Test your medicine knowledge with the MKSAP challenge, in partnership with the American College of Physicians.

A 28-year-old man is evaluated in follow-up for elevated liver chemistry test results, which were performed to assess a 3-month history of fatigue. He has no history of liver disease and has not had abdominal pain or fever. His medical history is significant for a 3-year history of diarrhea. Following a physical exam, lab results, and abdominal CT, what is the most appropriate next step in management?

On physical examination, vital signs are normal; BMI is 24. Spider angiomata and jaundice are absent. Abdominal examination reveals hepatomegaly but no splenomegaly or ascites.

Laboratory studies:

Aspartate aminotransferase	87 U/L
Alkaline phosphatase	456 U/L
Total bilirubin	1.2 mg/dL (20.5 µmol/L)
Direct bilirubin	0.4 mg/dL (6.8 µmol/L)

Abdominal CT shows a thickened extrahepatic bile duct but no intrahepatic biliary dilatation and no hepatic or pancreatic mass. Magnetic resonance cholangiopancreatography reveals changes consistent with primary sclerosing cholangitis.

Which of the following is the most appropriate next step in management?

A. Colonoscopy
B. Endoscopic retrograde cholangiopancreatography
C. Liver biopsy
D. Serum IgG4 measurement

MKSAP Answer and Critique

The correct answer is A: Colonoscopy.

The most appropriate next step in management is colonoscopy. Primary sclerosing cholangitis (PSC) is diagnosed by measuring liver enzymes and performing cholangiography. Serum alkaline phosphatase values are 3 to 10 times the upper limit of normal, and serum alanine aminotransferase and aspartate aminotransferase levels are two to three times the upper limit of normal. Serum total bilirubin levels may be normal in 60% of patients. Serum antinuclear and anti-smooth muscle antibodies are present in 20% to 50% of patients, but antimitochondrial antibodies are rarely found in PSC. The gold standard for diagnosis of PSC is cholangiography. Diagnostic findings consist of segmental bile duct fibrosis with saccular dilatation of normal intervening areas, resulting in the characteristic “beads on a string” appearance. Magnetic resonance cholangiopancreatography (MRCP) has been increasingly used and has an overall diagnostic accuracy rate of 90%. This patient’s clinical presentation and cholangiographic findings are consistent with PSC. Eighty percent of patients with PSC have ulcerative colitis. Given this patient’s 3-year history of diarrhea, colonoscopy should be performed to evaluate for ulcerative colitis. Patients with PSC and ulcerative colitis are at increased risk for colon cancer and should receive surveillance. There is no effective medical therapy for PSC. Endoscopic dilatation of biliary strictures and removal of stones may be necessary in patients with progressive cholestasis or symptoms of cholangitis. PSC is generally a progressive disease that often requires liver transplantation.

MRCP has already been performed; endoscopic retrograde cholangiopancreatography (ERCP) will not add any additional useful information to the clinical picture. ERCP will be useful in managing choledocholithiasis, occurring in 10% to 25% of symptomatic patients, and dilatation of dominant strictures, occurring in 5% to 10% of patients.

Liver biopsy is usually not necessary for the diagnosis of PSC. Liver biopsy is required for making a diagnosis of small-duct PSC when cholangiography is normal. Periductal fibrosis with inflammation, bile duct proliferation, and ductopenia are the main histologic findings.

IgG4-associated cholangitis may mimic PSC, but patients will usually have abnormalities in the pancreas on cross-sectional imaging. This patient did not have these findings, so serum IgG4 measurement is not required.

Key Point

• Eighty percent of patients with primary sclerosing cholangitis have ulcerative colitis.

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