恩替卡韦治疗HBeAg阳性慢性乙型肝炎病毒携带者PD-1^(+)CXCR5^(+)CD4^(+)T淋巴细胞和sPD-1水平观察  

Observation of PD-1^(+)CXCR5^(+)CD4^(+)T lymphocyte and sPD-1 levels in HBeAg positive chronic hepatitis B virus carriers treated with entecavir

作　　者：何建 姚云清[1] 夏仁祥 邱天霁 龙玲 汪燕[1] 蒋影 He Jian;Yao Yunqing;Xia Renxiang;Qiu Tianji;Long Ling;Wang Yan;Jiang Ying(Department of Infectious Diseases,the First Affiliated Hospital of Chongqing Medical University,Chongqing 400016,China)

机构地区：[1]重庆医科大学附属第一医院感染科,重庆400016

出　　处：《中华肝脏病杂志》2022年第3期316-322,共7页Chinese Journal of Hepatology

基　　金：重庆市医学科研计划重点资助项目 (2015ZDXM008)。

摘　　要：目的:动态观测恩替卡韦治疗HBeAg阳性慢性乙型肝炎病毒携带者的临床疗效及其外周血PD-1^(+)CXCR5^(+)CD4^(+)T淋巴细胞、可溶性程序性死亡受体1(sPD-1)水平变化并探讨其临床意义。方法:慢性乙型肝炎病毒携带者治疗(A)组31例,慢性乙型肝炎患者治疗(B)组32例,慢性乙型肝炎病毒携带者未治疗(C)组15例,收集并比较3组患者0周、24周、48周外周血标本和临床资料,流式细胞技术检测PD-1^(+)CXCR5^(+)CD4^(+)T淋巴细胞,酶联免疫吸附法检测sPD-1水平。3组间计量资料行方差分析检验与Spearman相关性分析。结果:0周时,A组、C组血清HBsAg、HBeAg和HBV DNA水平均显著高于B组;外周血PD-1^(+)CXCR5^(+)CD4^(+)T淋巴细胞,B组(4.70%±1.58%)显著高于A组(3.25%±1.01%)和C组(2.77%±0.67%)(F=16.65,P<0.05),A组与C组间差异不明显(P>0.05);外周血sPD-1,B组[(1866.62±1472.70)pg/ml]显著高于A组[(824.86±538.66)pg/ml]和C组[(618.19±602.62)pg/ml](F=10.95,P<0.05),A组与C组间差异不明显(P>0.05)。48周时血清HBsAg,A组、C组较基线无显著下降(P>0.05),均显著高于B组(P<0.05);血清HBeAg,A组、B组较基线均显著下降(P<0.05),但A组显著高于B组(P<0.05),A组与C组间差异不明显(P>0.05);血清HBV DNA水平,A组、B组较基线均显著下降(P<0.05),均显著低于C组(P<0.05),A组与B组差异不明显(P>0.05);外周血PD-1^(+)CXCR5^(+)CD4^(+)T淋巴细胞,A组(1.56%±0.73%)、B组(1.32%±0.43%)较基线均显著下降(P<0.05),均显著低于C组(2.64%±0.85%)(P<0.05),A组与B组无明显差异;外周血sPD-1,A组[(289.05±215.86)pg/ml]、B组[(236.01±173.92)pg/ml]较基线均显著下降(P<0.05),均显著低于C组[(650.34±598.46)pg/ml](P<0.05),A组与B组无明显差异(P>0.05)。相关性分析结果:48周时A组,PD-1^(+)CXCR5^(+)CD4^(+)T淋巴细胞比例下降水平与HBsAg、HBV DNA下降水平无相关性,与HBeAg下降水平呈正相关(r=0.376,P<0.05);sPD-1下降水平与HBsAg变化无相关性,与HBeAg、HBV DNA下降水平均呈正相�Objective To dynamically observe the clinical efficacy of entecavir and the changes of PD-1^(+)CXCR5^(+)CD4^(+)T lymphocytes and sPD-1 levels in peripheral blood of HBeAg-positive chronic hepatitis B virus carriers treated with entecavir,and further explore its clinical significance.Methods There were 31 cases of chronic hepatitis B virus carriers in the treatment group(A),32 cases of chronic hepatitis B virus carriers in the treatment group(B),and 15 cases of chronic hepatitis B virus carriers in the non-treatment group(C).Three groups peripheral blood samples and clinical data at 0,24 and 48 weeks were collected and compared.PD-1^(+)CXCR5^(+)CD4^(+)T lymphocytes were detected by flow cytometry,and the level of sPD-1 was detected by enzyme-linked immunosorbent assay.ANOVA and Spearman correlation analysis were performed on the measurement data among the three groups.Results At week 0,the serum levels of HBsAg,HBeAg and HBV DNA were significantly higher in groups A and C than group B.PD-1^(+)CXCR5^(+)CD4^(+)T lymphocytes in peripheral blood were significantly higher in group B(4.70%±1.58%)than group A(3.25%±1.01%)and group C(2.77%±0.67%)(F=16.65,P<0.05).There was no significant difference between group A and group C(P>0.05).Peripheral blood sPD-1 in group B[(1866.62±1472.70)pg/ml]was significantly higher than group A[(824.86±538.66)pg/ml]and group C[(618.19±602.62)pg/ml](F=10.95,P<0.05).There was no significant difference between group A and group C(P>0.05).At 48 weeks,the serum HBsAg did not decrease significantly in groups A and C than baseline(P>0.05),but were significantly higher than group B(P<0.05).Serum HBeAg levels were decreased significantly in groups A and B than baseline(P<0.05).<0.05),but group A was significantly higher than group B(P<0.05),and there was no significant difference between group A and group C(P>0.05).Serum HBV DNA level was significantly lower in groups A and B than group C(P<0.05),and there was no significant difference between group A and group B(P>0.05).Peripheral blood PD-1^

关 键 词：慢性乙型肝炎 T淋巴细胞 程序性死亡受体1 恩替卡韦 

分 类 号：R512.62[医药卫生—内科学]