# Efficacy and safety of PEG-IFN α-2b and tenofovir amibufenamide in combination therapy for chronic hepatitis B

## TL;DR

Combining PEG-IFN α-2b and tenofovir amibufenamide effectively reduces HBsAg in chronic hepatitis B patients, with early HBsAg decline predicting treatment success.

## Contribution

First evaluation of PEG-IFN α-2b and tenofovir amibufenamide combination for chronic hepatitis B.

## Key findings

- Combination therapy significantly reduced HBsAg levels and increased undetectable HBV DNA to 94.7% at week 48.
- Baseline HBsAg levels and week 24 HBsAg decline were strong predictors of serological response with AUCs of 0.856 and 0.821.
- HBsAg clearance rates were 25% in treatment-naïve and 26.7% in treatment-experienced patients.

## Abstract

This study aimed to explore the efficacy and safety of combination therapy with PEG-IFN α-2b and tenofovir amibufenamide (TMF) for the treatment of chronic hepatitis B (CHB).

This multicenter study enrolled 84 CHB patients, who received PEG-IFN α-2b (180 µg/weekly) and TMF (25 mg/day) for 48 weeks. Clinical and laboratory assessments were performed at baseline and at 12-week intervals (weeks 12, 24, 36, and 48). Serologic response (SR) was defined as hepatitis B surface antigen (HBsAg) loss (< 0.05 IU/mL), with or without HBsAg seroconversion (HBsAg < 0.05 IU/mL and HBsAb > 10 mIU/mL). Adverse events (AEs) were monitored at each assessment. Logistic regression and receiver operating characteristic curve analyses were used to identify predictors of HBsAg clearance.

The combination therapy of PEG-IFN α-2b and TMF resulted in significant reductions in HBsAg levels from baseline at weeks 24, 36, and 48. At these time points, the proportion of patients with undetectable HBV DNA increased progressively, with the proportion reaching 94.7% at week 48. In the SR group, the baseline HBsAg and HBeAg levels were significantly lower than those in the non-serological response (NSR) group, with greater reductions in HBsAg observed at weeks 12 and 24. Multivariate analysis revealed that baseline HBsAg levels and the degree of HBsAg decline at week 24 were independent predictors of HBsAg loss, with odds ratios of 4.609 and 3.237, respectively. The diagnostic performance of baseline HBsAg levels and their decline at week 24 demonstrated areas under the curves (AUCs) of 0.856 and 0.821, respectively, with a combined AUC of 0.908. The cumulative HBsAg clearance rates were 25% in treatment-naïve patients and 26.7% in treatment-experienced patients. The most frequently reported AEs included fever, fatigue, rash, alopecia, elevated ALT and AST levels, neutropenia, and thrombocytopenia.

PEG-IFN α-2b and TMF combination therapy effectively reduced HBsAg levels in CHB patients. Baseline HBsAg levels and the magnitude of their decline by week 24 served as robust predictors of serological response, exhibiting high diagnostic value.

First evaluation of the PEG-IFN α-2b and Tenofovir Alafenamide (TAF) combination for chronic hepatitis B (CHB).

The combination regimen demonstrates a significant rate of HBsAg loss.

Baseline HBsAg levels and on-treatment HBsAg reduction at week 24 are strong predictors of treatment success.

Provides a new strategy for optimizing functional cure in CHB patients.