Adjuvant pegylated interferon-alpha after nucleos(t)ide analog withdrawal drives a temporally coordinated expansion of regulatory B cells and contraction of HBV-specific T cells

Authors

• on behalf of the NUC-B Study Group
• Sandra Phillips, Foundation for Liver Research
• Alice Burton, University College London
• Helen Cooksley, Foundation for Liver Research
• Jessica Davies, University College London
• Nicola Harris, Foundation for Liver Research
• Dhruti Devshi, Foundation for Liver Research
• Dimple Zope, Foundation for Liver Research
• Niyati Raj, Foundation for Liver Research
• Kornelija Suveizdyte, University College London
• Emanuela Falaschetti, Imperial College London
• Hanna Box, Imperial College London
• Mariam Habib, Imperial College London
• Eleni Nastouli, University College London Hospitals NHS Foundation Trust
• Patrick F.L. Kennedy, Queen Mary University of London
• Kaushik Agarwal, King's College Hospital NHS Foundation Trust
• Jack Message, Imperial College London
• Mark Thursz, Imperial College London
• Shilpa Chokshi, Peninsula Medical School
• Mala K. Maini, University College London

ORCID

• Shilpa Chokshi: 0000-0003-1735-8538

Document Type

Article

Abstract

Background and Aims: – The NUC-B study showed that a 4-month course of pegylated interferon-alpha (PEG-IFNα) enhanced the outcome and reduced hepatic flares following nucleos(t)ide analog (NUC) withdrawal in HBeAg-negative chronic hepatitis B. Here, we investigated differential T- and regulatory B-cell (BREG) changes before and during these interventions in a substudy of 41 representative patients. Approach and Results: – Antigen-specific T cells were primarily evaluated using quality-controlled IFN-γ ELISpot with 15 pools of genotype-matched HBV core/small-surface peptides, confirmed by multiparameter flow cytometry. B-cell responses were tested with multiparameter flow cytometry and intracellular IL-10 staining. Broader baseline IFN-γ-producing-HBV-specific T cells correlated with higher sustained off-treatment viral control and reduced flares. PEG-IFNα led to a transient reduction in HBV-specific T cells that persisted for over 1 month after treatment. BREG producing the immunosuppressive cytokine IL-10 expanded more than 5-fold during adjuvant PEG-IFNα. The kinetics of BREG induction correlated with flares in both arms and showed a significant inverse temporal correlation with IFN-γ-producing-HBV-specific T-cell frequencies. Conclusions: – Baseline breadth and magnitude of HBV-specific T cells should be evaluated as biomarkers to select patients more likely to have favorable outcomes with NUC withdrawal ±PEG-IFNα. The expansion of BREG provides insights into homeostatic mechanisms induced by PEG-IFNα and withdrawal flares, which could constrain HBV-specific T cells while limiting inflammation.

DOI Link

10.1097/HEP.0000000000001839

Publication Date

2026-10-09

Publication Title

Hepatology

ISSN

0270-9139

Acceptance Date

2026-07-13

Deposit Date

2026-11-02

Additional Links

https://www.scopus.com/pages/publications/105053992529

Keywords

antiviral T cells, functional cure, hepatic flares, regulatory B cells, treatment interruption

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 International License.

Recommended Citation

on behalf of the NUC-B Study Group., Phillips, S., Burton, A., Cooksley, H., Davies, J., Harris, N., Devshi, D., Zope, D., Raj, N., Suveizdyte, K., Falaschetti, E., Box, H., Habib, M., Nastouli, E., Kennedy, P., Agarwal, K., Message, J., Thursz, M., Chokshi, S., & Maini, M. (2026) 'Adjuvant pegylated interferon-alpha after nucleos(t)ide analog withdrawal drives a temporally coordinated expansion of regulatory B cells and contraction of HBV-specific T cells', Hepatology, . Available at: 10.1097/HEP.0000000000001839