chinese Medicine, China.

  • Basic Operational Funding for Scientific Research from Beijing University of Chinese Medicine, China.

  • Grant number 2009DFA31460 from the International Cooperation Project of the Ministry of Science and Technology, China.

  • National Basic Research Program ('973' Program) Grant Number 2006CB504602 from the Ministry of Science and Technology, China.

Differences between protocol and review

None.

Characteristics of studies

Characteristics of included studies [ordered by study ID]

Cao 2011

Methods

Trial design: randomised, parallel group trial.

Language: Chinese.

Type of publication: journal article.

Date of trial: October 2009 to December 2010.

Judgement of the quality of the trial: high risk of bias.

Participants

Number of study centres: 1.

Setting: Zhang Jiakou Infectious Disease Hospital, Hebei Province.

Origin of the participants: outpatients.

Sample size calculation: not done.

Number of participants: 90. 45 received Huazhuo Xiaozhi decotion, 45 received Baisainuo.

Sex ratio: 49 males (54.4%), 41 females (45.6%).

Mean age: 43.5 years (range 26-67 years) in the treatment group; 46.2 years (range 27-68 years) in the control group.

Duration of fatty liver diseases: 3.2 years (range 0.7-5.7 years) in the treatment group; 3.1 years (range 1.1-5.2 years) in the control group.

Diagnostic criteria: Group of Fatty Liver and Alcoholic Liver Diseases, Society of Hepatology, Chinese Medical Association, diagnostic standard of non-alcoholic fatty liver (draft), Chinese Journal of Hepatology 2001 (CMA 2001a).

Inclusion criteria: not described.

Exclusion criteria: not described.

Dropouts: all participants randomised were analysed.

ITT analysis: not done.

Sources of funding: not specified.

Interventions

Intervention: Huazhuo Xiaozhi decoction, 1 decoction, 400 mL, twice/day.

Control: Baisainuo, 50 mg, po, 3 times/day.

Post-treatment follow-up: none.

Both groups received the same lifestyle changes.

Treatment duration: 2 months.

OutcomesOutcome(s): symptoms, signs, ALT, AST, GGT, TG, TC, LDL-C.
Notes 
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Unclear riskNo information on random sequence generation.
Allocation concealment (selection bias)Unclear riskNo allocation concealment method was described.
Blinding (performance bias and detection bias)
All outcomes
Unclear riskNot described.
Incomplete outcome data (attrition bias)
All outcomes
Low riskNo withdrawals or dropouts were reported. All participants randomised were analysed.
Selective reporting (reporting bias)Low riskAll predefined outcomes in the methods section of the article were reported in the results section.
Other biasHigh riskSample size calculation was not reported.
Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskNot described.
Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskNot described.

Chen 2007a

Methods

Trial design: randomised, parallel group trial.

Language: Chinese.

Type of publication: journal article.

Date of trial: not specified.

Judgement of the quality of the trial: high risk of bias.

Participants

Number of study centres: 1.

Setting: the First Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine.

Origin of the participants: outpatients.

Sample size calculation: not done.

Number of participants: 60. 30 received Zini Zhigan prescription, 30 received liptor.

Sex ratio: 37 males (61.7%), 23 females (38.3%).

Mean age: 43.43 years in the treatment group; 41.30 years in the control group.

Duration of fatty liver diseases: not specified.

Diagnostic criteria: Haozhu Chen, Practice of Internal Medicine, People's Medical Publishing House 2005 (Chen 2005).

Inclusion criteria: aged 18-65 years; the diagnosis were NAFLD and Pixushisheng type.

Exclusion criteria: current liver disease or previous episode of liver disease; current excessive drinking or history of heavy drinking; severe diseases of respiratory, digestive, circulatory, endocrine, and renal system or history of these diseases; gestation or lactating women; people taking drugs with drug-related drug allergy; psychosis or dementia.

Dropouts: all participants randomised were analysed.

ITT analysis: not done.

Sources of funding: not specified.

Interventions

Intervention: Zini Zhigan decoction, 1 dose, twice/day.

Control: liptor, 10 mg, po, once daily.

Post-treatment follow-up: none.

Treatment duration: 8 weeks.

OutcomesOutcome(s): symptoms, signs, B-ultrasonography, ALT, AST, GGT, TG, TC, LDL-C, HDL-C.
Notes 
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Unclear riskNo information on random sequence generation.
Allocation concealment (selection bias)Unclear riskNo allocation concealment method was described.
Blinding (performance bias and detection bias)
All outcomes
Unclear riskNot described.
Incomplete outcome data (attrition bias)
All outcomes
Low riskNo withdrawals or dropouts were reported. All participants randomised were analysed.
Selective reporting (reporting bias)Low riskAll predefined outcomes in the methods section of the article were reported in the results section.
Other biasHigh riskSample size calculation was not reported.
Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskNot described.
Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskNot described.

Chen 2007b

Methods

Trial design: randomised, parallel group trial.

Language: Chinese.

Type of publication: journal article.

Date of trial: July 2006 to December 2006.

Judgement of the quality of the trial: high risk of bias.

Participants

Number of study centres: 1.

Setting: Wenzhou Traditional Chinese Medicine Hospital.

Origin of the participants: outpatients.

Sample size calculation: not done.

Number of participants: 120. 60 received Jiangzhi Baogan, 60 received vitamin C and B placebo.

Sex ratio: 86 males (71.7%), 34 females (28.3%).

Mean age: 38.6 years (range 18-45 years) in the treatment group; 37.2 years (range 20-44 years) in the control group.

Duration of fatty liver diseases: not specified.

Diagnostic criteria: Group of Fatty Liver and Alcoholic Liver Diseases, Society of Hepatology, Chinese Medical Association, Diagnostic standard of non-alcoholic fatty liver diseases, Chinese Journal of Hepatology 2003 (CMA 2003c).

Inclusion criteria: not described.

Exclusion criteria: not described.

Dropouts: all participants randomised were analysed.

ITT analysis: not done.

Sources of funding: not specified.

Interventions

Intervention: Jiangzhi Baogan decotion, 2 dose decoction, twice/day.

Control: vitamin C 0.1 g and vitamin B complex 2 granules, po, 3 times/day.

Post-treatment follow-up: none.

Both groups received the same lifestyle changes.

Treatment duration: 3 months.

OutcomesOutcome(s): symptoms, signs, CT, ALT, TG, TC.
Notes 
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Unclear riskNo information on random sequence generation.
Allocation concealment (selection bias)Unclear riskNo allocation concealment method was described.
Blinding (performance bias and detection bias)
All outcomes
Unclear riskNot described.
Incomplete outcome data (attrition bias)
All outcomes
Low riskNo withdrawals or dropouts were reported. All participants randomised were analysed.
Selective reporting (reporting bias)High riskSome predefined outcomes in the methods section of the article were not reported in the results section.
Other biasHigh riskSample size calculation was not reported.
Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskNot described.
Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskNot described.

Chen 2010

Methods

Trial design: randomised, parallel group trial.

Language: Chinese.

Type of publication: journal article.

Date of trial: not specified.

Judgement of the quality of the trial: high risk of bias.

Participants

Number of study centres: 1.

Setting: Xinghua Hospital of Traditional Chinese Medicine, Jiangsu Province.

Origin of the participants: inpatients and outpatients.

Sample size calculation: not done.

Number of participants: 86. 47 received Huatan Huoxuefang, 39 received polyene phosphatidylcholine.

Sex ratio: 47 males (69%), 21 females (31%).

Mean age: 28.1 years (range 18-46 years).

Duration of fatty liver diseases: not specified.

Diagnostic criteria: Group of Fatty Liver and Alcoholic Liver Diseases, Society of Heoatology, Chinese Medical Association. Guidelines for diagnosis and treatment of non-alcoholic fatty liver. Chinese Journal of Hepatology 2006 (CMA 2006b).

Inclusion criteria: not described.

Exclusion criteria: not described.

Dropouts: not specified.

ITT analysis: not done.

Sources of funding: not specified.

Interventions

Intervention: Huatan Huoxuefang decoction, 300 mL, twice/day.

Control: polyene phosphatidylcholine capsules, 228-456 mg, po, twice/day.

Post-treatment follow-up: none.

Both groups received the same lifestyle changes.

Treatment duration: 12 weeks.

OutcomesOutcome(s): symptoms, signs, B-ultrasonography, ALT, AST, TG, TC.
Notes 
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Low riskRandom number table was used.
Allocation concealment (selection bias)Unclear riskNo information about allocation concealment.
Blinding (performance bias and detection bias)
All outcomes
Unclear riskNot described.
Incomplete outcome data (attrition bias)
All outcomes
Low riskNo withdrawals or dropouts were reported. All participants randomised were analysed.
Selective reporting (reporting bias)Low riskAll predefined outcomes in the methods section of the article were reported in the results section.
Other biasHigh riskSample size calculation was not reported.
Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskNo information about blinding.
Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskNot described.

Cheng 2006

Methods

Trial design: randomised, parallel group trial.

Language: Chinese.

Type of publication: journal article.

Date of trial: April 2003 to April 2006.

Judgement of the quality of the trial: high risk of bias.

Participants

Number of study centres: 1.

Setting: Hubei Hospital of Traditional Chinese Medicine.

Origin of the participants: inpatients and outpatients.

Sample size calculation: not done.

Number of participants: 100. 50 received Zhiyan Xiao decoction, 50 received UDCA.

Sex ratio: 45 males (45%), 55 females (55%).

Mean age: 42 years in the treatment group; 41.8 years in the control group.

Duration of fatty liver diseases: 2.5 years in the treatment group; 2.4 years in the control group.

Diagnostic criteria: varying degrees of weakness, lack of appetite, hepatic oppression or null pain; by B-ultrasonography liver showed diffuse enlargement, neat and smooth contour, expansion and blunting in the edge, intrahepatic small blood vessels unclear, liver and kidney in control significantly enhanced and weakened in deep, zigzag or turning wave in hepatic blood flow diagram; by CT liver density reduced; TC > 6.47 mmol/L, TG > 2.30 mmol/L; ALT, AST, GGT moderate to mild increase.

Inclusion criteria: not described.

Exclusion criteria: not described.

Dropouts: not specified.

ITT analysis: not done.

Sources of funding: not specified.

Interventions

Intervention: Zhiyan Xiao decoction, 1 dose decoction, bid.

Control: UDCA, 10 mg/kg/day, po, tid.

Post-treatment follow-up: none.

Both groups received the same lifestyle changes.

Treatment duration: 3 months.

OutcomesOutcome(s): symptoms, signs, B-ultrasonography, ALT, AST, GGT, TG, TC, LDL-C, HDL-C.
Notes 
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Unclear riskNo information on random sequence generation.
Allocation concealment (selection bias)Unclear riskNo allocation concealment method was described.
Blinding (performance bias and detection bias)
All outcomes
Unclear riskNot described.
Incomplete outcome data (attrition bias)
All outcomes
Low riskNo withdrawals or dropouts were reported. All participants randomised were analysed.
Selective reporting (reporting bias)High riskPrespecified outcome B-ultrasound in the methods section of the article were not reported in the results section.
Other biasHigh riskSample size calculation was not reported.
Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskNot described.
Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskNot described.

Chou 2006

Methods

Trial design: randomised, parallel group trial.

Language: Chinese.

Type of publication: journal article.

Date of trial: not specified.

Judgement of the quality of the trial: high risk of bias.

Participants

Number of study centres: 1.

Setting: Department of Health Management at Changgung Medical Center, Linkou.

Origin of the participants: outpatients.

Sample size calculation: not done.

Number of participants: 60. 30 received Gynostemma pentaphyllum, 30 received placebo.

Sex ratio: not specified.

Mean age: not specified.

Duration of fatty liver diseases: not specified.

Diagnostic criteria: not specified.

Inclusion criteria: participants at least 20 years old and diagnosed as having fatty liver on abdominal ultrasound scanning; increased ALT > 36 U/L or AST > 34 U/L.

Exclusion criteria: a history of cardiovascular diseases and cerebrovascular diseases; diseases that could affect liver function; current or prior use of medications that might have influenced liver function and plasma lipids; impaired renal function; hyperglycaemia that required an oral hypoglycaemia agent or insulin treatment; pregnancy or lactation; undergoing immunosuppressive therapy.

Dropouts: not specified.

ITT analysis: not done.

Sources of funding: not specified.

Interventions

Intervention: Gynostemma pentaphyllum, po, 3 times/day.

Control: placebo, po, 3 times/day.

Post-treatment follow-up: none.

Both groups received the same lifestyle changes.

Treatment duration: 6 months.

OutcomesOutcome(s): BMI, HDL-C, LDL-C, ALT, AST, ALP, uric acid, urea, creatinine, fasting GLU, insulin, HOMA-IR, fatty liver score, TG, TC.
Notes 
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Low riskDrawing lots.
Allocation concealment (selection bias)Unclear riskNot described.
Blinding (performance bias and detection bias)
All outcomes
Unclear riskNot described.
Incomplete outcome data (attrition bias)
All outcomes
High risk4 withdrew before the trial medicine treatment began. 56 with 28 in each group finished the study and were analysed.
Selective reporting (reporting bias)Low riskAll predefined outcomes in the methods section of the article were reported in the results section.
Other biasLow riskSample size calculation was reported.
Blinding of participants and personnel (performance bias)
All outcomes
Low riskParticipants were blinded by placebo capsules.
Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskNot described.

Dai 2009

Methods

Trial design: randomised, parallel group trial.

Language: Chinese.

Type of publication: journal article.

Date of trial: May 2006 to February 2008.

Judgement of the quality of the trial: high risk of bias.

Participants

Number of study centres: 1.

Setting: Zhangbei Country Chinese Medicine Hospital, Hebei Province.

Origin of the participants: outpatients.

Sample size calculation: not done.

