Vermehren Johannes, Bourlière Marc, Pol Stanislas, Marcellin Patrick, Hyland Robert H, Jiang Deyuan, Brainard Diana M, Zeuzem Stefan, Welzel Tania M
Medizinische Klinik 1, Universitätsklinikum Frankfurt, Frankfurt am Main, Germany.
Hépato-Gastroénterologie, Hôpital-Saint Joseph, Marseille, France.
J Clin Virol. 2017 Apr;89:51-56. doi: 10.1016/j.jcv.2017.02.008. Epub 2017 Feb 24.
Repeated measurements of hepatitis C virus (HCV) RNA levels during antiviral therapy are recommended to monitor treatment efficacy and adherence. Throughout most direct antiviral agent (DAA) approval studies, HCV RNA cutoffs and endpoints were established with the COBAS TaqMan assay for use with the High Pure System (HPS/CTM). Different assays used in clinical practice may yield different quantitative results and possibly impact treatment decisions.
The concordance of the fully-automated COBAS AmpliPrep/COBAS TaqMan assay (CAP/CTM) with HPS/CTM and its ability to predict response to DAA-treatment with ledipasvir/sofosbuvir was assessed in cirrhotic patients with HCV genotype-1-infection who had failed prior treatment with protease inhibitor-based regimens.
Serum samples from patients (n=154) treated in the phase-2 SIRIUS-study were collected at baseline and during antiviral therapy (weeks 1-8), and were tested in parallel by both assays.
The mean difference between HPS/CTM and CAP/CTM at baseline (n=153) was 0.32 log IU/mL HCV RNA. Discordant results were observed in 12% of samples collected at treatment weeks 1-8, with the greatest differences observed at weeks 2 and 4 (14% and 29%, respectively, for undetectable HCV RNA). SVR rates were 96%-97% in the study and were not significantly different between patients with detectable vs. undetectable HCV RNA according to both assays at weeks 1-4 of antiviral therapy.
CAP/CTM and HPS/CTM showed significantly different response rates during the early stages of ledipasvir/sofosbuvir treatment. However, on-treatment response was not predictive of SVR with either assay, indicating that determination of on-treatment HCV RNA levels may not be useful to guide treatment decisions.
建议在抗病毒治疗期间反复测量丙型肝炎病毒（HCV）RNA水平，以监测治疗效果和依从性。在大多数直接抗病毒药物（DAA）批准研究中，HCV RNA临界值和终点是通过用于高纯系统（HPS/CTM）的COBAS TaqMan检测法确定的。临床实践中使用的不同检测方法可能会产生不同的定量结果，并可能影响治疗决策。
在先前使用基于蛋白酶抑制剂的方案治疗失败的HCV 1型感染肝硬化患者中，评估全自动COBAS AmpliPrep/COBAS TaqMan检测法（CAP/CTM）与HPS/CTM的一致性及其预测对来迪派韦/索磷布韦DAA治疗反应的能力。
收集在2期SIRIUS研究中接受治疗的患者（n=154）在基线和抗病毒治疗期间（第1-8周）的血清样本，并通过两种检测方法进行平行检测。
基线时（n=153）HPS/CTM和CAP/CTM之间的平均差异为0.32 log IU/mL HCV RNA。在治疗第1-8周收集的样本中，12%观察到结果不一致，在第2周和第4周观察到的差异最大（对于不可检测的HCV RNA，分别为14%和29%）。研究中的持续病毒学应答（SVR）率为96%-97%，在抗病毒治疗第1-4周时，根据两种检测方法，HCV RNA可检测与不可检测的患者之间的SVR率无显著差异。
在来迪派韦/索磷布韦治疗的早期阶段，CAP/CTM和HPS/CTM显示出显著不同的反应率。然而，两种检测方法中治疗期反应均不能预测SVR，这表明测定治疗期HCV RNA水平可能无助于指导治疗决策。
