[Correlation of qAnti-HBc with antiviral efficacy in children with chronic hepatitis B and exploration of its possible immune mechanism].

Objective: To compare the baseline difference in the quantitative hepatitis B core antibody levels (qAnti-HBc) between non-response and response group in children with HBeAg-positive chronic hepatitis B (CHB) who received antiviral therapy, and further explore the proportion and functional activity of CD8 + memory T lymphocyte subsets with different qAnti-HBC levels in peripheral blood of children. Methods: The baseline anti-HBc quantification (qAnti-HBc) levels of 85 children with HBeAg-positive CHB who visited the Department of Infectious Diseases, Children's Hospital of Chongqing Medical University from June 2018 to December 2020 were detected retrospectively. The relationship between the baseline qAnti-HBc level and HBeAg serological response in 37 children who received antiviral therapy was analyzed. The proportion of CD8(+) memory T lymphocyte subsets and the secretion levels of interferon (IFN) γ, and tumor necrosis factor (TNF) α in peripheral blood of 59 children at baseline were detected by flow cytometry. The relationship between qAnti-HBc level and the proportion and functional activity of CD8(+) memory T lymphocyte subsets was analyzed. Pearson's Chi-square test was used to compare the count data. Mann-Whitney U test or Kruskal-Wallis test was used to compare measurement data between two or more groups, and Spearman's rank correlation analysis was used for the correlation between continuous variables. Results: Among 37 children who received entecavir (ETV, 21/37 cases) or pegylated interferon (Peg-IFN, 16/37 cases), 18 cases had developed HBeAg seroconversion (10/ 21 cases in the ETV group, 8/16 cases in the Peg-IFN group). The baseline qAnti-HBc level was significantly higher in the response group [4.71 (4.64~4.81) log(10)IU/ml] than the non-response group children [4.54 (4.45~4.64) log(10)IU/ml, Z = -3.316, P = 0.001]. The proportion of CD8(+) Tem, CD38(+)CD8(+) Tem, CD38(+)CD8(+) Temra cells and the levels of IFNγ and TNFα secreted by CD8(+) T lymphocytes were significantly higher in the high-qAnti-HBc group than the low-qAnti-HBc group (P < 0.05). The proportion of CD8(+) Tem, CD38(+)CD8(+) Tem and CD38(+)CD8(+) Temra cells was significantly higher in ALT > 1× upper limit of normal value (ULN) group than ALT≤1×ULN group (P < 0.05). However, there were no significant differences in the levels of IFNγ and TNFα secreted by CD8(+) T lymphocytes between the two groups (P > 0.05). Spearman's correlation analysis showed that qAnti-HBc was positively correlated with the proportion of CD8(+) Tem, CD38(+)CD8(+) Tem, CD38(+)CD8(+) Temra cells and the level of IFNγ secreted by CD8(+)T lymphocytes (P < 0.05). Additionally, ALT was only positively correlated with the proportion of CD38(+)CD8(+) TEM and CD38(+) CD8(+) Temra cells (P < 0.05). Conclusion: Raised baseline qAnti-HBc level is related to the HBeAg serological response to antiviral therapy in children with CHB. Peripheral blood effector CD8+ T lymphocytes of CHB children with higher qAnti-HBc show stronger phenotype and functional activation characteristics, which may shed some light on the underlying immune mechanism related to antiviral therapy efficacy in children with CHB.目的： 比较行抗病毒治疗的HBeAg阳性慢性乙型肝炎（CHB）患儿无应答组和应答组间基线乙型肝炎核心抗体定量（qAnti-HBc）水平的差异，以探讨不同qAnti-HBc水平患儿外周血CD8(+)记忆T细胞亚群比例及其功能活性。 方法： 回顾性检测2018年6月至2020年12月于重庆医科大学附属儿童医院感染科就诊的85例HBeAg阳性CHB患儿基线qAnti-HBc水平。分析其中37例抗病毒治疗患儿基线qAnti-HBc水平与HBeAg血清学应答的关系。流式细胞检测59例患儿基线外周血CD8(+)记忆T细胞亚群比例及干扰素（IFN）-γ、肿瘤坏死因子（TNF）-α分泌水平，分析qAnti-HBc水平与CD8(+)记忆T细胞亚群比例及其功能活性间的关系。计数资料比较采用Pearson’s Chi-square检验，两组或多组间计量资料比较采用Mann-Whitney U检验或Kruskal-Wallis检验，连续性变量间的相关性采用Spearman秩相关分析。 结果： 在37例接受恩替卡韦（ETV，21/37）或聚乙二醇干扰素（Peg-IFN，16/37）治疗的患儿中，有18例发生HBeAg血清学转换（ETV组10/21，Peg-IFN组8/16），应答组患儿基线qAnti-HBc水平[4.71（4.64~4.81）log(10)IU/ml]显著高于无应答组[4.54（4.45~4.64）log(10)IU/ml，Z = -3.316，P = 0.001]。高qAnti-HBc组CD8(+)Tem、CD38(+)CD8(+)Tem、CD38(+)CD8(+)Temra细胞比例及CD8(+)T细胞分泌的IFN-γ、TNF-α水平显著高于低qAnti-HBc组（P < 0.05）；ALT>1×正常值上限（ULN）组CD8(+)Tem、CD38(+)CD8(+)Tem、CD38(+)CD8(+)Temra细胞比例显著高于ALT≤1×ULN组（P<0.05），但两组CD8(+)T细胞分泌的IFN-γ、TNF-α水平差异无统计学意义（P>0.05）。Spearman相关分析显示，qAnti-HBc与CD8(+)Tem、CD38(+)CD8(+)Tem、CD38(+)CD8(+)Temra细胞比例及CD8(+)T细胞分泌的IFN-γ水平呈正相关（P<0.05）；ALT仅与CD38(+)CD8(+)Tem、CD38(+)CD8(+)Temra细胞比例呈正相关（P<0.05）。 结论： 较高的基线qAnti-HBc水平与CHB儿童患者抗病毒治疗HBeAg血清学应答相关；qAnti-HBc较高的CHB患儿外周血效应CD8(+)T细胞表现出更强的表型及功能活化特点，此研究可能对CHB儿童抗病毒治疗疗效相关的潜在免疫机制作出一定阐释。.