Pathogenesis of cholestatic liver disease and therapeutic approaches

Gastroenterology. 2010 Nov;139(5):1481-96. doi: 10.1053/j.gastro.2010.09.004. Epub 2010 Sep 16.


Cholestatic liver disorders are caused by genetic defects, mechanical aberrations, toxins, or dysregulations in the immune system that damage the bile ducts and cause accumulation of bile and liver tissue damage. They have common clinical manifestations and pathogenic features that include the responses of cholangiocytes and hepatocytes to injury. We review the features of bile acid transport, tissue repair and regulation, apoptosis, vascular supply, immune regulation, and cholangiocytes that are associated with cholestatic liver disorders. We now have a greater understanding of the physiology of cholangiocytes at the cellular and molecular levels, as well as genetic factors, repair pathways, and autoimmunity mechanisms involved in the pathogenesis of disease. These discoveries will hopefully lead to new therapeutic approaches for patients with cholestatic liver disease.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Apoptosis
  • Bile / metabolism
  • Cholagogues and Choleretics / therapeutic use*
  • Cholestasis* / complications
  • Cholestasis* / drug therapy
  • Cholestasis* / metabolism
  • Cytokines / immunology
  • Cytokines / metabolism
  • Hepatocytes / metabolism
  • Hepatocytes / pathology
  • Humans
  • Immunity, Cellular*
  • Immunosuppressive Agents / therapeutic use*
  • Liver Cirrhosis, Biliary* / drug therapy
  • Liver Cirrhosis, Biliary* / etiology
  • Liver Cirrhosis, Biliary* / metabolism
  • Prognosis
  • Risk Factors
  • Ursodeoxycholic Acid / therapeutic use*


  • Cholagogues and Choleretics
  • Cytokines
  • Immunosuppressive Agents
  • Ursodeoxycholic Acid