Therapeutic Approaches for Nonalcoholic Steatohepatitis ( NASH )

Abstract

Nonalcoholic fatty liver disease (NAFLD), the most prevalent liver disease worldwide, is the hepatic manifestation of metabolic syndrome, which often also includes obesity, type 2 diabetes, and dyslipidemia. While NAFLD was thought to be nonprogressive, it has been shown in several studies that 12–40% of NAFLD patients develop its progressive form nonalcoholic steatohepatitis (NASH), which is characterized by inflammatory changes that can lead to progressive liver damage, fibrosis, cirrhosis, and hepatocellular carcinoma. There are presently no approved pharmacological agents for the treatment of NAFLD and NASH, but numerous agents are currently being investigated in clinical trials. These innovative therapies include three main approaches: inhibiting or reducing hepatic fat accumulation; ameliorating oxidative stress, inflammation, and apoptosis; and improving hepatic fibrosis by inhibition of fibrogenesis or promoting fibrolysis. This article provides a brief introduction to the underlying disease features and describes the medicinal chemistry and current status of the main low‐molecular‐weight pharmacological agents currently in development for NASH.