Antioxidant supplements for non-alcoholic fatty liver disease and/or steatohepatitis

  • Review
  • Intervention

Authors

  • Flavio Lirussi,

    Corresponding author
    1. WHO Regional Office for Europe, European Office for Investment for Health and Development, Scientist, Socioeconomic Determinants of NCDs, Venice, Italy
    • Flavio Lirussi, Scientist, Socioeconomic Determinants of NCDs, WHO Regional Office for Europe, European Office for Investment for Health and Development, Campo Santo Stefano, San Marco 2847, Venice, I-30124, Italy. fli@ihd.euro.who.int.

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  • Lorenzo Azzalini,

    1. Hospital de la Santa Creu i Sant Pau, Servei de Cardiologia, Barcelona, Spain
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  • Serena Orando,

    1. Universitá Degli Studi di Firenze, Instituto di Anestesia e Rianimazione, Firenze, Italy
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  • Rocco Orlando,

    1. University of Padua Medical School, Department of Medical and Surgical Sciences, Padova, Italy
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  • Francesco Angelico

    1. IV Divisione di Clinica Medica - Policlinico Umberto 1, Dipartimento di Medicina Sperimentale e Patologia, Rome, Italy
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Abstract

Background

Non-alcoholic fatty liver disease (NAFLD) is characterised by fatty deposition in the hepatocytes of patients with minimal or no alcohol intake and without other known cause. NAFLD includes a wide spectrum of histologic abnormalities ranging from hepatic steatosis to non-alcoholic steatohepatitis (NASH), or even cirrhosis. Antioxidant supplements, therefore, could potentially protect cellular structures against oxidative stress and the resulting lipid peroxidation.

Objectives

To systematically evaluate the beneficial and harmful effects of antioxidant supplements versus no intervention, placebo, or other interventions for patients with NAFLD or NASH.

Search methods

We searched The Cochrane Hepato-Biliary Group Controlled Trials Register (June 2006), the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library (Issue 2, 2006), MEDLINE (1966 to June 2006), EMBASE (1980 to June 2006), and The Chinese Biomedical Database (1978 to June 2006). No language restrictions were applied.

Selection criteria

Randomised clinical trials evaluating any antioxidant supplements versus no intervention, placebo, or other interventions in patients with NAFLD or NASH. Our inclusion criteria for NAFLD or NASH were based on history of minimal or no alcohol intake, imaging techniques showing hepatic steatosis, and/or histological evidence of hepatic damage (including simple steatosis, fatty infiltration plus nonspecific inflammation, steatohepatitis, fibrosis, and cirrhosis), and by exclusion of other causes of hepatic steatosis.

Data collection and analysis

We extracted data from the identified trials and contacted authors. We used a random-effects model and fixed-effect model with the significant level set at P = 0.05. We evaluated the methodological quality of the randomised trials by looking at how the generation of allocation sequence, allocation concealment, blinding, and follow-up were performed. We made our analyses following the intention-to-treat method by imputing missing data.

Main results

We identified six trials: two were regarded of high methodological quality and four of low methodological quality. None of the trials reported any deaths. Treatment with antioxidant supplements showed a significant, though not clinically relevant, amelioration of aspartate aminotransferase levels, but not of alanine aminotransferase levels, as compared to placebo or other interventions. Gamma-glutamyl-transpeptidase was decreased, albeit not significantly, in the treatment arm. Radiological and histological data were too limited to draw any definite conclusions on the effectiveness of these agents. Adverse events were non-specific and of no major clinical relevance.

Authors' conclusions

There is insufficient data to either support or refute the use of antioxidant supplements for patients with NAFLD. It may be advisable to carry out large prospective randomised clinical trials on this topic.

