Division of Gastroenterology and Hepatology, University of São Paulo School of Medicine, São Paulo, Brazil.
Centro de Referência e Treinamento DST/AIDS, São Paulo, Brazil.
Ann Hepatol. 2018 Oct 16;17(6):959-968. doi: 10.5604/01.3001.0012.7196.
Approximately 650,000 people in Brazil have chronic hepatitis C virus (HCV) infection. We evaluated the safety and efficacy of ombitasvir (OBV)/paritaprevir (PTV)/ritonavir (r) plus dasabuvir (DSV) with/without ribavirin (RBV) in an openlabel multicenter phase 3b trial in treatment-naive or interferon (IFN) treatment-experienced Brazilian patients with advanced hepatic fibrosis (METAVIR F3/4) and HCV genotype (GT) 1 infection.
All patients received coformulated OBV/PTV/r daily + DSV twice daily (3-DAA). GT1a-infected patients received 3-DAA plus RBV for 12 weeks, except for prior pegIFN/RBV nonresponders with cirrhosis who were treated for 24 weeks. GT1b-infected patients received 3-DAA alone (F3) or in combination with RBV (F4) for 12 weeks. The primary endpoint was sustained virologic response (HCV RNA < 15 IU/mL) at post-treatment Week 12 (SVR12).
The study enrolled 222 patients, 214 achieved an SVR12 (96.4%; 95% CI, 93.1-98.2%), one GT1a-infected patient experienced virologic breakthrough, six (5 GT1a) relapsed, and one was lost to follow-up. SVR12 was achieved in 111/ 112 (99.1%) GT1b-infected patients, including 42/43 (97.7%) noncirrhotic, and 69/69 (100%) cirrhotic patients; and in 103/110 (93.6%) GT1a-infected patients, including 44/46 (95.7%) noncirrhotic and 59/64 (92.2%) cirrhotic patients. Overall there was a low rate of serious adverse events (n = 6, 2.7%). One patient experienced a treatment-related serious adverse event and one patient discontinued treatment because of an adverse event.
The results confirm that the 3-DAA regimen with/without RBV is well tolerated and had a favorable safety profile and is efficacious in GT1-infected patients with advanced fibrosis (METAVIR F3/4).
巴西约有 65 万人患有慢性丙型肝炎病毒（HCV）感染。我们评估了奥比帕韦（OBV）/帕利瑞韦（PTV）/利托那韦（r）加达萨布韦（DSV）联合或不联合利巴韦林（RBV）在巴西未经治疗或干扰素（IFN）治疗的初治患者中的安全性和疗效，这些患者患有晚期肝纤维化（METAVIR F3/4）和 HCV 基因型（GT）1 感染。
所有患者均接受联合制剂 OBV/PTV/r 每日一次+DSV 每日两次（3-DAA）治疗。GT1a 感染患者接受 3-DAA+RBV 治疗 12 周，除非肝硬化患者之前对聚乙二醇干扰素/RBV 无应答，需治疗 24 周。GT1b 感染患者接受 3-DAA 单药治疗（F3）或联合 RBV 治疗（F4）12 周。主要终点是治疗后第 12 周（SVR12）的持续病毒学应答（HCV RNA < 15 IU/mL）。
研究共纳入 222 例患者，214 例患者获得 SVR12（96.4%；95%可信区间，93.1-98.2%），1 例 GT1a 感染患者发生病毒学突破，6 例（5 例 GT1a）复发，1 例失访。112 例 GT1b 感染患者中的 111 例（99.1%）、43 例非肝硬化患者中的 42 例（97.7%）和 69 例肝硬化患者中的 69 例（100%）均获得 SVR12，110 例 GT1a 感染患者中的 103 例（93.6%）、46 例非肝硬化患者中的 44 例（95.7%）和 64 例肝硬化患者中的 59 例（92.2%）均获得 SVR12。总的来说，严重不良事件发生率较低（n=6，2.7%）。1 例患者发生与治疗相关的严重不良事件，1 例患者因不良事件停止治疗。
结果证实，在晚期纤维化（METAVIR F3/4）的 GT1 感染患者中，含或不含利巴韦林的 3-DAA 方案具有良好的耐受性，安全性良好，且有效。
