Efficacy and predictors of pegylated-interferon in hepatitis B surface antigen seroclearance in immune active and inactive chronic hepatitis B patients.

BACKGROUND AND

OBJECTIVES

Pegylated interferon (PegIFN) is one of the few strategies capable of achieving hepatitis B surface antigen (HBsAg) seroclearance in chronic hepatitis B (CHB) patients. However, its role in HBeAg-negative chronic HBV infection (also referred to as immune-inactive or "inactive carrier" phase) remains unclear. This study compared PegIFN efficacy between immune-inactive and immune-active patients and explored predictors of treatment response.

RESEARCH

METHODS

We retrospectively analyzed 211 consecutive HBeAg-negative patients treated with PegIFN α-2b in our center from 2019 to 2023, including 139 with immune-inactive chronic HBV infection and 72 immune-active CHB patients. Effectiveness was assessed in the full analysis set (FAS) and efficacy in the per-protocol set (PPS). Predictors of HBsAg seroclearance were identified using Cox regression.

RESULTS

At week 48, overall HBsAg seroclearance was 26.5 % (FAS), with comparable outcomes between immune-inactive and immune-active groups (26.6 % vs. 26.4 %, P > 0.05). Inactive patients receiving PegIFN + nucleos(t)ide analogues (NAs) showed no added benefit. In the PPS, clearance reached 69.1 %, but 40.3 % discontinued prematurely-mostly due to subjective intolerance-highlighting a major gap between real-world effectiveness and theoretical efficacy. Multivariate analysis identified two independent predictors: baseline HBsAg <100 IU/mL (HR 2.999, 95 % CI 1.625-5.536, P < 0.001) and on-treatment HBsAg decline ≥1 log10 IU/mL within any 12-week interval (HR 11.205, 95 % CI 4.379-28.674, P < 0.001).

CONCLUSIONS

PegIFN α-2b achieved clinically meaningful HBsAg seroclearance in both immune-inactive and immune-active patients. Early discontinuation markedly reduced real-world effectiveness. Baseline low HBsAg and dynamic on-treatment decline are pragmatic predictors for optimizing patient selection and guiding interferon-based strategies.