Daclatasvir and asunaprevir in hemodialysis patients with hepatitis C virus infection: a nationwide retrospective study in Japan
Daclatasvir and asunaprevir in hemodialysis patients with hepatitis C virus infection: a nationwide retrospective study in Japan
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DOI：
10.1007/s00535-017-1353-y
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发表时间：
2018-01-01
影响因子：
6.3
通讯作者：
Sakamoto, Naoya
中科院分区：
文献类型：
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作者：
Suda, Goki;Furusyo, Norihiro;Sakamoto, Naoya
丙型肝炎病毒（HCV）感染在血液透析患者中很常见，并使其预后恶化，而抗病毒治疗选择有限。最近，临床试验和现实世界的小规模研究报告了直接作用抗病毒药物对晚期慢性肾脏疾病患者的良好反应。然而，缺乏真实世界的大规模数据。这项大型多中心分析包括接受非结构蛋白5A （NS5A）抑制剂daclatasvir （DCV）和蛋白酶抑制剂asunaprevir （ASV）联合治疗的hcv感染血液透析患者。日本23个中心参与了这项研究，研究对象为123名基因型1型HCV感染的血液透析患者，这些患者在2014年11月至2016年3月期间接受了DCV/ASV联合治疗。我们收集并分析了有关治疗结果、基线临床信息、实验室测量（治疗期间和治疗后）和不良事件的数据。39例（31.7%）患者有晚期肝纤维化，12例（9.8%）患者有肝细胞癌（HCC）病史，18例（14.6%）患者有NS5A基线耐药相关变异（RAVs）。总体持续病毒学应答（SVR）率为95.9%（118/123）。值得注意的是，所有HCC患者和94.4%（17/18）的NS5A RAVs患者达到了SVR12。与非svr相关的重要因素是晚期纤维化和白细胞介素- 28b非tt基因型rs8099917。4名患者（3.3%）因不良事件停止治疗，包括血清丙氨酸转氨酶水平升高（n = 2）、皮疹（n = 1）和HCC (n = 1)；这些都达到了SVR12。这项现实世界的全国性研究表明，DCV/ASV联合治疗对于基因型HCV感染的血液透析患者是安全且高效的。本研究已在UMIN临床试验注册中心注册（UMIN000024227）。
Hepatitis C virus (HCV) infection is common in hemodialysis patients and worsens their prognosis, while antiviral therapy options are limited. Recently, clinical trial and real-world, small-scale studies have reported excellent responses to direct-acting antivirals in patients with advanced chronic kidney diseases. However, real-world, large-scale data were lacking. This large multicenter analysis included HCV-infected hemodialysis patients receiving combination therapy with a nonstructural protein 5A (NS5A) inhibitor, daclatasvir (DCV), and a protease inhibitor, asunaprevir (ASV).Twenty-three centers in Japan participated in this study of 123 hemodialysis patients with genotype 1 HCV infection, who received DCV/ASV combination therapy between November 2014 and March 2016. We collected and analyzed data relating to treatment outcome, baseline clinical information, laboratory measurements (during and after the treatment), and adverse events.Thirty-nine patients (31.7%) had advanced liver fibrosis, 12 (9.8%) had histories of hepatocellular carcinoma (HCC), and 18 (14.6%) had baseline resistance-associated variants (RAVs) of NS5A. The overall sustained virological response (SVR)12 rate was 95.9% (118/123). Notably, all patients with HCC and 94.4% (17/18) of those with NS5A RAVs achieved SVR12. Significant factors associated with non-SVR were advanced fibrosis and the interleukin-28B non-TT genotype at rs8099917. Four patients (3.3%) discontinued therapy because of adverse events including elevated serum alanine transaminase levels (n = 2), rash (n = 1), and HCC (n = 1); all of these achieved SVR12.This real-world, nationwide study revealed that DCV/ASV combination therapy was safe and highly effective for hemodialysis patients with genotype 1 HCV infections. This study was registered at the UMIN Clinical Trials Registry (UMIN000024227).