Diagnostic Impact of Liver Biopsy Among Antinuclear Antibody Positive Individuals With Mild Liver Enzyme Elevation

BACKGROUND AND AIMS: Abnormal liver enzyme elevations with positive antinuclear antibodies (ANA) frequently prompt investigation for autoimmune hepatitis after common causes such as viral hepatitis or drug-induced liver injury have been excluded. Current guidelines recommend liver biopsy for suspected autoimmune hepatitis, but its utility in patients with only mild transaminase elevation remains uncertain. This study evaluated the diagnostic yield of liver biopsy in such patients, particularly when alanine aminotransferase is below 101 U/L. METHODS: We retrospectively analysed 313 adults who underwent percutaneous liver biopsy at the University Hospital Heidelberg between 2019 and 2024 for unexplained liver enzyme elevation including suspected autoimmune hepatitis. Clinical data were extracted, and histology was classified according to the 2022 International Autoimmune Hepatitis Pathology Group consensus recommendations. Patients with malignancy, post-transplant biopsy, or incomplete data were excluded. RESULTS: The median age was 49 years; 55.3% were female. Median alanine aminotransferase and aspartate aminotransferase were 161 U/L and 106 U/L, respectively. Antinuclear antibodies were positive in 61.3% of cases. 22.4% of antinuclear antibody positive and 15.7% of antinuclear antibody negative patients had autoimmune hepatitis compatible histology. Among patients with positive antinuclear antibodies and alanine aminotransferase < 101 U/L, only 9% showed autoimmune hepatitis compatible histology and 3.8% (three patients) required long-term immunosuppression. Two of these three patients had compensated liver cirrhosis. CONCLUSIONS: Liver biopsy provides limited additional diagnostic value in ANA-positive, non-cirrhotic patients with alanine aminotransferase < 101 U/L and no alternative suspected aetiology. In such cases, the procedure can be safely deferred, reserving biopsy for higher enzyme elevations or unclear differential diagnoses.