TY - JOUR
T1 - Pathogenesis of cholestatic liver disease and therapeutic approaches
AU - Hirschfield, Gideon M.
AU - Heathcote, E. Jenny
AU - Gershwin, M. Eric
PY - 2010/11
Y1 - 2010/11
N2 - 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.
AB - 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.
KW - Cholestasis
KW - Primary Biliary Cirrhosis
KW - Primary Sclerosing Cholangitis
KW - Ursodeoxycholic Acid
UR - http://www.scopus.com/inward/record.url?scp=78049486376&partnerID=8YFLogxK
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U2 - 10.1053/j.gastro.2010.09.004
DO - 10.1053/j.gastro.2010.09.004
M3 - Article
C2 - 20849855
AN - SCOPUS:78049486376
VL - 139
SP - 1481
EP - 1496
JO - Gastroenterology
JF - Gastroenterology
SN - 0016-5085
IS - 5
ER -