Margusino-Framiñán L, Cid-Silva P, Mena-de-Cea A, Rodríguez-Osorio I, Pernas-Souto B, Delgado-Blanco M, Pertega-Díaz S, Martín-Herranz I, Castro-Iglesias A
Luis Margusino-Framiñán, Pharmacy Service. A Coruña Hospital. c/ As Xubias 84. 15006 A Coruña. Spain.
Rev Esp Quimioter. 2019 Apr;32(2):137-144. Epub 2019 Feb 12.
Direct-acting antivirals have shown high efficacy in all hepatitis C virus (HCV) genotypes, but genotype 3 (G3) treatments continue to be a challenge, mainly in cirrhotic patients. The aim of this study is to analyse effectiveness and safety of daclatasvir associated with sofosbuvir with or without ribavirin in G3-HCV infected patients in real clinical practice.
An observational, prospective, cohort study over 2.5 years, in G3-HCV infected adult patients, in all fibrosis stages including patients with decompensated cirrhosis. Treatment was a combination of sofosbuvir 400 mg/day + daclatasvir 60 mg/day, with or without a weight-adjusted dosing of ribavirin for 12 or 24 weeks. The primary efficacy endpoint was sustained virologic response rates 12 weeks after therapy (SVR12). The primary safety endpoint was treatment withdrawal rates secondary to severe adverse events.
A total of 111 patients were enrolled, 32.4% cirrhotics and 29.9% treatment-experienced. The global SVR12 rate was 94.6%, while the SVR12 rate in F3-4 fibrosis stage patients was 90.8% versus 100% in patients with F0-2 fibrosis (p=0.03). In cirrhotic patients, SVR12 was 100% versus 40% depending on whether ribavirin was added or not to daclatasvir/sofosbuvir (p=0.001). No other patient or treatment basal variables influenced the treatment effectiveness. No patient treatment withdrawal secondary to severe adverse events was observed.
Daclatasvir/sofosbuvir ± ribavirin is highly effective in G3-HCV infected patients. Advanced degrees of fibrosis significantly decrease the effectiveness of this treatment, which motivates the need for the addition of ribavirin in cirrhotic patients. The regimen was safe and well tolerated.
直接作用抗病毒药物在所有丙型肝炎病毒（HCV）基因型中均显示出高效性，但基因型3（G3）的治疗仍然是一项挑战，主要针对肝硬化患者。本研究的目的是分析在实际临床实践中，与索磷布韦联合使用或不联合使用利巴韦林的达卡他韦对G3-HCV感染患者的有效性和安全性。
一项为期2.5年的观察性、前瞻性队列研究，纳入G3-HCV感染的成年患者，涵盖所有纤维化阶段，包括失代偿期肝硬化患者。治疗方案为索磷布韦400mg/天 + 达卡他韦60mg/天，联合或不联合根据体重调整剂量的利巴韦林，疗程为12周或24周。主要疗效终点是治疗12周后的持续病毒学应答率（SVR12）。主要安全终点是因严重不良事件导致的治疗停药率。
共纳入111例患者，其中32.4%为肝硬化患者，29.9%有治疗史。总体SVR12率为94.6%，而F3-4纤维化阶段患者的SVR12率为90.8%，F0-2纤维化患者为100%（p = 0.03）。在肝硬化患者中，根据是否在达卡他韦/索磷布韦中添加利巴韦林，SVR12分别为100%和40%（p = 0.001）。没有其他患者或治疗基础变量影响治疗效果。未观察到因严重不良事件导致的患者治疗停药情况。
达卡他韦/索磷布韦±利巴韦林对G3-HCV感染患者高度有效。纤维化程度较高会显著降低该治疗的有效性，这促使在肝硬化患者中需要添加利巴韦林。该治疗方案安全且耐受性良好。
