PRIMARY BILIARY CHOLANGITIS CASE- FINDING: AN ITALIAN MULTICENTER OBSERVATIONAL STUDY ON PATIENTS WITH INCIDENTAL FINDING OF ANTI- MITOCHONDRIAL ANTIBODIES.

Background: Anti- mitochondrial antibodies (AMA) are a specific diagnostic marker of Primary Biliary Cholangitis(PBC). The widespread use of auto- antibody test panels in non- hepatological settings allows incidental findings of AMA in patients without a history of liver disease. The aims of this multicenter observational prospective study were to assess the proportion of AMA positive subjects referred to hepatological evaluation and the evidence of significant liver disease found in these patients. Methods: From September 2020 to August 2021, 334 consecutive adult patients without a known history of liver disease were incidentally found positive for immunofluorescent AMA testing, with immunoblotting confirmed M2 positivity, during diagnostic evaluation mainly for rheumatologic or endocrinologic conditions at 18 Institutions in Italy. Referral of these subjects to hepatological evaluation was recorded until February 2022. Evidence of concomitant liver disease was assessed by serum liver enzymes and Fib- 4 score (based on age, platelet count, AST, and ALT values). Results: One hundred forty- five subjects (43.4%) were not referred to hepatological evaluation and were lost to follow- up, while 189 patients (56.6%) were referred to hepatological evaluation and were analyzed. Female sex was predominant (n=162, 85.7%), median age: 63 years (range: 14- 92). In 129 (68.2%) patients, alkaline phosphatase (ALP) and transaminase values were within the normal range. ALP resulted elevated in 47 (24.9%) patients: 248.6 ± 157.8 IU/L, and normal in 142 (75.1%): 75.6 ± 21.6 IU/L. AST levels were increased in 31 (16.4%) patients: 97.0 ± 60.1 IU/L. In total, 60 patients (31.7%) had elevated ALP and/or AST values. Bilirubin levels were < 2.0 mg/dL in all but 9 patients (4.8%). The Fib- 4 score resulted < 1.3 in 75 (39.7%), between 1.3 and 2.67 in 86 (45.5%), and > 2.67 in 28 (14.8%) patients. Figure summarizes the proportion of AMA- positive patients with elevated or normal liver enzymes and a Fib- 4 score > or < 2.0. Conclusion: This real- world observational prospective study indicates that over 40% of subjects incidentally found positive for AMA are not referred to hepatological evaluation to assess the presence of PBC in clinical practice. Among AMA positive patients without a history of liver disease evaluated by hepatologists, about 1/4 to 1/3 show evidence of liver disease, suggestive of PBC. Patients without current evidence of PBC should be monitored and followed up. Our results indicate the need for an informational and educational campaign among rheumatologists and endocrinologists on the importance of a hepatological evaluation of patients with incidental AMA positivity.