慢性丙型肝炎患者外周血CD4^+ CD25^(high)调节性T细胞与抗病毒疗效的关系

Relationship between effect of antiviral therapy and CD4^+ CD25^(high) regulatory T cells in peripheral blood of patients with chronic hepatitis C

目的探讨慢性丙型肝炎患者外周血CD4+CD25high调节性T细胞(Treg)与抗病毒疗效的关系。方法选取83例完成抗病毒治疗和随访的慢性丙型肝炎患者作为研究对象(慢性丙型肝炎组)。分别在治疗前和治疗12、48周及随访24周时,采用流式细胞术检测外周血中CD4+CD25highTreg百分比,并进行血清丙型肝炎病毒核糖核酸(HCV-RNA)定量和肝功能指标丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)等指标的检测。设立正常对照组(n=32)。结果与正常对照组比较,治疗前慢性丙型肝炎组外周血中的CD4+CD25highTreg百分比和血清ALT、AST均显著升高(P<0.05)。在治疗12周时,32例患者获得早期病毒学应答(EVR),外周血CD4+CD25highTreg百分比和HCV-RNA定量结果与治疗前和未获得EVR患者比较,差异均有统计学意义(P<0.01),但血清ALT无明显变化。在治疗48周时,慢性丙型肝炎病毒学应答组(HCV-RNA定量结果低于最低检测限)(n=51)患者外周血中CD4+CD25highTreg百分比、HCV-RNA定量结果和血清ALT均显著低于治疗前和无病毒学应答组(n=32)(P<0.01),慢性丙型肝炎无病毒学应答组患者各项检测指标治疗前后比较差异无统计学意义(P>0.05)。治疗后随访24周时,病毒学应答组中有39例患者获得了持续病毒学应答(SVR),外周血中的CD4+CD25highTreg百分比、HCV-RNA定量及血清ALT均显著低于治疗前和未获得SVR患者(P<0.01);而未获得SVR患者的各项检测指标均较治疗结束时(48周末)明显升高(P<0.05)。结论慢性丙型肝炎患者抗病毒治疗及随访过程中外周血中CD4+CD25highTreg百分比的变化对预测疗效和复发有一定的价值。

Objective To investigate the relationship between the effect of antiviral therapy and CD4 ＋ CD25hish regulatory T cells （Treg） in peripheral blood of patients with chronic hepatitis C. Methods Eighty-three patients with chronic hepatitis C who completed antiviral therapy and received follow-up employed to determine the percentages of CD4＋CD25high were enrolled （chronic hepatitis C group）. Flow reg e treatment for 12 weeks, treatment for 48 weeks and follow-up ells in peripheral blood for 24 weeks, and s, at the time points of bef, was ent, hepatitis C-RNA （HCV-RNA）, alanine aminotransferase （ALT） and aspartate aminotransferase （AST） were quantified meanwhile. Besides, normal control group was established （n = 32）. Results The percentage of CD4＋CD25high Treg cells in peripheral blood and serum ALT and AST in chronic hepatitis C group were significantly higher than those in normal control group before treatment （P 〈 O. 05）. At 12 weeks of treatment, the percentage of CD4 ＋ CD25high Treg cells in peripheral blood and HCV-RNA quantity in 32 patients with early virology response （EVR） were significantly different from those of these patients before treatment and from patients without EVR （P 〈0.01）, while such difference was not found in serum ALT. At 48 weeks of treatment, the percentage of CD4＋CD25high Treg cells in peripheral blood, HCV-RNA quantity and serum ALT in chronic hepatitis C virology response group （HCV-RNA quantity below lowest detectable limit） （n = 51） were significantly lower than those of these patients before treatment and patients in chronic hepatitis C no-virology response group （n = 32） （P 〈 0.01）, and there was no significant difference between the parameters before treatment and those after treatment in chronic hepatitis C no- virology response group （P 〉 0. 05）. At 24 weeks of follow-up, the percentage of CD4 ＋ CD25high Treg cells in peripheral blood, HCV-RNA quantity and serum ALT in 39 patients with sustained viral response （SVR） in chronic hepatitis C virology response group were significantly lower than those of these patients before treatment and patients without SVR （P 〈 0.01）, and the parameters of patients without SVR were significantly higher than those at the end of treatment （at the end of 48 weeks） （P 〈 0.05）. Conclusion The percentages of CD4＋CD25high Treg cells in peripheral blood during antiviral therapy and follow-up have definite value in prediction of therapeutic effect and recurrence.