Clinical significance of anti-mitochondrial antibodies and PBC-specific anti-nuclear antibodies in evaluating atypical primary biliary cholangitis with normal alkaline phosphatase levels.

Objectives: The clinical implications of positive anti-mitochondrial antibodies (AMAs) and/or primary biliary cholangitis (PBC)-specific anti-nuclear antibodies (ANAs) in patients with normal alkaline phosphatase (ALP) remain uncertain.

Methods: Patients at The Second Hospital of Nanjing with positive AMAs/PBC-ANAs and normal ALP levels from January 2016 to July 2024 were categorized into three groups based on autoantibody profiles: [AMA/AMA-M2]⁺[gp210/sp100]⁺, [AMA/AMA-M2]⁺[gp210/sp100]^-, and [AMA/AMA-M2]^-[gp210/sp100]⁺. The study compared PBC diagnostic rates, clinical symptoms, laboratory results, and pathology across these groups.

Results: A total of 53.3 % (88/165) of the patients showed cholangitis activity diagnosed of PBC. The PBC diagnosis rate in the three groups was 82.1 % (23/28), 48.4 % (46/95), and 45.2 % (19/42) respectively. Multivariate analysis indicated a significant association between the absence of liver disease-related etiology (p<0.001), baseline serum immunoglobulin M (IgM) exceeding 0.796 times the upper limit of normal (ULN) (p<0.001), and the diagnosis of PBC as determined by liver biopsy. In the three groups of non-PBC patients, the major pathological injury patterns were minor nonspecific reactive changes (40.0 %/28.6 %/39.1 %), inflammation (40.0 %/24.5 %/47.8 %), and fatty changes (20 %/20.4 %/4.3 %). The diagnosis included viral hepatitis, autoimmune hepatitis, fatty liver disease, vascular liver disorders, drug-induced liver injury, congenital hepatic fibrosis, and porphyria.

Conclusions: Over 50 % of patients with positive PBC-specific antibodies and normal ALP have PBC. Liver biopsy is recommended when AMAs and/or PBC-specific ANAs are positive, especially when baseline serum IgM exceeds 0.796 × ULN, and when other etiologies related to liver disease are absent. The area under the curve (AUC) for these three indicators reaches 0.84.