Nonalcoholic steatohepatitis

Abstract

Nonalcoholic fatty liver disease (NAFLD) is an increasingly recognized condition whose symptoms and pathology resemble those of alcohol-induced liver injury. NAFLD includes fatty liver, steatohepatitis (NASH) with inflammatory changes and fibrosis, and cirrhosis. NAFLD is usually seen in association with obesity, diabetes, hypertension, and hypertriglyceridemia, as the hepatic component of a metabolic syndrome. Most NAFLD patients are asymptomatic and usually present with mild elevations in aminotransferases. The diagnosis should be established by liver biopsy. The natural history of this disease is not well defined, but progression to cirrhosis and hepatocellular carcinoma is well recognized in some patients. The pathogenesis is not well known but the accumulation of fat in the liver is probably related to insulin resistance, which leads to altered free fatty acid metabolism. The progression from NAFLD to NASH and cirrhosis is less clear but increasing evidence suggests that oxidative stress may enhance proinflammatory and profibrogenic cytokines and that this leads to mitochondrial dysfunction followed by development of inflammation, necrosis, and fibrosis. There is no established treatment for NASH, and current therapies are focused on correcting the insulin resistance or reducing oxidative stress. Although the results of some recent pilot studies are promising, prospective, randomized studies with clearly defined histological endpoints are needed.