A Pilot Study Using Simvastatin in the Treatment of Nonalcoholic Steatohepatitis

GOALS: This study was designed to assess the utility of statin therapy in patients with biopsy proven nonalcoholic steatohepatitis (NASH) and hyperlipidemia. BACKGROUND: Nonalcoholic fatty liver disease, as the hepatic manifestation of the metabolic syndrome, has become a growing public health concern. Nonalcoholic steatohepatitis (NASH) represents a subset of nonalcoholic fatty liver disease manifested by hepatic fatty infiltration and inflammation which may progress to cirrhosis and its subsequent complications, to include hepatocellular carcinoma. As the metabolic syndrome is thought to be central in the pathogenesis of NASH, it has been speculated that medications that improve metabolic profiles may be beneficial in treatment. In fact, recent studies have demonstrated potential benefit of 3-hydroxy-3-methyglutaryl-coenzyme A (HMG-CoA) reductase inhibitors (statins), which are used in clinical practice to improve lipid panels. STUDY: This double-blinded randomized placebo-controlled trial compared the HMG-CoA reductase inhibitor, simvastatin, with placebo in the treatment of NASH over a 12-month period using serum aminotransferases and repeat liver biopsy to assess for improvement. RESULTS: Sixteen patients with biopsy proven NASH were enrolled: 14 completed the study and 10 underwent 1-year repeat liver biopsy. Mean age: 53 years (+/-10.1), mean body mass index: 32.4 (+/-6.1) with 11 male and 5 female patients. Although a 26% reduction in low-density lipoprotein was seen in the simvastatin group compared with placebo, there was no statistically significant improvement in serum aminotransferases, hepatic steatosis, necroinflammatory activity or stage of fibrosis within or between groups. CONCLUSIONS: In this pilot trial, monotherapy with simvastatin does not seem to be an effective treatment for NASH.