Clinical Features and Laboratory Findings in Primary Sclerosing Cholangitis

PSC can be silent for years, and when it does cause symptoms they tend to come and go. The clinical picture therefore ranges from a chance abnormality on blood tests to established cirrhosis.

Clinical features

Studies show that 65–70% of patients with PSC have concomitant IBD, and among those the split is roughly four to one between the two main types: about 80% have ulcerative colitis and about 20% have Crohn disease. Because the bowel disease may be diagnosed before, after or at the same time as the liver disease, either can be the presentation that leads to the other.

The first presentation is varied. At one end lies an asymptomatic patient in whom a blood test simply shows a raised alkaline phosphatase; at the other, a patient who already has cirrhosis, liver failure or hepatic encephalopathy. When symptoms are present at diagnosis, the most common are jaundice, pruritus, fatigue and abdominal pain. Fever, chills, night sweats, weight loss and sleep disturbances occur less often at the first diagnosis and are more typical of an episode of cholangitis.

Most patients describe intermittent symptoms: episodes of jaundice, pruritus, abdominal pain and fatigue separated by intervals in which they feel well. This intermittency fits the idea of episodic biliary obstruction — a stricture that blocks bile for a time and then settles.

Laboratory findings

The common laboratory findings follow from cholestasis and, in more advanced disease, from impaired liver function:

• A chronic rise in alkaline phosphatase, usually 3–5 fold above the upper limit of normal (ULN) — the biochemical hallmark of PSC. A normal alkaline phosphatase is possible in about 5% of cases, which are still confirmed by cholangiographic imaging and, in some, by histology.
• Raised ALT and AST, rarely more than 4–5 fold above the ULN, especially in children. A larger rise should raise the possibility of another diagnosis or an overlap with autoimmune hepatitis.
• A fluctuating serum bilirubin, which rises with obstruction or with advanced disease.
• A prolonged prothrombin time (PT), which can reflect vitamin K deficiency caused by cholestasis rather than only liver failure.
• Hypergammaglobulinemia in more than half of patients, mainly due to an increase in IgM.
• Increased serum cholesterol, copper and ceruloplasmin.

Autoantibodies are common in PSC, but none is specific for it. Their main value is in supporting the diagnosis and in flagging an overlap with autoimmune hepatitis; the pattern is not what makes the diagnosis.