Adding HBV RNA and HBcrAg to HBsAg Improves Prediction of HBsAg Seroclearance in NAs ‐Suppressed CHB Treated With Peg‐ IFN ‐α

ABSTRACT Background and Aims Accurate prediction of hepatitis B surface antigen (HBsAg) seroclearance remains essential for optimising pegylated interferon‐α (Peg‐IFN‐α) therapy in chronic hepatitis B (CHB). While HBsAg is a conventional predictor, HBV RNA and hepatitis B core‐related antigen (HBcrAg) have emerged as potential biomarkers. However, whether combining these markers can improve the predictive value of HBsAg seroclearance remains unclear. Methods In this study, CHB patients with HBV DNA < 100 IU/mL, HBeAg‐negative and HBsAg level ≤ 1500 IU/mL after receiving ≥ 1 year of nucleos(t)ide analogues (NAs) therapy were enrolled and received 48 weeks of Peg‐IFN‐α add‐on therapy. Baseline clinical, biochemical and virological parameters (HBsAg, HBV RNA and HBcrAg) were evaluated for their predictive value of HBsAg seroclearance at week 48. Results Among 150 patients, 51 (34.0%) achieved HBsAg seroclearance after 48 weeks of Peg‐IFN‐α add‐on therapy. Baseline HBsAg (OR 4.27, p < 0.001), HBV RNA (OR 6.78, p = 0.004) and HBcrAg (OR 2.35, p = 0.044) were independent predictors of HBsAg seroclearance. Combining HBsAg, HBV RNA and HBcrAg improved predictive accuracy over HBsAg alone (AUROC 0.845 vs. 0.785). Patients meeting the criteria of HBsAg < 200 IU/mL, HBV RNA < 130 copies/mL and HBcrAg < 3.5 log 10 U/mL had a substantially higher HBsAg seroclearance rate (81.5%) compared with those meeting only one or two criteria (28.1%) or none (7.4%). Conclusions Compared to baseline HBsAg alone, the combination of HBsAg, HBV RNA and HBcrAg can better identify NAs‐suppressed CHB patients who are likely to achieve HBsAg seroclearance with Peg‐IFN‐α add‐on therapy.