恩替卡韦治疗后慢性乙型肝炎患者外周血T淋巴细胞表面程序性死亡受体1表达与HBeAg血清学转换的关系  

Relationship between PD-1 expression on peripheral T lymphcytes and HBeAg seroconversion after entecavir treatment in chronic hepatitis B patients

作　　者：夏娟[1] 许林[1] 刘勇[1] 严晓敏[1] 李新慧[1] 郝迎迎[1] 程健[1] 吴超[1] 

机构地区：[1]南京医科大学鼓楼临床医学院感染科,科研部,210008

出　　处：《中华肝脏病杂志》2011年第2期93-97,共5页Chinese Journal of Hepatology

基　　金：基金项目：南京市医学重点科技发展项目（ZKXl0015）

摘　　要：目的动态观察慢性乙型肝炎患者恩替卡韦抗病毒治疗后不同时期外周血T淋巴细胞（简称T细胞）表面程序性死亡受体1（PD-1）表达的变化，并探讨其与HBeAg血清学转换间的关系。方法对20例HBeAg阳性慢性乙型肝炎患者予以恩替卡韦抗病毒治疗并随访51周，根据HBeAg是否发生血清学转换分为：HBeAg未转换组（14例），HBeAg转换组（6例）。分别于治疗前（基线，TO）、治疗2～4周（T1）、治疗5～10周（T2）、治疗11～20周（T3）、治疗21～30周（T4）、治疗31～51周（T5）收集外周血，流式细胞术检测CD4^＋、CD8^＋T细胞表面PD—1的表达水平，实时荧光定量PCR检测血清HBVDNA载量，同时检测血清ALT水平。正态分布资料采用独立样本t检验，非正态分布者采用Mann—WhitneyU检验比较组间差异，相关性分析采用Pearson相关分析。结果治疗前两组患者血清HBVDNA载量分别为（7．54±0．67）log10拷贝／ml、（7．30±0．79）log10拷贝／ml（P〉0．05），ALT水平为（187．26±184．15）U／L、（272．17±215．07）U／L（P〉0．05），外周血CD4＋T细胞表面PD-1表达水平为6．040／0±3．71％、6．77％±2．88％（P〉0．05），CD8^＋T细胞表面PD1表达水平为6．39％±3．33％、8．88％±2．84％（P〉0．05）。恩替卡韦抗病毒治疗后两组患者血清HBVDNA载量、ALT水平的下降与CD4^＋、CD8^＋T细胞表面PD1表达的下调呈显著正相关（r=0．212，P=0．05；r=0．377，P〈0．01；r=0．279，P〈0．05；r=0．347，P〈0．01）。在相同的随访时间段内，HBeAg转换组血清HBVDNA载量、ALT水平及外周血CD4^＋、CD8^＋T细胞表面PD-1表达的下降率均高于HBeAg未转换组，且两组间△T0～T1、△T0～T2期HBVDNA的下降率及△T0～T2、△T0～T3期CD8^＋T细胞表面PD1表达的下降率差异有统计学意义（分别为49．9％对比37．3％，56．7%对比47．4％，70．1％对比-4．2％，66�Objective To observe longitudinally the expression of Programmed death 1（PD-1） on peripheral blood T cells in chronic hepatitis B patients underwent antiviral treatment with entecavir （ETV） and to explore the relationship between PD-1 expression and HBeAg seroconversion. Methods Twenty HBeAg positive patients underwent antiviral treatment with ETV were followed up for 51 weeks. 14 patients remained HBeAg positive and 6 patients achieved HBeAg seroconversion. Peripheral blood was collected at six time points： TO： baseline, TI： 2-4week; T2： 5-10week; T3：11-20week; T4： 21-30week： T5： 31-51week. PD-1 expressions on T cells were assessed by flow cytometry. Serum HBV DNA loads were determined by real-time fluorescent quantitative polymerase chain reaction （PCR） and serum ALT levels were examined at the same time. Results At baseline, serum HBV DNA load of patients without HBeAg seroconversion and with HBeAg seroconversion were （7.54 ± 0.67） log,0 copies/ml and （7.30 ± 0.79） log10 copies/ml （P 〉 0.05）, the ALT levels were （187.26 ± 184.15） U/L and （272.17 ± 215.07） U/L （P 〉 0.05）, PD-1 exprissions on CD4^± T cells were 6.04% ± 3.71% and 6.77% ± 2.88% （P 〉 0.05）, PD-1 exprissions on CD8^±T cells were 6.39% ± 3.33% and 8.88% ± 2.84% （P 〉 0.05）. After ETV treatment, serum HBV DNA loads and ALT levels both decreased gradually, which was positively correlated with PD-1 expressions on CD4^＋ and CD8^＋ T cells （r = 0.212, P = 0.05; r = 0.377, P 〈 0.01; r = 0.279, P 〈 0.05; r = 0.347, P 〈 0.01）. During the same monitoring period, the HBV DNA loads, ALT levels and PD-1 expressions on T cells of the patients with HBeAg seroconversion decreased significantly as compared with the patients without HBeAg seroconversion. Besides, the decrease of HBV DNA loads during period A T0-T1 and A T0-T2 and PD-1 expressions on CD8^＋ T cells during period △ T0-T2 and △ T0-T3 were significantly different between these two kinds of patients （49.9% vs

关 键 词：肝炎 乙型 慢性 肝炎E抗原 乙型 程序性死亡受体1 恩替卡韦 

分 类 号：R512.62[医药卫生—内科学]