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 log₁₀ 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.

Keywords: HBV RNA; HBcrAg; Peg‐IFN‐α therapy; chronic hepatitis B.