恩替卡韦抗病毒治疗对乙肝肝硬化患者HBV特异性细胞毒T淋巴细胞PD-1的表达及免疫功能影响的研究

Effect of PD-1 Expression of HBV-specific Cytotoxic T Lymphocytes and Immune Function in Patients with Hepatitis B Liver Cirrhosis on Entecavir Antiviral Therapy

目的探讨恩替卡韦抗病毒治疗对乙肝肝硬化患者HBV特异性细胞毒T淋巴细胞PD-1的表达及免疫功能的影响。方法选取20例乙型肝炎肝硬化患者,予恩替卡韦抗病毒治疗,并于0、3、6、12个月随访观察特异性细胞毒T淋巴细胞上PD-1及HBeAg、HBVDNA、细胞因子IFN-γ、TNF-α、child-pugh评分、肝脏病理的变化情况,分析它们之间的相互关系。结果 child-pugh评分、HBVDNA拷贝数、HBeAg阳性比例和肝脏病理的Knodell HAI评分均随着治疗时间的延长而逐渐降低少,而HBV CD8+T细胞比率、特异性PD-1表达以及IFN-γ、TNF-α水平则逐渐升高。PD-1表达水平与child-pugh评分、HBV DNA拷贝数、HBeAg阳性率之间呈正相关,与HBVCD8+T细胞百分比、IFN-γ和TNF-α水平间呈明显的负相关。结论应用恩替卡韦治疗乙肝肝硬化可以明显抑制乙肝病毒复制,降低乙肝病毒载量,降低HBeAg水平,恢复HBV特异性细胞毒T淋巴细胞功能,减轻肝脏病理改变,并且PD-1与HBeAg、HBVDNA、细胞因子IFN-γ、TNF-α、child-pugh评分、肝脏病理间存在密不可分的内在联系,掌握这些规律有利于指导HBV的抗病毒治疗。

Objective To explore the effect of PD-1 on expression of HBV-specific cytotoxic T lymphocytes and immune function in patients with hepatitis B liver cirrhosis on entecavir antiviral therapy.Methods A total of 20 patients with cirrhosis were cared by entecavir.The changes of specific cytotoxic T lymphocytes of PD-1,HBeAg,HBV DNA,IFN-γ,TNF-α,child-pugh score,and pathology in liver at 0,3rd,6th and 12th month were analyzed.Results Child-pugh score,HBVDNA copies,HBeAg-positive ratio and Knodell HAI score,decreased along with the treatment.HBV CD8 ＋ T cell ratio,specific PD-1 expression and IFN-γ,TNF-α level were gradually increased.The expression level of PD-1 was positively correlated with child-pugh score,HBV DNA copies or HBeAg-positive ratio,and was significantly negative correlated with HBV CD8＋T cells percentage,IFN-γ or TNF-α level.Conclusion There are significantly changes in the HBV replication inhibition,the reduction of HBeAg level,the restoration of HBV specificity cytotoxic T lymphocyte function,the reduction of the liver pathological damage by antiviral therapy with entacavir.And there is a close intrinsic link among PD-1,HBeAg,HBV DNA,IFN-γ,TNF-α and child-pugh score.These rules are helpful for guiding the HBV antiviral therapy.