Dalgard Olav, Martinot-Peignoux Michelle, Verbaan Hans, Bjøro Kristian, Ring-Larsen Helmer, Marcellin Patrick
Department of Infectious Diseases, Akershus University Hospital, Lørenskog, Norway; Faculty of Medicine, University of Oslo, Oslo, Norway.
Institut National de la Santé et de la Recherche Médicale, U-773, Centre de Recherche Biomédicale Bichat-Beaujon CRB3, Université Paris VII, Paris, France.
PLoS One. 2015 Aug 28;10(8):e0120866. doi: 10.1371/journal.pone.0120866. eCollection 2015.
The aim of this study was to determine in patients with HCV genotype 2 or 3 the performance at week 4 of two assays with different sensitivities for HCV RNA detection, for the prediction of SVR and stratification for treatment duration (14 and 24 weeks). Recruitment was from two trials comparing 14 and 24 weeks treatment to patients with rapid virological response (RVR) (n = 550). RVR was originally defined as HCV RNA <50 IU/ml at week 4. Patients with an available frozen plasma sample drawn at week 4 and with follow-up data week 24 post-treatment were included (n = 429). HCV-RNA was prospectively measured with COBAS Amplicor V2, Roche (CA) (lower detection limit 50 IU/ml) and retrospectively assessed with VERSANT HCV-RNA Qualitative Assay, Siemens (TMA) (lower limit detection 10 IU/ml). Genotype 3 was present in 80% and genotype 2 in 20%. A SVR was achieved in 82%. At week 4 HCV-RNA was undetectable in 74.8% and 63% of serum samples tested with CA and TMA, respectively. CA undetectable/TMA positive was observed in 61/341 (18%) of the samples. In genotype 3 patients a relapse was seen in 9% of the patients with both CA and TMA undetectable and in 25% of the patients who were CA undetectable/TMA positive (p = 0.006). In patients allocated to 14 weeks treatment a relapse was observed in 11% of TMA undetectable patients and 26% of TMA positive (p = 0.031). In genotype 2 patients treated for 14 weeks relapse was observed in 6% of the patients with both CA and TMA undetectable week 4. Assays with high sensitivity for HCV RNA identifies patients at week 4 with high risk of virological relapse. We recommend that patients with genotype 3 and detectable HCV RNA at levels below 50 IU/ml do not receive truncated therapy with pegIFN and ribavirin.
本研究的目的是确定在丙型肝炎病毒（HCV）基因2型或3型患者中，两种对HCV RNA检测具有不同灵敏度的检测方法在第4周时的表现，用于预测持续病毒学应答（SVR）以及治疗疗程（14周和24周）的分层。研究对象来自两项将14周和24周治疗方案与快速病毒学应答（RVR）患者（n = 550）进行比较的试验。RVR最初定义为第4周时HCV RNA <50 IU/ml。纳入在第4周采集了可用冷冻血浆样本且有治疗后第24周随访数据的患者（n = 429）。前瞻性地使用罗氏公司（加利福尼亚州）的COBAS Amplicor V2检测HCV-RNA（检测下限50 IU/ml），并回顾性地使用西门子公司的VERSANT HCV-RNA定性检测（转录介导扩增法，TMA）（检测下限10 IU/ml）进行评估。基因3型占80%，基因2型占20%。82%的患者实现了SVR。在第4周时，分别用COBAS Amplicor V2和TMA检测的血清样本中，74.8%和63%的样本HCV-RNA检测不到。在61/341（18%）的样本中观察到COBAS Amplicor V2检测不到/TMA检测为阳性。在基因3型患者中，COBAS Amplicor V2和TMA均检测不到的患者中有9%复发，而COBAS Amplicor V2检测不到/TMA检测为阳性的患者中有25%复发（p = 0.006）。在接受14周治疗的患者中，TMA检测不到的患者中有11%复发，TMA检测为阳性的患者中有26%复发（p = 0.031）。在接受14周治疗的基因2型患者中，第4周时COBAS Amplicor V2和TMA均检测不到的患者中有6%复发。对HCV RNA具有高灵敏度的检测方法可在第4周时识别出病毒学复发高风险的患者。我们建议基因3型且HCV RNA检测水平低于50 IU/ml但仍可检测到的患者不要接受聚乙二醇干扰素和利巴韦林的缩短疗程治疗。
