Primary sclerosing cholangitis

Primary sclerosing cholangitis is the classic hepatobiliary manifestation of infl ammatory bowel disease and is generally chronic and progressive. Patients frequently present with asymptomatic, anicteric cholestasis, but many develop progressive biliary strictures with time, leading to recurrent cholangitis, biliary cirrhosis, and end-stage liver disease. Medical treatment does not slow the progression of disease, and many patients need liver transplantation, after which recurrent disease is a risk. The increased incidence of hepatobiliary cancer, which is not related to the underlying severity of biliary fi brosis, is of particular concern. Risk of colorectal cancer is also increased in patients with coexistent infl ammatory bowel disease. Mechanistic insights have arisen from studies of secondary sclerosing cholangitis, in which a similar clinical profi le is associated with a specifi c cause, and genomic studies have elucidated potential disease-initiating pathways in the primary form. The close association between infl ammatory bowel disease and primary sclerosing cholangitis underscores the need to further understand the role of environmental factors in generation of lymphocytes that are postulated to be retargeted, deleteriously, to the biliary tree. Treatment of primary sclerosing cholangitis is confi ned to supportive measures, but advances in pathobiology suggest that new stratifi ed approaches will soon be available.