Efficacy and safety of ledipasvir/sofosbuvir with ribavirin in chronic hepatitis C patients who failed daclatasvir/asunaprevir therapy: pilot study
Efficacy and safety of ledipasvir/sofosbuvir with ribavirin in chronic hepatitis C patients who failed daclatasvir/asunaprevir therapy: pilot study
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DOI：
10.1007/s00535-017-1380-8
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发表时间：
2018-04-01
影响因子：
6.3
通讯作者：
Chayama, Kazuaki
中科院分区：
文献类型：
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作者：
Kawakami, Yoshiiku;Ochi, Hidenori;Chayama, Kazuaki
在日本，达卡他韦（DCV）和asunaprevir（ASV）治疗是第一个获得批准的无IFN治疗，数千名患者已成功治疗，SVR率约为90%。然而，匡威的是，大约10%的患者未能实现病毒根除，必须使用不同的方法重新治疗。本研究旨在评价雷迪帕韦/索非布韦联合利巴韦林治疗DCV和ASV治疗无效患者的疗效。我们评估了治疗结束后12周的持续病毒学应答率（SVR 12），并检查了ledipasvir/sofosbuvir和利巴韦林治疗期间不良事件的发生率。检测治疗失败病例中NS 5A和NS 5 B耐药相关变异（RAVs），总的SVR 12检出率为86.7%（26/30）。在无肝硬化的患者中观察到平均log（10）HCV RNA水平大幅下降，这些患者的SVR 12率为100%（12/12）。肝硬化患者中，SVR 12阳性率为72.2%（13/18）。治疗失败病例的共同因素是存在肝硬化和NS 5A L31 M/I和Y 93 H RAV。在复发患者中，治疗前后RAV的频率没有变化。雷迪帕韦/索非布韦联合病毒唑是对既往达卡他韦和阿舒那匹韦治疗无效的慢性丙型肝炎患者的有效再治疗选择。
In Japan, daclatasvir (DCV) and asunaprevir (ASV) therapy was the first IFN-free treatment to be approved, and thousands of patients have since been successfully treated, with an SVR rate of around 90%. The converse, however, is that around 10% of patients fail to achieve viral eradication and must be retreated using a different approach. This study is to evaluate treatment efficacy of ledipasvir/sofosbuvir and ribavirin in patients who failed to respond to DCV and ASV therapy.Thirty patients were treated with 12 weeks of ledipasvir/sofosbuvir and ribavirin. We evaluated the rate of sustained virological response 12 weeks after the end of treatment (SVR12) and examined the incidence of adverse events during ledipasvir/sofosbuvir and ribavirin treatment. NS5A and NS5B resistance-associated variants (RAVs) in treatment failure cases were examined.The overall SVR12 rate was 86.7% (26/30). Large decreases in mean log(10) HCV RNA levels were observed in patients without cirrhosis, and the SVR12 rate for these patients was 100% (12/12). In cases of cirrhosis, SVR12 rate was 72.2% (13/18). The common factors in treatment failure cases were the presence of liver cirrhosis and both NS5A L31M/I and Y93H RAVs. The frequency of RAVs did not change before and after treatment among patients who relapsed.Ledipasvir/sofosbuvir with ribavirin is an effective retreatment option for patients with chronic hepatitis C who failed to respond to prior daclatasvir and asunaprevir therapy.