Sustained HBsAg clearance induced by pegylated interferon α-2b in HBeAg-negative patients with low baseline HBsAg

Background Patients with low HBsAg levels, HBeAg-negative status and undetectable HBV DNA are recognized as the advantaged population for pegylated interferon α-2b (Peg-IFNα-2b) therapy. However, there are limited reports on the sustainability of HBsAg loss in this population. This study aims to explore the patterns of sustained response following HBsAg clearance in low HBsAg level patients treated with Peg-IFNα-2b through long-term follow-up, providing guidance for clinical practice. Methods This retrospective study analyzed patients with baseline HBsAg 200 IU/mL, HBeAg negativity and undetectable baseline HBV DNA, who achieved HBsAg clearance and received either Peg-IFNα-2b monotherapy or nucleos(t)ide analog (NA) combination therapy. HBV biomarkers and clinical biochemical indicators were assessed during follow-up. Results We evaluated sustained HBsAg loss and investigated the risk factors of HBsAg reversion. A total of 203 patients with baseline HBsAg200IU/ml, HBeAg-negativity and undetectable HBV DNA were enrolled in this study. The median follow-up duration was 96 weeks (range:72 to 120 weeks). 44 (21.67%) patients were observed HBsAg reversion during follow-up, 91.36% (40/44) of which occurred within 96 weeks. Kaplan-Meier stratification analysis revealed that higher end-of-treatment (EOT) HBsAb levels and longer consolidation therapy duration were independently associated with higher sustained HBsAg clearance rates (P 0.001). Specifically, patients with EOT HBsAb 1000 IU/mL achieved a 100% sustained clearance rate (no reversion observed). Cox regression analysis identified EOT HBsAb levels ≥100 IU/mL (HR = 0.238, P = 0.003)) and consolidation therapy ≥12 weeks (HR = 0.492, P = 0.027) as independent predictor against HBsAg reversion. No ALT flares and adverse events were observed in these HBsAg reverted patients during follow-up, while six patients had detectable HBV DNA. Conclusion Low HBsAg and HBeAg negative patients exhibited favorable long-term persistence of HBsAg clearance induced by Peg-IFNα-2b. We identified the EOT HBsAb levels (with levels 1000 IU/mL predicting 100% sustained clearance) and the duration of consolidation therapy as key determinants of long-term treatment success, and proposed 96 weeks as the optimal follow-up time point for these patients.