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Drugs improving insulin resistance for non-alcoholic fatty liver disease and/or non-alcoholic steatohepatitis

  • Review
  • Intervention

Authors

  • Francesco Angelico,

    Corresponding author
    1. IV Divisione di Clinica Medica - Policlinico Umberto 1, Dipartimento di Medicina Sperimentale e Patologia, Rome, Italy
    • Francesco Angelico, Dipartimento di Medicina Sperimentale e Patologia, IV Divisione di Clinica Medica - Policlinico Umberto 1, Centro per l'Atero-trombosi, Università La Sapienza, viale del Policlinico 155, Rome, 00161, Italy. francesco.angelico@uniroma1.it.

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  • Marco Burattin,

    1. University La Sapienza, Rome, Italy, Department of Clinics and Applied Medical Therapy, Rome, Italy
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  • Cesare Alessandri,

    1. University La Sapienza, Rome, Italy, Experimental Medicine and Pathology, Rome, Italy
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  • Maria Del Ben,

    1. University La Sapienza, Rome, Italy, Experimental Medicine and Pathology, Rome, Italy
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  • Flavio Lirussi

    1. WHO Regional Office for Europe, European Office for Investment for Health and Development, Scientist, Socioeconomic Determinants of NCDs, Venice, Italy
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Abstract

Background

Non-alcoholic fatty liver disease (NAFLD) is characterized by fat accumulation in the liver, which may progress to non-alcoholic steatohepatitis (NASH) and cirrhosis. It is suspected in persons with elevated aminotransferase levels and features of insulin resistance (or metabolic) syndrome. The pathogenesis of NAFLD is not clear and there is no universal treatment.

Objectives

To assess beneficial and harmful effects of drugs improving insulin resistance for NAFLD and/or NASH.

Search methods

We searched The Cochrane Hepato-Biliary Group Controlled Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, MEDLINE, EMBASE, Science Citation Index Expanded, and The Chinese Biomedical Database until February 2006.

Selection criteria

We included randomised clinical trials assessing the effects of drugs improving insulin resistance for patients with NAFLD or NASH.

Data collection and analysis

We evaluated the methodological quality of the randomised clinical trials by the generation of the allocation section, allocation concealment, and follow-up. Two independent observers extracted data from each trial. Dichotomous outcomes were reported as odds ratio (OR) with 95% confidence interval (CI).

Main results

Only three randomised clinical trials could be included. Two of the trials had unclear allocation concealment. None was blinded regarding outcome assessment. In two trials, metformin was associated with significantly higher normalization of serum alanine aminotransferase (OR fixed 2.83, 95% CI 1.27 to 6.31 versus diet and OR fixed 7.75, 95% CI 2.37 to 25.35 versus vitamin E) and improvement of liver echographic response (OR fixed 5.25, 95% CI 1.09 to 25.21). An improvement of fatty infiltration was observed in a limited number of patients undergoing liver biopsy. In the single pioglitazone trial, a statistically significant improvement of NASH histology was demonstrated.

Authors' conclusions

At present, there is insufficient data to either support or refute the use of drugs improving insulin resistance for patients with NAFLD, although current limited information suggests a favourable role of drugs improving insulin resistance. It is advisable to carry out large randomised trials on this topic employing clinically relevant outcome measures and adequate methodology, including blinded outcome assessment.

摘要

背景

改善非酒精性脂肪肝疾病及或非酒精性脂肪肝炎胰島素抗性的藥物.

“非酒精性脂肪肝疾病”(NAFLD)其特徵在於脂肪堆積於肝臟,甚至可能導致非酒精性脂肪肝炎及肝硬化。若病人有肝功能異常合併胰島素抗性(或代謝症候群)時,應懷疑此病。“非酒精性脂肪肝疾病”的病理機轉目前不明,也沒有一致的治療。

目標

評估藥物改善“非酒精性脂肪肝疾病”或非酒精性脂肪肝炎胰島素抗性的利弊.

搜尋策略

搜尋2006年2月前的Cochrane HepatoBiliary Group Controlled Trials Register, the Cochrane Central Register of Controlled Trials(CENTRAL) in The Cochrane Library, MEDLINE, EMBASE, Science Citation Index Expanded,以及The Chinese Biomedical Database。

選擇標準

我們收納評估藥物改善“非酒精性脂肪肝疾病”或非酒精性脂肪肝炎患者胰島素抗性的胰島素抗性效果的隨機臨床試驗。

資料收集與分析

我們以分派序列方法、分配隱匿性及追蹤來評量隨機臨床試驗研究方法的品質。兩位獨立的觀察者從每個臨床試驗擷取數據。二分結果以勝算比(OR)與95% 信賴區間(CI)呈現。

主要結論

只有三個隨機臨床試驗被納入。其中兩個的分配隱匿性不明確。對結果評估方面,沒有試驗採用盲法。有兩個試驗顯示metformin對於血清谷丙轉氨? 有顯著較高正常化(與飲食控制比較勝算比2.83,其95%信賴區間1.27至6.31;另與維他命E比, 勝算比7.75,其95%信賴區間2.37至25.35),以及有助於肝臟超音波表現改善(勝算比5.25,其95%信賴區間1.09至25.21)。在有限採樣的病人身上,可觀察到肝臟切片下脂肪浸潤的改善。在單一pioglitazone臨床試驗上,顯示組織學統計學上有意義地改善“非酒精性脂肪肝疾病”。

作者結論

目前為止,沒有足夠的數據支持或反對使用藥物治療非酒精性脂肪肝疾病/肝炎胰島素抗性的病人。即使目前有限的資訊顯現藥物有正向的角色。建議針對這個議題以臨床相關的測量結果方法及適當的方法研究(包括盲法的評量) 進行大規模的隨機臨床試驗。

翻譯人

本摘要由臺中榮民總醫院張崇信翻譯。

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

總結

目前無證據支持或反對以嘗試以藥物影響“非酒精性脂肪肝疾病”或“非酒精性脂肪肝炎”患者的胰島素抗性。“非酒精性脂肪肝疾病”及“非酒精性脂肪肝炎”臨床病理的特徵為病人無過量酒精攝取卻脂肪堆積於肝細胞。肝臟的損傷或許可藉由藥物改善胰島素抗性而改善。本系統性回顧納入三個隨機臨床試驗。metformin和pioglitazone不會導致任何肝臟相關或非相關的死亡,並且只有些微非特異性的副作用。以metformin治療後,和安慰劑組相比, 血清谷丙轉氨?有明顯的改善。放射影像學或組織學的數據未足以下定論。未來仍需對照控制試驗進一步確認。

Plain language summary

No evidence to support or refute drugs trying to influence insulin resistance in patients with non-alcoholic fatty liver disease and/or steatohepatitis

Non-alcoholic fatty liver disease and steatohepatitis are clinical-pathological conditions characterised by fatty deposition in the hepatocytes without excessive alcohol intake. Hepatic injury might be ameliorated by drugs improving insulin resistance. This systematic review identified three randomised clinical trials. Metformin and pioglitazone did not cause any liver-related or unrelated deaths, and were associated with only minor, non-specific adverse events. Treatment with metformin showed a significant amelioration of serum aminotransferase as compared with placebo. Data on radiological and/or histological response were too limited to draw any conclusions. Further placebo-controlled trials are necessary.

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