Chapter 52. Primary Sclerosing Cholangitis

• Progressive inflammatory, sclerosing, and obliterative disease of the extrahepatic or intrahepatic bile ducts, or both.
• Disproportionate elevation of serum alkaline phosphatase (4–10 times normal) is seen in almost all patients.
• MRCP or ERCP shows multifocal stricturing of the intrahepatic and extrahepatic bile ducts.
• Small duct disease is diagnosed by liver biopsy.
• Liver biopsy findings that are highly specific include fibrous obliteration of small bile ducts with concentric replacement by connective tissue in an "onion skin" pattern.
• Patients have an 8–15% lifetime risk of developing cholangiocarcinoma, and it is often difficult to distinguish a dominant stricture from a cholangiocarcinoma.

Primary sclerosing cholangitis (PSC) is a disorder of unknown etiology that is characterized by a progressive, inflammatory, sclerosing, and obliterative process affecting medium-sized and large extrahepatic or intrahepatic bile ducts, or both. A vast majority of patients (prevalence rates range from 70% to 90%) have underling inflammatory bowel disease, especially ulcerative colitis. PSC has also been associated (although rarely) with multifocal fibrosclerosis syndromes such as retroperitoneal, mediastinal, and periureteral fibrosis. In retrospect, it appears that some of these latter cases actually represented patients with autoimmune pancreatitis and bile duct strictures masquerading as PSC.

The median survival of patients with PSC from time of diagnosis to death in several series has ranged from 9 to 12 years. Late in the course of the disease, complete biliary obstruction, secondary biliary cirrhosis, portal hypertension with bleeding varices, liver failure, and development of cholangiocarcinoma may occur.

Symptoms and Signs

Patients with PSC are often asymptomatic at the time of diagnosis. The disorder is often suspected in patients with inflammatory bowel disease who have a persistent and otherwise unexplained abnormal elevation in serum alkaline phosphatase (ie, values at least two times the upper limit of normal), and with abnormal values persisting for longer than 6 months. Asymptomatic patients with persistent elevations of serum alkaline phosphatase are often screened for PSC, and many actually turn out to have the disease.

Symptomatic patients who have PSC often present with signs and symptoms of chronic biliary obstruction, right upper quadrant abdominal pain, pruritus, jaundice, and acute cholangitis. Fatigue and pruritus are common features at presentation.

Laboratory Findings

Liver tests usually demonstrate a cholestatic pattern, with serum alkaline phosphatase disproportionately elevated to levels 4–10 times normal and serum aminotransferase that is usually 300 IU/L or less. Serum albumin and globulin levels are usually normal except in patients with advanced disease. As noted later, in the discussion of differential diagnosis, the presence of positive tests for antinuclear antibodies or smooth muscle antibodies, or both, should raise the suspicion of PSC–autoimmune hepatitis (AIH) overlap syndrome.

Imaging Studies

The diagnosis of PSC is usually established by demonstration of the characteristic multifocal ...