Number of participants: 60. 30 received Shuli Qingzhi powder, 30 received simvastatin tablets.

Sex ratio: 40 males (66.7%), 20 females (23.3%).

Mean age: 36.5 years (range 27-60 years) in the treatment group; 38.7 years (range 26-62 years) in the control group.

Duration of fatty liver diseases: not specified.

Diagnostic criteria: Ministry of Health of the People's Republic of China. Guidelines for clinical research of Traditional Chinese Drug Research. China Press of Traditional Chinese Medicine 2005 (China 2005).

Inclusion criteria: not described.

Exclusion criteria: not described.

Dropouts: all participants randomised were analysed.

ITT analysis: not done.

Sources of funding: Administration of Traditional Chinese Medicine of Hebei.

Interventions

Intervention: Shuli Qingzhi powder, 10 g, po, twice/day.

Control: simvastatin tablets, 10 mg, po, once daily.

Post-treatment follow-up: none.

Both groups received the same lifestyle changes.

Treatment duration: 3 months.

OutcomesOutcome(s): symptoms, signs, B-ultrasound, ALT, AST, TG, TC, HDL-C, LDL-C, GGT.
Notes 
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Unclear riskNo information on random sequence generation.
Allocation concealment (selection bias)Unclear riskNo allocation concealment method was described.
Blinding (performance bias and detection bias)
All outcomes
Unclear riskNot described.
Incomplete outcome data (attrition bias)
All outcomes
Low riskNo withdrawals or dropouts were reported. All participants randomised were analysed.
Selective reporting (reporting bias)High riskSome predefined outcomes in the methods section of the article were not reported in the results section.
Other biasUnclear riskSample size calculation was not reported.
Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskNot described.
Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskNot described.

Dang 2007

Methods

Trial design: randomised, parallel group trial.

Language: Chinese.

Type of publication: journal article.

Date of trial: May 2003 to May 2005.

Judgement of the quality of the trial: high risk of bias.

Participants

Number of study centres: 1.

Setting: Henan Province Hospital of the Chinese Medicine.

Origin of the participants: inpatients and outpatients.

Sample size calculation: not done.

Number of participants: 100. 50 received Shiwenzhigankang, 50 received Dongbao Gantai.

Sex ratio: 76 males (76%), 24 females (24%).

Mean age: 39 years (range 18-60 years).

Duration of fatty liver diseases: 5.46 years.

Diagnostic criteria: Group of Fatty Liver and Alcoholic Liver Diseases, Society of Heoatology, Chinese Medical Association. Diagnosis of non-alcoholic fatty liver. Chinese Journal of Hepatology 2003 (CMA 2003a).

Inclusion criteria: not described.

Exclusion criteria: not described.

Dropouts: all participants randomised were analysed.

ITT analysis: not done.

Sources of funding: not specified.

Interventions

Intervention: Shiweizhigankang capsule, 4 granules, po, 3 times/day.

Control: Dongbao Gantai tablets, 4 tablets, po, 3 times/day.

Post-treatment follow-up: none.

Treatment duration: 3 months.

OutcomesOutcome(s): symptoms, signs, B-ultrasound, ALT, AST, TG, TC, HDL-C, LDL-C, GGT, ALP, blood GLU, blood, urine, stool routines, ECG.
Notes 
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Low riskRandom number table was used.
Allocation concealment (selection bias)Unclear riskNot described.
Blinding (performance bias and detection bias)
All outcomes
Unclear riskNot described.
Incomplete outcome data (attrition bias)
All outcomes
Low riskNo withdrawals or dropouts were reported. All participants randomised were analysed.
Selective reporting (reporting bias)Low riskAll predefined outcomes in the methods section of the article were reported in the results section.
Other biasHigh riskSample size calculation was not reported.
Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskNot described.
Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskNot described.

Deng 2003a

Methods

Trial design: randomised, parallel group trial.

Language: Chinese.

Type of publication: journal article.

Date of trial: not specified.

Judgement of the quality of the trial: high risk of bias.

Participants

Number of study centres: 1.

Setting: Guangxi Chinese Medicine Hospital.

Origin of the participants: inpatients and outpatients.

Sample size calculation: not done.

Number of participants: 100. 50 received Huanglong Ganzhixiao, 50 received fenofibrate.

Sex ratio: 53 males (53%), 47 females (47%).

Mean age: 39.3 years (range 28-59 years) in the treatment group; 37.2 years (range 31-53 years) in the control group.

Duration of fatty liver diseases: 2.4 years (range 0.4-3.2 years) in the treatment group; 2.2 years (range 0.3-2.9 years) in the control group.

Diagnostic criteria: not specified.

Inclusion criteria: not described.

Exclusion criteria: not described.

Dropouts: all participants randomised were analysed

ITT analysis: not done.

Sources of funding: not specified.

Interventions

Intervention: Huanglong Ganzhixiao decoction, 100 mL, po, twice/day.

Control: fenofibrate, 0.1 g, po, 3 times/day.

Post-treatment follow-up: none.

Treatment duration: 8 weeks.

OutcomesOutcome(s): symptoms, signs, B-ultrasonography, ALT, TG, TC, HDL-C, LDL-C.
Notes 
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Unclear riskNo information on random sequence generation.
Allocation concealment (selection bias)Unclear riskNo allocation concealment method was described.
Blinding (performance bias and detection bias)
All outcomes
High riskNo blinding was applied.
Incomplete outcome data (attrition bias)
All outcomes
Low riskNo withdrawals or dropouts were reported. All participants randomised were analysed.
Selective reporting (reporting bias)High riskSome predefined outcomes in the methods section of the article were not reported in the results section.
Other biasHigh riskSample size calculation was not reported.
Blinding of participants and personnel (performance bias)
All outcomes
High riskNo blinding.
Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskNot described.

Deng 2010

Methods

Trial design: randomised, parallel group trial.

Language: Chinese.

Type of publication: journal article.

Date of trial: May 2004 to September 2008.

Judgement of the quality of the trial: high risk of bias.

Participants

Number of study centres: 1.

Setting: Huangshi Infectious Disease Hospital, Hubei Province.

Origin of the participants: not specified.

Sample size calculation: not done.

Number of participants: 76. 39 received Xiaoyao, 37 received legalon.

Sex ratio: 47 males (61.8%), 29 females (38.1%).

Mean age: 35.6 years (range 16-67 years) in the treatment group; 36.3 years (range 16-68 years) in the control group.

Duration of fatty liver diseases: not specified.

Diagnostic criteria: Group of Fatty Liver and Alcoholic Liver Diseases, Society of Heoatology, Chinese Medical Association. Guidelines for diagnosis and treatment of non-alcoholic fatty liver diseases. Chinese Hepatology 2006 (CMA 2006a).

Inclusion criteria: not described.

Exclusion criteria: not described.

Dropouts: all participants randomised were analysed.

ITT analysis: not done.

Sources of funding: not specified.

Interventions

Intervention: Xiaoyao tablets, 10 granules, po, 3 times/day plus legalon, 140 mg, po, 3 times/day.

Control: legalon, 140 mg, po, 3 times/day.

Post-treatment follow-up: none.

Treatment duration: 8 weeks.

OutcomesOutcome(s): symptoms, signs, B-ultrasonography, ALT, TG, TC, HDL-C, LDL-C.
Notes 
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Unclear riskNo information on random sequence generation.
Allocation concealment (selection bias)Unclear riskNo allocation concealment method was described.
Blinding (performance bias and detection bias)
All outcomes
Unclear riskNot described.
Incomplete outcome data (attrition bias)
All outcomes
Low riskNo withdrawals or dropouts were reported. All participants randomised were analysed.
Selective reporting (reporting bias)High riskSome predefined outcomes in the methods section of the article were not reported in the results section.
Other biasHigh riskSample size calculation was not reported.
Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskNot described.
Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskNot described.

Fei 2009

Methods

Trial design: randomised, parallel group trial.

Language: Chinese.

Type of publication: journal article.

Date of trial: August 2006 to August 2008.

Judgement of the quality of the trial: high risk of bias.

Participants

Number of study centres: 1.

Setting: Huashan Hospital, Fudan University.

Origin of the participants: outpatients.

Sample size calculation: not done.

Number of participants: 42. 22 received Yuqin, 20 received placebo.

Sex ratio: 22 males (52.4%), 20 females (47.6%).

Mean age: 28.1 years (range 18-46 years).

Duration of fatty liver diseases: not specified.

Diagnostic criteria: CMA 2003a; CMA 2003b.

Inclusion criteria: not described.

Exclusion criteria: people with alcoholic fatty liver disease, viral hepatitis, drug-induced hepatitis, autoimmune disease, hepatolenticular degeneration, malignant tumour. 

Dropouts: all participants randomised were analysed.

ITT analysis: not done.

Sources of funding: not specified.

Interventions

Intervention: Yuqin capsule, 3 granules, po, 3 times/day.

Control: placebo, 3 granules, po, 3 times/day.

Post-treatment follow-up: none.

Both groups received the same lifestyle changes.

Treatment duration: 3 months.

OutcomesOutcome(s): symptoms, signs, ALT, GGT.
Notes 
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Low riskRandom number table was used.
Allocation concealment (selection bias)Unclear riskNot described.
Blinding (performance bias and detection bias)
All outcomes
Unclear riskNot described.
Incomplete outcome data (attrition bias)
All outcomes
Low riskNo withdrawals or dropouts were reported. All participants randomised were analysed.
Selective reporting (reporting bias)Low riskAll predefined outcomes in the methods section of the article were reported in the results section.
Other biasHigh riskSample size calculation was not reported.
Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskNot described.
Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskNot described.

Gu 2007a

Methods

Trial design: randomised, parallel group trial.

Language: English.

Type of publication: journal article.

Date of trial: June 2004 to July 2005.

Judgement of the quality of the trial: high risk of bias.

Participants

Number of study centres: 1.

Setting: Ruyang Hospital of Traditional Chinese Medicine.

Origin of the participants: inpatients and outpatients.

Sample size calculation: not done.

Number of participants: 130. 101 received herbal, 29 received thiola tablet.

Sex ratio: 98 males (75.4%), 32 females (24.6%).

Mean age (± standard deviation): intervention group: 47.38 ± 9.5 years (range 20-61 years); control group: 43.34 ± 10.54 years (range 22-59 years).

Duration of fatty liver diseases: 2 months to 6 years.

Diagnostic criteria: Group of Fatty Liver and Alcoholic Liver Diseases, Society of Hepoatology, Chinese Medical Association. Guidelines for diagnosis and treatment of non-alcoholic fatty liver. Chinese Journal of Hepatology 2006 (CMA 2006b).

Inclusion criteria: people who matched the diagnostic standard of NAFLD, aged 18-65 years; knew and granted consent to the scenario, volunteered to be tested with informed consent; used good clinical practice.

Exclusion criteria: people with fatty liver caused by chronic malnutrition or other factors; with viral hepatitis or with liver function decompensation; had received other treatment for uncomplicated fatty liver; aged < 18 years or > 65 years or pregnant and lactating women; people with serious primary disease or suspected to have a history of alcoholism or misuse of drugs.

Dropouts: all participants randomised were analysed.

ITT analysis: not done.

Sources of funding: not specified.

Interventions

Intervention: Tiaozhi Yanggan decoction, 1 dose decoction, twice/day.

Control: thiola tablets, 200 mg, po, 3 times/day.

Post-treatment follow-up: none.

Both groups received the same conventional lifestyle changes.

Treatment duration: 12 weeks.

OutcomesOutcome(s): symptoms, signs, BMI, ALT, AST, TG, TC, L/S CT, HDL-C, LDL-C.
Notes 
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Low riskRandom number table was used.
Allocation concealment (selection bias)Unclear riskNot described.
Blinding (performance bias and detection bias)
All outcomes
Unclear riskNot described.
Incomplete outcome data (attrition bias)
All outcomes
Low riskNo withdrawals or dropouts were reported. All participants randomised were analysed.
Selective reporting (reporting bias)Low riskAll predefined outcomes in the methods section of the article were reported in the results section.
Other biasHigh riskSample size calculation was not reported.
Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskNot described.
Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskNot described.

Gu 2007b

Methods

Trial design: randomised, parallel group trial.

Language: Chinese.

Type of publication: journal article.

Date of trial: January 2004 to May 2006.

Judgement of the quality of the trial: high risk of bias.

Participants

Number of study centres: 1.

Setting: Hubei Province Chinese Medicine Hospital.

Origin of the participants: outpatients.

Sample size calculation: not done.

Number of participants: 80. 40 received Zhongyibianzheng, 20 received Zhongyibianzheng plus silybininon tablets, 20 received silybininon tablets.

Mean age: 37 years (range 18-56 years).

Duration of fatty liver diseases: not specified.

Diagnostic criteria: CMA 2003a; CMA 2003b.

Inclusion criteria: not described.

Exclusion criteria: virus hepatitis, hypertension, and diabetes.

Dropouts: none.

ITT analysis: not done.

Sources of funding: not specified.

Interventions

Intervention: Zhongyibianzheng, po, every day.

Control: silybininon tablets, po, 3 times/day.

Another intervention group: Zhongyibianzheng, po, every day plus silybininon tablets, 200 mg, po, 3 times/day.

Post-treatment follow-up: none.

Cointervention: received the same lifestyle changes.

Treatment duration: 12 weeks

OutcomesOutcome(s): symptoms, signs, B-ultrasonography, ALT, AST, TG, TC.
Notes 
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Unclear riskNo information on random sequence generation.
Allocation concealment (selection bias)Unclear riskNo allocation concealment method was described.
Blinding (performance bias and detection bias)
All outcomes
Unclear riskNot described.
Incomplete outcome data (attrition bias)
All outcomes
Low riskNo withdrawals or dropouts were reported. All participants randomised were analysed.
Selective reporting (reporting bias)High riskSome predefined outcomes in the methods section of the article were not reported in the results section.
Other biasHigh riskSample size calculation was not reported.
Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskNot described.
Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskNot described.

