A physician-validated, board-style question from the Active Transport QBank. Try it, then check the reasoning for every option.
A 35-year-old man presents with yellow discoloration of his eyes and skin for the past week. He also says he has pain in the right upper quadrant for the past few days. He is fatigued constantly and has recently developed acute onset itching all over his body. The patient denies any allergies. Past medical history is significant for ulcerative colitis diagnosed 2 years ago, managed medically. He is vaccinated against hepatitis A and B and denies any recent travel abroad. There is scleral icterus present, and mild hepatosplenomegaly is noted. The remainder of the physical examination is unremarkable. Laboratory findings are significant for:
Total bilirubin 3.4 mg/dL
Prothrombin time 12 s
Aspartate transaminase (AST) 158 IU/L
Alanine transaminase (ALT) 1161 IU/L
Alkaline phosphatase 502 IU/L
Serum albumin 3.1 g/dL
Perinuclear antineutrophil cytoplasmic antibodies (p-ANCA) positive
Which of the following is the most likely diagnosis in this patient?
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A
Hepatitis EIncorrect. Hepatitis E causes acute hepatitis (predominantly elevated transaminases, not cholestasis); it does not produce p-ANCA positivity or the chronic UC association.
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B
Primary sclerosing cholangitisCorrect. PSC — a chronic fibroinflammatory disease of intra- and extrahepatic bile ducts — is strongly associated with ulcerative colitis, positive p-ANCA in ~70%, and a cholestatic lab pattern (elevated ALP, conjugated bilirubin, pruritus).
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C
Hepatitis AIncorrect. Hepatitis A causes acute self-limited hepatitis (the patient is vaccinated anyway), with elevated AST/ALT in the thousands and no chronicity or p-ANCA association.
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D
Primary biliary cirrhosisIncorrect. Primary biliary cirrhosis/cholangitis (PBC) affects middle-aged WOMEN and is characterized by positive anti-mitochondrial antibodies (AMA) — not p-ANCA — and is not strongly associated with UC.
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E
Autoimmune hepatitisIncorrect. Autoimmune hepatitis presents with high transaminases and positive ANA/anti-smooth-muscle antibodies in young women, but is not strongly associated with ulcerative colitis or p-ANCA — the UC/p-ANCA combination with cholestatic labs is characteristic of PSC.
↑ Tap an answer to reveal the reasoning
Answer: B. A young man with ulcerative colitis presents with jaundice, pruritus, RUQ pain, fatigue, scleral icterus, hepatosplenomegaly, a markedly elevated alkaline phosphatase (502) disproportionate to mildly elevated transaminases, and positive p-ANCA. This is the classic profile of primary sclerosing cholangitis (PSC) — a chronic fibrosing inflammatory disease of intrahepatic and extrahepatic bile ducts.
Key associations: 70–80% of PSC patients have inflammatory bowel disease, almost always ulcerative colitis. Conversely, ~5% of UC patients develop PSC. p-ANCA is positive in approximately 70% of PSC cases. The cholestatic pattern (markedly elevated ALP) reflects bile duct injury, and pruritus is from bile salt accumulation.
Diagnosis is by MRCP (or ERCP), showing the characteristic "beaded" appearance of multifocal strictures alternating with dilations in the biliary tree. Liver biopsy is supportive but not always required, showing periductal "onion-skin" fibrosis. Major complications include cholangiocarcinoma (~10–15% lifetime risk), colon cancer (especially with concurrent UC), and progressive cirrhosis. Definitive treatment is liver transplant; ursodeoxycholic acid improves labs but not survival. Primary biliary cirrhosis affects middle-aged women, presents with positive anti-mitochondrial antibodies, and is not associated with IBD.
**Why each option:**
**A.** Hepatitis E causes acute hepatitis (predominantly elevated transaminases, not cholestasis); it does not produce p-ANCA positivity or the chronic UC association.
**B.** Correct. PSC — a chronic fibroinflammatory disease of intra- and extrahepatic bile ducts — is strongly associated with ulcerative colitis, positive p-ANCA in ~70%, and a cholestatic lab pattern (elevated ALP, conjugated bilirubin, pruritus).
**C.** Hepatitis A causes acute self-limited hepatitis (the patient is vaccinated anyway), with elevated AST/ALT in the thousands and no chronicity or p-ANCA association.
**D.** Primary biliary cirrhosis/cholangitis (PBC) affects middle-aged WOMEN and is characterized by positive anti-mitochondrial antibodies (AMA) — not p-ANCA — and is not strongly associated with UC.