Michele M. Tana, MD, MHS1Gideon M. Hirschfield, MA, MBBChir, PhD2
Primary biliary cholangitis (PBC) is a chronic autoimmune liver disease that causes small bile duct destruction, impaired bile flow, and biliary fibrosis. Increased liver fibrosis severity is associated with worse survival and, if untreated, 40% of patients develop cirrhosis within 10 years of diagnosis.1 PBC typically affects females (90%) aged 40 to 60 years, and prevalence is 40 per 100 000 in the US and 18 per 100 000 globally.2,3 More than 90% of patients with PBC have antimitochondrial antibodies.1 Approximately 50% of patients have another autoimmune disease such as hypothyroidism, Sjögrens syndrome, celiac disease, lupus, or rheumatoid arthritis. Compared with individuals without a family history, first-degree relatives of patients with PBC have a 9-fold increased risk of developing this disease, although only 3% developed PBC when followed up longitudinally.
At least 50% of patients have asymptomatic, early-stage PBC, detected by elevated alkaline phosphatase (ALP) during routine laboratory testing or by testing individuals with autoimmune diseases.3 Approximately 80% of patients with PBC experience fatigue and pruritus; other symptoms include sicca complex (dry eyes, mouth, vagina), Raynaud phenomenon, abdominal discomfort, arthralgias, brain fog, and impaired sleep.
PBC is diagnosed when at least 2 of the following 3 features are present in individuals without other liver disease: persistently abnormal cholestatic liver tests (elevated ALP predominantly, usually >1.5 times the upper limit of normal [ULN]); positive antimitochondrial antibodies [AMA]); or liver biopsy demonstrating small bile duct inflammatory cholangitis.4 Abdominal ultrasonography imaging, performed to exclude biliary obstruction, is usually normal in patients with PBC, but may demonstrate cirrhosis and portal hypertension (splenomegaly). Among AMA-negative (~10%) patients, 50% have PBC-specific antinuclear antibody reactivity (anti-gp210, anti-sp100, or anticentromere). The combination of unexplained cholestasis (eg, no hepatotoxic drugs or infiltrative disorder such as sarcoidosis) and a positive AMA test (≥1:20 by immunofluorescence or positive enzyme-linked immunosorbent assay test result) has 95% positive predictive value for histologic diagnosis of PBC.4 Liver biopsy is considered for patients with test results negative for AMA and/or PBC-specific antinuclear antibodies or to assess for other liver disease (eg, steatosis, autoimmune hepatitis)
