Pioglitazone and Nonalcoholic Steatohepatitis

Abstract

Introduction: Nonalcoholic steatohepatitis is part of a spectrum of liver pathology ranging from simple steatosis to steatohepatitis, advanced fibrosis, and cirrhosis [1]. Nonalcoholic steatohepatitis is characterized by insulin resistance, accumulation of hepatic fat, and predominantly lobular necroinflammation with or without centrilobular fibrosis. This disorder is common. In one study involving obese patients with type 2 diabetes (T2DM), 50% had steatohepatitis and 19% had cirrhosis [2]. Once cirrhosis develops, 30% to 50% of patients die from liver-related causes during a 10-year period [3]. Because the association of obesity and T2DM increases the risk for the development of nonalcoholic steatohepatitis, weight loss remains the standard of care. Pharmacologic interventions including pentoxifylline, orlistat, vitamin E, ursodeoxycholic acid, and lipid-lowering agents have been attempted with variable success. Thiazolidinediones (TZDs), which are peroxisome proliferator-activated receptoragonists, and which improve insulin resistance, glucose, and lipid metabolism in patients with T2DM, have been suggested to reverse many of the abnormalities associated with nonalcoholic steatohepatitis [4].