Elbasvir plus grazoprevir for patients with chronic hepatitis C genotype 1: A multicenter, real-world cohort study focusing on chronic kidney disease
Elbasvir plus grazoprevir for patients with chronic hepatitis C genotype 1: A multicenter, real-world cohort study focusing on chronic kidney disease
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DOI：
10.1016/j.antiviral.2018.10.003
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发表时间：
2018-11-01
影响因子：
7.6
通讯作者：
Hayashi, Jun
中科院分区：
文献类型：
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作者：
Ogawa, Eiichi;Furusyo, Norihiro;Hayashi, Jun
全口服直接作用抗病毒药物（DAAs）治疗慢性丙型肝炎（HCV）感染和慢性肾脏疾病（CKD）的实际有效性和安全性尚未完全阐明。本研究评估了elbasvir （EBR）和grazoprevir （GZR）在HCV基因型1感染患者中的临床应用，重点是CKD期3-5D。这项多中心、真实世界队列研究包括282名日本患者，他们接受EBR （50 mg）加GZR （100 mg）治疗，固定持续12周。我们评估了治疗结束后12周的持续病毒反应率（SVR12）、纵向肝脏和肾脏参数以及根据肝硬化和CKD状态的不良反应。在入选的患者中，89例（31.6%）为CKD 3-5期，21例（7.4%）为CKD 5D期（血液透析依赖）。每个方案人群的总体和CKD期3-5D SVR12率分别为98.6%（272/276）和98.1%（101/103）。几乎在所有组中观察到高SVR12率，除了先前的全口服DAA失败与NS5A耐药相关的替代。无论CKD状态如何，在治疗或随访期间，肾小球滤过率的估计值没有显著变化。血清补体水平（C3和C4）升高，其中C3升高有显著性意义。无论是eGFR正常组还是CKD组，严重的不良反应都非常罕见，只有6例（2.1%）患者需要停药。无论CKD状态如何，EBR加GZR治疗HCV基因型1非常有效，不良反应发生率低。此外，肝脏参数和补体水平也有纵向改善。
The real-world effectiveness and safety of all-oral direct-acting antivirals (DAAs) for chronic hepatitis C (HCV) infection and chronic kidney disease (CKD) have not been fully elucidated. This study assesses elbasvir (EBR) plus grazoprevir (GZR) for patients with HCV genotype 1 infection in the clinical setting, focusing on CKD stage 3-5D. This multicenter, real-world cohort study consisted of 282 Japanese patients who were treated with EBR (50 mg) plus GZR (100 mg) for a fixed 12-week duration. We evaluated the sustained viral response rate 12 weeks after the end of treatment (SVR12), longitudinal liver and renal parameters, and adverse effects according to the cirrhosis and CKD status. Of those enrolled, 89 (31.6%) were CKD stage 3-5 and 21 (7.4%) were CKD stage 5D (hemodialysis-dependent). The overall and CKD stage 3-5D SVR12 rates in the per protocol populations were 98.6% (272/276) and 98.1% (101/103). High SVR12 rates were observed in almost all groups, except for prior all-oral DAA failure with NS5A resistance-associated substitutions. There was no significant change during treatment or follow-up period in estimated glomerular filtration rate, irrespective of CKD status. In contrast, the serum complement level (C3 and C4) increased, with significance for C3. Serious adverse effects were very rare, both in the groups with normal eGFR and CKD, and discontinuation was required for only six (2.1%) patients. EBR plus GZR for HCV genotype 1 was highly effective with a low rate of adverse effects, regardless of CKD status. In addition, liver parameters and complement levels improved longitudinally.