Background: While dysfunctional exhausted CD8+ T cells hamper viral control when children acquire hepatitis B virus (HBV) infection, it’s crucial to recognize that CD8+ T cells have diverse phenotypes and functions. This study explored a subset of CD8+ T cells expressing C - C chemokine receptor type 5 (CCR5) in children with HBV infection. Methods: 36 patients in the immune tolerant (IT) group, 33 patients in the immune active (IA) group, and 55 patients in the combined response (CR) group were enrolled. The frequency, functional molecules and effector functions of the CCR5+CD8+ T cells population in different groups were evaluated. Results: The frequency of CCR5+CD8+ T cells correlated positively with the frequency of CCR5+ CD4+ T cells and patient age, and it correlated negatively with ALT, AST, HBV DNA, HBsAg and lactic dehydrogenase levels. CCR5+CD8+ T cells had higher levels of inhibitory and activated receptors and produced higher levels of IFN-γ, IL-2, and TNF-α than CCR5-CD8+ T cells. Conclusion：CCR5+CD8+T cells were partially exhausted but possessed a stronger antiviral activity than CCR5-CD8+T cells. The identification of this subset increases our understanding of CD8+ T cell functions and serve as a potential immunotherapeutic target for children with HBV infection.

Background & Aims: Hepatitis B s antigen (HBsAg) is an important reference for the amount of covalently closed circular DNA. Patients may benefit from low HBsAg levels. We evaluated changes in HBsAg and cytokines in chronic hepatitis B (CHB) patients with low HBsAg levels who underwent oral antiviral therapy. Methods: A total of 197 CHB patients with HBsAg < 3,000 IU/ml and HBV DNA ≤1,000 IU/ml after more than a year of antiviral therapy were divided into a nucleotide analogs (NAs) group and an entecavir (ETV) group. HBsAg levels were determined every 6 months until 42 months. The serum chemokine and cytokine levels at baseline and 6, 18, and 30 months among 54 hepatitis B e antigen (HBeAg)-positive patients were measured. Results: HBsAg loss (1.72%), HBsAg reduction below 100 IU/ml (13.79%) and HBsAg reduction ≥0.5 log10 (24.14%) occurred in the NAs group. The cumulative incidences of HBsAg reduction and the HBsAg change in the NAs group were better than those in the ETV group (P<0.05). HBsAg reduction ≥0.5 log10 was associated with NAs therapy, MDC, interleukin (IL) 4, IL23 and alanine aminotransferase (ALT) in baseline and ALT levels change>60 U/L during antiviral therapy (P<0.05). ALT change and IL4 level were identified as independent factors for HBsAg reduction (p=0.006; OR=30.491 [2.626-351.312], and p=0.027; OR=1.847 [1.071-3.186], respectively). Conclusions: NAs therapy had some advantages in promoting a reduction in HBsAg. In clinical practice, ALT, MDC, IL4, and IL23 may be biomarkers for predicting HBsAg reduction.