Short-term pegylated interferon alpha in chronic HBV patients with ultra-low HBsAg: a retrospective study

Background and aims Hepatitis B surface antigen (HBsAg) clearance—defined as an HBsAg level below the lower limit of detection—is critical for the functional cure of chronic hepatitis B (CHB). This study evaluated the efficacy of short-term pegylated interferon alpha (Peg-IFNα) therapy in achieving HBsAg clearance in CHB patients with ultra-low HBsAg levels (<50 IU/ml). Methods A total of 378 CHB patients with HBsAg levels <50 IU/ml were enrolled, including 206 nucleos(t)ide analogue (NUC)-treated patients and 172 inactive HBsAg carriers (IHCs). The NUC-treated cohort was divided into 83 patients receiving additional Peg-IFNα treatment (NUC add-on Peg-IFNα group) and 123 patients continuing NUC monotherapy (NUC group). The IHC cohort was divided into 86 patients receiving Peg-IFNα treatment (Peg-IFNα group) and 86 untreated patients (untreated group). The primary endpoint was the HBsAg clearance rate at week 24. Results At week 24, the HBsAg clearance rates in the NUC add-on Peg-IFNα group and Peg-IFNα group were 69.88% and 55.81%, respectively (p = 0.059), both significantly higher than the zero clearance rates in the NUC and untreated groups (p < 0.001). Patients with baseline HBsAg <10 IU/ml achieved higher clearance rates [81.82% vs. 73.81% (p = 0.144)]. A decline of ≥95.8% in HBsAg levels from baseline to week 12 predicted HBsAg clearance at week 24 (AUC ≥0.9, sensitivity 0.765, specificity 0.961). Conclusions Short-term Peg-IFNα therapy achieved high and comparable HBsAg clearance rates within 24 weeks in NUC-treated patients and IHCs with ultra-low HBsAg levels. Clinical trial registration https://www.medicalresearch.org.cn/login , identifier MR-50-24-011565.