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Semin Liver Dis 2006; 26(1): 003-021
DOI: 10.1055/s-2006-933559
Copyright © 2006 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA.

Etiopathogenesis of Primary Sclerosing Cholangitis

Christine A. O'Mahony1 , John M. Vierling2
  • 1Departments of Surgery, Baylor Liver Health, Baylor College of Medicine, Houston, Texas
  • 2Departments of Medicine, Baylor Liver Health, Baylor College of Medicine, Houston, Texas
Further Information

Publication History

Publication Date:
23 February 2006 (online)

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ABSTRACT

The etiopathogenesis of primary sclerosing cholangitis (PSC) remains undefined. Immunopathogenetic mechanisms appear to be involved, based on human leukocyte antigen complex susceptibility associations, existence of multiple autoantibodies, and presence of inflammatory bowel disease in > 75% of patients. PSC may represent an autoimmune disease with atypical features or an immune-mediated inflammatory disease, similar to inflammatory bowel disease itself. Immunogenetic susceptibility is closely linked to ligands for innate immune cells and capacity for sustained production of proinflammatory cytokines. Immunopathogenesis involves a multistep process initiated by the activation of cholangiocyte by bacterial pathogen-associated molecular patterns (stimuli of innate immunity) and proinflammatory cytokines in conjunction with aberrant expression of gut-specific chemokines and endothelial cell adhesion molecules in the liver. After recruitment of gut-primed memory T cells into the portal tracts and peribiliary space, additional mechanisms produce focal, fibrous, obliterative lesions. Progressive periductal fibrosis, chronic inflammation, and ischemic atrophy of biliary epithelia result in ductopenia, cholestasis, and obstructive strictures, culminating in secondary biliary cirrhosis.

KEYWORDS

Primary sclerosing cholangitis - biliary - biliary cirrhosis - etiology - pathogenesis - immunology - inflammatory bowel disease - colitis - ulcerative colitis - Crohn colitis

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John M VierlingM.D. FACP 

Professor of Medicine and Surgery Baylor College of Medicine

1709 Dryden, Suite 1500, Houston, TX 77030

Email: vierling@bcm.tmc.edu

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