Department of Gastroenterology and Metabolism, Applied Life Sciences, Institute of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan.
Department of Center for Integrated Medical Research, Hiroshima University, Hiroshima, Japan.
J Gastroenterol. 2018 Apr;53(4):548-556. doi: 10.1007/s00535-017-1380-8. Epub 2017 Aug 16.
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 (SVR) 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 SVR rate was 86.7% (26/30). Large decreases in mean log HCV RNA levels were observed in patients without cirrhosis, and the SVR rate for these patients was 100% (12/12). In cases of cirrhosis, SVR 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.
在日本，达卡他韦（DCV）和asunaprevir（ASV）联合治疗是首个被批准的无干扰素治疗方法，此后数千名患者成功接受了治疗，SVR 率约为 90%。然而，相反的是，约有 10%的患者未能实现病毒清除，必须采用不同的方法进行再治疗。本研究旨在评估 ledipasvir/sofosbuvir 和利巴韦林治疗对 DCV 和 ASV 治疗无应答患者的疗效。
30 例患者接受了 12 周的 ledipasvir/sofosbuvir 和利巴韦林治疗。我们评估了治疗结束后 12 周持续病毒学应答（SVR）的比率，并检查了 ledipasvir/sofosbuvir 和利巴韦林治疗期间不良事件的发生率。在治疗失败的病例中，我们还检测了 NS5A 和 NS5B 耐药相关变异（RAVs）。
总的 SVR 率为 86.7%（26/30）。无肝硬化患者的平均 HCV RNA 水平显著下降，这些患者的 SVR 率为 100%（12/12）。肝硬化患者的 SVR 率为 72.2%（13/18）。治疗失败病例的共同因素是存在肝硬化以及 NS5A L31M/I 和 Y93H RAVs。复发患者的 RAVs 频率在治疗前后没有变化。
对于对先前的达卡他韦和asunaprevir 治疗无应答的慢性丙型肝炎患者，ledipasvir/sofosbuvir 联合利巴韦林是一种有效的再治疗选择。
