Snapshot A 45-year-old woman presents to her primary care physician for months of fatigue and generalized pruritus. She had been already examined in the dermatology clinic, when scabies and tinea were ruled out. On physical exam, she is noted to be jaundiced with scleral icterus and mild hepatomegaly. Laboratory results reveal a mild transaminitis and positive anti-mitochondrial antibodies but negative anti-nuclear antibody and anti-smooth-muscle antibodies. She is started on ursodeoxycholic acid and scheduled for an ultrasound to evaluate her hepatobiliary system. Introduction Overview primary biliary cholangitis (PBC) is a granulomatous autoimmune condition resulting in destruction of the interlobular bile ducts also known as primary biliary cirrhosis Associated conditions other autoimmune diseases CREST syndrome rheumatoid arthritis celiac disease Hashimoto thyroiditis scleroderma Epidemiology Demographics female > male middle-aged (>40 years of age) Risk factors family history ETIOLOGY Pathogenesis autoimmune attack on anti-mitochondrial antigens on biliary epithelial cells autoantibodies anti-mitochondrial antibodies (AMAs) Presentation Symptoms common symptoms fatigue pruritus worse at night secondary to bile salts deposited in the skin dark urine light-colored stool right upper quadrant pain Physical exam inspection jaundice hepatosplenomegaly may have xanthomas or xanthelasma Imaging Ultrasound indication to assess for hepatobiliary disease views right upper quadrant findings cirrhosis, including increased nodularity, atrophy, or hypertrophy distinguish between intra and extrahepatic biliary obstruction ERCP (endoscopic retrograde cholangiopancreatography) indication ultrasound is inconclusive findings multifocal strictures and dilation of bile ducts “string of beads” Studies Serum labs liver function tests showing cholestasis pattern ↑ direct bilirubin ↑ alkaline phosphatase autoantibodies + anti-mitochondrial antibody (AMA) 90-95% sensitivity > 99% specificity + anti-smooth muscle antibody (ASMA) in 50% of patients + anti-nuclear antibody (ANA) in 50% of patients ↑ IgM ↑ cholesterol Invasive studies liver biopsy indication in AMA-negative patients in whom clinical suspicion is strong for PBC findings nonsuppurative cholangitis and destruction of interlobular biliary ducts degenerating bile duct with lymphoid structures and granulomas Diagnosis with 2 or more of alkaline phosphatase > 1.5x upper limit of normal for 6 months or more + AMA in serum liver biopsy showing signs of PBC Differential Hemochromatosis key distinguishing factor triad of cirrhosis, diabetes, and skin bronze pigmentation Wilson disease key distinguishing factors patients typically present before age 40 cirrhosis, neurologic disease, psychiatric disease, and Kayser-Fleischer rings in the eyes Treatment Lifestyle avoidance of alcohol vaccination against hepatitis A and B Medical ursodeoxycholic acid indications all patients cholestyramine indications pruritus Surgical liver transplantation indications decompensated liver disease severe pruritus refractory to other therapies Complications Portal hypertension Cirrhosis Osteoporosis monitor with DEXA scan supplement with vitamin D3