title: Chronic cholestatic liver diseases: clues from histopathology for pathogenesis.
abstract: Chronic cholestatic liver diseases include fibrosing cholangiopathies such as primary biliary cirrhosis or primary sclerosing cholangitis. These and related cholangiopathies clearly display pathologies associated with (auto)immunologic processes. As the cholangiocyte's apical membrane is exposed to the toxic actions of the bile fluid, the interaction of bile with cholangiocytes and the biliary tree in general must be considered to completely understand the pathogenesis of cholangiopathies. While the molecular processes involved in the hepatocellular formation of bile are well understood in both normal and pathophysiologic conditions, those in the bile ducts of normal liver and in livers with cholangiopathies lag behind. This survey highlights key mechanisms known to date that are important for the formation of bile by hepatocytes and its modification by the biliary tree. It also delineates the clinical pathophysiologic findings for cholangiopathies and puts them in perspective with current experimental models to reveal the pathogenesis of cholangiopathies and develop novel therapeutic approaches.
authors.affiliation: Division of Gastroenterology and Hepatology, Laboratory of Experimental and Molecular Hepatology, Department of Internal Medicine, Medical University of Graz, Austria; Institute of Pathology, Medical University of Graz, Austria.
authors.forename: Marion J
authors.initials: MJ
authors.lastname: Pollheimer
authors.affiliation: Division of Gastroenterology and Hepatology, Laboratory of Experimental and Molecular Hepatology, Department of Internal Medicine, Medical University of Graz, Austria; Institute of Pathology, Medical University of Graz, Austria. Electronic address: peter.fickert@medunigraz.at.
authors.forename: Peter
authors.initials: P
authors.lastname: Fickert
authors.affiliation: Department of Clinical Pharmacology and Toxicology, University Hospital Zurich, Zurich, Switzerland. Electronic address: bstieger@kpt.uzh.ch.
authors.forename: Bruno
authors.initials: B
authors.lastname: Stieger
mesh_terms: D001652:Bile Ducts / Q000473:pathology; D015209:Cholangitis, Sclerosing / Q000473:pathology* / Q000628:therapy; D002779:Cholestasis / Q000473:pathology* / Q000628:therapy; D002908:Chronic Disease; D006801:Humans; D008099:Liver / Q000473:pathology; D008105:Liver Cirrhosis, Biliary / Q000473:pathology*
keywords: Animal models; Cholangiopathies; Cholestasis; Liver fibrosis; Primary biliary cirrhosis; Primary sclerosing cholangitis