Pathogenesis of cholestatic liver disease and therapeutic approaches

Gideon M. Hirschfield, E. Jenny Heathcote, M. Eric Gershwin

Research output: Contribution to journalArticle

149 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1481-1496
Number of pages16
JournalGastroenterology
Volume139
Issue number5
DOIs
StatePublished - Nov 2010

Keywords

  • Cholestasis
  • Primary Biliary Cirrhosis
  • Primary Sclerosing Cholangitis
  • Ursodeoxycholic Acid

ASJC Scopus subject areas

  • Gastroenterology

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