Guan 2010

Methods

Trial design: randomised, parallel group trial.

Language: Chinese.

Type of publication: journal article.

Date of trial: December 2007 to December 2008.

Judgement of the quality of the trial: high risk of bias.

Participants

Number of study centres: 1.

Setting: Hongxing Hospital of Hami, Xinjiang Province.

Origin of the participants: outpatients.

Sample size calculation: not done.

Number of participants: 58. 31 received wild apricot, 27 received vitamin B plus vitamin C.

Sex ratio: 52 males (89%), 6 females (11%).

Mean age: 37.5 years (range 15-60 years).

Duration of fatty liver diseases: not specified.

Diagnostic criteria: CMA 2003a.

Inclusion criteria: not described.

Exclusion criteria: viral hepatitis, drug-induced hepatitis, autoimmune hepatitis, and metabolic liver diseases.

Dropouts: none.

ITT analysis: not done.

Sources of funding: not specified.

Interventions

Intervention: wild apricot, 30 mg, po, twice/day.

Control: vitamin B plus vitamin C, 6 tablets, po, 3 times/day.

Post-treatment follow-up: none.

Treatment duration: 12 weeks.

OutcomesOutcome(s): symptoms, signs, B-ultrasonography, ALT, AST, TG, TC.
Notes 
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Unclear riskNo information on random sequence generation.
Allocation concealment (selection bias)Unclear riskNo allocation concealment method was described.
Blinding (performance bias and detection bias)
All outcomes
Unclear riskNot described.
Incomplete outcome data (attrition bias)
All outcomes
Low riskNo withdrawals or dropouts were reported. All participants randomised were analysed.
Selective reporting (reporting bias)Low riskAll predefined outcomes in the methods section of the article were reported in the results section.
Other biasHigh riskSample size calculation was not reported.
Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskNot described.
Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskNot described.

Guo 2007

Methods

Trial design: randomised, parallel group trial.

Language: Chinese.

Type of publication: journal article.

Date of trial: March 2005 to June 2006.

Judgement of the quality of the trial: high risk of bias.

Participants

Number of study centres: 1.

Setting: Hospital of college of traditional Chinese medicine, Shannxi Province.

Origin of the participants: outpatients.

Sample size calculation: not done.

Number of participants: 66. 36 received Hegan Yin, 30 received tiopronin.

Sex ratio: 52 males (79%), 14 females (21%).

Mean age: 49.36 years in the treatment group; 51.06 years in the control group.

Duration of fatty liver diseases: not specified.

Diagnostic criteria: Group of Fatty Liver and Alcoholic Liver Diseases, Society of Hepatology, Chinese Medical Association. Guidelines for diagnosis and treatment of non-alcoholic fatty liver. Chinese Journal of Hepatology 2006 (CMA 2006b).

Inclusion criteria: people who matched the diagnostic standard for NAFLD and tanyuhujie pattern of traditional Chinese medicine; aged 18-65 years; people who took drugs for NAFLD in the past 2 months.

Exclusion criteria: cirrhosis; pregnant women; serious damage in other organs; diagnosis of personality or mental disorder; people with allergies.

Dropouts: none.

ITT analysis: not done.

Sources of funding: not specified.

Interventions

Intervention: Hegan Yin, 1 dose decoction, twice/day.

Control: tiopronin, 200 mg, po, 3 times/day.

Post-treatment follow-up: none.

Both groups received the same conventional treatment of liver protection drugs and lifestyle changes.

Treatment duration: 6 months.

OutcomesOutcome(s): symptoms, signs, B-ultrasonography, ALT, AST, TG, TC.
Notes 
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Unclear riskNo information on random sequence generation.
Allocation concealment (selection bias)Unclear riskNo allocation concealment method was described.
Blinding (performance bias and detection bias)
All outcomes
Unclear riskNot described.
Incomplete outcome data (attrition bias)
All outcomes
Low riskNo withdrawals or dropouts were reported. All participants randomised were analysed.
Selective reporting (reporting bias)High riskPrespecified outcome B-ultrasound in the methods section of the article were not reported in the results section.
Other biasHigh riskSample size calculation was not reported.
Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskNot described.
Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskNot described.

Guo 2010

Methods

Trial design: randomised, parallel group trial.

Language: Chinese.

Type of publication: journal article.

Date of trial: April 2009 to March 2010.

Judgement of the quality of the atria: high risk of bias.

Participants

Number of study centres: 1.

Setting: Hospital of Chinese Medicine, Heilongjiang Province.

Origin of the participants: outpatients.

Sample size calculation: not done.

Number of participants: 62. 32 received Xiaogan Jiangzhifang, 30 received Ganle.

Sex ratio: 41 males (66.1%), 21 females (33.9%).

Mean age: 45 years (range 20-60 years).

Duration of fatty liver diseases: not specified.

Diagnostic criteria: Guidelines for diagnosis and treatment of non-alcoholic liver diseases, 2006; Guiding principle of clinical research on new drugs of TCM, 2003 (CMA 2003b).

Inclusion criteria: 62 participants confirmed diagnosis.

Exclusion criteria: alcoholic liver diseases; chronic viral hepatitis; fatty liver resulted by other factors.

Dropouts: none.

ITT analysis: not done.

Sources of funding: not specified.

Interventions

Intervention: Xiaogan Jiangzhifang, po, every day.

Control: Ganle tablets, 40 mg, po, twice/day.

Post-treatment follow-up: none.

Both groups received the same lifestyle changes.

Treatment duration: 12 weeks.

OutcomesOutcome(s): symptoms, signs, B-ultrasonography, ALT, AST, TG, TC.
Notes 
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Unclear riskNo information on random sequence generation.
Allocation concealment (selection bias)Unclear riskNo allocation concealment method was described.
Blinding (performance bias and detection bias)
All outcomes
Unclear riskNot described.
Incomplete outcome data (attrition bias)
All outcomes
Low riskNo withdrawals or dropouts were reported. All participants randomised were analysed.
Selective reporting (reporting bias)High riskPrespecified outcome B-ultrasound in the methods section of the article were not reported in the results section.
Other biasHigh riskSample size calculation was not reported.
Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskNot described.
Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskNot described.

Hu 2010

Methods

Trial design: randomised, parallel group trial.

Language: Chinese.

Type of publication: journal article.

Date of trial: April 2001 to March 2007.

Judgement of the quality of the trial: high risk of bias.

Participants

Number of study centres: 1.

Setting: Wuhan Hospital of Traditional Chinese Medicine, Hubei Province.

Origin of the participants: inpatients and outpatients.

Sample size calculation: not done.

Number of participants: 110. 56 received Tangganjian, 54 received Erjiashuanggua.

Sex ratio: 59 males (54%), 51 females (46%).

Mean age: 51 years (range 37-65 years).

Duration of fatty liver diseases: not specified.

Diagnostic criteria: CMA 2006b.

Inclusion criteria: age range 38-65 years; people were diagnosed with diabetes, fatty liver, and ganyupixu and shireyunjie.

Exclusion criteria: diabetes; diabetes with diabetic ketoacidosis or other acute complications; serious primary diseases with heart, brain, kidney, etc; alcoholic hepatitis, viral hepatitis, drug-induced hepatitis, etc; mental disease.

Dropouts: all participants randomised were analysed.

ITT analysis: not done.

Sources of funding: not specified.

Interventions

Intervention: Tangganjian, 1 dose decoction, twice/day.

Control: Erjiashuanggua tablets, 0.25-0.5 g, po, 3 times/day.

Post-treatment follow-up: none.

Both groups received the same conventional treatment of liver protection drugs and lifestyle changes.

Treatment duration: 12 weeks

OutcomesOutcome(s): symptoms, signs, FBG, P2HBG, HbA1C, ALT, AST, TG, TC, HDL-C, LDL-C, BMI.
Notes 
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Unclear riskNo information on random sequence generation.
Allocation concealment (selection bias)Unclear riskNo allocation concealment method was described.
Blinding (performance bias and detection bias)
All outcomes
Unclear riskNot described.
Incomplete outcome data (attrition bias)
All outcomes
Low riskNo withdrawals or dropouts were reported. All participants randomised were analysed.
Selective reporting (reporting bias)High riskSome prespecified outcomes in the methods section of the article were not reported in the results section.
Other biasHigh riskSample size calculation was not reported.
Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskNot described.
Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskNot described.

Huang 2005

Methods

Trial design: randomised, parallel group trial.

Language: Chinese.

Type of publication: journal article.

Date of trial: February 2002 to February 2004.

Judgement of the quality of the trial: high risk of bias.

Participants

Number of study centres: 1.

Setting: First Affiliated Hospital of Guangxi Chinese Medicine University.

Origin of the participants: inpatients.

Sample size calculation: not done.

Number of participants: 141. 78 received Shugan Lipi San, 63 received GSH.

Sex ratio: all participants were male.

Mean age: 39 years (range 28-62 years).

Duration of fatty liver diseases: not specified.

Diagnostic criteria: Group of Fatty Liver and Alcoholic Liver Diseases, Society of Hepatology, Chinese Medical Association. Guidelines for diagnosis and treatment of non-alcoholic fatty liver. 2000. Diagnostic source was not given and we could not find the article on these diagnostic criteria.

Inclusion criteria: not specified.

Exclusion criteria: not specified.

Dropouts: all participants randomised were analysed.

ITT analysis: not done.

Sources of funding: not specified.

Interventions

Intervention: Shugan Lipi San. The usage and dosage did not state.

Control: GSH, 1.2 g, vigtt, once daily.

Post-treatment follow-up: none.

Both groups received the same conventional treatment of liver protection drugs and lifestyle changes.

Treatment duration: 2 months.

OutcomesOutcome(s): symptoms, signs, ALT, GGT, TG, L/S CT ratio.
Notes 
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Unclear riskNo information on random sequence generation.
Allocation concealment (selection bias)Unclear riskNo allocation concealment method was described.
Blinding (performance bias and detection bias)
All outcomes
Unclear riskNot described.
Incomplete outcome data (attrition bias)
All outcomes
Low riskNo withdrawals or dropouts were reported. All participants randomised were analysed.
Selective reporting (reporting bias)High riskSome prespecified outcomes in the methods section of the article were not reported in the results section.
Other biasHigh riskSample size calculation was not reported.
Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskNot described.
Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskNot described.

Huang 2011

Methods

Trial design: randomised, parallel group trial.

Language: Chinese.

Type of publication: journal article.

Date of trial: December 2008 to December 2009.

Judgement of the quality of the trial: high risk of bias.

Participants

Number of study centres: 1.

Setting: First Affiliated Hospital of Guangxi Chinese Medicine University.

Origin of the participants: inpatients.

Sample size calculation: not done.

Number of participants: 120. 60 received Quyu Huazhuo, 60 received polyene phosphatidylcholine.

Sex ratio: not specified.

Mean age: not specified.

Duration of fatty liver diseases: not specified.

Diagnostic criteria: Group of Fatty Liver and Alcoholic Liver Diseases, Society of Heoatology, Chinese Medical Association. Guidelines for diagnosis and treatment of non-alcoholic fatty liver. Chinese Journal of Hepatology 2006 (CMA 2006b).

Inclusion criteria: people diagnosed with CMA 2006; ALT and AST rose and AST was 2 times higher than the normal value or greater.

Exclusion criteria: age < 18 years or > 65 years; pregnant women; primary diseases and diagnosis of personality or mental disorder; infectious diseases.

Dropouts: all participants randomised were analysed.

ITT analysis: not done.

Sources of funding: not specified.

Interventions

Intervention: Quyu Huazhuo decoction, 1 dose decoction, twice/day.

Control: polyene phosphatidylcholine capsules, 3 granules, po, 3 times/day.

Post-treatment follow-up: none.

Both groups received the same lifestyle changes.

Treatment duration: 3 months.

OutcomesOutcome(s): symptoms, signs, ALT, AST, TG, TC.
Notes 
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Unclear riskNo information on random sequence generation.
Allocation concealment (selection bias)Unclear riskNo allocation concealment method was described.
Blinding (performance bias and detection bias)
All outcomes
Unclear riskNot described.
Incomplete outcome data (attrition bias)
All outcomes
Low riskNo withdrawals or dropouts were reported. All participants randomised were analysed.
Selective reporting (reporting bias)Low riskAll predefined outcomes in the methods section of the article were reported in the results section.
Other biasHigh riskSample size calculation was not reported.
Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskNot described.
Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskNot described.

Huo 2008

Methods

Trial design: randomised, parallel group trial.

Language: Chinese.

Type of publication: journal article.

Date of trial: March 2006 to December 2006.

Judgement of the quality of the trial: high risk of bias.

Participants

Number of study centres: 1.

Setting: Nanyang Central Hospital.

Origin of the participants: inpatients and outpatients.

Sample size calculation: not done.

Number of participants: 76. 38 received Kezhi, 38 received polyene phosphatidylcholine.

Sex ratio: 51 males (67.1%), 25 females (32.9%).

Mean age: 42.6 years in the treatment group; 40.8 years in the control group.

Duration of fatty liver diseases: not specified.

Diagnostic criteria: CMA 2006b.

Inclusion criteria: not specified.

Exclusion criteria: not specified.

Dropouts: all participants randomised were analysed.

ITT analysis: not done.

Sources of funding: not specified.

Interventions

Intervention: Kezhi capsules, 5/day and polyene phosphatidylcholine capsules, 456 mg, po, 3 times/day.

Control: polyene phosphatidylcholine capsules, 456 mg, po, 3 times/day.

Post-treatment follow-up: none.

Both groups received the same lifestyle changes.

Treatment duration: 12 weeks.

