Poordad Fred, Schiff Eugene R, Vierling John M, Landis Charles, Fontana Robert J, Yang Rong, McPhee Fiona, Hughes Eric A, Noviello Stephanie, Swenson Eugene S
The Texas Liver Institute, University of Texas Health Science Center, San Antonio, TX.
Schiff Center for Liver Diseases, University of Miami Miller School of Medicine, Miami, FL.
Hepatology. 2016 May;63(5):1493-505. doi: 10.1002/hep.28446. Epub 2016 Mar 7.
Chronic hepatitis C virus (HCV) infection with advanced cirrhosis or post-liver transplantation recurrence represents a high unmet medical need with no approved therapies effective across all HCV genotypes. The open-label ALLY-1 study assessed the safety and efficacy of a 60-mg once-daily dosage of daclatasvir (pan-genotypic NS5A inhibitor) in combination with sofosbuvir at 400 mg once daily (NS5B inhibitor) and ribavirin at 600 mg/day for 12 weeks with a 24-week follow-up in two cohorts of patients with chronic HCV infection of any genotype and either compensated/decompensated cirrhosis or posttransplantation recurrence. Patients with on-treatment transplantation were eligible to receive 12 additional weeks of treatment immediately after transplantation. The primary efficacy measure was sustained virologic response at posttreatment week 12 (SVR12) in patients with a genotype 1 infection in each cohort. Sixty patients with advanced cirrhosis and 53 with posttransplantation recurrence were enrolled; HCV genotypes 1 (76%), 2, 3, 4, and 6 were represented. Child-Pugh classifications in the advanced cirrhosis cohort were 20% A, 53% B, and 27% C. In patients with cirrhosis, 82% (95% confidence interval [CI], 67.9%-92.0%) with genotype 1 infection achieved SVR12, whereas the corresponding rates in those with genotypes 2, 3, and 4 were 80%, 83%, and 100%, respectively; SVR12 rates were higher in patients with Child-Pugh class A or B, 93%, versus class C, 56%. In transplant recipients, SVR12 was achieved by 95% (95% CI, 83.5%-99.4%) and 91% of patients with genotype 1 and 3 infection, respectively. Three patients received peritransplantation treatment with minimal dose interruption and achieved SVR12. There were no treatment-related serious adverse events.
The pan-genotypic combination of daclatasvir, sofosbuvir, and ribavirin was safe and well tolerated. High SVR rates across multiple HCV genotypes were achieved by patients with post-liver transplantation recurrence or advanced cirrhosis.
慢性丙型肝炎病毒（HCV）感染合并晚期肝硬化或肝移植后复发代表了一种尚未满足的高度医疗需求，目前尚无对所有HCV基因型均有效的获批疗法。开放标签的ALLY-1研究评估了每日一次60毫克剂量的达卡他韦（泛基因型NS5A抑制剂）联合每日一次400毫克的索磷布韦（NS5B抑制剂）和每日600毫克的利巴韦林治疗12周，并对两个队列中任何基因型的慢性HCV感染且伴有代偿性/失代偿性肝硬化或移植后复发的患者进行24周随访的安全性和有效性。正在接受治疗时进行移植的患者在移植后可立即额外接受12周治疗。主要疗效指标是每个队列中基因型1感染患者在治疗后第12周的持续病毒学应答（SVR12）。共纳入60例晚期肝硬化患者和53例移植后复发患者；涵盖了HCV基因型1（76%）、2、3、4和6。晚期肝硬化队列中Child-Pugh分级为A的占20%，B的占53%，C的占27%。在肝硬化患者中，基因型1感染患者的SVR12率为82%（95%置信区间[CI]，67.9%-92.0%），而基因型2、3和4感染患者的相应率分别为80%、83%和100%；Child-Pugh A或B级患者的SVR12率更高，为93%，而C级患者为56%。在移植受者中，基因型1和3感染患者的SVR12率分别为95%（95%CI，83.5%-99.4%）和91%。3例患者在移植前后接受了最小剂量中断的治疗并实现了SVR12。未发生与治疗相关的严重不良事件。
达卡他韦、索磷布韦和利巴韦林的泛基因型联合用药安全且耐受性良好。肝移植后复发或晚期肝硬化患者在多种HCV基因型中均实现了高SVR率。
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