Gu Y, Lian Y, Zheng Q, et al. - Researchers investigated how antiviral cytokines produced by natural killer (NK) and T cells are associated with clinical-virological characteristics in untreated chronic hepatitis B (CHB) patients. In the assessed cohort with chronic hepatitis B virus (HBV) infection, distinct cytokine signatures characterized HBV clinical phases. In immune active (IA) phase, they noted significantly higher levels of interferon-gamma (IFN-γ)₊ and tumor necrosis factor-alpha (TNF-α) ₊ CD4₊ and CD8₊ T cells than in other phases. The lowest expression of IFN-γ by NK and natural killer T (NKT) cells, and TNF-α by NK cells was observed among immune tolerant (IT) patients. IA and gray zone (GZ) phases were similar in terms of IFN-γ₊, TNF-α₊ and IL-2₊ CD4₊ and CD8₊ T cells frequencies. They performed principal component analysis based on cytokines and established that most IT patients significantly differed from inactive carriers (IC) and IA patients, while GZ patients were widely scattered. In multivariate analysis, significant association was noted of both T and NK cells producing IFN-γ and TNF-α, but not IL-2, with serum alanine aminotransferase. Moreover, association was observed of IFN-γ₊ NKT cells with HBV DNA, while IFN-γ₊ CD4+ and CD8₊ T cells were correlated with age. Findings suggest that the cytokine signatures were correlated with viral features in these untreated CHB patients.