Leroy Vincent, Angus Peter, Bronowicki Jean-Pierre, Dore Gregory J, Hezode Christophe, Pianko Stephen, Pol Stanislas, Stuart Katherine, Tse Edmund, McPhee Fiona, Bhore Rafia, Jimenez-Exposito Maria Jesus, Thompson Alexander J
Clinique Universitaire d'Hepato-Gastroentérologie, Pôle Digidune, CHU de Grenoble and Unité INSERM/Université Grenoble Alpes U823, IAPC Institut Albert Bonniot, Grenoble, France.
Austin Hospital, Heidelberg, Australia.
Hepatology. 2016 May;63(5):1430-41. doi: 10.1002/hep.28473. Epub 2016 Mar 4.
Patients with hepatitis C virus (HCV) genotype 3 infection, especially those with advanced liver disease, are a challenging population in urgent need of optimally effective therapies. The combination of daclatasvir (DCV; pangenotypic nonstructural protein 5A inhibitor) and sofosbuvir (SOF; nucleotide nonstructural protein 5B inhibitor) for 12 weeks previously showed high efficacy (96%) in noncirrhotic genotype 3 infection. The phase III ALLY-3+ study (N = 50) evaluated DCV-SOF with ribavirin (RBV) in treatment-naïve (n = 13) or treatment-experienced (n = 37) genotype 3-infected patients with advanced fibrosis (n = 14) or compensated cirrhosis (n = 36). Patients were randomized 1:1 to receive open-label DCV-SOF (60 + 400 mg daily) with weight-based RBV for 12 or 16 weeks. The primary endpoint was sustained virological response at post-treatment week 12 (SVR12). SVR12 (intention-to-treat) was 90% overall (45 of 50): 88% (21 of 24) in the 12-week (91% observed) and 92% (24 of 26) in the 16-week group. All patients with advanced fibrosis achieved SVR12. SVR12 in patients with cirrhosis was 86% overall (31 of 36): 83% (15 of 18) in the 12-week (88% observed) and 89% (16 of 18) in the 16-week group; for treatment-experienced patients with cirrhosis, these values were 87% (26 of 30), 88% (14 of 16; 93% observed), and 86% (12 of 14), respectively. One patient (12-week group) did not enter post-treatment follow-up (death unrelated to treatment). There were 4 relapses (2 per group) and no virological breakthroughs. The most common adverse events (AEs) were insomnia, fatigue, and headache. There were no discontinuations for AEs and no treatment-related serious AEs.
The all-oral regimen of DCV-SOF-RBV was well tolerated and resulted in high and similar SVR12 after 12 or 16 weeks of treatment among genotype 3-infected patients with advanced liver disease, irrespective of past HCV treatment experience.
丙型肝炎病毒（HCV）基因3型感染患者，尤其是那些患有晚期肝病的患者，是迫切需要最佳有效治疗方法的具有挑战性的人群。此前，达拉他韦（DCV；泛基因型非结构蛋白5A抑制剂）和索磷布韦（SOF；核苷酸非结构蛋白5B抑制剂）联合使用12周在非肝硬化基因3型感染中显示出高疗效（96%）。III期ALLY-3+研究（N = 50）评估了DCV-SOF联合利巴韦林（RBV）用于初治（n = 13）或经治（n = 37）的基因3型感染且伴有晚期纤维化（n = 14）或代偿期肝硬化（n = 36）的患者。患者按1:1随机分组，接受开放标签的DCV-SOF（每日60 + 400 mg）联合基于体重的RBV治疗12周或16周。主要终点是治疗后第12周的持续病毒学应答（SVR12）。总体SVR12（意向性分析）为90%（50例中的45例）：12周组为88%（24例中的21例）（观察到的为91%），16周组为92%（26例中的24例）。所有晚期纤维化患者均实现SVR12。肝硬化患者的总体SVR12为86%（36例中的31例）：12周组为83%（18例中的15例）（观察到的为88%），16周组为89%（18例中的16例）；对于经治的肝硬化患者，这些值分别为87%（30例中的26例）、88%（16例中的14例；观察到的为93%）和86%（14例中的12例）。1例患者（12周组）未进入治疗后随访（与治疗无关的死亡）。有4例复发（每组2例），无病毒学突破。最常见的不良事件（AE）为失眠、疲劳和头痛。无因AE停药情况，也无治疗相关严重AE。
DCV-SOF-RBV全口服方案耐受性良好，在基因3型感染的晚期肝病患者中，无论既往HCV治疗史如何，治疗12周或16周后均产生高且相似的SVR12。
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