【作者】 李雪芬； 叶波； 杨先知； 陈瑜； 鲁海峰； 吴炜；

【Author】 LI Xuefen,YE Bo,YANG Xianzhi,LU Haifeng,WU Wei,CHEN Yu.Department of Laboratory Medicine,the First Affiliated Hospital of Medical College,Zhejiang University,79 QingChun Road, Hangzhou,310003,China

【机构】 浙江大学医学院附属第一医院临床检验中心； 浙江大学医学院附属第一医院传染病诊治国家重点实验室；

【摘要】 目的探讨CHB患者接受替比夫定治疗前后不同时期外周血CD4+、CD8+T淋巴细胞亚群数量和功能的变化及其与治疗疗效的相关性。方法选取给予替比夫定抗病毒治疗的CHB患者73例,在治疗前及治疗后12、24、36及48周,分别以荧光定量PCR检测血清HBV DNA水平,ELISA法检测HBV标志物,全自动生化分析仪检测ALT水平;采用流式细胞术方法分别检测外周血CD4+、CD8+T淋巴细胞比率,通过ELISPOT技术分析其分泌细胞因子IFN-γ的功能,并采用Spearman分析这些变量的相关性。结果 73例CHB患者在48周疗程结束后,有58例出现完全病毒学应答,15例出现不完全应答。58例完全应答者,治疗早期(12周)即出现明显细胞学应答CD4+(35.8±1.17%)、CD4+/CD8+(1.56±0.13)及细胞因子IFN-γ分泌(251±57 SFC/106PBMC),与治疗前(0周)时相比,差异有统计学意义(P<0.05),随时间推移及病毒复制的控制CD4+T细胞及CD4+/CD8+比率逐渐升高,但服药12周与服药24、36、48周比较无显著性差异(P>0.05)。不完全应答组上述指标变化差异无统计学意义。结论不同治疗效果患者呈现出不同的淋巴细胞亚群表达,早期持续有效的细胞免疫应答与抗病毒治疗疗效密切相关。更多还原

【Abstract】 Objective To explore the relationship between the dynamic fluctuations of peripheral CD4+,CD8+ T-lymphocyte subpopulations and serum viral load of chronic hepatitis B patients and their correlation during telbivudine therapy.Methods Seventy-three chronic hepatitis B patients were recruited and received telbivudine therapy for 48 weeks.Before and during the 12,24,36,48 weeks of treatment,serum HBV DNA load was measured by real time PCR.Markers of hepatitis B virus infection were detected by ELISA assay and levels of alanine aminotransferase in the serum were measured.Flow cytometry was used to detect the proportion of peripheral blood CD4+,CD8+ T lymphocytes subgroups and the secretion of IFN-γwith PBMC was observed using ELISPOT.Spearman test was used to analyse the correlation between these variables.Results Of the 73 patients after 48 weeks treatment,58 patients had complete virological response and 15 patients had incomplete response.Concomitantly with a quantitative reduction in viral replication,the frequency of CD4+ T cells,CD4+/CD8+ ratio and IFN-γincreased in the 58 patients with complete virological response during the early period(≤12 week)(CD4+,35.8 + 1.17%;CD4+/CD8+,1.56±0.13;and IFN-γ,251±57 SFC/106PBMC).The percentage of peripheral blood CD4+ T-cells,CD4+/CD8+ ratio and IFN-γcontinued to improve and achieved a highly significant difference from the baseline(P < 0.05) by the 12th week.With serum HBV DNA levels markedly reduced in the complete response groups,CD4+ T-cells and CD4+/CD8+ ratio gradually and steadily increased,but there was not significant among week 12,24,36 and 48.In the incomplete response, the frequency of T cell subgroups exhibited no significant difference among the five time points of the study.Conclusion Patients showed different lymphocyte subgroup fluctuations between complete response and incomplete response.Sustained and effective early immune response is closely correlated with the treatment efficacy of antiviral therapy.更多还原