To investigate the risk factors for significant liver damage (SLD) in patients with chronic hepatitis B (CHB) during the immune-tolerant phase (IT-CHB) and establish a diagnostic model to guide clinical decisions on initiating antiviral therapy.

A retrospective analysis was conducted on the clinical data (including age, gender, examination and test results, etc.) of IT-CHB patients who were hospitalized and undergoing liver biopsy at the Fifth Medical Center of the PLA General Hospital from August 2018 to June 2022. Patients were stratified into SLD group [≥ G2 (inflammation) or S2 (fibrosis) according to Scheuer classification] and non-SLD group. Influencing factors were identified and diagnostic models were established by univariate and multivariate Logistic regression analysis, and the diagnostic performance was evaluated by receiver operating characteristic (ROC) curve and mosaic plots.

Among the 478 enrolled IT-CHB patients, the age was (32.9 ± 10.1) years old, with 62.1% males (297 cases), 21.1% cases (101/478) showed SLD (SLD group), 377 cases (78.9%) showed no SLD (non-SLD group). The results of the multivariate Logistic regression analysis showed that age (OR = 1.07, 95%CI: 1.04-1.11, P < 0.001), aspartate aminotransferase (AST) (OR = 1.09, 95%CI: 1.05-1.14, P < 0.001), platelet (PLT) (OR = 0.99, 95%CI: 0.98-0.99, P < 0.001), hepatitis B virus (HBV) DNA (OR = 0.51, 95%CI: 0.29-0.91, P = 0.017) and liver stiffness measurement (LSM) (OR = 2.25, 95%CI: 1.81-2.78, P < 0.001) were all independent influencing factors for SLD. The diagnostic model (IT-CHB-5) integrating these factors achieved an AUC of 0.89 (optimal cut-off: 23.8), with the sensitivity of 77.3%, the specificity of 89.2%, and the accuracy of 95.4% for SLD detection.

A substantial proportion of IT-CHB patients present SLD. The non-invasive IT-CHB-5 model provides an objective tool to timely initiation of antiviral therapy for IT-CHB patients who refuse liver biopsy.