目的 观察慢性乙型肝炎病毒（HBV）感染者不同疾病时期及长效干扰素治疗前后外周血T细 胞及其亚群 CD107a 分泌的细胞毒功能变化。方法 将慢性 HBV 感染患者分为未抗病毒治疗组（n = 300） 和干扰素治疗组（n = 36），再进一步将未抗病毒治疗组患者分成免疫耐受期（IT）组（n = 29）、免疫活动期 （IA）组（n = 174）、非活动期（IC）组（n = 44）和灰色区（GZ）组（n = 53）。纳入 17 例健康志愿者作为健康对 照（HC）组。采集外周血、利用流式细胞术检测 T 细胞 CD107a，并进行统计分析。结果 （1）免疫活跃期 患者 T 细胞及其亚群（CD4 及 CD8 T 细胞）CD107a 分泌水平显著高于免疫耐受期及非活动期患者。（2）患者 T 细胞及其亚群 CD107a 分泌水平与肝脏炎症指标及纤维化指标均呈正相关。（3）与 HBeAg（⁃）患者相 比，HBeAg（+）患者T细胞及其亚群 CD107a 分泌水平更高，HBV DNA > 106 IU/mL 患者也显著高于 HBV DNA < 106 IU/mL 患者。（4）与 Peg 干扰素抗病毒治疗前相比，治疗 48 周后，患者的T细胞及其亚群 CD107a 分泌能力显著提高（均 P < 0.000 1）。结论 慢性 HBV 感染者 T 细胞 CD107a 分泌的细胞毒作用与疾病状 态及分期有关，且长效干扰素治疗可进一步增强T细胞的细胞毒作用。

Objective To observe the changes of CD107a production by T cells and their subsets in peripheral blood at different stages of patients with chronic HBV infection and during the antiviral treatment with Peg⁃interferon，and to explore the rule of the change of T cell cytotoxicity during different stages of chronic HBV infection and antiviral therapy with interferon. Methods Patients with chronic HBV infection were enrolled into the study，with a cross⁃section cohort（n = 300，treatment⁃naive）and a longitudinal cohort（n = 36，HBeAg⁃positive， ALT > 2 ULN，receiving Peg⁃interferon therapy after enrollment）. Peripheral blood before and after antiviral treat⁃ ment was collected from the two cohorts of patients. The production of CD107a by T cells was detected by flow cytometry. Results （1）The levels of CD107a produced by CD3+，CD4+ and CD8+ T cells in patients of immune⁃ active stage（IA）were significantly higher than that in patients of immune⁃tolerant stage（IT）and inactive carrier stage（IC）.（2）The levels of CD107a production by CD3+，CD4+ and CD8+ T cells was found positively correlated with liver inflammatory indexes（ALT，AST and total bilirubin）.（3）The levels of CD107a production by CD3 +， CD4+ and CD8+ T cells were also showed a significant positive correlation with liver fibrosis（liver stiffness measure⁃ ment，APRI and FIB⁃4 score）.（4）The levels of CD107a production by CD3+，CD4+ and CD8+ T cells were signifi⁃ cantly higher in HBeAg（+）patients than those in HBeAg（-）patients，and those in patients with HBV DNA > 106 IU/mL was significantly higher than those in patients with HBV DNA < 106 IU/mL.（5）The levels of CD107a production by CD3+，CD4+ and CD8+ T cells were significantly increased after 48 weeks of treatment with PEG⁃ interferon compared with those before treatment. Conclusion The cytotoxic effect of T cells to secret CD107a is not only positively correlated with liver inflammation and fibrosis，but also with HBV replication level. The cytotoxic effect of T cells is obvious higher in immune active stage of chronic HBV infection，and moreover，that capacity of T cells could be significantly enhanced after antiviral treatment with Peg⁃interferon.