Challenges and opportunities in drug and biomarker development for nonalcoholic steatohepatitis: findings and recommendations from an American Association for the Study of Liver Diseases-U.S. Food and Drug Administration Joint Workshop.

Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease (CLD) in North America. It is a growing contributor to the burden of CDL requiring liver transplantation. Cirrhosis is also associated with an increased risk of hepatocellular cancer, which may occur even in the absence of cirrhosis in subjects with nonalcoholic steatohepatitis (NASH), the histological form of NAFLD associated with increased liver-related mortality. The diagnosis of NASH currently requires a liver biopsy. There are also no U.S. Food and Drug Administration (FDA)-approved therapies for NASH. Therefore, there is a need to develop better diagnostic and therapeutic strategies for patients with NASH, targeting both those with early-stage disease as well as those with advanced liver fibrosis. There are unique challenges in the design of studies for these target populations. The long relatively asymptomatic time interval in the progression of NAFLD and NASH to cirrhosis and ultimately liver failure, along with gaps in knowledge regarding disease modifiers, combine to present significant challenges in trial design. Therefore, there is an urgent need to develop methods to identify the populations at particular risk of disease progression and validate endpoints that reflect meaningful changes in health status in this population. This article summarizes the discussion at a joint workshop held September 5 and 6, 2013 in Silver Spring, Maryland, sponsored by the FDA and the American Association for the Study of Liver Diseases to develop guidance on diagnostic and therapeutic modalities for NASH.