OutcomesOutcome(s): symptoms, signs, ALT, AST, TG, TC.
Notes 
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Unclear riskNo information on random sequence generation.
Allocation concealment (selection bias)Unclear riskNo allocation concealment method was described.
Blinding (performance bias and detection bias)
All outcomes
Unclear riskNot described.
Incomplete outcome data (attrition bias)
All outcomes
Low riskNo withdrawals or dropouts were reported. All participants randomised were analysed.
Selective reporting (reporting bias)Low riskAll predefined outcomes in the methods section of the article were reported in the results section.
Other biasHigh riskSample size calculation was not reported.
Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskNot described.
Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskNot described.

Ji 2005

Methods

Trial design: multicentre randomised double-blinded parallel trial.

Language: Chinese.

Type of publication: journal article.

Date of trial: September 2003 to October 2004.

Judgement of the quality of the trial: high risk of bias.

Participants

Number of study centres: 4.

Setting: Longhua Hospital Shanghai University of TCM, Shanghai First People's Hospital of the Jiao Tong University, Shuguang Hospital Shanghai University of TCM, Digestive Disease Institute, Shanghai City.

Origin of the participants: inpatients and outpatients.

Sample size calculation: not done.

Number of participants: 144. 102 received Danning, 33 received UDCA.

Sex ratio: 102 males (75.6%), 33 females (24.4%).

Mean age: 48.37 years (range 22-59 years) in the treatment group; 44.43 years (range 24-56 years) in the control group.

Duration of fatty liver diseases: 0.86 years (range 0.2-6 years) in the treatment group; 0.93 years (range 0.2-7 years) in the control group.

Diagnostic criteria: CMA 2001a.

Inclusion criteria: aged 18-65 years, informed consent.

Exclusion criteria: fatty liver due to chronic heart failure, malnutrition and other reasons; fatty liver with viral hepatitis and liver function discompensation; already taking traditional Chinese medicine and Western medicine for simple fatty liver after this attack; pregnancy and lactation; primary diseases, history of alcoholic and drug abuse.

Dropouts: 4 dropouts in the treatment group and 3 dropouts in the control group; the reasons were not specified.

ITT analysis: not done.

Sources of funding: not specified.

Interventions

Intervention: Danning tablet, 5 tablets, po, 3 times/day.

Control: UDCA, 250 mg, po, 3 times/day.

Post-treatment follow-up: none.

Both groups received the same lifestyle changes.

Treatment duration: 24 weeks

OutcomesOutcome(s): symptoms, BWI, B-ultrasound, CT, ALT, AST, γGGT, TG, TC.
Notes 
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Low riskStratified blocked randomisations.
Allocation concealment (selection bias)Low riskCenter randomised.
Blinding (performance bias and detection bias)
All outcomes
Unclear riskClaimed double-blinded, but did not reported who were blinded.
Incomplete outcome data (attrition bias)
All outcomes
High riskFive people were lost to follow-up, 2 could not finish the observation and 2 dropped out due to diarrhoea.
Selective reporting (reporting bias)Low riskAll predefined outcomes in the methods section of the article were reported in the results section.
Other biasHigh riskSample size calculation was not reported.
Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskClaimed double-blinded, but did not reported who were blinded.
Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskClaimed double-blinded, but did not reported who were blinded.

Jia 2003

Methods

Trial design: randomised, parallel group trial.

Language: Chinese.

Type of publication: journal article.

Date of trial: 1993 to October 2002.

Judgement of the quality of the trial: high risk of bias.

Participants

Number of study centres: 1.

Setting: First People's Hospital of Raodu region, Fenlin City, Shanxi Province.

Origin of the participants: not specified.

Sample size calculation: not done.

Number of participants: 200. 102 received Juge Yigan, 98 received conventional therapy.

Sex ratio: 158 males (79%), 42 females (21%).

Mean age: range 19-58 years.

Duration of fatty liver diseases: not specified.

Diagnostic criteria: long-term history of heavy drinking; no obvious symptoms or low-grade abdominal distention, nausea and hepatic null pain; hepatomegaly; serum transaminases elevated and were more than 5 times the normal value; obvious AST elevation, and AST/ALT ratio > 2, but serum transaminases 2 times the normal value after 2 weeks of temperance; low-grade or moderate hepatomegaly by B-ultrasonography or CT; exclude non-alcoholic fatty liver, viral hepatitis, and drug-induced liver injury; strict temperance in the trial.

Inclusion criteria: not described.

Exclusion criteria: not described.

Dropouts: all participants randomised were analysed.

ITT analysis: not done.

Sources of funding: not specified.

Interventions

Intervention: Juge Yigan decoction, 1 dose decoction/day.

Control: vitamin B1, B2, B6, 30 mg and folic acid, 10 mg, po, 3 times/day.

Post-treatment follow-up: none.

Both groups received the same lifestyle changes.

Treatment duration: 3 months.

OutcomesOutcome(s): symptoms, signs, AST, ALT, GGT, L/S CT ratio.
Notes 
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Unclear riskNo information on random sequence generation.
Allocation concealment (selection bias)Unclear riskNo allocation concealment method was described.
Blinding (performance bias and detection bias)
All outcomes
Unclear riskNot described.
Incomplete outcome data (attrition bias)
All outcomes
Low riskNo withdrawals or dropouts were reported. All participants randomised were analysed.
Selective reporting (reporting bias)Low riskAll predefined outcomes in the methods section of the article were reported in the results section.
Other biasHigh riskSample size calculation was not reported.
Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskNot described.
Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskNot described.

Jia 2009

Methods

Trial design: randomised, parallel group trial.

Language: Chinese.

Type of publication: journal article.

Date of trial: January 2004 to December 2006.

Judgement of the quality of the trial: high risk of bias.

Participants

Number of study centres: 1.

Setting: First People's Hospital of Raodu region, Fenlin City, Shanxi Province.

Origin of the participants: inpatients and outpatients.

Sample size calculation: not done.

Number of participants: 124. 62 received Shengqing Jiangzhuo, 62 received lifestyle intervention.

Sex ratio: 82 males (66.1%), 42 females (33.9%).

Mean age: 38.4 years (range 23-60 years) in the treatment group; 37.6 years (range 21-61 years) in the control group.

Duration of fatty liver diseases: not specified.

Diagnostic criteria: CMA 2003a; CMA 2006b.

Inclusion criteria: not described.

Exclusion criteria: people who did not drink alcohol or had total alcohol intake > 140 g/week (male) and 70 g/week (female); chronic HBV and HCV or HIV; drug-induced hepatitis; agnogenic hepatic masses; applied glucocorticoid in the past or present; cirrhosis or hepatic insufficiency; agnogenic fatty liver; pregnancy; diabetes; TG > 0.5 mmol/L.

Dropouts: 21 participants dropped out of the study, including 8 from the treatment group and 13 from the control group. The reasons for leaving were described.

ITT analysis: not done.

Sources of funding: not specified.

Interventions

Intervention: Shengqing Jiangzhuo granules, 1 dose 200 mL, po, twice/day.

Control: lifestyle intervention.

Post-treatment follow-up: none.

Both groups received the same lifestyle changes.

Treatment duration: 12 months.

OutcomesOutcome(s): symptoms, signs, AST, ALT, GGT, TC, TG, LDL-C, FBG, BMI.
Notes 
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Unclear riskNo information on random sequence generation.
Allocation concealment (selection bias)Unclear riskNo allocation concealment method was described.
Blinding (performance bias and detection bias)
All outcomes
Unclear riskNot described.
Incomplete outcome data (attrition bias)
All outcomes
Low risk21 participants dropped from the study, including 8 from the treatment group and 13 from the control group. The reason for missing was described.
Selective reporting (reporting bias)High riskPrespecified outcome FPG, CT, B-ultrasound in the methods section of the article were not reported in the results section.
Other biasHigh riskSample size calculation was not reported.
Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskNot described.
Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskNot described.

Jiang 2009

Methods

Trial design: randomised, double-blinded, parallel group trial.

Language: Chinese.

Type of publication: journal article.

Date of trial: March 2006 to March 2008.

Judgement of the quality of the trial: high risk of bias.

Participants

Number of study centres: 1.

Setting: Guangdong Province Chinese Medicine Hospital.

Origin of the participants: outpatients.

Sample size calculation: not done.

Number of participants: 58. 30 received Zhishi Xiaopi, 28 received polyene phosphatidylcholine.

Sex ratio: 43 males (74.1%), 15 females (25.9%).

Mean age: 39.2 years in the treatment group; 40.6 years in the control group.

Duration of fatty liver diseases: not specified.

Diagnostic criteria: CMA 2006b.

Inclusion criteria: not described.

Exclusion criteria: lactating or pregnant women.

Dropouts: all participants randomised were analysed.

ITT analysis: not done.

Sources of funding: not specified.

Interventions

Intervention: Zhishi Xiaopi decoction, 1 dose decoction, twice/day.

Control: polygene phosphatidylcholine capsule, 228 mg, po, 3 times/day.

Post-treatment follow-up: none.

Both groups received the same lifestyle changes.

Treatment duration: 12 weeks.

OutcomesOutcome(s): symptoms, signs, BMI, WC, AST, ALT, GGT, TC, TG, HDL-C.
Notes 
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Unclear riskNo information on random sequence generation.
Allocation concealment (selection bias)Unclear riskNo allocation concealment method was described.
Blinding (performance bias and detection bias)
All outcomes
Unclear riskNot described.
Incomplete outcome data (attrition bias)
All outcomes
Low riskNo withdrawals or dropouts were reported. All participants randomised were analysed.
Selective reporting (reporting bias)Low riskAll predefined outcomes in the methods section of the article were reported in the results section.
Other biasHigh riskSample size calculation was not reported.
Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskNot described.
Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskNot described.

Kong 2010

Methods

Trial design: randomised, double-blinded, parallel group trial.

Language: Chinese.

Type of publication: journal article.

Date of trial: 2006-2008.

Judgement of the quality of the trial: high risk of bias.

Participants

Number of study centres: 1.

Setting: Fifth Affiliated Hospital, Sun Yet-Sen University.

Origin of the participants: inpatients and outpatients.

Sample size calculation: not done.

Number of participants: 100. 50 received lipid-lowering, 50 received polygene phosphatetidylcholine.

Sex ratio: 65 males (65%), 35 females (35%).

Mean age: 46.61 years.

Duration of fatty liver diseases: 3.21 years.

Diagnostic criteria: Group of Fatty Liver and Alcoholic Liver Diseases, Society of Hepatology, Chinese Medical Association. Diagnostic standard of non-alcoholic fatty liver (Draft). Chinese Hepatology 2001 (CMA 2001b).

Inclusion criteria: people who matched the diagnostic standard of NAFLD; aged 18-65 years; understood and granted consent to the scenario; using GCP.

Exclusion criteria: people with severe fatty liver; organic lesion, serious primary disease, diagnosis of personality or mental disorder; lactating or pregnant women; people with allergies.

Dropouts: all participants randomised were analysed.

ITT analysis: not done.

Sources of funding: not specified.

Interventions

Intervention: lipid-lowering granules, 1 dose taken in 2 potions every day.

Control: polygene phosphatidylcholine capsule, 1 granule, po, 3 times/day.

Post-treatment follow-up: none.

Treatment duration: 3 months.

OutcomesOutcome(s): symptoms, signs, BWI, B-ultrasonography, ALT, CT.
Notes 
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Low riskRandom number table was used.
Allocation concealment (selection bias)Low riskSealed envelopes were used.
Blinding (performance bias and detection bias)
All outcomes
Unclear riskNot described.
Incomplete outcome data (attrition bias)
All outcomes
Low riskNo withdrawals or dropouts were reported. All participants randomised were analysed.
Selective reporting (reporting bias)Low riskAll predefined outcomes in the methods section of the article were reported in the results section.
Other biasHigh riskSample size calculation was not reported.
Blinding of participants and personnel (performance bias)
All outcomes
Low riskStatisticians were blinded.
Blinding of outcome assessment (detection bias)
All outcomes
Low riskOutcome assessors were blinded.

Li 2005

Methods

Trial design: randomised, double-blinded, parallel group trial.

Language: Chinese.

Type of publication: journal article.

Date of trial: not specified.

Judgement of the quality of the trial: high risk of bias.

Participants

Number of study centres: 1.

Setting: Yantai Yu Huangding Hospital of the Affiliated Hospital, Qingdao Medicine University.

Origin of the participants: inpatients and outpatients.

Sample size calculation: not done.

Number of participants: 86. 45 received Huoxue Qinggan, 41 received polyene phosphatidylcholine.

Sex ratio: all participants were male.

Mean age: range 33-56 years.

Duration of fatty liver diseases: not specified.

Diagnostic criteria: Chinese Society of Hepatology. Diagnostic standard of alcoholic fatty liver, 2002. Diagnostic source did not state. We could not find the article on the diagnostic criteria.

Inclusion criteria: not specified.

Exclusion criteria: not specified.

Dropouts: all participants randomised were analysed.

ITT analysis: not done.

Sources of funding: not specified.

Interventions

Intervention: Huoxue Qinggan decoction, 1 dose decoction once daily plus polyene phosphatidylcholine capsules plus Danshen injections 10 mL, 5% GLU 20 mL, iv, once daily.

Control: polygene phosphatidylcholine capsule.

Post-treatment follow-up: none.

Both groups received the same lifestyle changes and conventional treatment.

Treatment duration: 6 weeks.

OutcomesOutcome(s): symptoms, signs, B-ultrasonography, ALT, AST, TBIL, GGT, ALB, PT, IV-C.
Notes 
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Unclear riskNo information on random sequence generation.
Allocation concealment (selection bias)Unclear riskNo allocation concealment method was described.
Blinding (performance bias and detection bias)
All outcomes
Unclear riskNot described.
Incomplete outcome data (attrition bias)
All outcomes
Low riskNo withdrawals or dropouts were reported. All participants randomised were analysed.
Selective reporting (reporting bias)Low riskAll predefined outcomes in the methods section of the article were reported in the results section.
Other biasHigh riskSample size calculation was not reported.
Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskNot described.
Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskNot described.

