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.

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.

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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 strategy: 

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.

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