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BibTex format

@article{Phillips:2026:10.1097/HEP.0000000000001839,
author = {Phillips, S and Burton, A and Cooksley, H and Davies, J and Harris, N and Devshi, D and Zope, D and Raj, N and Suveizdyte, K and Falaschetti, E and Box, H and Habib, M and Nastouli, E and Kennedy, PFL and Agarwal, K and Message, J and Thursz, M and Chokshi, S and Maini, MK and NUC-B, Study Group},
doi = {10.1097/HEP.0000000000001839},
journal = {Hepatology},
title = {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.},
url = {http://dx.doi.org/10.1097/HEP.0000000000001839},
year = {2026}
}
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TY  - JOUR
AB  - 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.
AU  - Phillips,S
AU  - Burton,A
AU  - Cooksley,H
AU  - Davies,J
AU  - Harris,N
AU  - Devshi,D
AU  - Zope,D
AU  - Raj,N
AU  - Suveizdyte,K
AU  - Falaschetti,E
AU  - Box,H
AU  - Habib,M
AU  - Nastouli,E
AU  - Kennedy,PFL
AU  - Agarwal,K
AU  - Message,J
AU  - Thursz,M
AU  - Chokshi,S
AU  - Maini,MK
AU  - NUC-B,Study Group
DO  - 10.1097/HEP.0000000000001839
PY  - 2026///
TI  - 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.
T2  - Hepatology
UR  - http://dx.doi.org/10.1097/HEP.0000000000001839
UR  - https://www.ncbi.nlm.nih.gov/pubmed/42853556
ER  -
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