Li 2006a

Methods

Trial design: randomised, parallel group trial.

Language: Chinese.

Type of publication: journal article.

Date of trial: not specified.

Judgement of the quality of the trial: high risk of bias.

Participants

Number of study centres: 1.

Setting: Linyi Chinese Medicine Hospital.

Origin of the participants: inpatients and outpatients.

Sample size calculation: not done.

Number of participants: 80. 40 received Baogan Xiaozhi plus lifestyle changes, 40 received lifestyle changes.

Sex ratio: 51 males (63.8%), 29 females (36.2%).

Mean age: 46 years (range 27-65 years) in the treatment group; 45 years (range 26-66 years) in the control group.

Duration of fatty liver diseases: 4.4 years (range 1-10 years) in the treatment group; 4.6 years (range 1-10 years) in the control group.

Diagnostic criteria: CMA 2003a; CMA 2003b.

Inclusion criteria: not described.

Exclusion criteria: not described.

Dropouts: all participants randomised were analysed.

ITT analysis: not done.

Sources of funding: not specified.

Interventions

Intervention: Baogan Xiaozhi powder, 12 g, po, twice/day plus lifestyle changes.

Control: lifestyle changes.

Post-treatment follow-up: none.

Treatment duration: 3 months.

OutcomesOutcome(s): symptoms, signs, ALT, AST, TG, TC, HDL-C, LDL-C, IAI, IR, FIns, B-ultrasonography.
Notes 
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Unclear riskNo information on random sequence generation.
Allocation concealment (selection bias)Unclear riskNo allocation concealment method was described.
Blinding (performance bias and detection bias)
All outcomes
Unclear riskNot described.
Incomplete outcome data (attrition bias)
All outcomes
Low riskNo withdrawals or dropouts were reported. All participants randomised were analysed.
Selective reporting (reporting bias)Low riskAll predefined outcomes in the methods section of the article were reported in the results section.
Other biasHigh riskSample size calculation was not reported.
Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskNot described.
Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskNot described.

Li 2006b

Methods

Trial design: randomised, parallel group trial.

Language: Chinese.

Type of publication: journal article.

Date of trial: 2002-2004.

Judgement of the quality of the trial: high risk of bias.

Participants

Number of study centres: 1.

Setting: Laiwu Chinese Medicine Hospital, Shandong Province.

Origin of the participants: inpatients and outpatients.

Sample size calculation: not done.

Number of participants: 82. 42 received Baogan Xiaozhi plus lifestyle intervention, 40 received vitamin E nicotinic capsules plus lifestyle intervention.

Sex ratio: not specified.

Mean age: not specified.

Duration of fatty liver diseases: not specified.

Diagnostic criteria: Group of Epidemic disease and Verminosis, Society of Hepatology, Chinese Medical Association. National Program for Prevention and Treatment of Viral Hepatitis. Chinese Journal of Hepatology 2000 (CMA 2000).

Inclusion criteria: not described.

Exclusion criteria: not described.

Dropouts: all participants randomised were analysed.

ITT analysis: not done.

Sources of funding: not specified.

Interventions

Intervention: Baogan Xiaozhi pellet, 9 g, po, 3 times/day plus lifestyle intervention.

Control: vitamin E nicotinic capsules, 0.2 g, po, 3 times/day plus lifestyle intervention.

Post-treatment follow-up: none.

Both groups received the same lifestyle changes.

Treatment duration: 45 days.

OutcomesOutcome(s): symptoms, signs, ALT, AST, γ-GT, TG, TC, B-ultrasonography.
Notes 
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Unclear riskNo information on random sequence generation.
Allocation concealment (selection bias)Unclear riskNo allocation concealment method was described.
Blinding (performance bias and detection bias)
All outcomes
Unclear riskNot described.
Incomplete outcome data (attrition bias)
All outcomes
Low riskNo withdrawals or dropouts were reported. All participants randomised were analysed.
Selective reporting (reporting bias)High riskPrespecified outcome B-ultrasound in the methods section of the article were not reported in the results section.
Other biasHigh riskSample size calculation was not reported.
Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskNot described.
Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskNot described.

Li 2007

Methods

Trial design: randomised, parallel group trial.

Language: Chinese.

Type of publication: journal article.

Date of trial: November 2005 to October 2006.

Judgement of the quality of the trial: high risk of bias.

Participants

Number of study centres: 1.

Setting: Affiliated Hospital of Ningxia Medicine University.

Origin of the participants: outpatients.

Sample size calculation: not done.

Number of participants: 66. 36 received Shuanghu Qinggan plus tiopronin, 30 received tiopronin.

Sex ratio: 27 males (68.2%), 21 females (31.8%).

Mean age: 42 years (range 27-68 years) in the treatment group; 41 years (range 24-68 years) in the control group.

Duration of fatty liver diseases: not specified.

Diagnostic criteria: Group of Fatty Liver and Alcoholic Liver Diseases, Society of Heoatology, Chinese Medical Association. Diagnosis of non-alcoholic fatty liver. Chinese Journal of Hepatology 2003 (CMA 2003a).

Inclusion criteria: not described.

Exclusion criteria: not described.

Dropouts: all participants randomised were analysed.

ITT analysis: not done.

Sources of funding: not specified.

Interventions

Intervention: Shuanghu Qinggan granules, 1 bag, po, twice/day, plus tiopronin, 0.2 g, po, 3 times/day.

Control: tiopronin, 0.2 g, po, 3 times/day.

Post-treatment follow-up: none.

Both groups received the same lifestyle changes.

Treatment duration: 12 weeks.

OutcomesOutcome(s): symptoms, signs, ALT, γ-GT, TG, TC, B-ultrasonography.
Notes 
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Unclear riskNo information on random sequence generation.
Allocation concealment (selection bias)Unclear riskNo allocation concealment method was described.
Blinding (performance bias and detection bias)
All outcomes
Unclear riskNot described.
Incomplete outcome data (attrition bias)
All outcomes
Low riskNo withdrawals or dropouts were reported. All participants randomised were analysed.
Selective reporting (reporting bias)High riskPrespecified outcome B-ultrasound in the methods section of the article were not reported in the results section.
Other biasHigh riskSample size calculation was not reported.
Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskNot described.
Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskNot described.

Li 2008

Methods

Trial design: randomised, parallel group trial.

Language: Chinese.

Type of publication: journal article.

Date of trial: not specified.

Judgement of the quality of the trial: high risk of bias.

Participants

Number of study centres: 2.

Setting: No. 1 Hospital affiliated to General Hospital of Guangzhou University of Chinese Medicine; No. 1 Hospital affiliated to General Hospital of GuangXi Traditional Chinese Medicine University.

Origin of the participants: inpatients and outpatients.

Sample size calculation: not done.

Number of participants: 89. 46 received Shenling Baizhu plus Erchen, 43 received zocor plus diammonium.

Sex ratio: 60 males (67.4%), 29 females (32.2%).

Mean age: 42.56 years (range 31-60 years) in the treatment group; 43.32 years (range 32-59 years) in the control group.

Duration of fatty liver diseases: not specified.

Diagnostic criteria: Group of Fatty Liver and Alcoholic Liver Diseases, Society of Hepatology, Chinese Medical Association. Diagnostic standard of non-alcoholic fatty liver. Chinese Journal of Hepatology 2003 (CMA 2003c).

Inclusion criteria: aged 30-60 years.

Exclusion criteria: pregnant, lactating women, or alcoholic; viral hepatitis and other type of hepatitis; primary diseases and diagnosis of personality or mental disorder; poor compliancewith medicine; not able to judge the effectiveness; incomprehensive materials.

Dropouts: all participants randomised were analysed.

ITT analysis: not done.

Sources of funding: not specified.

Interventions

Intervention: Shenling Baizhu powder plus Erchen decoction, 200 mL decoction, twice/day.

Control: zocor, 20 mg, po, twice/day, plus diammonium, 100 mg, po, 3 times/day.

Post-treatment follow-up: none.

Both groups received the same lifestyle changes.

Treatment duration: 8 weeks.

OutcomesOutcome(s): symptoms, signs, B-ultrasonography, HDL-C, LDL-C, ALT, AST, γ-GGT, TG, TC, SOD, MDA.
Notes 
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Low riskRandom number table was used.
Allocation concealment (selection bias)Unclear riskNot described.
Blinding (performance bias and detection bias)
All outcomes
Unclear riskNot described.
Incomplete outcome data (attrition bias)
All outcomes
Low riskNo withdrawals or dropouts were reported. All participants randomised were analysed.
Selective reporting (reporting bias)Low riskAll predefined outcomes in the methods section of the article were reported in the results section.
Other biasHigh riskSample size calculation was not reported.
Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskNot described.
Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskNot described.

Li 2009

Methods

Trial design: randomised, parallel group trial.

Language: Chinese.

Type of publication: journal article.

Date of trial: January 2007 to January 2008.

Judgement of the quality of the trial: high risk of bias.

Participants

Number of study centres: 1.

Setting: Second Chinese Medicine Hospital, Nanchong City.

Origin of the participants: outpatients.

Sample size calculation: not done.

Number of participants: 40. 20 received Qinggan, 20 received tiopronin.

Sex ratio: 27 males (67.5%), 13 females (32.5%).

Mean age: 45.3 years.

Duration of fatty liver diseases: not specified.

Diagnostic criteria: Group of Fatty Liver and Alcoholic Liver Diseases, Society of Heoatology, Chinese Medical Association. Diagnosis of non-alcoholic fatty liver. Chinese Journal of Hepatology 2003 (CMA 2003a).

Inclusion criteria: not described.

Exclusion criteria: occupying lesions in liver, cirrhosis of the liver, acute fatty liver of pregnancy, Reye syndrome, alcoholic liver disease.

Dropouts: all participants randomised were analysed.

ITT analysis: not done.

Sources of funding: not specified.

Interventions

Intervention: Qinggan decoction, 1 dose, twice/day.

Control: tiopronin, 200 mg, po, 3 times/day.

Post-treatment follow-up: none.

Both groups received the same lifestyle changes.

Treatment duration: 12 weeks.

OutcomesOutcome(s): symptoms, signs, LDL-C, ALT, AST, TG, TC.
Notes 
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Low riskRandom number table was used.
Allocation concealment (selection bias)Unclear riskNot described.
Blinding (performance bias and detection bias)
All outcomes
Unclear riskNot described.
Incomplete outcome data (attrition bias)
All outcomes
Unclear riskNo information on whether there subjects withdrew or were lost to follow-up.
Selective reporting (reporting bias)Low riskAll predefined outcomes in the methods section of the article were reported in the results section.
Other biasHigh riskSample size calculation was not reported.
Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskNot described.
Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskNot described.

Li 2010

Methods

Trial design: randomised, parallel group trial.

Language: Chinese.

Type of publication: journal article.

Date of trial: January 2007 to December 2009.

Judgement of the quality of the trial: high risk of bias.

Participants

Number of study centres: 1.

Setting: Chinese Medicine Hospital of Fuzuo country, Chongzuo, Guangxi Province.

Origin of the participants: inpatients.

Sample size calculation: not done.

Number of participants: 66. 33 received Xiaotanjiagnzhi, 33 received polyene phosphatidylcholine (Yishanfu).

Sex ratio: 40 males (60.6%), 26 females (39.4%).

Mean age: 45.7 years.

Duration of fatty liver diseases: 9.28 years.

Diagnostic criteria: CMA 2003a.

Inclusion criteria: not described.

Exclusion criteria: not described.

Dropouts: not specified.

ITT analysis: not done.

Sources of funding: not specified.

Interventions

Intervention: Xiaotanjiagnzhi, once/day; polyene phosphatidylcholine (Yishanfu), 456 mg, 5% glucose, 250 mL, iv once daily.

Control: polyene phosphatidylcholine (Yishanfu), 456 mg, 5% glucose, 250 mL, iv, once daily.

Post-treatment follow-up: none.

Both groups received the same lifestyle changes.

Treatment duration: 12 weeks.

OutcomesOutcome(s): symptoms, signs, L/S CT ratio, ALT, AST, GGT, TG, TC.
Notes 
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Unclear riskNo information on random sequence generation.
Allocation concealment (selection bias)Unclear riskNo allocation concealment method was described.
Blinding (performance bias and detection bias)
All outcomes
Unclear riskNot described.
Incomplete outcome data (attrition bias)
All outcomes
Low riskNo withdrawals or dropouts were reported. All participants randomised were analysed.
Selective reporting (reporting bias)Low riskAll predefined outcomes in the methods section of the article were reported in the results section.
Other biasHigh riskSample size calculation was not reported.
Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskNot described.
Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskNot described.

Liang 2008

Methods

Trial design: randomised, parallel group trial.

Language: Chinese.

Type of publication: journal article.

Date of trial: October 2004 to October 2007.

Judgement of the quality of the trial: high risk of bias.

Participants

Number of study centres: 1.

Setting: Yuhuan Xian Hospital of TCM.

Origin of the participants: inpatients.

Sample size calculation: not done.

Number of participants: 146. 73 received herbal medicine plus conventional therapy, 73 received conventional therapy.

Sex ratio: all participants were males.

Mean age: 46.8 years (range 26-56 years).

Duration of fatty liver diseases: not specified.

Diagnostic criteria: Group of Fatty Liver and Alcoholic Liver Diseases, Society of Heoatology, Chinese Medical Association. Diagnosis of non-alcoholic fatty liver. Chinese Journal of Hepatology 2003 (CMA 2003a).

Inclusion criteria: not specified.

Exclusion criteria: not specified.

