Dual Positivity for AMA / AMA ‐ M2 and Anti‐gp210/sp100 Shows Highest Diagnostic Value for Primary Biliary Cholangitis

BACKGROUND: Primary biliary cholangitis (PBC)-related antibodies-including anti-mitochondrial antibodies (AMA), AMA-M2, anti-gp210, and anti-sp100-can occur in non-PBC liver diseases. We evaluated single and combined antibody positivity, focusing on dual positivity, using liver biopsy as the reference standard. METHODS: This retrospective study included antibody-positive patients who underwent liver biopsy. Patients were classified into three groups: only AMA(s) positive group, only anti-gp210/sp100 positive group, and dual-antibody positive group. Clinical and biochemical characteristics were compared to evaluate diagnostic performance and disease severity. Antibody-positive patients who did not initially meet diagnostic criteria for PBC were followed to assess diagnostic conversion. RESULTS: Among 733 antibody-positive patients, 80.22% (588/733) were diagnosed with PBC, while 19.78% (145/733) were non-PBC. Diagnostic rates were 80.05% (313/391) in the only AMA(s) positive group, 53.85% (63/117) in the only anti-gp210/sp100 positive group, and 94.22% (212/225) in the dual antibody positive group (p < 0.05). Dual antibody positive patients showed the most severe cholestatic profile, with significantly higher alkaline phosphatase, gamma-glutamyl transferase, total bile acid, and immunoglobulin M levels. The only anti-gp210/sp100 positive group had the highest rate of gastrointestinal bleeding. Autoimmune hepatitis overlap was more common in the dual-positive group than the only AMA(s) positive group (p < 0.05). Among 145 non-PBC patients followed for a median of 39.10 months, 2.07% (3/145) progressed to PBC, with a cumulative incidence of 7.40%. CONCLUSIONS: Histopathology remains the definitive standard for diagnosing PBC. Dual positivity for AMA/AMA-M2 and anti-gp210/sp100 showed the highest diagnostic value in identifying PBC.