恩替卡韦对慢性乙型肝炎患者外周血Th1/Th2型细胞因子表达水平的影响

Study on the correlation of the effect of entecavir on Th1/Th2 cytokines level in the treatment of chronic hepatitis

目的探讨恩替卡韦抗病毒治疗过程中慢性乙型肝炎（CHB）患者外周血Th1／Th2型细胞因子表达水平的变化，以及各细胞因子表达水平之间、各细胞因子与HBVDNA载量之间的关系。方法采用悬液芯片技术检测CHB患者外周血Th1／Th2型细胞因子的表达水平；同时采用全自动生物化学分析仪检测肝功能，PCR法检测HBVDNA载量，化学发光法检测HBV血清病毒学标志物。计量资料比较采用方差分析；相关性分析采用Pearson相关分析法。结果CHB患者抗病毒治疗前外周血Th1型细胞因子干扰素y表达水平较对照组升高明显（P=0．010），肿瘤坏死因子（TNF）α表达水平与对照组比较差异无统计学意义（P=0．095）；Th2型细胞因子白细胞介素（IL）-4、IL-6、IL-10表达水平均明显低于对照组，差异有统计学意义（P=0．039，P=0．014，P=0．026）。CHB患者接受ETV抗病毒治疗48周后，外周血中Th1型细胞因子干扰素y和TNFα表达水平较治疗前均明显降低，分别为（19．2±5．03）pg／ml对（24．69±6．51）pg／ml、（6．09±4．99）pg／ml对（9．50±7．34）pg／ml，差异有统计学意义（P〈0．001，P=0．016）；Th2型细胞因子IL-4和IL-6表达水平较治疗前均明显升高，分别为（33．86±22．47）pg／ml对（21．32±12．84）pg／ml、（11．65±6．91）pg／ml对（8．51±4．94）pg／ml，差异有统计学意义（P=0．004，P=0．029），IL-10表达水平与治疗前比较有所升高，差异无统计学意义（P=0．081）。恩替卡韦抗病毒治疗前后CHB患者外周血中Th1／Th2型细胞因子之间相关关系紊乱，无明显规律，且各细胞因子与HBVDNA载量间均未见相关性。结论恩替卡韦抗病毒治疗既能抑制HBVDNA复制，降低病毒载量，又有助于调节CHB患者外周血中Th1／Th2型细胞因子表达水平，但各细胞因子表达水平之间、细胞因子与HBVDNA载量之间均未见相关性。

Objective To explore the expression level of peripheral blood Th1/Th2 type cytokines of chronic hepatitis b （CHB） patients in the entecavir （ETV） antiviral treatment, analyze the relationship between various cytokines, and the correlation among ofcytokines and HBV DNA loads. Methods Luminex Liquid Chip Technology was applied to detect the peripheral blood Th1/Th2 type cytokines expression level of CHB patients; At the same time, liver fimction was detected by Fully Automatic Biochemical Analyzer; HBV DNA loads were detected by PCR Method; Hepatitis b virology markers were detected by Chemil Method. F-test and Pearson correlation analysis were used for statistical analysis. Results Before ETV antiviral treatment, peripheral blood Thl cytokines IFN gamma expression level in patients with CHB increased significantly （P = 0.010） compared with the healthy control group while TNF alpha expression level having no statistically significant difference （P = 0.095）; Th2 type cytokines IL-4, IL-6, IL-10 levels decreased obviously （P = 0.039, P = 0.014, P = 0.026） compared with those in the control group. After 48 weeks of treatment, Th 1 cytokines IFN gamma and TNF alpha expression levels were reduced significantly （19.2±5.03 pg/ml vs 24.69±6.51 pg/ml, and 6.09±4.99 pg/ml vs 9.50±7.34 pg/ml, P 〈 0.001, and P = 0.016） compared with that before treatment; Th2 type cytokines IL-4, IL-6 expression level increased significantly （33.86±22.47 pg/ml vs 21.32±12.84 pg/ml, and 11.65±6.91 pg/ml vs 8.51±4.94 pg/ml, P = 0.004, andP = 0.029） compared with that before treatment while IL-10 expression level having no statistical significance （P = 0.081）. There was disorder and irregularity in the correlation between the levels of Th1/Th2 type cytokines. And there was no correlation between the various cytokines and HBV DNA loads in patients with CHB. Conclusion ETV can not only inhibit HBV DNA replication, reducing HBV DNA loads, but also contribute to regulate Th1/ Th2 type cytokines expression level in patients with CHB, but there was no correlation between the levels of various cytokines, various cytokines and HBV DNA loads.