摘要

背景

抗氧化輔助劑對非酒精性脂肪肝疾病和/或肝炎的效果

非酒精性脂肪性肝病(NAFLD)的特點是脂肪沉積在肝細胞的患者很少或沒有飲酒,沒有其他已知的原因。 NAFLD包括的組織學異常範圍很廣,從脂肪肝、非酒精性肝炎(NASH)、甚至肝硬化。因此補充抗氧化輔助劑有可能保護細胞結構對抗氧化應力與因而產生的脂質過氧化。

目標

系統性評估抗氧化輔助劑與沒處置或與安慰劑或其他治療措施對NAFLD或NASH患者的利弊。

搜尋策略

作者檢索了Cochrane Controlled Trials Register肝膽病組(2006年6月)、the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library (2006 第2 期)、MEDLINE(1966年至2006年6月)、EMBASE(1980年至2006年6月)和Chinese Biomedical Database(1978年至2006 年6月)。沒有設語言限制。

選擇標準

評量對NAFLD或NASH患者任何抗氧化輔助劑與沒處置或與安慰劑或其他治療措施的隨機臨床試驗。NAFLD或NASH納入標準是病史:很少或沒有飲酒、影像檢查術顯示脂肪肝和/或肝組織學損害的證據(包括單純性脂肪肝、脂肪浸潤加上非特異性炎症、肝炎、肝纖維化和肝硬化),並排除其他原因的脂肪肝。

資料收集與分析

作者從已確定的試驗提取的數據和聯繫作者。我們使用了隨機效應模型和固定效應模型,顯著差異標準為P = 0.05。我們評估隨機試驗研究實驗設計品質判定由如何執行產生分配順序、分配隱藏、盲法、與追蹤。我們依循治療意向分析法分析丟失的數據。

主要結論

作者找到六個試驗:兩個被視為高品質試驗和四個低品質試驗。所有試驗沒有死亡報告。與安慰劑或其他治療措施相比,抗氧化輔助劑治療表現出顯著(但不是臨床有關地)改善aspartate aminotransferase值,而alanine aminotransferase則沒顯著變化。在治療組Gammaglutamyltranspeptidase下降,儘管沒有顯著。放射學檢查與組織學檢查數據有限致使難以確定這些藥物療效。不良反應為非特異性而且沒有重大的臨床意義。

作者結論

沒有足夠的數據來支持或反駁對NAFLD的患者使用抗氧化輔助劑。也許應該就這議題進行大規模的前瞻性隨機臨床試驗。

翻譯人

本摘要由臺中榮民總醫院何鴻鋆翻譯。

此翻譯計畫由臺灣國家衛生研究院(National Health Research Institutes, Taiwan)統籌。

總結

沒有證據支持或反對對非酒精性脂肪肝和/或肝炎患者使用抗氧化輔助劑。非酒精性脂肪肝特點是脂肪沉積在肝細胞中沒有過量飲酒和其他已知原因的脂肪肝。抗氧化輔助劑可能會改善肝的損傷。本系統性回顧確定納入六個隨機臨床試驗。其中沒有肝臟有關或無關的死亡發生。不良反應也是輕微和非特異性。與安慰劑或其他治療措施相比,抗氧化輔助劑治療表現出顯著(但不是臨床有關地)改善aspartate aminotransferase值,而alanine aminotransferase則沒顯著變化。放射學檢查與組織學檢查數據有限致使難以確定這些藥物療效。進一步的安慰劑對照試驗是必要的

Plain language summary

No evidence to support or refute antioxidant supplements for patients with non-alcoholic fatty liver disease and/or steatohepatitis

Non-alcoholic fatty liver disease is characterised by fatty deposition in the hepatocytes in the absence of excessive alcohol intake and of other known causes of fatty liver. Hepatic injury might be improved by antioxidant supplements. This systematic review identified six randomised clinical trials. No liver-related or unrelated deaths occurred in any of the included trials. Adverse events were minor and non-specific. Treatment with antioxidant supplements showed a significant, though not clinically relevant, amelioration of aspartate aminotransferase, but not of alanine aminotransferase, as compared to placebo or other interventions. Data on the radiological and/or histological response were too limited to draw any conclusions. Further placebo-controlled trials are necessary.