Incidence and predictors of HBsAg loss following addition of pegylated interferon Alfa-2b in chronic hepatitis B patients suppressed by nucleos(t)ide analogues: a multicenter, prospective, cohort study.

BACKGROUNDS &AIMS: Nucleos(t)ide analog (NAs) treatment achieves limited HBsAg loss rates; switching to or adding Peginterferon (PegIFN) therapy may improve outcomes. This study aimed to evaluate the efficacy of adding PegIFNα-2b therapy in chronic hepatitis B (CHB) patients who are virally suppressed by NAs.

METHOD: 250 CHB patients on NAs treatment with HBsAg < 1500 IU/mL, serum HBV DNA < 20 IU/mL, and ALT ≤ 1.5 × ULN were enrolled. Patients continued their NAs regimen and initiated PegIFNα-2b (180 µg/week) for 48 weeks, with follow-up until week 72. In addition to routine biochemistry, HBsAg and HBV RNA levels were measured at each visit; HBcrAg was assessed at baseline, week 12, and week 24.

RESULTS

214 patients completed 48 weeks of PegIFNα-2b therapy, and 34.6% achieved HBsAg loss at week 72. Lower baseline HBsAg was associated with higher rates of HBsAg clearance. Specifically, patients with baseline HBsAg < 10 IU/mL and 10-100 IU/mL achieved HBsAg clearance rates of 76.2% and 45.5% at week 72, respectively. In univariate analysis, baseline HBsAg and its decline at week 12 demonstrated the strongest predictive performance for HBsAg loss, while younger age and higher ALT were also associated with HBsAg clearance. However, in multivariate analysis, only age and HBsAg decline at week 12 remained independent predictors of HBsAg loss.

CONCLUSIONS

CHB patients with low HBsAg levels and virologic suppression on NAs can achieve significant HBsAg loss after adding PegIFNα-2b. A two-step strategy based on baseline HBsAg and week-12 HBsAg decline may aid patient selection and treatment optimization.