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A Journal on Gastroenterology, Nutrition and Dietetics

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Minerva Gastroenterologica e Dietologica 2003 March;49(1):41-52

language: English

Intrahepatic bile duct loss in immune-mediated ductopenic biliary diseases with an emphasis on biliary epithelial apoptosis

Harada K., Nakanuma Y.


The biliary epithelial apoptosis is thought to be a major pathogenic process of bile duct loss in a number of immune-mediated ductopenic biliary diseases, though its exact mechanism and process seem still speculative. Clarification of pathologic microenvironments around the bile ducts as well as pathobiology of biliary epithelial cells undergoing apoptosis in these diseases are mandatory. Several steps and mechanisms during induction and progression of biliary epithelial apoptosis followed by bile duct loss are now being proposed in immune-mediated ductopenic biliary diseases: 1) the presentation of target antigens including autoantigen(s) in biliary epithelial cells; 2) network of cytokine and its imbalance around the damaged bile ducts; 3) migration of immune-competent cells into the biliary layer followed by cell-to-cell and cell-to-matrix interaction and antibody-mediated cell dysfunction of biliary epithelial cells; and 4) increased susceptibility and decreased threshold for biliary epithelial apoptosis and aggravation of biliary epithelial apoptosis by infectious agents. We review here the pathogenetic processes of immune-mediated ductopenic biliary diseases.

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