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目的观察难治性慢性丙型肝炎的NK细胞和Treg细胞动态变化,分析与抗病毒疗效相关的免疫因素。方法采用开放性、前瞻性临床队列研究。入组2009年9月-2010年10月收治的难治性慢性丙型肝炎患者41例(初治组30例和无应答组11例)和健康对照(HC)者11例,初治组给予聚乙二醇干扰素(PEG-IFN)α-2a 180μg/周联合利巴韦林10.6~15 mg·kg-1·d-1治疗48周,无应答组给予PEG-IFNα-2a 180μg/周联合利巴韦林15 mg·kg-1·d-1治疗72周;动态留取细胞和血清,进行HCV RNA、肝功能和NK细胞和Treg细胞的检测,分析与疗效相关的免疫因素。计量资料采用t检验或秩和检验,计数资料采用χ2检验。结果所有患者均完成抗病毒治疗和24周随访,初治获得SVR者17例(56.7%),未获得SVR(nSVR)者13例;无应答组获得SVR者3例(27.2%),未获得SVR(RFP)者为8例(72.7%)。基线总体患者的NK细胞频率低于HC组,Treg细胞频率高于HC组;同时抗病毒治疗疗程中,初治获得SVR者24周NK细胞频率较基线和4周明显增加,Treg细胞频率较基线和4周明显下降;同时初治nSVR者Treg细胞频率24周时较基线和4周明显升高;无应答组再治疗仍未获得SVR者无论NK细胞频率或者Treg细胞频率均未见明显变化。结论 NK细胞频率的降低以及Treg细胞频率的增加与HCV慢性感染有关;抗病毒治疗后NK细胞及Treg细胞的动态变化,可以预测抗病毒疗效:疗程中NK细胞频率的增加以及Treg细胞频率的下降与疗效好有关。
Objective To observe the dynamic changes of NK cells and Treg cells in patients with refractory chronic hepatitis C and to analyze the immune factors related to antiviral efficacy. Methods Open-label, prospective clinical cohort study. Thirty-one patients with refractory chronic hepatitis C who were admitted to our hospital from September 2009 to October 2010 (11 in control group and 11 in non-responsive group) and 11 in control group (HC) Pegylated interferon (PEG-IFN) α-2a 180μg / week combined with ribavirin 10.6-15 mg · kg-1 · d-1 for 48 weeks, no response group given PEG-IFNα-2a 180μg / week The combination of ribavirin 15 mg · kg-1 · d-1 for 72 weeks; dynamic collection of cells and serum, HCV RNA, liver function and NK cells and Treg cells were detected, and efficacy-related immune factors. Measurement data using t test or rank sum test, counting data using χ2 test. Results All patients received antiretroviral therapy and follow-up for 24 weeks. There were 17 cases (56.7%) with SVR in initial treatment, 13 cases without SVR (nSVR), 3 cases (27.2%) with SVR in non-responder group, SVR (RFP) were 8 cases (72.7%). The frequency of NK cells in baseline patients was lower than that in HC patients and the frequency of Treg cells was higher than that in HC patients. At the same time, the frequency of NK cells in SVR patients was significantly higher than that in baseline and 4 weeks And significantly decreased in 4 weeks. At the same time, the frequency of Treg cells in newly diagnosed nSVR patients was significantly higher than that in baseline and 4 weeks after 24 weeks of treatment. No response to NKT or NK cells was observed in non-responders group. Conclusion The decrease of NK cell frequency and the increase of Treg cell frequency are related to the chronic infection of HCV. The dynamic changes of NK cells and Treg cells after antiviral therapy can predict the antiviral effect: the increase of NK cell frequency during treatment and the decrease of Treg cell frequency And good effect.