Primary biliary cholangitis
Formal Definition
A chronic autoimmune cholestatic liver disease predominantly affecting middle-aged women, characterized by progressive destruction of interlobular bile ducts leading to cholestasis, fibrosis, and cirrhosis; diagnosed by elevated alkaline phosphatase (ALP) >1.5x upper limit, positive anti-mitochondrial antibodies (AMA, specifically anti-PDC-E2 in >95% of patients), and characteristic liver biopsy findings of florid bile duct lesions; treated with ursodeoxycholic acid (UDCA) and obeticholic acid.
How It's Used on the Ward
"PBC" — the autoimmune disease where the body attacks the small bile ducts in the liver, causing progressive cholestasis, fatigue, and pruritus; predominantly affects women in their 40s-60s; the anti-mitochondrial antibody (AMA) is a very specific test for it.
Example
""44-year-old woman with 2 years of progressive fatigue and generalized pruritus, especially at night. No alcohol use. Labs: ALP 387 U/L (3x upper limit), GGT 210, normal AST/ALT, total bilirubin 1.1. Anti-mitochondrial antibodies positive at 1:320 titer. Abdominal ultrasound normal (no biliary obstruction). Diagnosis: primary biliary cholangitis. Liver biopsy showing florid bile duct lesions and lymphocytic portal infiltrates confirms diagnosis. Started ursodeoxycholic acid 13-15 mg/kg/day. Enrolled in transplant registry given MELD-Na progression risk.""
Clinical Context
Epidemiology: >90% female, median diagnosis age 50-60. Classic presentation: fatigue (most common, often debilitating) + pruritus (characteristically worse at night, often precedes jaundice by years) + dry eyes/dry mouth (Sjögren overlap). Physical exam: hepatomegaly, jaundice, xanthelasma, scratch marks. Labs: cholestatic pattern (ALP > GGT > AST/ALT), elevated bilirubin in later stages, elevated IgM. Autoantibodies: AMA (anti-PDC-E2) positive in 95% — highly specific. Anti-gp210 and anti-sp100 (nuclear envelope antibodies) = PBC-specific, may be positive even if AMA negative. Ursodeoxycholic acid (UDCA 13-15 mg/kg/day): first-line, slows progression, improves transplant-free survival. Obeticholic acid (FXR agonist): second-line, approved for UDCA-intolerant or non-responders. Fibrates (bezafibrate, fenofibrate) — emerging, promising data for non-responders. Liver transplant for end-stage disease (bilirubin >6 or MELD >15). Associated conditions: Sjögren syndrome, thyroid disease, Raynaud, scleroderma.