ABSTRACT
Primary sclerosing cholangitis is a generally progressive, sometimes fatal, chronic hepatobiliary disorder for which no effective medical or surgical therapy now exists. The syndrome occurs most frequently in young men and is characterized by chronic cholestasis, frequent association with CUC, a paucity of serologic markers, hepatic copper overload, and characteristic abnormalities in some liver biopsy specimens and in virtually all cholangiograms. The natural history of the syndrome is still somewhat unclear; the disease likely progresses slowly and relentlessly over a decade or longer from an asymptomatic stage to a condition characterized by symptoms of cholestasis and complicated by cirrhosis and portal hypertension and carcinoma of the bile ducts. Management should first involve a thoughtful decision to observe, which is reasonable in the symptomatic patient with early disease, or to intervene, particularly in patients with symptoms. Therapeutic goals should be defined and should concentrate on either alleviating symptoms, dealing with complications, or attempting to affect the underlying hepatobiliary disease. Symptomatic treatment and therapy for complications is similar to that employed in other chronic liver diseases, but also involves balloon dilatation of dominant strictures in appropriately selected symptomatic patients. Biliary tract reconstructive surgery may alleviate symptoms in selected patients with PSC, but its effect on the natural history of the syndrome has not been determined. Proctocolectomy for CUC in a patient with CUC and PSC does not beneficially affect the progression of the underlying hepatobiliary disease. In contrast, orthotopic liver transplantation may be life-saving for patients with advanced disease. Medical therapy directed at arresting the progression of the underlying hepatobiliary disease is currently experimental and includes cupruretic, immunosuppressive, antifibrogenic, and choleretic agents. Although a single recently completed controlled trial makes it unlikely that cupruretic agents will be helpful in this syndrome, immunosuppressive (i.e. cyclosporin A and methotrexate) and choleretic (i.e. ursodeoxycholic acid) agents alone or in combination are currently undergoing evaluation in randomized trials