Asselah Tarik, Pol Stanislas, Hezode Christophe, Loustaud-Ratti Veronique, Leroy Vincent, Ahmed Si Nafa Si, Ozenne Violaine, Bronowicki Jean-Pierre, Larrey Dominique, Tran Albert, Alric Laurent, Nguyen-Khac Eric, Robertson Michael N, Hanna George J, Brown Deborah, Asante-Appiah Ernest, Su Feng-Hsiu, Hwang Peggy, Hall Jessie Durrand, Guidoum Amir, Hagen Karin, Haber Barbara A, Talwani Rohit, Serfaty Lawrence
Department of Hepatology and Gastroenterology, University Paris Diderot, Sorbonne Paris Cité, CRI, UMR 1149 INSERM, Paris, France.
Department of Hepatology, AP-HP Hôpital Beaujon, Clichy, France.
Liver Int. 2020 May;40(5):1042-1051. doi: 10.1111/liv.14313. Epub 2020 Mar 22.
BACKGROUND & AIMS: Hepatitis C virus (HCV) genotype (GT) 4 infection is prevalent in sub-Saharan Africa and the Middle East, particularly in Egypt. This study evaluated the safety and efficacy of elbasvir/grazoprevir administered for 8 and 12 weeks in participants with HCV GT4 infection.
In this partially randomized, open-label multicentre study conducted in France (NCT03111108; Protocol MK5172-096), treatment-naive participants with GT4 infection and F0-F2 fibrosis were randomized 2:1 to elbasvir (50 mg)/grazoprevir (100 mg) for 8 or 12 weeks. Treatment-naive participants with F3-F4 fibrosis and all treatment-experienced participants (F0-F4) were assigned to elbasvir/grazoprevir for 12 weeks. The primary endpoint was sustained virologic response (SVR) 12 weeks after the end of therapy.
One hundred and seventeen participants were enrolled. Among treatment-naive participants with F0-F2 fibrosis, SVR was achieved by 94% (50/53) and 96% (26/27) of those receiving elbasvir/grazoprevir for 8 or 12 weeks, respectively, and four participants relapsed. In the 12-week arm, 95% (35/37) achieved SVR and two participants relapsed. NS5A resistance-associated substitutions were present at baseline and virologic failure in five of the participants with relapse. Drug-related adverse events occurred in 42% (n = 22) and 50% (n = 32) of participants receiving 8 and 12 weeks of treatment, respectively. No participant discontinued treatment owing to an adverse event.
These data confirm the efficacy of elbasvir/grazoprevir administered for 12 weeks in treatment-experienced individuals with HCV GT4 infection and those with advanced fibrosis. Treatment-naive individuals with mild fibrosis can be treated effectively with an 8-week regimen.
丙型肝炎病毒（HCV）基因4型（GT4）感染在撒哈拉以南非洲和中东地区较为普遍，尤其是在埃及。本研究评估了艾尔巴韦/格拉瑞韦治疗HCV GT4感染患者8周和12周的安全性和疗效。
在法国进行的这项部分随机、开放标签的多中心研究（NCT03111108；方案MK5172 - 096）中，未接受过治疗且感染GT4且纤维化程度为F0 - F2的参与者按2:1随机分组，接受艾尔巴韦（50mg）/格拉瑞韦（100mg）治疗8周或12周。未接受过治疗且纤维化程度为F3 - F4的参与者以及所有接受过治疗的参与者（F0 - F4）均接受艾尔巴韦/格拉瑞韦治疗12周。主要终点是治疗结束后12周的持续病毒学应答（SVR）。
共纳入117名参与者。在未接受过治疗且纤维化程度为F0 - F2的参与者中，接受艾尔巴韦/格拉瑞韦治疗8周和12周的患者分别有94%（50/53）和96%（26/27）实现了SVR，4名参与者复发。在12周治疗组中，95%（35/37）实现了SVR，2名参与者复发。5名复发参与者在基线和病毒学失败时存在NS5A耐药相关替代突变。接受8周和12周治疗的参与者中，分别有42%（n = 22）和50%（n = 32）发生了与药物相关的不良事件。没有参与者因不良事件而停药。
这些数据证实了艾尔巴韦/格拉瑞韦治疗12周对有治疗史的HCV GT4感染患者和晚期纤维化患者的疗效。未接受过治疗且纤维化程度较轻的患者可通过8周疗程有效治疗。
