Dietz Julia, Vermehren Johannes, Matschenz Katrin, Buggisch Peter, Klinker Hartwig, Schulze Zur Wiesch Julian, Hinrichsen Holger, Peiffer Kai-Henrik, Graf Christiana, Discher Thomas, Trauth Janina, Schattenberg Jörn M, Piecha Felix, Mauss Stefan, Niederau Claus, Müller Tobias, Neumann-Haefelin Christoph, Berg Christoph P, Zeuzem Stefan, Sarrazin Christoph
Department of Internal Medicine 1, University Hospital, Goethe University, Frankfurt, Germany; German Center for Infection Research (DZIF), External Partner Site Frankfurt, Germany.
Institute for Interdisciplinary Medicine IFI, Hamburg, Germany.
Liver Int. 2020 Jul 8. doi: 10.1111/liv.14591.
BACKGROUND&AIMS: The presence of baseline resistance-associated substitutions (RASs) reduced sustained virologic response (SVR) rates in chronic hepatitis C virus (HCV) genotype 1a infected patients treated with Elbasvir/Grazoprevir (EBR/GZR). This study aimed to evaluate the frequency of NS5A RASs and treatment outcomes in patients for whom EBR/GZR was intended.
We sequenced NS5A in 832 samples from German genotype1a-infected DAA-naïve patients population-based, which were collected in the European Resistance Database. Treatment outcomes and clinical parameters were evaluated in 519 of these patients retrospectively.
Overall, 6.5% of patients harbored EBR-specific NS5A RASs at baseline, including Q30H/R (3.3%), L31M (1.8%), Y93H (1.6%) and other individual variants. Antiviral treatment, including EBR/GZR, was initiated in 88% of patients. In the absence of RASs, the majority of patients received EBR/GZR for 12 weeks (57%) and the SVR rate was 97% compared to 99% SVR achieved using other DAA regimens (LDV/SOF±RBV, G/P, PrOD+RBV, VEL/SOF). Various regimens were used in the presence of RASs and SVR rates were high following treatment with LDV/SOF (100%), G/P (83%), PrOD/RBV (100%), VEL/SOF (100%), SMV/SOF (100%) and EBR/GZR+RBV for 16 weeks (100%). However, two patients received EBR/GZR for 16 weeks without RBV and one relapsed.
EBR/GZR treatment with or without RBV for 12 or 16 weeks according to a baseline RAS analysis was highly effective with ≥97% SVR in patients with genotype 1a. EBR/GZR without RBV should be avoided in patients with RASs. High SVR rates were also achieved using other 8 or 12 weeks DAA regimens.
基线耐药相关替代位点（RASs）的存在降低了接受艾尔巴韦/格拉瑞韦（EBR/GZR）治疗的慢性丙型肝炎病毒（HCV）1a型感染患者的持续病毒学应答（SVR）率。本研究旨在评估EBR/GZR适用患者中NS5A RASs的频率及治疗结果。
我们对来自德国基于人群的1a型感染、初治DAA患者的832份样本中的NS5A进行测序，这些样本收集于欧洲耐药数据库。对其中519例患者的治疗结果和临床参数进行回顾性评估。
总体而言，6.5%的患者在基线时携带EBR特异性NS5A RASs，包括Q30H/R（3.3%）、L31M（1.8%）、Y93H（1.6%）及其他个别变异。88%的患者开始了抗病毒治疗，包括EBR/GZR。在无RASs的情况下，大多数患者接受EBR/GZR治疗12周（57%），SVR率为97%，而使用其他DAA方案（来迪派韦/索磷布韦±利巴韦林、格卡瑞韦/哌仑他韦、泛基因型方案+利巴韦林、维帕他韦/索磷布韦）达到的SVR率为99%。在存在RASs的情况下使用了各种方案，使用来迪派韦/索磷布韦（100%）、格卡瑞韦/哌仑他韦（83%）、泛基因型方案/利巴韦林（100%）、维帕他韦/索磷布韦（100%）、司美匹韦/索磷布韦（100%）以及EBR/GZR联合利巴韦林治疗16周（100%）后SVR率较高。然而，两名患者接受EBR/GZR治疗16周未联合利巴韦林，其中一名复发。
根据基线RAS分析，EBR/GZR联合或不联合利巴韦林治疗12周或16周对1a型患者高度有效，SVR≥97%。有RASs的患者应避免使用不联合利巴韦林的EBR/GZR。使用其他8周或12周的DAA方案也可达到较高的SVR率。
