Peg-IFN-alpha treatment in HBeAg-negative chronic hepatitis B yields virological and serological responses.

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Frontiers in Medicine Published April 14, 2026 Medically reviewed April 25, 2026 DOI ↗ By Dr. Amelia Tan, PhD · Internal Medicine & Chronic Disease

Key Takeaway

Note that ADAR1, N4BP1, and PSME1 mRNA levels may predict early response to Peg-IFN-alpha in chronic hepatitis B.

This prospective cohort study investigated the efficacy of pegylated interferon alpha (Peg-IFN-alpha) in patients with HBeAg-negative chronic hepatitis B virus infection. The primary outcomes assessed were virological response (VR) and serological response (SR), with follow-up conducted over 48 weeks. The study population consisted of patients with chronic hepatitis B, though the specific sample size and setting were not reported in the available data.

The main results indicated that the VR rate was 47.25% and the SR rate was 35.16%. Dynamic changes in the mRNA levels of ADAR1, N4BP1, and PSME1 differed significantly between the VR and non-VR groups, as well as between the SR and non-SR groups. Furthermore, ADAR1 was independently associated with both VR and SR at weeks 12 and 24. N4BP1 was independently associated with VR at weeks 12 and 24, while PSME1 was independently associated with VR and SR at weeks 12 and 24.

Predictive performance was evaluated using area under the curve (AUC) values. The AUC for ADAR1 predicting VR at week 24 was 0.9230, and for predicting SR at week 24 was 0.8554. The AUC for N4BP1 predicting VR at week 12 was 0.7393, predicting SR at week 24 was 0.7198. Similarly, the AUC for PSME1 predicting VR at week 12 was 0.7418, and for SR at week 12 was 0.7426. Safety data, including adverse events and tolerability, were not reported in the study.

The study identifies ADAR1, N4BP1, and PSME1 as novel biomarkers for early therapeutic response to Peg-IFN-alpha and HBsAg clearance. However, as this is an observational study, causal relationships between these biomarkers and treatment outcomes cannot be definitively established. The lack of reported safety data and sample size limits the immediate clinical application of these findings. Clinicians should interpret these biomarker associations with caution until further validation is performed in larger, controlled trials.

Study Details

Study typeCohort

EvidenceLevel 3

PublishedApr 2026

View Original Abstract ↓

Background and aimsPegylated interferon alpha (Peg-IFN-α) has the potential for eradicating hepatitis B surface antigen (HBsAg). The aim of our study is to investigate whether the expression levels of adenosine deaminase acting on RNA 1 (ADAR1), NEDD4-binding protein 1 (N4BP1), proteasome activator complex subunit 1 (PSME1) mRNAs in peripheral blood mononuclear cells (PBMCs) of HBeAg-negative chronic hepatitis B virus (HBV) patients are associated with the response to Peg-IFN-α treatment and HBsAg clearance.MethodsIn this prospective study, HBeAg-negative chronic HBV patients treated with Peg-IFN-α were followed for 48 weeks. Patients were categorized into the virological response (VR) group and non-virological response (NVR) group based on the observed changes in HBV DNA and HBsAg levels at week 48 of treatment. Additionally, patients were classified into a serological response (SR) group and a non-serological response (NSR) group according to whether serum HBsAg loss or seroconversion occurred. The expression levels of ADAR1, N4BP1, and PSME1 mRNAs in PBMCs were detected by real-time quantitative PCR. The diagnostic performance of ADAR1, N4BP1, and PSME1 was assessed by analyzing the receiver operating characteristic (ROC) curve and calculating the area under the curve (AUC).ResultsAfter the treatment period, the VR and SR rates were 47.25% and 35.16%, respectively. Dynamic changes in ADAR1, N4BP1, and PSME1 mRNA levels differed significantly between the VR and NVR groups, as well as between the SR and NSR groups. Multivariate analysis revealed that ADAR1 was independently associated with VR and SR at weeks 12 and 24; N4BP1 was independently associated with VR at weeks 12 and 24; PSME1 was independently associated with VR and SR at weeks 12 and 24. At week 24, the AUCs for ADAR1 in predicting VR and SR were 0.9230 and 0.8554. N4BP1 had AUCs of 0.7393 for VR at week 12 and 0.7198 for SR at week 24, while PSME1 had AUCs of 0.7418 for VR and 0.7426 for SR at week 12.ConclusionsADAR1, N4BP1, and PSME1 are novel biomarkers for early therapeutic response to Peg-IFN-α and HBsAg clearance.Clinical Trial Registrationhttps://www.medicalresearch.org.cn/login, identifier 2023−311.

Peg-IFN-alpha treatment in HBeAg-negative chronic hepatitis B yields virological and serological responses.

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Peg-IFN-alpha treatment in HBeAg-negative chronic hepatitis B yields virological and serological responses.

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