Noninvasive models for patient selection and Early response monitoring of interferon therapy for HBsAg clearance in patients with chronic hepatitis B

BACKGROUND: Hepatitis B surface antigen (HBsAg) clearance is a critical step toward functional cure and is associated with improved virological control, as well as a reduced risk of cirrhosis and hepatocellular carcinoma (HCC). Pegylated interferon-α (Peg-IFN-α) has shown promise in achieving HBsAg clearance in selected patient subsets. Precise identification of these "advantaged populations" and early assessment of treatment response are critical for optimizing personalized therapy. METHODS: We retrospectively analyzed 239 chronic hepatitis B (CHB) patients, including 175 patients with baseline HBsAg levels < 1500 IU/mL, who received Peg-IFN-α therapy. Parameters were compared between HBsAg clearance and non-clearance groups. We developed/validated Model 1 (gender, age, baseline HBsAg) to identify treatment-advantaged patients. Model 2 incorporated week-12 dynamics: platelet count change (ΔPLT), alanine aminotransferase-to-aspartate aminotransferase ratio (ALT/AST) rates of change, and HBsAg level. The generalizability of Model 1 and Model 2 was further validated in an independent external cohort (n = 92). RESULTS: Model 1 demonstrated superior performance over individual predictors and existing models (ALT/qHBsAg and Zhang's model), with validation in an independent cohort. Decision curve analysis (DCA) further confirmed Model 1's clinical utility advantage over existing models (ALT/qHBsAg and Zhang's model). Additionally, through receiver operating characteristic (ROC) curve analysis, DCA, and Cox regression, Model 2 outperformed both week-12 HBsAg level and ALT/qHBsAg in predicting HBsAg clearance, providing a robust early on-treatment response indicator. CONCLUSIONS: We propose two clinically applicable models: Model 1 identifies advantaged patients suitable for Peg-IFN-α therapy based on baseline characteristics, while Model 2 predicts treatment response using week-12 dynamics. These tools provide a framework for precision medicine approaches to achieve HBsAg clearance in CHB.