title: Pathogenesis of cholestatic liver disease and therapeutic approaches.
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.
authors.affiliation: Liver Centre, Toronto Western Hospital, Toronto, Ontario, Canada.
authors.forename: Gideon M
authors.initials: GM
authors.lastname: Hirschfield
authors.forename: E Jenny
authors.initials: EJ
authors.lastname: Heathcote
authors.forename: M Eric
authors.initials: ME
authors.lastname: Gershwin
mesh_terms: D000818:Animals; D017209:Apoptosis; D001646:Bile / Q000378:metabolism; D002756:Cholagogues and Choleretics / Q000627:therapeutic use*; D002779:Cholestasis / Q000150:complications / Q000188:drug therapy / Q000378:metabolism; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D022781:Hepatocytes / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007111:Immunity, Cellular; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D008105:Liver Cirrhosis, Biliary / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism; D011379:Prognosis; D012307:Risk Factors; D014580:Ursodeoxycholic Acid / Q000627:therapeutic use*
chemical_list: D002756:Cholagogues and Choleretics; D016207:Cytokines; D007166:Immunosuppressive Agents; D014580:Ursodeoxycholic Acid