Epidemiology and natural history of primary sclerosing cholangitis

Primary sclerosing cholangitis (PSC) is defined as a disease of the medium and large bile ducts in which inflammation leads to segmental, concentric fibrosis with dilation of the more proximal portion of the bile duct. The diagnosis is typically made in the setting of inflammatory bowel disease with a cholangiogram demonstrating the classic beading of intrahepatic and/or extrahepatic ducts. PSC has been best studied in Northern European populations, most notably in Scandinavia where the prevalence appears to be the highest. Although estimates of the incidence of PSC have been increasing over time, it remains unclear if this is a true increase in incidence or a result of increased awareness and imaging leading to an increase in diagnosis. The natural history of PSC is extremely variable but frequently is one of the progressive fibrosis leading to biliary cirrhosis and ultimately liver failure or liver transplantation. Complicating the natural history are risks for cholangiocarcinoma, gallbladder cancer, and colon cancer as well as bacterial cholangitis and hepatic osteodystrophy. Several subgroups of PSC have been identified, and in whom the natural history of the disease varies. Understanding the natural history of PSC and the development of surrogate markers for clinically meaningful outcomes is critical to the evaluation of therapies in clinical trials.