慢性乙型肝炎患者抗病毒治疗与停药复发后体内乙型肝炎核心抗原特异性T淋巴细胞变化  

Changes of hepatitis B core antigen-specific cytotoxic T lymphocytes in chronic hepatitis B patients during antiviraltreatment and relapse after withdrawal of treatment

作　　者：刘碧霞[1] 张伦理[2] 张文峰[2] 

机构地区：[1]江西省肿瘤医院重症医学科,南昌330029 [2]南昌大学第一附属医院传染科

出　　处：《中华传染病杂志》2016年第8期480-484,共5页Chinese Journal of Infectious Diseases

基　　金：江西省教育厅青年科学基金立项项目（GJJ14175）;江西省研究生创新专项资金立项项目（YC2013-S011）.

摘　　要：目的探讨停用核苷（酸）类似物后CHB患者短时间内出现严重肝损伤的可能机制。方法纳入2014年8月至2015年3月在南昌大学第一附属医院传染科住院的49例慢性HBV感染者及8名健康志愿者，均经人类白细胞抗原（HLA）-A2等位型鉴定为阳性。慢性HBV感染者中免疫耐受组15例，持续抗病毒治疗组20例，停药复发组14例。应用流式细胞术结合HLA-A＊0201限制性表位肽/五聚体复合物定量检测慢性HBV感染者外周血HBcAg18-27表位特异性CD8＋T淋巴细胞，酶联免疫斑点法（ELISPOT）检测HBcAg18-27表位特异性CD8＋T淋巴细胞分泌γ干扰素、TNF-α的水平。统计学分析采用非参数U检验。结果健康对照组、免疫耐受组、持续抗病毒治疗组和停药复发组的HBcAg特异性CD8＋T淋巴细胞频数分别为（0.17±0.16）%、（1.46±0.72）%、（3.24±1.60）%和（4.67±2.43）%，免疫耐受组、持续抗病毒治疗组、停药复发组与健康对照组比较，差异均有统计学意义（Z值分别为－3.583、－4.018和－3.823，均P〈0.01）；免疫耐受组、停药复发组与持续抗病毒治疗组比较，差异有统计学意义（Z值分别为－3.400和－2.030，均P〈0.05）；免疫耐受组与停药复发组比较，差异均有统计学意义（Z＝－3.230，P〈0.01）。健康对照组、免疫耐受组、持续抗病毒治疗组和停药复发组HBcAg特异性CD8＋T淋巴细胞表达γ干扰素水平分别为2（0～6）、16（2～53）、106（14～254）和156（28～395）斑点形成细胞（SFC）/106PBMC，免疫耐受组、持续抗病毒治疗组及停药复发组与健康对照组比较，差异均有统计学意义（Z值分别为－3.585、－4.069和－3.824，均P〈0.01）；停药复发组明显高于持续抗病毒治疗组（Z＝－2.205，P＝0.027）；持续抗病毒治疗组明显高于免疫耐受组（Z＝－4.700，P〈0.01）。各组HBcAg特异性CD8＋T淋巴细胞表达TNF-α水平分别为2（0～5�Objective To explore the potential mechanism of severe liver injury shortly after withdrawal of antiviral therapy in chronic hepatitis B （CHB） patients. Methods Forty-nine patients with chronic hepatitis B virus （HBV） infection from the Department of Infectious Diseases of the First Affiliated Hospital of Nanchang University and 8 healthy volunteers from August 2014 to March 2015 were included in this study. All of them were human leukocyte antigen （HLA）-A2-positive. CHB patients were classified into three groups, including 15 cases in immune-tolerance group, 20 cases in sustained antiviral treatment group, and 14 cases in recurrence of drug withdrawal group. The frequency ofperipheral HLA-A0201-restricted hepatitis B core antigen （HBcAg）18-27 pentamer complex specific CD8＋ T cells in CHB patients was analyzed by flow cytometry. Enzyme linked immunospot assay（ELISPOT） was used to detect interferon-gamma （IFN-3） and tumor necrosis factor-a （TNF-a） secretions of HBcAg18-27-specific CD8 T cells. The experimental data were analyzed using non-parametric U tests. Results In healthy control group, immune-tolerance group, sustained antiviral treatment group and recurrence of drug withdrawal group, the frequencies of HBcAg-specific CI）8＋ T cells were （O. 17 ± 0.16）%, （1. 46±0.72）X, （3. 24±1.60）% and （4.67±2.43）%, respectively. Compared with healthy control group, the difference were all statistically significant in the three groups （Z= --3. 583, --4. 018 and --3. 823, respectively; all P〈0.01）. The frequencies of HBcAg-specific CD8＋T cells in immune- tolerance group or recurrence of drug withdrawal group were both significantly different from that in sustained antiviral therapy group （Z= --3. 400 and --2. 030, respectively both P〈0.05）. The difference between immune-tolerance group and recurrence of drug withdrawal group was also significant （Z = --3. 230, P〈0.01）. The secretion levels of IFN-7 of HBcAg-specific CD8＋ T cells in healthy control gro

关 键 词：肝炎 乙型 T淋巴细胞 细胞毒性 抗病毒治疗 复发 

分 类 号：R512.62[医药卫生—内科学]