Special reports and reviewsThe cholangiopathies: Disorders of biliary epithelia
Section snippets
Possible pathogenetic mechanisms in the cholangiopathies
The spectrum of cholangiopathies ranges from acquired conditions in which the cholangiocyte is damaged by disordered immunity (e.g., PBC, GVHD), infectious agents (e.g., cytomegalovirus, cryptosporidium), ischemia (e.g., posttransplant hepatic artery stenosis, chronic liver transplant rejection), and toxic compounds (e.g., drugs, toxins) to genetically transmitted or developmental diseases such as cystic fibrosis, Alagille’s syndrome, biliary atresia, and fibropolycystic diseases (Table 1).
Obstructive cholestasis and experimental bile duct ligation
Obstructive cholestasis is frequent in clinical practice, the etiology of obstruction ranging from common causes like bile duct stones to rare malformative diseases such as biliary atresia.68 A useful animal experimental model of obstructive cholestasis is common bile duct ligation (BDL).69 Major changes noted in cholangiocytes after BDL include (1) induction of an intense ductal proliferative response (i.e., increase of cholangiocyte mass in liver); (2) stimulation of ion secretory properties
Proposed pathogenetic pattern of cholangiopathies and future directions
In the last decade, we have witnessed substantial progress in understanding the cholangiocyte structure and function because of the development and implementation of novel experimental models. Also key to this progress was the now widely accepted concept that the cholangiocyte is a dynamic participant in normal liver function and not simply a component of passive conduits for delivery of hepatic bile to the intestine (Figures 1 and 2). Furthermore, we now appreciate the relevance of
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Supported by grants from the National Institutes of Health (DK24031, DK57993 to N.F.L.); by a Research Scholar Award from the Foundation for Digestive Health and Nutrition and by the Palumbo Foundation (to K.N.L.); by Telethon grant (E-873 to M.S.), MIUR grant (2003, 20033060498 001 to M.S.), and Fondazione San Martino-ONLUS (to M.S.); and by the Mayo Foundation.
Copyright: Mayo Foundation 2004–06–30