The Cholangiopathies

Cholangiocytes (ie, the epithelial cells that line the bile ducts) are an important subset of liver cells. They are actively involved in the modification of bile volume and composition, are activated by interactions with endogenous and exogenous stimuli (eg, microorganisms, drugs), and participate in liver injury and repair. The term cholangiopathies refers to a category of chronic liver diseases that share a central target: the cholangiocyte. The cholangiopathies account for substantial morbidity and mortality given their progressive nature, the challenges associated with clinical management, and the lack of effective medical therapies. Thus, cholangiopathies usually result in end-stage liver disease requiring liver transplant to extend survival. Approximately 16% of all liver transplants performed in the United States between 1988 and 2014 were for cholangiopathies. For all these reasons, cholangiopathies are an economic burden on patients, their families, and society. This review offers a concise summary of the biology of cholangiocytes and describes a conceptual framework for development of the cholangiopathies. We also present the recent progress made in understanding the pathogenesis of and how this knowledge has influenced therapies for the 6 common cholangiopathies-primary biliary cirrhosis, primary sclerosing cholangitis, cystic fibrosis involving the liver, biliary atresia, polycystic liver disease, and cholangiocarcinoma-because the latest scientific progress in the field concerns these conditions. We performed a search of the literature in PubMed for published papers using the following terms: cholangiocytes, biliary epithelia, cholestasis, cholangiopathy, and biliary disease. Studies had to be published in the past 5 years (from June 1, 2009, through May 31, 2014), and non-English studies were excluded.