Progress in promising anti-fibrotic therapies

Expert Rev Gastroenterol Hepatol. 2019 Dec;13(12):1145-1152. doi: 10.1080/17474124.2019.1688659. Epub 2019 Nov 30.


Introduction: Liver cirrhosis is the most deleterious consequence of chronic liver diseases of different etiologies. Progression of liver diseases to cirrhosis, irrespective of etiology, involves chronic parenchymal injury, persistent activation of inflammatory response, sustained activation of fibrogenesis and wound-healing response. Despite intensive research on antifibrotic drugs, novel therapeutics specifically for liver have not been yet licensed. This review will examine compounds currently under development and key challenges in specific settings as for example that of NAFLD associated fibrosis.Areas covered: Results of the main phase II and III trial, including those with negative results, are presented and discussed. The endpoints selected and their limitations highlighted in order to suggest potential options to move forward.Expert opinion: Strategies based on single-molecule targets, associated so far with some disappointing results, may be unlikely to succeed in the context of such complex pathogenesis. Blocking at the same time different pathways that drive fibrosis progression may be required to provide significant benefit.

Keywords: FXR; Fibrosis; NAFLD; apoptosis; chemokine; diabetes; insulin sensitizing drugs; lipotoxicity; nuclear receptors; steatohepatitis (NASH).

Publication types

  • Review

MeSH terms

  • Animals
  • Diffusion of Innovation
  • Drug Development / trends*
  • Drug Discovery / trends*
  • Humans
  • Liver / drug effects*
  • Liver / metabolism
  • Liver / pathology
  • Liver Cirrhosis / drug therapy*
  • Liver Cirrhosis / metabolism
  • Liver Cirrhosis / pathology
  • Molecular Targeted Therapy / trends*
  • Signal Transduction