Liver fibrosis

J Clin Invest. 2005 Feb;115(2):209-18. doi: 10.1172/JCI24282.

Abstract

Liver fibrosis is the excessive accumulation of extracellular matrix proteins including collagen that occurs in most types of chronic liver diseases. Advanced liver fibrosis results in cirrhosis, liver failure, and portal hypertension and often requires liver transplantation. Our knowledge of the cellular and molecular mechanisms of liver fibrosis has greatly advanced. Activated hepatic stellate cells, portal fibroblasts, and myofibroblasts of bone marrow origin have been identified as major collagen-producing cells in the injured liver. These cells are activated by fibrogenic cytokines such as TGF-beta1, angiotensin II, and leptin. Reversibility of advanced liver fibrosis in patients has been recently documented, which has stimulated researchers to develop antifibrotic drugs. Emerging antifibrotic therapies are aimed at inhibiting the accumulation of fibrogenic cells and/or preventing the deposition of extracellular matrix proteins. Although many therapeutic interventions are effective in experimental models of liver fibrosis, their efficacy and safety in humans is unknown. This review summarizes recent progress in the study of the pathogenesis and diagnosis of liver fibrosis and discusses current antifibrotic strategies.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Angiotensin II / metabolism
  • Animals
  • Humans
  • Hypertension, Portal / etiology
  • Hypertension, Portal / physiopathology
  • Leptin / metabolism
  • Liver Cirrhosis* / diagnosis
  • Liver Cirrhosis* / etiology
  • Liver Cirrhosis* / physiopathology
  • Liver Cirrhosis* / therapy
  • Liver Failure / etiology
  • Liver Failure / physiopathology
  • Transforming Growth Factor beta / metabolism

Substances

  • Leptin
  • Transforming Growth Factor beta
  • Angiotensin II