Promising therapies for treatment of nonalcoholic steatohepatitis.

INTRODUCTION: Non-alcoholic fatty liver disease (NAFLD) has become the most common etiology for abnormal aminotransferase levels and chronic liver disease. Its growing prevalence is largely linked to the presence of metabolic syndrome, particularly diabetes and insulin resistance. It is estimated that 60-80% of the type 2 diabetic population has NAFLD. NAFLD encompasses a range of conditions ranging from simple steatosis to non-alcoholic steatohepatitis (NASH). A subset of patients with hepatic steatosis progress to NASH, while 15-20% of patients with NASH develop cirrhosis. This progression is thought to be multifactorial, and there are currently no FDA-approved medications for the treatment of NASH. AREAS COVERED: We review drugs currently in Phase II and III clinical trials for treatment of NAFLD and NASH, including their mechanisms of action, relationship to the pathophysiology of NASH, and rationale for their development. EXPERT OPINION: The treatment of NASH is complex and necessitates targeting a number of different pathways. Combination therapy, preferably tailored toward the disease stage and severity, will be needed to achieve maximum therapeutic effect. With multiple agents currently being developed, there may soon be an ability to effectively slow or even reverse the disease process in many NAFLD/NASH patients.