Primary sclerosing cholangitis is a chronic liver disease of unknown cause characterized by patchy progressive inflammation of the biliary tree resulting in destruction and fibrosis. This liver disease can occur in children or adults. Disease progression, although variable, is almost universal in all patients, resulting in a loss of intrahepatic bile ducts leading to biliary cirrhosis and eventually liver failure. There is an increased risk of bile duct cancer, cholangiocarcinoma, in individuals with primary sclerosing cholangitis.
Previously considered rare, the prevalence of primary sclerosing cholangitis has increased as a result of screening patients with inflammatory bowel disease (IBD) for abnormal liver function tests. The close association between primary sclerosing cholangitis and inflammatory bowel disease has been well established. Fifty percent to 75% of patients with primary sclerosing cholangitis have inflammatory bowel disease, particularly ulcerative colitis. The course of the biliary disease is unrelated to the clinical course of the colitis.
There is increasing evidence that immune mechanisms play an essential role in the pathogenesis of primary sclerosing cholangitis. It has yet to be established whether the immune cascade is the cause or consequence of the bile duct injury. There are potential non-immune mechanisms that play a role in the pathogenesis of this liver disease. These include a toxic agent, possibly liberated by gut bacteria or ischemic injury. There have been many trials of pharmacological agents of which none have shown resolution in the effects of primary sclerosing cholangitis.