Nonalcoholic Steatohepatitis (NASH) and Hepatic Fibrosis: Emerging Therapies

Annu Rev Pharmacol Toxicol. 2018 Jan 6;58:649-662. doi: 10.1146/annurev-pharmtox-010617-052545. Epub 2017 Oct 20.

Abstract

Nonalcoholic fatty liver disease remains a major cause of liver-related morbidity and mortality worldwide. It is a complex disease associated with obesity, diabetes, and dyslipidemia but is increasingly recognized in normal-weight individuals. Its progressive inflammatory phenotype, nonalcoholic steatohepatitis (NASH), currently has no effective treatment apart from lifestyle interventions. Multiple pathogenic pathways are involved in disease progression, and targets for intervention have been identified. These targets mediate glucose, lipid, and bile acid metabolism; inflammation; apoptosis; and fibrosis. Novel therapeutic agents are being developed in each of these pathways, and several have shown promise in early phase testing. Given the complexity of the disease, intervention trials are large and long and require histologic confirmation as a primary endpoint for disease improvement or regression. We highlight active Phase 2 and 3 therapeutic trials for NASH as this field rapidly expands in development.

Keywords: bile acids; fatty liver; fibrosis; nonalcoholic steatohepatitis.

Publication types

  • Review

MeSH terms

  • Animals
  • Clinical Trials, Phase II as Topic
  • Clinical Trials, Phase III as Topic
  • Humans
  • Liver / drug effects
  • Liver / pathology
  • Liver Cirrhosis / drug therapy*
  • Liver Cirrhosis / pathology*
  • Non-alcoholic Fatty Liver Disease / drug therapy*
  • Non-alcoholic Fatty Liver Disease / pathology*