Direct-Acting Antiviral Prophylaxis in Kidney Transplantation From Hepatitis C Virus-Infected Donors to Noninfected Recipients: An Open-Label Nonrandomized Trial.
Direct-Acting Antiviral Prophylaxis in Kidney Transplantation From Hepatitis C Virus-Infected Donors to Noninfected Recipients: An Open-Label Nonrandomized Trial.
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DOI：
10.7326/m17-2871
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发表时间：
2018-04-17
影响因子：
39.2
通讯作者：
Desai NM
中科院分区：
文献类型：
--
作者：
Durand CM;Bowring MG;Brown DM;Chattergoon MA;Massaccesi G;Bair N;Wesson R;Reyad A;Naqvi FF;Ostrander D;Sugarman J;Segev DL;Sulkowski M;Desai NM
鉴于终末期肾病透析患者的高死亡率以及当前丙型肝炎病毒 (HCV) 治疗的有效性和安全性，目前来自 HCV 感染 (HCV+) 捐献者的废弃肾脏可能是一种被忽视的公共卫生资源。确定 HCV+ 供体肾移植 (KT) 联合直接作用抗病毒药物 (DAA) 作为移植前和移植后预防的耐受性和可行性。开放标签、非随机试验。 （ClinicalTrials.gov：NCT02781649）单中心。 10 名 50 岁以上未感染 HCV 的 KT 候选者，没有可用的活体捐赠者。来自 13-50 岁已故捐赠者的 KT，HCV RNA 和 HCV 抗体检测呈阳性。所有受者在移植前立即接受一剂格拉唑瑞韦 100 毫克/艾尔巴韦 50 毫克 (GZR/EBR)。对于基因 1 型供体，受者在移植后继续 GZR/EBR 12 周；对于基因型 2 或 3 供体，在 GZR/EBR 中添加索非布韦 400 mg，进行 12 周的三联疗法。主要安全性结果是与 GZR-EBR 相关的不良事件的发生率。主要疗效结果是预防后 12 周 HCV RNA 低于定量下限的受者比例。在 10 名 HCV D+/R− 患者中，没有出现与治疗相关的不良事件，治疗后 12 周也没有在任何接受者中检测到 HCV RNA。非随机研究设计和少量患者。移植前和移植后 HCV 治疗是安全的，并且可以预防 HCV D+/R− KT 中的慢性丙型肝炎。如果在更大规模的研究中得到证实，这一策略将显着扩大器官选择并降低 HCV−KT 候选者的死亡率。
Given the high mortality rate for those with end-stage kidney d sease on dialysis and the efficacy and safety of current hepatitis C virus (HCV) treatments, currently-discarded kidneys from HCV-infected (HCV+) donors may be a neglected public health resource. To determine the tolerability and feasibility of kidney transplantation (KT) from HCV+ donors to HCV-uninfected recipients (HCV D+/R−) in combination with direct-acting antivirals (DAAs) as pre- and post-transplant prophylaxis. Open-label, non-randomized trial. (ClinicalTrials.gov: NCT02781649) Single-center. 10 HCV-uninfected KT candidates over the age of 50 years with no available living donors. KT from deceased donors ages 13–50 years with a positive HCV RNA and HCV antibody test. All recipients received a dose of grazoprevir 100 mg/elbasvir 50 mg (GZR/EBR) immediately prior to transplant. For genotype 1 donors, recipients continued GZR/EBR for 12 weeks post-transplant; for genotype 2 or 3 donors, sofosbuvir 400 mg was added to GZR/EBR for 12 weeks of triple-therapy. The primary safety outcome was the incidence of adverse events related to GZR-EBR. The primary efficacy outcome was the proportion recipients with HCV RNA less than the lower limit of quantification 12 weeks after prophylaxis. Among 10 HCV D+/R− there were no treatment-related adverse events and HCV RNA was not detected in any recipient 12 weeks after treatment. Nonrandomized study design and small number of patients. Pre- and post-transplant HCV treatment was safe and prevented chronic hepatitis C in HCV D+/R− KT. If confirmed in larger studies, this strategy should markedly expand organ options and reduce mortality for HCV− KT candidates.