Will we ever model PSC? - "it's hard to be a PSC model!"

Abstract

Cholangiopathies such as primary sclerosing cholangitis (PSC) represent an important group of liver diseases of the intra- and extrahepatic bile ducts frequently causing end-stage liver disease with significant morbidity and mortality due to limited treatment options. The relatively low incidence of PSC and the difficult accessibility of the human bile duct system for longitudinal studies may represent some of the critical reasons for the lack of profound knowledge in regard to PSC pathophysiology. Therefore, there is an urgent need for reliable, well-defined and easily reproducible animal models to learn more about the pathophysiology of PSC and to test novel treatment modalities. In an ideal world, immunogenetically predisposed animals would develop fibrous-obliterative cholangitis of the intra- and extrahepatic bile ducts in association with inflammation of the gut (especially colitis) in a highly reproducible manner allowing to test new drugs. To date, however, no such animal model is available. We aimed to provide a systematic overview of current available rodent models for sclerosing cholangitis and biliary fibrosis and therefore critically analyzed the characteristics of models for chemically-induced cholangitis, knock-out mouse models with cholangitis, cholangitis induced by infectious agents, models of experimental biliary obstruction, models involving enteric bacterial cell-wall components or colitis, and models of primary biliary epithelial and endothelial cell injury.