Cutting Edge Issues in Primary Sclerosing Cholangitis |
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Authors: | Christopher L Bowlus |
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Institution: | (1) Division of Gastroenterology and Hepatology, University of California Davis Medical Center, 4150 V Street, PSSB 3500, Sacramento, CA 95817, USA |
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Abstract: | Primary sclerosing cholangitis (PSC) is a chronic inflammatory liver disease characterized by the destruction of medium- to
large-sized bile ducts and intense concentric fibrosis. Complications from PSC include bacterial cholangitis, cirrhosis, and
cholangiocarcinoma and a therapy that might alter the natural history of the disease remains lacking. Our understanding of
the pathogenesis of PSC also remains rudimentary but the strong association between PSC and inflammatory bowel disease suggest
causal links between the diseases. The male predominance in PSC, lack of a defined, pathogenic auto-antigen, and the potential
role of the innate immune system suggest that PSC may be due to dysregulation of immunity rather than a classic autoimmune
disease. However, PSC shares several genetic susceptibility loci with other autoimmune diseases including the human leukocyte
antigen DRB01*03 haplotype. The precise immune response of PSC is largely unknown but likely involves activation of the innate immune system
by bacterial components delivered to the liver via the portal vein. Induction of adhesion molecules and chemokines leads to
the recruitment of intestinal lymphocytes. Bile duct injury results from the sustained inflammation and production of inflammatory
cytokines. Biliary strictures may cause further damage as a result of bile stasis and recurrent secondary bacterial cholangitis.
Progress in our basic understanding of PSC is desperately needed in order to rationally design new therapeutic approaches
to this disease. |
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