Dropouts: all participants randomised were analysed.

ITT analysis: not done.

Sources of funding: not specified.

Interventions

Intervention: 60 mL herbal mixture administered via coloclysis and kept in the intestines for 1 h plus conventional therapy.

Control: conventional therapy.

Post-treatment follow-up: none.

Both groups received the same conventional treatment of liver protection drugs or lifestyle changes.

Treatment duration: 4 weeks.

OutcomesOutcome(s): symptoms, signs, B-ultrasonography, ALT, AST, γ-GGT, TG, TC.
NotesIntervention was a herbal mixture via coloclysis (colon dialysis) composed of Atractylodes lancea, Pogostemon cablin, Eupatorium fortunei, Pinellia ternate, Cyperus rotundus, Citrus aurtantium, Cassia obtusifolia, Salvia miltiorrhiza, Crataegus pinnatifida, Rheum palmatum. The coloclysis treatment was used to insert the medicines to the intestine, where they were kept for 1 h.
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Low riskRandom number table was used.
Allocation concealment (selection bias)Unclear riskNot described.
Blinding (performance bias and detection bias)
All outcomes
Unclear riskNot described.
Incomplete outcome data (attrition bias)
All outcomes
Low riskNo withdrawals or dropouts were reported. All participants randomised were analysed.
Selective reporting (reporting bias)Low riskAll predefined outcomes in the methods section of the article were reported in the results section.
Other biasHigh riskSample size calculation was not reported.
Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskNot described.
Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskNot described.

Liang 2010

Methods

Trial design: randomised, parallel group trial.

Language: Chinese.

Type of publication: journal article.

Date of trial: February 2008 to February 2010.

Judgement of the quality of the trial: high risk of bias.

Participants

Number of study centres: 1.

Setting: the hospital of South China Normal University, Guangzhou City.

Origin of the participants: outpatients.

Sample size calculation: not done.

Number of participants: 75. 40 received Jiangpi Huazhou, 35 received polyene phosphatidylcholine.

Sex ratio: 41 males (54.7%), 34 females (45.3%).

Mean age: 42.7 years (range 20-60 years) in the treatment group; 42.5 years (range 19-60 years) in the control group.

Duration of fatty liver diseases: 5.1 years (range 1-12 years) in the treatment group; 5.2 years (range 1-11 years) in the control group.

Diagnostic criteria: Group of Fatty Liver and Alcoholic Liver Diseases, Society of Heoatology, Chinese Medical Association. Guidelines for diagnosis and treatment of non-alcoholic fatty liver diseases. Chinese Hepatology 2006 (CMA 2006a).

Inclusion criteria: people met the diagnostic standard of NAFLD, aged 18-65 years; no hepatoprotectants, antilipidaemic agents or diet tablets were taken 2 weeks before trial.

Exclusion criteria: people with serious cardiovascular, cerebral, and kidney diseases; with acute or chronic viral hepatitis; value of ALT, AST, r-GT 5 times over the regular value; serious damage of liver function.

Dropouts: all participants randomised were analysed.

ITT analysis: not done.

Sources of funding: not specified.

Interventions

Intervention: Jianpi Huashi decoction, 1 dose, decocted 150 mL in water and take in 2 potions every day.

Control: polyene phosphatidylcholine capsule, 2 granules, po, 3 times/day.

Post-treatment follow-up: none.

Both groups received the same lifestyle changes.

Treatment duration: 12 weeks.

OutcomesOutcome(s): symptoms, signs, BWI, L/S CT, cholesterol, LDL-C, ALT, AST, γ-GGT, TG.
Notes 
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Low riskRandom number table was used.
Allocation concealment (selection bias)Unclear riskNot described.
Blinding (performance bias and detection bias)
All outcomes
Unclear riskNot described.
Incomplete outcome data (attrition bias)
All outcomes
Low riskNo withdrawals or dropouts were reported. All participants randomised were analysed.
Selective reporting (reporting bias)Low riskAll predefined outcomes in the methods section of the article were reported in the results section.
Other biasHigh riskSample size calculation was not reported.
Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskNot described.
Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskNot described.

Liang 2011

Methods

Trial design: randomised, parallel group trial.

Language: Chinese.

Type of publication: journal article.

Date of trial: October 2007 to October 2009.

Judgement of the quality of the trial: high risk of bias.

Participants

Number of study centres: 1.

Setting: the first affiliated Hospital of Heilongjiang University of Chinese Medicine.

Origin of the participants: inpatients and outpatients.

Sample size calculation: not done.

Number of participants: 80. 40 received Baogan Xiaozhikeli, 40 received Dongbao Gantai.

Sex ratio: 48 males (60%), 32 females (40%).

Mean age: 46.2 years.

Duration of fatty liver diseases: not specified.

Diagnostic criteria: CMA 2006a.

Inclusion criteria: not described.

Exclusion criteria: not described.

Dropouts: none.

ITT analysis: not done.

Sources of funding: YJSCX2009-177HLJ.

Interventions

Intervention: Baogan Xiaozhikeli, 1 bag, po, 3 times/day.

Control: Dongbao Gantai tablets, 3 tablets, po, 3 times/day.

Post-treatment follow-up: none.

Treatment duration: 6 weeks.

OutcomesOutcome(s): symptoms, signs, B-ultrasonography, ALT, AST, TG.
Notes 
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Low riskComputer generated random number.
Allocation concealment (selection bias)Unclear riskNo allocation concealment method was described.
Blinding (performance bias and detection bias)
All outcomes
Unclear riskNot described.
Incomplete outcome data (attrition bias)
All outcomes
Low riskNo withdrawals or dropouts were reported. All participants randomised were analysed.
Selective reporting (reporting bias)Low riskAll predefined outcomes in the methods section of the article were reported in the results section.
Other biasHigh riskSample size calculation was not reported.
Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskNot described.
Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskNot described.

Lin 2010a

Methods

Trial design: randomised, parallel group trial.

Language: Chinese.

Type of publication: journal article.

Date of trial: January 2008 to December 2009.

Judgement of the quality of the trial: high risk of bias.

Participants

Number of study centres: 1.

Setting: Xiamen Chinese Medicine Hospital.

Origin of the participants: inpatients.

Sample size calculation: not done.

Number of participants: 75. 40 received Xiaozhi Jiangpi, 35 received polyene phosphatidylcholine.

Sex ratio: 41 males (54.7%), 34 females (45.3%).

Mean age: 42.36 years in the treatment group; 43.34 years in the control group.

Duration of fatty liver diseases: 16.24 years in the treatment group; 17.12 years in the control group.

Diagnostic criteria: Group of Fatty Liver and Alcoholic Liver Diseases, Society of Heoatology, Chinese Medical Association. Guidelines for diagnosis and treatment of non-alcoholic fatty liver. Chinese Journal of Hepatology 2006 (CMA 2006b).

Inclusion criteria: not specified.

Exclusion criteria: not specified.

Dropouts: all participants randomised were analysed.

ITT analysis: not done.

Sources of funding: not specified.

Interventions

Intervention: Xiaozhi Jianpi decoction, 100 mL, twice/day.

Control: polyene phosphatidylcholine, 1 granule, po, 3 times/day.

Post-treatment follow-up: none.

Both groups received the same lifestyle changes.

Treatment duration: 2 months.

OutcomesOutcome(s): symptoms, signs, B-ultrasonography, ALT, AST, TC, TG.
Notes 
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Unclear riskNo information on random sequence generation.
Allocation concealment (selection bias)Unclear riskNo allocation concealment method was described.
Blinding (performance bias and detection bias)
All outcomes
Unclear riskNot described.
Incomplete outcome data (attrition bias)
All outcomes
Low riskNo withdrawals or dropouts were reported. All participants randomised were analysed.
Selective reporting (reporting bias)Low riskAll predefined outcomes in the methods section of the article were reported in the results section.
Other biasHigh riskSample size calculation was not reported.
Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskNot described.
Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskNot described.

Lin 2010b

Methods

Trial design: randomised, parallel group trial.

Language: Chinese.

Type of publication: journal article.

Date of trial: May 2006 to October 2009.

Judgement of the quality of the trial: high risk of bias.

Participants

Number of study centres: 1.

Setting: Buji People's Hospital of Shenzhen City.

Origin of the participants: outpatients.

Sample size calculation: not done.

Number of participants: 112. 57 received Zini Jianpi Huatan, 55 received polyene phosphatid.

Sex ratio: 72 males (64.3%), 40 females (35.7%).

Mean age: 34.1 years (range 23-60 years) in the treatment group; 33.6 years (range 21-60 years) in the control group.

Duration of fatty liver diseases: not described.

Diagnostic criteria: Group of Fatty Liver and Alcoholic Liver Diseases, Society of Heoatology, Chinese Medical Association. Guidelines for diagnosis and treatment of non-alcoholic fatty liver. Chinese Journal of Hepatology 2006 (CMA 2006b).

Inclusion criteria: not specified.

Exclusion criteria: specific diseases may cause fatty liver such as viral hepatitis, drug-induced liver disease, total parenteral nutrition, hepatolenticular degeneration; lactating or pregnant women; severe primary diseases with cardiovascular, liver, kidney, haematology, lung, or effects on survival.

Dropouts: all participants randomised were analysed.

ITT analysis: not done.

Sources of funding: not specified.

Interventions

Intervention: Zini Jianpi Huatan formula, 1 dose decoction, twice/day.

Control: polyene phosphatid, 456 mg, po, 3 times/day.

Post-treatment follow-up: none.

Both groups received the same lifestyle changes and conventional treatment.

Treatment duration: 3 months.

OutcomesOutcome(s): symptoms, BMI, B-ultrasonography, ALT, GGT, TC, TG.
Notes 
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Unclear riskNo information on random sequence generation.
Allocation concealment (selection bias)Unclear riskNo allocation concealment method was described.
Blinding (performance bias and detection bias)
All outcomes
Unclear riskNot described.
Incomplete outcome data (attrition bias)
All outcomes
Low riskNo withdrawals or dropouts were reported. All participants randomised were analysed.
Selective reporting (reporting bias)High riskPrespecified outcome B-ultrasound in the methods section of the article were not reported in the results section.
Other biasHigh riskSample size calculation was not reported.
Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskNot described.
Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskNot described.

Lin 2011

Methods

Trial design: randomised, parallel group trial.

Language: Chinese.

Type of publication: journal article.

Date of trial: February 2005 to February 2007.

Judgement of the quality of the trial: high risk of bias.

Participants

Number of study centres: 1.

Setting: the First Affiliated Hospital, Sun Yat-sen University.

Origin of the participants: not specified.

Sample size calculation: not done.

Number of participants: 65. 33 received Yunpi Tongluo, 32 received UDCA.

Sex ratio: 37 males (56.9%), 28 females (43.1%).

Mean age: 38.8 years (range 18-60 years) in the treatment group; 37.5 years (range 18-60 years) in the control group.

Duration of fatty liver diseases: 3.5 years (range 0.9-11.5 years) in the treatment group; 3.1 years (range 0.8-10.5 years) in the control group.

Diagnostic criteria: American Gastroenterological Association. American Gastroenterological Association medical position statement: nonalcoholic fatty liver disease. Gastroenterology 2002 (AGA 2002).

Inclusion criteria: participants conforming NAFLD criteria, aged 18-60 years.

Exclusion criteria: pregnant or lactating women; people with HAV, HBV, HCV, HDV, HEV, HIV, or liver cancer; decompensated liver cirrhosis; nephrotic syndrome; diabetes; hypothyroidism; acute hepatobiliary disease; people who took lipid-lowering agents, β-blockers, phenothiazines, adrenal steroid or contraceptives during the previous month; the acute primary diseases of liver, kidney, and hematopoietic system,

people refused to sign the informed consent; people with acute myocardial infarction, cerebrovascular events, hepatic and renal dysfunction, malignant tumour and other serious diseases during the previous 6 months; diagnosis of personality or mental disorder; compensated cirrhosis.

Dropouts: all participants randomised were analysed.

ITT analysis: not done.

Sources of funding: National Eleventh Five-Year Science and Technology Major Project; Guangdong Science and Plan Foundation; Guangdong National Science Foundation.

Interventions

Intervention: Yunpi Tongluo formula, 1 dose decoction, 3 times/day.

Control: UDCA, 2 granules, po, twice/day.

Post-treatment follow-up: none.

Both groups received the same lifestyle changes.

Treatment duration: 6 months.

OutcomesOutcome(s): symptoms and signs, B-ultrasonography, ALT, AST, GGT, MBI, TC, TG, LDL-C, HDL-C, TNF-α, IL-8, SOD, MDA.
Notes 
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Low riskRandom number table was used.
Allocation concealment (selection bias)Unclear riskNo allocation concealment method was described.
Blinding (performance bias and detection bias)
All outcomes
Unclear riskNot described.
Incomplete outcome data (attrition bias)
All outcomes
High risk2 dropped from the study, including 1 from the treatment group and 1 from the control group left. But the reason was not specified.
Selective reporting (reporting bias)Low riskAll predefined outcomes in the methods section of the article were reported in the results section.
Other biasHigh riskSample size calculation was not reported.
Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskNot described.
Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskNot described.

Liu 2008

Methods

Trial design: randomised, parallel group trial.

Language: Chinese.

Type of publication: journal article.

Date of trial: January 2007 to December 2007.

Judgement of the quality of the trial: high risk of bias.

Participants

Number of study centres: 1.

Setting: Xinjiang Uygur Autonomous Region Chinese Medicine Hospital.

Origin of the participants: inpatients and outpatients.

Sample size calculation: not done.

Number of participants: 70. 35 received Qiyin, 35 received polyene phosphatidylcholine.

Sex ratio: 53 males (75.7%), 17 females (24.3%).

Mean age: not specified.

Duration of fatty liver diseases: not specified.

