恩替卡韦治疗慢性乙型肝炎病毒携带者疗效的免疫学观察

Immunological observation of the efficacy of entecavir antiviral therapy in chronic hepatitis B virus carriers

摘要:

目的：从免疫学角度观察恩替卡韦治疗慢性乙型肝炎病毒携带者（chronic hepatitis B virus carriers，CHBc）的疗效，为CHBc的治疗提供依据。方法：纳入CHBc 61例为实验组，慢性乙型肝炎（chronic hepatitis B，CHB）30例为阳性对照组，健康人30例为正常对照（normal control，NC）组。CHBc组和CHB组接受恩替卡韦治疗24周，NC组不接受任何治疗。收集初次就诊和恩替卡韦治疗24周后的外周血样本，Treg、Th17细胞频率用流式检测仪进行检测，白细胞介素（interleukin，IL）-10、转化生长因子（transforming growth factor，TGF）-β1和IL-17水平采用酶联免疫吸附法检测。结果：治疗前，CHBc组（18.58±10.79）Treg/Th17比值较NC组（6.26±3.29）、CHB组（2.68±1.39）高（P=0.000），NC组又较CHB组更高（P=0.000）。恩替卡韦治疗24周后，CHBc、CHB组Treg/Th17比值均降低（P=0.000），且CHBc组（6.60±5.27）较NC组（6.26±3.29）、CHB组（1.09±0.72）高（P=0.000），NC组、CHBc组之间没有明显差异（P=0.986）。CHBc组（r=0.827；r=0.353；r=0.391）和CHB组（r=0.826；r=0.529；r=0.580）Treg/Th17比值与HBV-DNA、HBsAg和HBeAg均呈正相关关系（P=0.000）。结论：恩替卡韦可以调节CHBc的免疫应答，使Treg/Th17比值下降，从而促进乙肝病毒（hepatitis B virus，HBV）及HBV标志物的清除，远期可能有助于减缓肝纤维化、肝硬化的进展。本研究证实CHBc有必要进行抗病毒治疗，且疗效佳、安全。

Abstract:

Objective：To observe the efficacy of entecavir in the treatment of chronic hepatitis B virus carriers（CHBc） from the im－munological perspective and to provide the basis for the treatment of chronic hepatitis B virus carriers. Methods：Sixty-one chronic hepatitis B virus carriers were enrolled as experimental group，thirty chronic hepatitis B（CHB） were enrolled as positive control group，thirty healthy people were enrolled as normal control（NC） in this study. CHBc and CHB groups received entecavir for 24 weeks，while NC group did not receive any treatment. Peripheral blood samples were collected before and after 24 weeks entecavir treatment. The frequencies of Treg，Th17 cells were detected by flow cytometric analysis，and the levels of IL-10，TGF-β1 and IL-17 were detected by enzyme-linked immunosorbent assay（ELISA）. Results：Before treatment，the ratio of Treg/Th17 in CHBc（18.58±10.79） group was higher than that in NC（6.26±3.29），CHB（2.68±1.39） groups（P=0.000），and NC group was higher than CHB（P=0.000） group. After 24 weeks entecavir treatment，the ratio of Treg/Th17 in CHBc and CHB groups decreased（P=0.000），and the CHBc（6.60±5.27） group was higher than that in NC（6.26±3.29），CHB（1.09±0.72） groups（P=0.000），and there was no sig－nificant difference between the NC and CHBc（P=0.986） groups. The ratio of Treg/Th17 in CHBc（r=0.827；r=0.353；r=0.391） and CHB（r=0.826；r=0.529；r=0.580） groups were positively correlated with HBV-DNA，HBsAg and HBeAg（P=0.000）. Conclusion：En－tecavir can regulate the immune response of chronic HBV carriers，reduce the ratio of Treg/Th17 and promote the clearance of HBV and HBV markers，forward may slow down the progress of liver fibrosis and cirrhosis. This study confirms that it is necessary for chronic HBV carriers to receive antiviral therapy，and the efficacy is good and safe.