Efficacy and tolerability of interferon-free antiviral therapy in kidney transplant recipients with chronic hepatitis C
Efficacy and tolerability of interferon-free antiviral therapy in kidney transplant recipients with chronic hepatitis C
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DOI：
10.1016/j.jhep.2016.12.020
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发表时间：
2017-04-01
影响因子：
25.7
通讯作者：
Londono, Maria-Carlota
中科院分区：
文献类型：
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作者：
Fernandez, Inmaculada;Munoz-Gomez, Raquel;Londono, Maria-Carlota
背景与目的：直接作用抗病毒药物（DAA）的开发是丙型肝炎（HCV）治疗的重要一步。这项研究的目的是评估DAA在肾移植（KT）recipient.Methods的疗效和耐受性：肝-C是西班牙注册的DAA治疗患者的临床，病毒学和分析数据进行了前瞻性的。我们报告的数据从103 KT收件人谁收到DAAs.Results：最常用的DAA组合是索非布韦/ledipasvir（n = 59，57%）和索非布韦+达卡他韦（n = 18，17%）。41%的患者使用利巴韦林。12周后的持续病毒应答（SVR 12）率为98%。14例（33%）接受利巴韦林治疗的患者出现2级或3级贫血，9例（15%）未接受利巴韦林治疗的患者出现2级或3级贫血（p = 0.03）。有三次急性体液移植排斥反应。无患者因不良事件而停止治疗。重要的是，57例（55%）患者需要调整免疫抑制剂量。总体而言，治疗前后血清肌酐、eGFR和蛋白尿的平均水平无统计学显著差异。尽管如此，17例（16%）患者在抗病毒治疗期间出现肾功能不全（血清肌酐增加>25%），其中65%为肾功能不全，而只有29%的肾功能不全患者没有出现显著的肾功能不全（p = 0.004）。然而，一个不可忽视的患者，其中大多数是糖尿病，轻度移植物功能障碍和一个显着比例的患者需要免疫抑制剂量调整，administrating密切跟进therapeutic.Lay摘要：丙型肝炎病毒感染是经常发现在肾移植患者和它的存在增加死亡率和移植失败。我们研究了新的直接作用丙型肝炎抗病毒药物在这一人群中的疗效和安全性，其中以前的信息很少。我们的数据表明，在非移植环境中，新的抗HCV抗病毒药物对肾移植患者非常有效。总的来说，这种治疗也是相当安全的，尽管在抗病毒治疗期间，在16%的患者中观察到肾功能恶化，但对移植物功能进行了密切的随访观察。(C)2016年欧洲肝脏研究协会。由Elsevier B出版。V.保留所有权利。
Background & Aims: The development of direct-acting antiviral agents (DAAs) is a major step forward in the treatment of hepatitis C (HCV). The aims of the study were to evaluate the efficacy and tolerability of DAAs in kidney transplant (KT) recipients.Methods: Hepa-C is a Spanish registry of patients treated with DAAs in which clinical, virological and analytical data were prospectively included. We report on the data from 103 KT recipients who received DAAs.Results: The most commonly used DAAs combinations were sofosbuvir/ledipasvir (n = 59, 57%) and sofosbuvir + daclatasvir (n = 18, 17%). Ribavirin was used in 41% of patients. Sustained viral response after 12 weeks (SVR12) rate was 98%. Grade 2 or 3 anemia appeared in 14 (33%) of patients receiving ribavirin and in 9 (15%) without (p = 0.03). There were three episodes of acute humoral graft rejection. No patient discontinued therapy due to adverse events. Importantly, 57 (55%) patients required immunosuppression dose adjustment. Overall, there were no statistically significant differences in the mean level of serum creatinine, eGFR and proteinuria before and after treatment. Nonetheless, seventeen (16%) patients experienced renal dysfunction (increase in serum creatinine >25%) during antiviral therapy, of whom 65% were cirrhotic in comparison with only 29% cirrhotic patients who did not develop significant renal dysfunction (p = 0.004).Conclusions: Antiviral therapy with DAAs was highly efficacious and safe in KT recipients. Nevertheless, a non-negligible number of patients, most of them cirrhotic, developed mild allograft dys-function and a significant proportion of patients required immunosuppression dose adjustment, warranting a close follow-up during therapy.Lay summary: Infection by hepatitis C virus is often found in kidney transplant patients and its presence increases mortality and graft failure. We investigated the efficacy and safety of the new direct-acting hepatitis C antivirals in this population, in which previous information is scarce. Our data shows that, as occurs in the non-transplant setting, new anti-HCV antivirals are highly efficacious kidney transplant patients. Overall, this therapy is also quite safe, although worsening of renal function is observed in 16% of patients warranting a close follow-up observation of graft function during antiviral therapy. (C) 2016 European Association for the Study of the Liver. Published by Elsevier B. V. All rights reserved.