Diagnostic criteria: Group of Fatty Liver and Alcoholic Liver Diseases, Society of Hepatology, Chinese Medical Association. Diagnostic standard of non-alcoholic fatty liver and alcoholic liver diseases. Chinese Journal of Hepatology 2006 (CMA 2006c).

Inclusion criteria: inpatients and outpatients; their diagnostic criteria was Diagnostic standard of non-alcoholic fatty liver and alcoholic liver diseases and 2 high qualification doctors made their symptoms and signs integral.

Exclusion criteria: pregnant or lactating women, and people refused to sign the informed consent; people with acute myocardial infarction, cerebrovascular events, hepatic and renal dysfunction, malignant tumour, and other serious diseases during the previous 6 months; diagnosis of personality or mental disorder; compensated cirrhosis.

Dropouts: all participants randomised were analysed.

ITT analysis: not done.

Sources of funding: not specified.

Interventions

Intervention: Qiyin granules, 1 dose, 2 potions every day.

Control: polyene phosphatidylcholine capsule, 1 granule, po, 3 times/day.

Post-treatment follow-up: none.

Both groups received the same lifestyle changes.

Treatment duration: 8 weeks.

OutcomesOutcome(s): symptoms, signs, B-ultrasonography, ALT, AST, TG, TC.
Notes 
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Low riskRandom number table was used.
Allocation concealment (selection bias)Unclear riskNot described.
Blinding (performance bias and detection bias)
All outcomes
Unclear riskNot described.
Incomplete outcome data (attrition bias)
All outcomes
Low riskNo withdrawals or dropouts were reported. All participants randomised were analysed.
Selective reporting (reporting bias)Low riskAll predefined outcomes in the methods section of the article were reported in the results section.
Other biasHigh riskSample size calculation was not reported.
Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskNot described.
Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskNot described.

Liu 2009

Methods

Trial design: randomised, parallel group trial.

Language: Chinese.

Type of publication: journal article.

Date of trial: December 2006 to February 2008.

Judgement of the quality of the trial: high risk of bias.

Participants

Number of study centres: 1.

Setting: the Chines Medicine hospital of Jinghai Country, Tianjing City.

Origin of the participants: inpatients and outpatients.

Sample size calculation: not done.

Number of participants: 105. 65 received Xiaoyu Huatan Yin, 40 received methionine and choline bitartrate.

Sex ratio: 77 males (73.3%), 28 females (26.7%).

Mean age: 41.5 years (range 28-65 years) in the treatment group; 42.1 years (range 30-64 years) in the control group.

Duration of fatty liver diseases: 3.7 years (range 0.5-7 years) in the treatment group; 4 years (range 1-7 years) in the control group.

Diagnostic criteria: Group of Fatty Liver and Alcoholic Liver Diseases, Society of Heoatology, Chinese Medical Association. Diagnosis of non-alcoholic fatty liver. Chinese Journal of Hepatology 2003 (CMA 2003a).

Inclusion criteria: not described.

Exclusion criteria: not described.

Dropouts: all participants randomised were analysed.

ITT analysis: not done.

Sources of funding: not specified.

Interventions

Intervention: Xiaoyu Huatan Yin, 1 dose, decoction 300 mL, twice/day.

Control: methionine plus choline bitartrate tablet, 3 tablets, po, 3 times/day.

Post-treatment follow-up: none.

Both groups received the same lifestyle changes.

Treatment duration: 8 weeks.

OutcomesOutcome(s): B-ultrasonography, ALT, AST, TG, TC.
Notes 
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Low riskDrawing lots.
Allocation concealment (selection bias)Unclear riskNot described.
Blinding (performance bias and detection bias)
All outcomes
Unclear riskNot described.
Incomplete outcome data (attrition bias)
All outcomes
Low riskNo withdrawals or dropouts were reported. All participants randomised were analysed.
Selective reporting (reporting bias)High riskPrespecified outcome FPG, FNS, HOMA-IR in the methods section of the article were reported in the results section.
Other biasHigh riskSample size calculation was not reported. And there was imbalanced distribution of participants in 2 groups.
Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskNot described.
Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskNot described.

Lou 2008

Methods

Trial design: randomised, parallel group trial.

Language: Chinese.

Type of publication: journal article.

Date of trial: July 2006 to December 2007.

Judgement of the quality of the trial: high risk of bias.

Participants

Number of study centres: 1.

Setting: Shanghai Huashan Integrated Traditional Chinese and Western Hospital.

Origin of the participants: outpatients.

Sample size calculation: not done.

Number of participants: 67. 39 received Yiqi, 28 received placebo.

Sex ratio: 44 males (65.7%), 23 females (34.3%).

Mean age: 52.6 years in the treatment group; 54.8 years in the control group.

Duration of fatty liver diseases: not specified.

Diagnostic criteria: Group of Fatty Liver and Alcoholic Liver Diseases, Society of Heoatology, Chinese Medical Association. Guidelines for diagnosis and treatment of non-alcoholic fatty liver diseases. Chinese Hepatology 2006 (CMA 2006a).

Inclusion criteria: not described.

Exclusion criteria: history of alcohol or alcohol intake > 140 g/week for males, > 70 g/week for females; specific diseases may cause fatty liver such as viral hepatitis, drug-induced liver disease, total parenteral nutrition, hepatolenticular degeneration.

Dropouts: all participants randomised were analysed.

ITT analysis: not done.

Sources of funding: not specified.

Interventions

Intervention: Yiqi formula, 2 bags, po, twice/day.

Control: placebo, 2 bags, po, twice/day.

Post-treatment follow-up: none.

Both groups received the same lifestyle changes.

Treatment duration: 12 weeks.

OutcomesOutcome(s): symptoms, BMI, WC, CT, HDL-C, LDL-C, ALT, AST, TG, TC, HOMA2-IR, TNF-α, hs-CRP.
Notes 
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Low riskRandom number table was used.
Allocation concealment (selection bias)Unclear riskNot described.
Blinding (performance bias and detection bias)
All outcomes
Unclear riskNot described.
Incomplete outcome data (attrition bias)
All outcomes
Low riskNo withdrawals or dropouts were reported. All participants randomised were analysed.
Selective reporting (reporting bias)Low riskAll predefined outcomes in the methods section of the article were reported in the results section.
Other biasHigh riskSample size calculation was not reported.
Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskNot described.
Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskNot described.

Ma 2009

Methods

Trial design: randomised, parallel group trial.

Language: Chinese.

Type of publication: journal article.

Date of trial: March 2004 to February 2008.

Judgement of the quality of the trial: high risk of bias.

Participants

Number of study centres: 1.

Setting: Xi'an City the Eighth Hospital.

Origin of the participants: inpatients and outpatients.

Sample size calculation: not done.

Number of participants: 60. 30 received Zhiganqing, 30 received tiopronin.

Sex ratio: 39 males (65%), 21 females (35%).

Mean age: 38 years (range 20-60 years) in the treatment group; 39 years (range 19-60 years) in the control group.

Duration of fatty liver diseases: not specified.

Diagnostic criteria: Group of Fatty Liver and Alcoholic Liver Diseases, Society of Heoatology, Chinese Medical Association. Guidelines for diagnosis and treatment of non-alcoholic fatty liver. Chinese Journal of Hepatology 2006 (CMA 2006b).

Inclusion criteria: not described.

Exclusion criteria: not described.

Dropouts: all participants randomised were analysed.

ITT analysis: not done.

Sources of funding: not specified.

Interventions

Intervention: Zhiganqing granules, 1 bag, po, 3 times/day.

Control: tiopronin, 2 granules, po, 3 times/day.

Post-treatment follow-up: none.

Both groups received the same lifestyle changes.

Treatment duration: 24 weeks.

OutcomesOutcome(s): symptoms, signs, HDL-C, LDL-C, ALT, AST, TG, TC, ALP, GGT, B-ultrasonography.
Notes 
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Unclear riskNo information on random sequence generation.
Allocation concealment (selection bias)Unclear riskNo allocation concealment method was described.
Blinding (performance bias and detection bias)
All outcomes
Unclear riskNot described.
Incomplete outcome data (attrition bias)
All outcomes
Low riskNo withdrawals or dropouts were reported. All participants randomised were analysed.
Selective reporting (reporting bias)High riskSome predefined outcomes in the methods section of the article were reported in the results section.
Other biasHigh riskSample size calculation was not reported.
Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskNot described.
Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskNot described.

Ma 2010

Methods

Trial design: randomised, parallel group trial.

Language: Chinese.

Type of publication: journal article.

Date of trial: June 2006 to June 2009.

Judgement of the quality of the trial: high risk of bias.

Participants

Number of study centres: 1.

Setting: First Affiliated Hospital of Heilongjiang Chinese Medicine University.

Origin of the participants: inpatients and outpatients.

Sample size calculation: not done.

Number of participants: 80. 40 received Qinggan Xiaozhi plus GSH, 40 received GSH.

Sex ratio: not specified.

Mean age: not specified.

Duration of fatty liver diseases: not specified.

Diagnostic criteria: Group of Fatty Liver and Alcoholic Liver Diseases, Society of Heoatology, Chinese Medical Association. Guidelines for diagnosis and treatment of non-alcoholic fatty liver diseases. Chinese Hepatology 2006 (CMA 2006a).

Inclusion criteria: not described.

Exclusion criteria: people with fatty liver caused by chronic malnutrition or other factors; with viral hepatitis or with liver function decompensation; aged < 18 years or > 70 years; pregnant or lactating women; serious primary disease or diagnosis of personality or mental disorder; people with allergies.

Dropouts: all participants randomised were analysed.

ITT analysis: not done.

Sources of funding: not specified.

Interventions

Intervention: Qinggan Xiaozhi decoction, 150 mL, po, twice/day, plus GSH, 1.2 g with 250 mL 5% GLU, iv, once daily.

Control: GSH, 1.2 g, 250 mL 5% GLU, iv, once daily.

Post-treatment follow-up: none.

Both groups received the same lifestyle changes.

Treatment duration: 12 weeks.

OutcomesOutcome(s): symptoms, signs, BWI, L/S CT ratio, ALT, AST, GGT, HDL-C, TG, TC.
Notes 
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Low riskRandom number table was used.
Allocation concealment (selection bias)Unclear riskNo allocation concealment method was described.
Blinding (performance bias and detection bias)
All outcomes
Unclear riskNot described.
Incomplete outcome data (attrition bias)
All outcomes
Low riskNo withdrawals or dropouts were reported. All participants randomised were analysed.
Selective reporting (reporting bias)Low riskAll predefined outcomes in the methods section of the article were reported in the results section.
Other biasHigh riskSample size calculation was not reported.
Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskNot described.
Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskNot described.

Mi 2010

Methods

Trial design: randomised, parallel group trial.

Language: Chinese.

Type of publication: journal article.

Date of trial: November 2007 to May 2008.

Judgement of the quality of the trial: high risk of bias.

Participants

Number of study centres: 1.

Setting: Tianjin Infectious Disease Hospital; Tianjin Liver Disease Study Institute.

Origin of the participants: inpatients and outpatients.

Sample size calculation: not done.

Number of participants: 120. 60 received Jiangganjiangzhi, 60 received silibinin.

Sex ratio: 87 males (72.5%), 33 females (27.5%).

Mean age: 42.7 years (range 20-60 years) in the treatment group; 40.7 years (range 19-60 years) in the control group.

Duration of fatty liver diseases: 4.8 years (range 1-12 years) in the treatment group; 4.7 years (range 1-11 years) in the control group.

Diagnostic criteria: Group of Fatty Liver and Alcoholic Liver Diseases, Society of Heoatology, Chinese Medical Association. Guidelines for diagnosis and treatment of non-alcoholic fatty liver diseases. Chinese Hepatology 2006 (CMA 2006a).

Inclusion criteria: aged > 15 years, < 70 years.

Exclusion criteria: allergic constitution; severe cardiovascular, cerebral, or kidney disease.

Dropouts: all participants randomised were analysed.

ITT analysis: not done.

Sources of funding: not specified.

Interventions

Intervention: Jianganjiangzhi tablets, 2 tablets, po, 3 times/day.

Control: silibinin capsule, 4 granules, po, 3 times/day.

Post-treatment follow-up: none.

Both groups received the same lifestyle changes.

Treatment duration: 12 weeks.

OutcomesOutcome(s): symptoms, signs, BWI, B-ultrasonography, LDL-C, ALT, AST, γ-GGT, TG, FBG, cholesterol.
Notes 
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Low riskRandom number table was used.
Allocation concealment (selection bias)Unclear riskNo allocation concealment method was described.
Blinding (performance bias and detection bias)
All outcomes
Unclear riskNot described.
Incomplete outcome data (attrition bias)
All outcomes
Low riskNo withdrawals or dropouts were reported. All participants randomised were analysed.
Selective reporting (reporting bias)Low riskAll predefined outcomes in the methods section of the article were reported in the results section.
Other biasHigh riskSample size calculation was not reported.
Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskNot described.
Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskNot described.

Pu 2009

Methods

Trial design: randomised, parallel group trial.

Language: Chinese.

Type of publication: journal article.

Date of trial: January 2006 to October 2008.

Judgement of the quality of the trial: high risk of bias.

Participants

Number of study centres: 1.

Setting: Jiangyin Chinese Medicine Hospital.

Origin of the participants: outpatients.

Sample size calculation: not done.

Number of participants: 100. 53 received modified Wendan, 47 received polyene phosphatidylcholine.

Sex ratio: 54 males (54%), 46 females (46%).

Mean age: 36.9 years (range 18-65 years) in the treatment group; 37.1 years (20-66 years) in the control group.

Duration of fatty liver diseases: 7.12 years (range 0.2-10 years) in the treatment group; 7.1 years (range 0.5-10 years) in the control group.

