Abstract
BACKGROUND: Chronic hepatitis B (HBV) is frequently accompanied by immune dysregulation, and autoantibodies are intermittently detected in clinical practice. However, the clinical significance of autoantibody positivity across different HBV-related disease stages and its relationship with non-invasive fibrosis indices remains unclear. METHODS: We retrospectively analyzed 151 patients with HBV-related liver disease, including chronic hepatitis B (CHB), liver cirrhosis (LC), and hepatocellular carcinoma (HCC). Antinuclear antibodies (ANA) and extended autoantibody profiles were evaluated together with the aspartate aminotransferase–to–platelet ratio index (APRI) and fibrosis-4 index (FIB-4). Clinical and laboratory parameters were compared across disease groups, and receiver operating characteristic (ROC) curves were constructed to assess the diagnostic performance of APRI and FIB-4 for identifying advanced liver disease. RESULTS: ANA positivity increased progressively from CHB to LC and HCC, whereas extended autoimmune liver–specific autoantibodies remained rare across all stages. APRI and FIB-4 showed stepwise elevation with advancing disease severity, with FIB-4 demonstrating better diagnostic performance for advanced liver disease. ANA positivity showed no significant association with fibrosis indices, suggesting that these features may reflect distinct aspects of disease-related immune dysregulation. CONCLUSION: ANA positivity in chronic HBV infection appears to primarily reflect nonspecific immune activation rather than true autoimmune liver disease. FIB-4 provides practical and readily available information for identifying advanced liver disease, particularly in settings where liver biopsy or elastography is unavailable. Consideration of autoantibody patterns in conjunction with fibrosis indices may aid laboratory interpretation and support more informed clinical assessment in HBV-related liver disease. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12876-026-04718-4.