Antifibrotic therapy in nonalcoholic steatohepatitis: time for a human-centric approach

Paul Brennan, Ahmed M. Elsharkawy, Timothy J. Kendall, Rohit Loomba, Derek A. Mann (Lead / Corresponding author), Jonathan A. Fallowfield (Lead / Corresponding author)

Research output: Contribution to journalArticlepeer-review

15 Citations (Scopus)
16 Downloads (Pure)

Abstract

Nonalcoholic steatohepatitis (NASH) might soon become the leading cause of end-stage liver disease and indication for liver transplantation worldwide. Fibrosis severity is the only histological predictor of liver-related morbidity and mortality in NASH identified to date. Moreover, fibrosis regression is associated with improved clinical outcomes. However, despite numerous clinical trials of plausible drug candidates, an approved antifibrotic therapy remains elusive. Increased understanding of NASH susceptibility and pathogenesis, emerging human multiomics profiling, integration of electronic health record data and modern pharmacology techniques hold enormous promise in delivering a paradigm shift in antifibrotic drug development in NASH. There is a strong rationale for drug combinations to boost efficacy, and precision medicine strategies targeting key genetic modifiers of NASH are emerging. In this Perspective, we discuss why antifibrotic effects observed in NASH pharmacotherapy trials have been underwhelming and outline potential approaches to improve the likelihood of future clinical success.

Original languageEnglish
Pages (from-to)679–688
Number of pages10
JournalNature Reviews Gastroenterology & Hepatology
Volume20
Early online date2 Jun 2023
DOIs
Publication statusPublished - Oct 2023

Keywords

  • Hepatic stellate cells
  • Liver fibrosis
  • Non-alcoholic fatty liver disease
  • Non-alcoholic steatohepatitis

ASJC Scopus subject areas

  • Gastroenterology
  • Hepatology

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