Week #7 Case Study: The Thrice-Hit Liver – Autoimmune, Alcohol, and Metabolic Overlap in a 65-Year-Old with Fatigue

This comprehensive case study presents Robert Johnson, a 65-year-old male with persistent nausea, profound fatigue (4 weeks), dark urine, light stools, 10-lb unintentional weight loss, mild RUQ discomfort, and jaundice (per wife). Past medical history includes hypertension, type 2 diabetes mellitus, and hyperlipidemia. Medications include lisinopril, metformin, and atorvastatin. Social history reveals significant alcohol use (3-4 glasses of whiskey/night for 20 years) and former smoking (30 pack-years). Physical exam findings include scleral icterus, palpable liver edge (2 cm below RCM, firm), mild RUQ tenderness, and no asterixis, ascites, or peripheral edema. Initial labs show mild anemia (Hgb 11.8), elevated AST (185), ALT (220), markedly elevated ALP (380), total bilirubin (3.2), low albumin (3.0), and elevated INR (1.4) – a cholestatic pattern with synthetic dysfunction. Diagnostic workup: ultrasound/CT (hepatomegaly, steatosis, no obstruction), viral hepatitis serology (negative), ANA/ASMA (negative), and strongly positive anti-mitochondrial antibody (AMA 1:160) with elevated IgM. Primary diagnosis is Primary Biliary Cholangitis (PBC) Stage 2-3, with overlapping alcohol-associated liver disease (ALD) and metabolic dysfunction-associated steatotic liver disease (MASLD). Management includes ursodeoxycholic acid (UDCA), alcohol cessation, switching metformin to insulin, holding atorvastatin, fat-soluble vitamins, and calcium. Follow-up at 12 weeks shows improved ALP (195), bilirubin (1.8), albumin (3.4), and FibroScan showing F2-F3 fibrosis. Ideal for learning cholestatic liver disease, PBC diagnosis, overlapping etiologies, and comprehensive hepatology management.