恩替卡韦治疗慢性乙型肝炎患者免疫功能变化的研究  

Study of immune function change in chronic hepatitis B patients with enticarvir antiviral treatment

作　　者：宋春辉[1] 张纪元[1] 石峰[1] 王玉[1] 陈黎明[1] 王福生[1] 

机构地区：[1]解放军第三0二医院肝病生物治疗研究中心,北京100039

出　　处：《国际流行病学传染病学杂志》2011年第2期82-86,共5页International Journal of Epidemiology and Infectious Disease

摘　　要：目的 研究恩替卡韦（ETV）治疗慢性乙型肝炎过程中患者免疫功能的变化。方法在应用ETV治疗的不同时间点抽取HBV感染患者及健康对照者静脉血，对HBV表面标志物、HBVDNA、ALT水平进行检测；分离血清及外周血单核细胞（PMBC），检测并对比治疗前后血清细胞因子、经CD3／CD28细胞和HBV核心抗原（HBcAg）两种刺激PBMC分泌的细胞因子以及外周血中免疫细胞的频数。结果应用ETV治疗后，HBV感染组患者ALT水平及HBVDNA从第4周开始出现明显下降，分别为（73．78±93．34）U／L和（3．98±0．75）IU／mL，与治疗前比较差异有统计学意义（t=3．816、2．795，P〈0．05），至第48周时均降至正常范围。治疗4周后，血清及刺激后血清中的IFNγ明显降低，与治疗前比较差异有统计学意义（t=2．386、2．358、2．448，P〈0．05）。血清IL-10逐渐下降，至48周时达（78．12±24．01）pg／mL，仍高于健康对照组的（64．97±15：51）pg／mL（t=2．823，P〈0.05）。血清及刺激后血清中IL-17在治疗第4周出现明显升高，与治疗前相比差异有统计学意义（t=3．580、2．448、2.464，P〈0．05）。血清IL-22治疗4周时升高至（85．22±38．37）pg／mL，但仍明显低于对照组的（161．93±42．22）pg／mL，差异有统计学意义（t=2．272，P〈0．05）。Th1和Th17类细胞的频数在第4周时出现一个明显的升高，与治疗前相比差异有统计学意义（t=2．386、2．998，P〈0．05），后逐渐下降至接近治疗前，48周时仍高于健康对照；Th2类细胞频数治疗4周后明显高于治疗前（t=3．062，P〈0．05），12周达到峰值，在48周时低于健康对照组（t=2．690，P〈0．05）；调节性T细胞频数下降接近健康水平。结论刚在有效抑制病毒复制的同时，能够降低体内炎症反应，同时也可能削弱机体清除病毒的能力。Objective To investigate the feature of immune function in chronic hepatitis B（CHB） patients with enticarvir （ETV） therapy. Methods The venous blood samples in health controls and CHB patients at different time points after ETV therapy were collected. Serum and PBMCs were isolated, HBV markers, HBV DNA, ALT, serum cytokines and the cytokines were stimulated by CD3/CD28 cells and HBcAg, the frequency of immune cells were detected and compared with pretreatment. Results ALT and HBV DNA levels in patients at the 4th week decreased significantly, which were （73.78 ±93.34） U/L and （3.98 ± 0.75）IU/mL respectively （ t = 3.816,2.795, P 〈 0.05）, and the both returned to normal after 48-week therapy of ETV. IFN γ in serum and two stimulation supernatant decreased significantly compared to baseline after 4-week therapy （t = 2.386, 2.358,2.448, P 〈 0.05）. IL-10 level in serum decreased to （78.12 ± 24.01 ） pg/mL and was still higher than that in the health controls at the 48th week（ t = 2.823, P 〈 0.05）. IL-17 in serum and two stimulation supematant increased significantly compared to baseline at the 4th week （ t = 3.580, 2.448,2.464, P 〈 0.05）. IL-22 in serum increased to （85.22 ± 38.37） pg/mL and was still lower than that in health controls at the 4th week （ t = 2.272, P 〈 0.05）. The frequency of Thl and Th17 cells increased signiticandy at the 4th week （t = 2.386, 2.998, P 〈 0.05）; and then decreased gradually but still higher than that in health controls at the 48th week. The frequency of Th2 cells increased obviously at the 4th week （ t = 3.062, P 〈 0.05）, and was the highest at the 12th week, then was lower than that in health controls at the 48th week（ t = 2.690, P 〈 0.05）. The frequency of Treg cells decreased to normal after the treatment. Conclusions ETV suppresses HBV replication efficiently, which may attenuate hepatic inflammation but impair the ability of HBV clearing in the disease.

关 键 词：肝炎 乙型 慢性 恩替卡韦 细胞因子 免疫功能 

分 类 号：R512.62[医药卫生—内科学]