Diagnostic criteria: Group of Fatty Liver and Alcoholic Liver Diseases, Society of Heoatology, Chinese Medical Association. Diagnosis of non-alcoholic fatty liver. Chinese Journal of Hepatology 2003 (CMA 2003a).

Inclusion criteria: not described.

Exclusion criteria: not described.

Dropouts: none.

ITT analysis: not done.

Sources of funding: not specified.

Interventions

Intervention: modified Wendan decoction, 1 dose decoction, twice/day.

Control: polyene phosphatidylcholine, 2 capsules, po, 3 times/day.

Post-treatment follow-up: none.

Both groups received the same lifestyle changes.

Treatment duration: 8 weeks.

OutcomesOutcome(s): symptoms, B-ultrasonography, AST, ALT.
Notes 
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Unclear riskNo information on random sequence generation.
Allocation concealment (selection bias)Unclear riskNo allocation concealment method was described.
Blinding (performance bias and detection bias)
All outcomes
Unclear riskNot described.
Incomplete outcome data (attrition bias)
All outcomes
Low riskNo withdrawals or dropouts were reported. All participants randomised were analysed.
Selective reporting (reporting bias)High riskPrespecified outcome B-ultrasound in the methods section of the article were not reported in the results section.
Other biasHigh riskSample size calculation was not reported.
Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskNot described.
Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskNot described.

Song 2006

Methods

Trial design: randomised, parallel group trial.

Language: Chinese.

Type of publication: journal article.

Date of trial: not specified.

Judgement of the quality of the trial: high risk of bias.

Participants

Number of study centres: 1.

Setting: Kunming Third People's Hospital.

Origin of the participants: inpatients and outpatients.

Sample size calculation: not done.

Number of participants: 73. 42 received diammonium glycyrrihizinate with Panax Notoginseng, 31 received tiopronin.

Sex ratio: 54 males (74%), 19 females (26%).

Mean age: 34.5 years (range 21-58 years) in the treatment group; 36 years (range 19-60 years) in the control group.

Duration of fatty liver diseases: not specified.

Diagnostic criteria: Group of Fatty Liver and Alcoholic Liver Diseases, Society of Heoatology, Chinese Medical Association. Diagnosis of non-alcoholic fatty liver. Chinese Journal of Hepatology 2003 (CMA 2003a).

Inclusion criteria: not described.

Exclusion criteria: not described.

Dropouts: none.

ITT analysis: not done.

Sources of funding: not specified.

Interventions

Intervention: diammonium glycyrrihizinate capsules, 150 mg, po, 3 times/day and Panax Notoginseng powder, 5 g, po, twice/day.

Control: tiopronin, 0.2 g, po, 3 times/day.

Post-treatment follow-up: none.

Both groups received the same lifestyle changes.

Treatment duration: 8 weeks.

OutcomesOutcome(s): symptoms, B-ultrasonography, AST, ALT, TC, TG.
Notes 
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Unclear riskNo information on random sequence generation.
Allocation concealment (selection bias)Unclear riskNo allocation concealment method was described.
Blinding (performance bias and detection bias)
All outcomes
Unclear riskNot described.
Incomplete outcome data (attrition bias)
All outcomes
Low riskNo withdrawals or dropouts were reported. All participants randomised were analysed.
Selective reporting (reporting bias)Low riskAll predefined outcomes in the methods section of the article were reported in the results section.
Other biasHigh riskSample size calculation was not reported.
Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskNot described.
Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskNot described.

Wang 2006

Methods

Trial design: randomised, parallel group trial.

Language: Chinese.

Type of publication: journal article.

Date of trial: December 2003 to December 2005.

Judgement of the quality of the trial: high risk of bias.

Participants

Number of study centres: 1.

Setting: Dazhou Central Hospital.

Origin of the participants: outpatients.

Sample size calculation: not done.

Number of participants: 66. 36 received Chuige Jiugan plus tiopronin, 30 received tiopronin.

Sex ratio: all males.

Mean age: 40.25 years (range 25-56 years).

Duration of fatty liver diseases: 6.5 years (range 5-8 years).

Diagnostic criteria: Chinese Society of Hepatology, Diagnosis of alcoholic fatty liver, 2002. Diagnostic source was not given and we could not find the article on these diagnostic criteria.

Inclusion criteria: not described.

Exclusion criteria: liver failure diseases such as viral hepatitis, drug-induced hepatitis, metabolic liver diseases, merged hepatic encephalopathy, or hepatorenal syndrome.

Dropouts: none.

ITT analysis: not done.

Sources of funding: not specified.

Interventions

Intervention: Chuige Jiugan decoction, 1 dose plus tiopronin, 0.2 g, po, 3 times/day.

Control: tiopronin, 0.2 g, po, 3 times/day.

Post-treatment follow-up: none.

Both groups received the same conventional treatment and lifestyle changes.

Treatment duration: 8 weeks.

OutcomesOutcome(s): symptoms, B-ultrasonography, AST, ALT, GGT.
Notes 
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Unclear riskNo information on random sequence generation.
Allocation concealment (selection bias)Unclear riskNo allocation concealment method was described.
Blinding (performance bias and detection bias)
All outcomes
Unclear riskNot described.
Incomplete outcome data (attrition bias)
All outcomes
Low riskNo withdrawals or dropouts were reported. All participants randomised were analysed.
Selective reporting (reporting bias)Low riskAll predefined outcomes in the methods section of the article were reported in the results section.
Other biasHigh riskSample size calculation was not reported.
Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskNot described.
Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskNot described.

Wang 2008a

Methods

Trial design: randomised, parallel group trial.

Language: Chinese.

Type of publication: journal article.

Date of trial: June 2002 to August 2006.

Judgement of the quality of the trial: high risk of bias.

Participants

Number of study centres: 1.

Setting: Mentou Gou Chinese Medicine Hospital.

Origin of the participants: outpatients.

Sample size calculation: not done.

Number of participants: 98. 64 received Sisheng Jiangzhi, 34 received simvastatin.

Sex ratio: 54 males (55.1%), 44 females (44.9%).

Mean age: 48.63 years (range 34-67 years) in the treatment group; 53.06 years (range 38-69 years) in the control group.

Duration of fatty liver diseases: 2.83 years (range 0.5-5 years) in the treatment group; 2.35 years (range 0.3-4.5 years) in the control group.

Diagnostic criteria: Group of Fatty Liver and Alcoholic Liver Diseases, Society of Hepatology, Chinese Medical Association. Diagnostic standard of non-alcoholic fatty liver. Chinese Journal of Hepatology 2003 (CMA 2003c).

Inclusion criteria: not described.

Exclusion criteria: not described.

Dropouts: not specified.

ITT analysis: not done.

Sources of funding: not specified.

Interventions

Intervention: Sisheng Jiangzhi formula, 1 dose, 150 mL, po, twice/day.

Control: simvastatin, 20 mg, po, twice/day.

Post-treatment follow-up: none.

Treatment duration: 12 weeks.

OutcomesOutcome(s): symptoms, B-ultrasonography, HDL-C, LDL-C, ALT, AST, γ-GGT, TG, TC, kidney function tests.
Notes 
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Low riskRandom number table was used.
Allocation concealment (selection bias)Unclear riskNot described.
Blinding (performance bias and detection bias)
All outcomes
Unclear riskNot described.
Incomplete outcome data (attrition bias)
All outcomes
Unclear riskWe could not judge whether subjects withdrew or were lost to follow-up.
Selective reporting (reporting bias)Low riskAll predefined outcomes in the methods section of the article were reported in the results section.
Other biasHigh riskSample size calculation was not reported.
Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskNot described.
Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskNot described.

Wang 2008b

Methods

Trial design: randomised, parallel group trial.

Language: Chinese.

Type of publication: journal article.

Date of trial: April 2005 to June 2007.

Judgement of the quality of the trial: high risk of bias.

Participants

Number of study centres: 2.

Setting: Shanghai First People's Hospital; Shanghai TCM-Integrated Hospital.

Origin of the participants: inpatients and outpatients.

Sample size calculation: not done.

Number of participants: 120. 63 received modified Jiangzhiligan, 57 received lifestyle intervention.

Sex ratio: 64 males (53.3%), 56 females (46.7%).

Mean age: 52.88 years in the treatment group; 53.14 years in the control group.

Duration of fatty liver diseases: 3.43 years in the treatment group; 3.65 years in the control group.

Diagnostic criteria: Group of Fatty Liver and Alcoholic Liver Diseases, Society of Heoatology, Chinese Medical Association. Diagnosis of non-alcoholic fatty liver. Chinese Journal of Hepatology 2003 (CMA 2003a).

Inclusion criteria: people who matched the diagnostic standard of NAFLD; aged 18-75 years; understood and granted consent to the scenario; using GCP.

Exclusion criteria: pregnant or lactating women; allergic to this medicine combined with serious primary disease, diagnosis of personality or mental disorder, or malignant tumour; none compliance of medication.

Dropouts: all participants randomised were analysed.

ITT analysis: not done.

Sources of funding: not specified.

Interventions

Intervention: modified Jiangzhiligan decoction, 1 dose, decocted in water and 2 potions every day.

Control: lifestyle intervention.

Post-treatment follow-up: none.

Both groups received the same lifestyle changes.

Treatment duration: 12 weeks.

OutcomesOutcome(s): symptoms, signs, BWI, B-ultrasonography, ALT, AST, r-GT, TG, TC.
Notes 
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Low riskRandom number table was used.
Allocation concealment (selection bias)Unclear riskNot described.
Blinding (performance bias and detection bias)
All outcomes
Unclear riskNot described.
Incomplete outcome data (attrition bias)
All outcomes
Low riskNo withdrawals or dropouts were reported. All participants randomised were analysed.
Selective reporting (reporting bias)Low riskAll predefined outcomes in the methods section of the article were reported in the results section.
Other biasHigh riskSample size calculation was not reported.
Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskNot described.
Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskNot described.

Wang 2010

Methods

Trial design: randomised, parallel group trial.

Language: Chinese.

Type of publication: journal article.

Date of trial: March 2007 to March 2009.

Judgement of the quality of the trial: high risk of bias.

Participants

Number of study centres: 1.

Setting: Xinjiang Uygur Autonomous Region People's Hospital.

Origin of the participants: inpatients.

Sample size calculation: not done.

Number of participants: 108. 54 received Chaihu Shugan, 54 received fenofibrate.

Sex ratio: 56 males (51.9%), 52 females (48.1%).

Mean age: 40 years (range 26-62 years) in the treatment group; 40 years (range 29-65 years) in the control group.

Duration of fatty liver diseases: 3.2 years (range 0.5-5.4 years) in the treatment group; 3.1 years (range 0.4-5.6 years) in the control group.

Diagnostic criteria: Haozhu Chen. Practice of Internal Medicine. People's Medical Publishing House 1997 (Chen 1997).

Inclusion criteria: not described.

Exclusion criteria: age < 18 years or > 65 years; pregnancy and lactating women; severe liver diseases, viral hepatitis, schistosomiasis hepatitis, alcoholic hepatitis or other genetic and metabolic liver diseases; people with cancer or mental disorders; people that did not co-operate with the doctor or took similar drugs in previous 3 months.

Dropouts: not specified.

ITT analysis: not done.

Sources of funding: not specified.

Interventions

Intervention: Chaihu Shugan powder, 1 dose 300 mL decoction, twice/day.

Control: fenofibrate sustained release capsules, 250 mg, po, once daily.

Post-treatment follow-up: none.

Both groups received the same lifestyle changes.

Treatment duration: 3 months.

OutcomesOutcome(s): symptoms, B-ultrasonography, HDL-C, LDL-C, TG, TC.
Notes 
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Unclear riskNo information on random sequence generation.
Allocation concealment (selection bias)Unclear riskNo allocation concealment method was described.
Blinding (performance bias and detection bias)
All outcomes
Unclear riskNot described.
Incomplete outcome data (attrition bias)
All outcomes
Low riskNo withdrawals or dropouts were reported. All participants randomised were analysed.
Selective reporting (reporting bias)Low riskAll predefined outcomes in the methods section of the article were reported in the results section.
Other biasHigh riskSample size calculation was not reported.
Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskNot described.
Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskNot described.

Wang 2011a

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Methods

Trial design: randomised, parallel group trial.

Language: Chinese.

Type of publication: journal article.

Date of trial: July 2006 to July 2008.

Judgement of the quality of the trial: high risk of bias.

Participants

Number of study centres: not specified.

Setting: not specified.

Origin of the participants: not specified.

Sample size calculation: not done.

Number of participants: 112. 56 received Tiaoganlizhong plus Qingbai, 56 received Shuifeijibinjiaan plus fufanggancaosuangan plus vitamin C plus vitamin B.

Sex ratio: all male.

Mean age: 35 years (range 35-70 years).

Duration of fatty liver diseases: 5.1 years (range 1-9.1 years).

Diagnostic criteria: Group of Fatty Liver and Alcoholic Liver Diseases, Society of Hepatology, Chinese Medical Association. Diagnostic standard of alcoholic fatty liver diseases. Diagnostic source was given incorrectly and we could not find the correct article for these diagnostic criteria.

Inclusion criteria: not described.

Exclusion criteria: not described.

Dropouts: not specified.

ITT analysis: not done.

Sources of funding: Shandong Province.

Interventions

Intervention: Tiaoganlizhong decoction 1 dose, po, 3 times/day; Qingbai powder 2 tablets, po, twice/day or 3 times/day.

Control: Shuifeijibinpujiaan tablets, 100 mg plus fufanggancaosuangan tablets, 50 mg plus vitamin C, 200 mg plus vitamin B, 2 tablets, po, 3 times/day.

Post-treatment follow-up: none.

Both groups received the same conventional treatment of lifestyle changes.

Treatment duration: 8 weeks.

OutcomesOutcome(s): symptoms, signs, ALT, AST, γ-GT, TBIL.
Notes 
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)