Efficacy and Safety of Direct Acting Antivirals in Kidney Transplant Recipients with Chronic Hepatitis C Virus Infection

The prevalence of Hepatitis C Virus (HCV) infection is significantly higher in patients with end-stage renal disease compared to the general population and poses important clinical challenges in patients who undergo kidney transplantation. Historically, interferon-based treatment options have been limited by low rates of efficacy and significant side effects, including risk of precipitating rejection. Limited data exist on the use of all-oral, interferon-free direct-acting antiviral (DAA) therapies in kidney transplant recipients. In this study, we performed a retrospective chart review with prospective clinical follow-up of post-kidney transplant patients treated with DAA therapies at three major hospitals in Boston, MA. A total of 24 kidney recipients with HCV infection received all-oral DAA therapy post-transplant. Patients were predominantly male (79%) with a median age of 60 years (range 34–70 years), median creatinine of 1.2 mg/dL (0.66–1.76), and 42% had advanced fibrosis or cirrhosis. The majority had HCV genotype 1a infection (58%). All patients received full-dose sofosbuvir; it was paired with simeprevir (9 patients without and 3 patients with ribavirin), ledipasvir (7 patients without and 1 patient with ribavirin) or ribavirin alone (4 patients). The overall sustained virologic response (SVR12) was 91% (21 out of 23 patients). One patient achieved SVR4 but demised prior to SVR12 check point due to treatment unrelated cause. Two treatment failures were successfully retreated with alternative DAA regimens and achieved SVR. Both initials failures occurred in patients with advanced fibrosis or cirrhosis, with genotype 1a infection, and prior HCV treatment failure. Adverse events were reported in 11 patients (46%) and were managed clinically without discontinuation of therapy. Calcineurin inhibitor trough levels did not significantly change during therapy. In this multi-center series of patients, all-oral DAA therapy appears to be safe and effective in post-kidney transplant patients with chronic HCV infection.

与普通人群相比，终末期肾病（end-stage renal disease）患者的丙型肝炎病毒（Hepatitis C Virus, HCV）感染率显著更高，且在接受肾移植的患者中带来了严峻的临床挑战。既往基于干扰素的治疗方案因疗效低下且伴随严重不良反应（包括诱发排斥反应的风险）而应用受限。目前关于全口服、无干扰素的直接抗病毒药物（direct-acting antiviral, DAA）在肾移植受者中的应用数据仍较为有限。本研究对美国马萨诸塞州波士顿市三家大型医院中接受直接抗病毒药物治疗的肾移植术后患者开展了回顾性病历审查与前瞻性临床随访。最终纳入24例合并HCV感染的肾移植受者，均接受全口服DAA治疗。受试者以男性为主（占比79%），中位年龄60岁（范围34~70岁），中位肌酐水平1.2 mg/dL（范围0.66~1.76 mg/dL），其中42%的患者存在进展性肝纤维化或肝硬化。多数患者为HCV 1a型感染（占比58%）。所有患者均接受全剂量索磷布韦（sofosbuvir），联合用药方案包括：西美普韦（simeprevir，9例未联用利巴韦林、3例联用利巴韦林）、莱迪帕韦（ledipasvir，7例未联用利巴韦林、1例联用利巴韦林），或单独使用利巴韦林（4例）。整体持续病毒学应答（SVR12）率为91%（23例患者中21例达到应答）。1例患者达成持续病毒学应答4周（SVR4），但因与治疗无关的原因在SVR12评估节点前去世。2例治疗失败患者接受了替代DAA方案的挽救治疗并最终达成SVR。2例初始治疗失败均发生于合并进展性肝纤维化或肝硬化、HCV 1a型感染且既往存在HCV治疗失败史的患者中。共有11例患者（占比46%）报告了不良反应，经临床处理后均未终止治疗。治疗期间钙调磷酸酶抑制剂（calcineurin inhibitor）的谷浓度无显著变化。本多中心队列研究结果显示，全口服DAA治疗方案对于合并慢性HCV感染的肾移植术后患者而言，安全性与有效性均表现良好。