Review Question - QID 104830

This patient presents with primary biliary cirrhosis (PBC), which is caused by autoimmune interlobular bile duct destruction.

PBC is an autoimmune condition in which interlobular bile ducts are destroyed. This causes the liver to be unable to excrete bile, causing a conjugated hyperbilirubinemia and elevated alkaline phosphatase. Patients with PBC tend to be female and present in middle age with an insidious onset of pruritus, jaundice, xanthelasma (Figure A), dark urine, light stools, and hepatosplenomegaly. PBC is associated with other autoimmune conditions such as CREST syndrome, rheumatoid arthritis, and celiac disease. On labs, elevated antimitochondrial antibodies are observed, and liver biopsy will show lymphocytic infiltrate and granulomas. The first line treatment for PBC is ursodeoxycholic acid which decreases symptoms and increases transplant-free survival time.

Roche and Kobos review the diagnosis and management of jaundice in the adult patient. They state that jaundice in an adult patient can be caused by a wide variety of benign or life-threatening disorders. Organizing the differential diagnosis by prehepatic, intrahepatic, and posthepatic causes may help make the work-up more manageable. The conjugated (direct) bilirubin level is often elevated by alcohol, infectious hepatitis, drug reactions, and autoimmune disorders such as PBC.

Dyson et al. examine novel therapeutic targets in PBC. They state that potential targets include the 'upstream' immune response, 'midstream' biliary injury, and 'downstream' fibrotic processes. Combination therapy targeting several pathways or the development of novel agents addressing multiple components of the disease pathway might be required.


Figure A demonstrates xanthelasma (yellowish deposit of fat underneath the skin), which is commonly observed in PBC. Figure B is a classic liver biopsy of PBC demonstrating lymphocytic infiltration and periductal inflammation. Illustration A is an immunofluorescent staining of the antimitochondrial antibodies observed in PBC. Illustration B demonstrates the pathophysiology of PBC.

Incorrect answers:
Answer 2: Intra- and extrahepatic bile duct fibrosis is observed in primary sclerosing cholangitis.
Answer 3: Extrahepatic bile duct obstruction is observed in secondary biliary cirrhosis caused by etiologies such as gallstones, biliary stricture, and carcinoma of the head of the pancreas.
Answer 4: Absent UDP-glucuronyl transferase is observed in Crigler-Najjar syndrome, type I, which produces an increased unconjugated bilirubin level and causes patients to die in the first few years of life.
Answer 5: Decreased bilirubin uptake cause Gilbert's syndrome, which causes an unconjugated bilirubinemia but otherwise has no clinical consequences.