Emerging drugs for the treatment of hepatic fibrosis on nonalcoholic steatohepatitis

Abstract

Introduction: Approved drug therapies for nonalcoholic steatohepatitis (NASH) are lacking, for which various agents are currently being tested in clinical trials. Effective drugs for liver fibrosis, the factor most associated with prognosis in NASH, are important.

Areas covered: This study reviewed the treatment of NASH with a focus on the effects of existing drugs and new drugs on liver fibrosis.

Expert opinion: Considering the complex pathophysiology of fibrosis in NASH, drug therapy may target multiple pathways. The method of assessing fibrosis is important when considering treatment for liver fibrosis in NASH. The Food and Drug Administration considers an important fibrosis endpoint to be histological improvement in at least one fibrosis stage while preventing worsening of fatty hepatitis. To obtain approval as a drug for NASH, efficacy needs to be demonstrated on endpoints such as liver-related events and myocardial infarction. Among the current therapeutic agents for NASH, thiazolidinedione, sodium-glucose co-transporter 2, and selective peroxisome proliferator-activated receptors α modulator have been reported to be effective against fibrosis, although further evidence is required. The effects of pan-peroxisome proliferator-activated receptors, obeticholic acid, and fibroblast growth factor-21 analogs on liver fibrosis in the development stage therapeutics for NASH are of particular interest.

Keywords: Non-alcoholic fatty liver disease; fibroblast growth factor; non-alcoholic steatohepatitis; obeticholic acid; peroxisome proliferator-activated receptors.