Nonalcoholic fatty liver disease (NAFLD), the hepatic manifestation of metabolic syndrome, is the leading cause of liver disease worldwide. Nonalcoholic steatohepatitis (NASH) represents the progressive form of NAFLD, in which steatosis is accompanied by inflammation and fibrosis that can lead to cirrhosis. Despite the increasing prevalence of NASH and NASH cirrhosis, there are no Food and Drug Administration (FDA)–approved pharmacotherapies that reduce liver-related outcomes in patients with NASH. In liver disease, the progression of fibrosis to cirrhosis and the development of decompensation, including hepatic encephalopathy, variceal hemorrhage, and ascites, occur over decades and randomized clinical trials are not well-equipped to evaluate these outcomes. Thus, evaluation of potentially effective therapies to prevent liver-related events requires novel study designs.
Source: JAMA Online First