Primary sclerosing cholangitis: Advances in diagnosis, etiopathogenesis and treatment

Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease most likely related to autoimmune damage of the biliary tree. PSC is frequently associated with inflammatory bowel disease, most commonly chronic ulcerative colitis, and the presence of the HLA DR3 haplotype is often found, which is frequently associated with autoimmune conditions. PSC usually begins insidiously with the finding of a cholestatic biochemical profile, which later progresses to symptoms of fatigue, pruritus, and in the end-stage, jaundice and complications of portal hypertension. The disease usually progresses over a period of 12–20 years. Histologic evolution of PSC results in irreversible damage to the bile ducts, which ultimately leads to cholestasis, fibrosis, cirrhosis, and premature death from liver failure unless liver transplantation is performed. The histologic finding of the presence of fibrous obliterative cholangitis is nearly pathognomonic of the disease in a patient with chronic ulcerative colitis. Long-term follow up of PSC patients reveals a high incidence of colon cancer in patients with chronic ulcerative colitis and a high incidence of cholangiocarcinoma, which increases with disease duration. Both of these complications seem to be related to the chronic inflammatory state involved in these two organs. A number of medical (including ursodeoxycholic acid therapy), endoscopic, and surgical therapies have been evaluated for the treatment of PSC. However, to date, no therapy achieves a complete clinical, biochemical, or histologic remission. Radiologic or endoscopic intervention is indicated for those patients who have increasing jaundice or in those who have recurrent bouts of cholangitis. However, until the etiopathogenesis of PSC is better defined, effective therapy is unlikely to be found. Thus, liver transplantation, in which excellent results have been achieved, continues to be an important therapeutic intervention for the management of patients with end-stage PSC.