HCV-1b慢性感染患者接受无干扰素的直接抗病毒药物治疗过程中病毒特异性T细胞的应答

发布时间：2018-04-15 23:26

本文选题：HCV-1b + 直接抗病毒药物　；参考：《吉林大学》2017年硕士论文

【摘要】：目的:本研究旨在观察接受无干扰素的直接抗病毒药物治疗方案的HCV-1b慢性感染患者在治疗过程中HCV特异性T细胞应答是否可以重建。方法:本实验从两个丙型肝炎直接抗病毒治疗临床药物试验中总共招募了20个HCV-1b慢性感染患者。其中9个初治患者来自临床试验“AI447-114”:daclatasvir联合asunaprevir的24周无干扰素疗法。其余来自临床试验“M13-767”:paritaprevir,ritonavir,ombitasvir合剂联合dasabuvir的12周无干扰素疗法,其中部分患者曾接受过传统干扰素(IFN)联合利巴韦林(RBV)治疗。跟踪检测患者不同时间点的转氨酶水平和病毒载量,同时收集病人外周血样本,并分离外周血单个核细胞(PBMCs)。使用总共376条覆盖HCV-1b全长序列的多肽刺激PBMCs,再通过酶联免疫斑点(ELISPOT)测定法来检测在无干扰素的直接抗病毒药物治疗过程中HCV特异性IFN-γ的分泌情况。结果:两个临床试验中所有患者的丙肝病毒定量在治疗第1周急速下降,绝大多数患者在治疗第4周以后低于检测下限,只有1个患者在治疗第16周以后发生病毒学突破。随着病毒定量的变化,两个临床试验中大多数患者的ALT和AST水平在治疗第1周后也急速下降,第2周后基本恢复至正常范围。两个临床试验患者分泌的丙肝病毒特异性IFN-γ在整个治疗过程中都保持在一个相对较低的水平,并且在各个时间点之间没有显示出较大的变化。结论:HCV-1b慢性感染患者在经过无干扰素的直接抗病毒药物治疗后,即使病毒得到快速清除,早期丙肝病毒特异性T细胞应答亦不能重建。
[Abstract]:Aim: to investigate whether the HCV specific T cell response can be reconstructed in patients with chronic HCV-1b infection receiving interferon-free direct antiviral therapy.Methods: a total of 20 patients with chronic HCV-1b infection were recruited from two clinical trials of direct antiviral therapy for hepatitis C.Nine of the first-time patients came from the clinical trial of "AI447-114": daclatasvir combined with asunaprevir for 24 weeks without interferon therapy.The rest came from the clinical trial of "M13-767": ritonavirombitasvir combined with dasabuvir for 12 weeks without interferon therapy, some of which had been treated with conventional interferon therapy combined with ribavirin.The levels of transaminase and viral load were measured at different time points, and peripheral blood samples were collected, and PBMCsof peripheral blood mononuclear cells were isolated.A total of 376 polypeptides covering the full-length sequence of HCV-1b were used to stimulate PBMCs. The secretion of HCV specific IFN- 纬 was detected by enzyme-linked immunoblot assay (Elisa) during direct antiviral therapy without interferon.Results: in the two clinical trials, the quantity of HCV in all patients decreased rapidly in the first week of treatment, most of the patients were below the detection limit after the fourth week of treatment, only one patient had a virological breakthrough after the 16th week of treatment.The levels of ALT and AST in most of the patients in the two clinical trials decreased rapidly after the first week of treatment and returned to normal level after the second week.Hepatitis C virus specific IFN- 纬 secreted by two clinical trial patients remained at a relatively low level throughout the course of treatment and showed no significant changes between different time points.Conclusion the early HCV specific T cell response can not be reconstructed in patients with chronic HCV-1b infection after direct antiviral therapy without interferon, even if the virus is cleared quickly.
【学位授予单位】：吉林大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R512.63

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