Osaka City University Graduate School of Medicine, Osaka, Japan Department of Hepatology.
Ann Hepatol. 2017 Sep-Oct;16(5):734-741. doi: 10.5604/01.3001.0010.2732.
The efficacy and safety of asunaprevir + daclatasvir combination therapy for treatment of hepatitis C virus (HCV) in compensated cirrhotic patients was not fully evaluated in real-world. Outcomes were assessed in cirrhotic patients with sustained viral response (SVR).
A total of 145 patients without resistance-associated substitutions (RASs) at L31 and Y93 in the nonstructural protein 5A of HCV genotype 1b, consisting of 49 hepatic cirrhotic and 96 non-cirrhotic patients, were enrolled to the therapy. The patients were treated with 100 mg asunaprevir twice daily plus 60 mg daclatasvir once daily for 24 weeks. The primary endpoint was SVR 24 weeks after completing treatment. In addition, we evaluated the improvement of liver function and development of HCC for 1 year from the end of treatment (EOT).
The SVR24 rate was 96% (47/49) in the cirrhotic group and 96% (91/95) in the non-cirrhotic group (p = 0.69). During treatment, grade III/IV adverse events occurred more frequently in cirrhotic patients (10/49; 20.4%) than in non-cirrhotic patients (10/96; 10.4%) (p = 0.099). After EOT, alanine aminotransferase and AFP levels were significantly decreased in cirrhotic patients with SVR. In addition, serum levels of albumin and platelet counts were significantly increased. On the other hand, the rates of HCC recurrence (43%) and development (7.4%) were higher in cirrhotic patients than in the non-cirrhotic patients (12.5% and 1.1%, respectively).
RAS-oriented asunaprevir/daclatasvir therapy has a strong anti-HCV effect in patients with HCV genotype 1b. However, careful management is necessary in patients with cirrhosis.
在真实世界中，未充分评估asunaprevir + daclatasvir 联合治疗方案对代偿期肝硬化患者丙型肝炎病毒（HCV）的疗效和安全性。在获得持续病毒学应答（SVR）的肝硬化患者中评估了结局。
共纳入 145 例无 HCV 基因型 1b 非结构蛋白 5A 区 L31 和 Y93 耐药相关替换（RAS）的患者，其中 49 例为肝纤维化患者，96 例为非肝纤维化患者，接受 100 mg asunaprevir 每日两次加 60 mg daclatasvir 每日一次治疗 24 周。主要终点为治疗结束后 24 周的 SVR。此外，我们还评估了治疗结束后 1 年（EOT）时肝功能改善和 HCC 发生情况。
肝纤维化组的 SVR24 率为 96%（47/49），非肝纤维化组为 96%（91/95）（p=0.69）。治疗期间，肝纤维化患者（10/49；20.4%）比非肝纤维化患者（10/96；10.4%）更常发生 3/4 级不良事件（p=0.099）。EOT 后，SVR 的肝纤维化患者丙氨酸氨基转移酶和 AFP 水平显著降低。此外，血清白蛋白和血小板计数水平显著升高。另一方面，肝纤维化患者 HCC 复发率（43%）和发生率（7.4%）均高于非肝纤维化患者（分别为 12.5%和 1.1%）。
针对 RAS 的 asunaprevir/daclatasvir 治疗方案对 HCV 基因型 1b 患者具有强大的抗 HCV 作用。然而，对于肝硬化患者需要进行谨慎管理。
