Sarrazin Christoph, Dierynck Inge, Cloherty Gavin, Ghys Anne, Janssen Katrien, Luo Donghan, Witek James, Buti Maria, Picchio Gaston, De Meyer Sandra
J. W. Goethe University, Medizinische Klinik 1, Frankfurt, Germany.
Janssen Infectious Diseases BVBA, Beerse, Belgium.
J Clin Microbiol. 2015 Apr;53(4):1264-9. doi: 10.1128/JCM.03030-14. Epub 2015 Feb 4.
Protease inhibitor (PI)-based response-guided triple therapies for hepatitis C virus (HCV) infection are still widely used. Noncirrhotic treatment-naive and prior relapser patients receiving telaprevir-based treatment are eligible for shorter, 24-week total therapy if HCV RNA is undetectable at both weeks 4 and 12. In this study, the concordance in HCV RNA assessments between the Roche High Pure System/Cobas TaqMan and Abbott RealTime HCV RNA assays and the impacts of different HCV RNA cutoffs on treatment outcome were evaluated. A total of 2,629 samples from 663 HCV genotype 1 patients receiving telaprevir/pegylated interferon/ribavirin in OPTIMIZE were analyzed using the High Pure System and reanalyzed using Abbott RealTime (limits of detection, 15.1 IU/ml versus 8.3 IU/ml; limits of quantification, 25 IU/ml versus 12 IU/ml, respectively). Overall, good concordance was observed between the assays. Using undetectable HCV RNA at week 4, 34% of the patients would be eligible for shorter treatment duration with Abbott RealTime versus 72% with the High Pure System. However, using <12 IU/ml for Abbott RealTime, a similar proportion (74%) would be eligible. Of the patients receiving 24-week total therapy, 87% achieved a sustained virologic response with undetectable HCV RNA by the High Pure System or <12 IU/ml by Abbott RealTime; however, 92% of the patients with undetectable HCV RNA by Abbott RealTime achieved a sustained virologic response. Using undetectable HCV RNA as the cutoff, the more sensitive Abbott RealTime assay would identify fewer patients eligible for shorter treatment than the High Pure System. Our data confirm the <12-IU/ml cutoff, as previously established in other studies of the Abbott RealTime assay, to determine eligibility for shortened PI-based HCV treatment. (The study was registered with ClinicalTrials.gov under registration no. NCT01241760.).
基于蛋白酶抑制剂（PI）的应答引导三联疗法仍广泛用于治疗丙型肝炎病毒（HCV）感染。初治且无肝硬化以及既往复发的患者，若接受基于替拉韦的治疗，且在第4周和第12周时HCV RNA均检测不到，则有资格接受为期24周的较短疗程的全疗程治疗。在本研究中，评估了罗氏高纯系统/ Cobas TaqMan与雅培实时HCV RNA检测法在HCV RNA评估方面的一致性，以及不同HCV RNA临界值对治疗结果的影响。对来自OPTIMIZE研究中663例接受替拉韦/聚乙二醇化干扰素/利巴韦林治疗的HCV 1型患者的2629份样本，先用高纯系统进行分析，再用雅培实时检测法重新分析（检测限分别为15.1 IU/ml和8.3 IU/ml；定量限分别为25 IU/ml和12 IU/ml）。总体而言，两种检测法之间观察到良好的一致性。以第4周时HCV RNA检测不到为标准，使用雅培实时检测法时，34%的患者有资格接受较短疗程的治疗，而使用高纯系统时这一比例为72%。然而，若雅培实时检测法采用<12 IU/ml作为标准，则有资格接受较短疗程治疗的患者比例相似（74%）。在接受24周全疗程治疗的患者中，87%通过高纯系统检测到HCV RNA检测不到或通过雅培实时检测法检测到<12 IU/ml时实现了持续病毒学应答；然而，雅培实时检测法检测到HCV RNA检测不到的患者中，92%实现了持续病毒学应答。以HCV RNA检测不到为临界值时，更灵敏的雅培实时检测法确定符合较短疗程PI治疗条件的患者比高纯系统少。我们的数据证实了<12 IU/ml的临界值，正如之前在雅培实时检测法的其他研究中所确立的那样，可用于确定基于PI的HCV缩短疗程治疗的资格。（该研究已在ClinicalTrials.gov注册，注册号为NCT01241760。）
