NUC-B substudy links interferon to regulatory B-cell expansion after HBV treatment withdrawal

An immunology substudy of NUC-B, published in Hepatology, evaluated 41 patients with HBeAg-negative chronic hepatitis B undergoing nucleos(t)ide analog withdrawal, with or without a four-month course of adjuvant pegylated interferon-alpha (PEG-IFNα). Investigators assessed HBV-specific T cells using IFN-γ ELISpot with genotype-matched viral peptide pools and confirmatory flow cytometry. Regulatory B-cell responses were assessed using flow cytometry and intracellular IL-10 staining.

Broader baseline IFN-γ-producing HBV-specific T-cell responses correlated with greater sustained off-treatment viral control and fewer hepatic flares. PEG-IFNα was associated with a transient reduction in HBV-specific T cells that persisted for more than one month after treatment. IL-10-producing regulatory B cells expanded more than fivefold during PEG-IFNα treatment. Their induction tracked with flares in both study arms and showed a significant inverse temporal correlation with HBV-specific T-cell frequencies.

The findings suggest that regulatory B-cell expansion may constrain antiviral T-cell responses while limiting inflammation. Baseline HBV-specific T-cell breadth and magnitude warrant evaluation as biomarkers for selecting patients for treatment withdrawal. However, this small substudy establishes immune associations rather than validated selection criteria or a causal mechanism; the supplied report provides no absolute viral-control or flare rates.