Hepatitis C Treatment in Chronic Kidney Disease Patients: The Kidney Disease Improving Global Outcomes Perspective

Background: Hepatitis C virus (HCV) infection is a very common infection found among hemodialysis (HD) and kidney transplant patients. It is associated with substantial morbidity and mortality. Direct-acting antiviral agents (DAAs) have much better efficacy (sustained viral response (SVR)) and tolerance than interferon-based regimens. Very recent studies extend this breakthrough finding to chronic kidney disease (CKD) populations. Summary: CKD patients with an estimated glomerular filtration rate (eGFR) > 30 ml/min/ 1.73 m(2) can be treated with any licensed DAA regimen. In CKD stages 4-5 (mostly HD), the combination of grazoprevir (100 mg) and elbasvir (50 mg), a once-daily oral regimen active against genotypes 1 and 4, induced in a very recent RCT an SVR rate > 95%, with tolerance similar to that of placebo. Case series suggest that other DAA regimens are also very effective and well tolerated in HD patients. In kidney transplant recipients, 2 case series have reported 100% SVR with good tolerance of sofosbuvir-based regimens. Importantly, there is a risk of drug-drug interaction of several DAAs including calcineurin inhibitors. Finally, the availability of HCV+ grafts may markedly shorten the waiting time for transplantation. Key Messages: (1) In patients with an eGFR > 30, all licensed DAAs regimens can be used. (2) Cure of HCV appears at hand in CKD stages 4- 5, including dialysis patients, and in kidney transplant recipients. (3) The choice of DAA regimen in CKD should be based on HCV genotype, viral load, eGFR, concomitant medications, transplant candidacy and comorbidities. (4) The timing of treatment in potential kidney transplantation candidates (before versus after transplantation) should be decided in collaboration with the transplant center. (C) 2017 S. Karger AG, Basel.

背景：丙型肝炎病毒（HCV）感染在血液透析（HD）和肾移植患者中是一种非常常见的感染。它与较高的发病率和死亡率相关。直接作用抗病毒药物（DAAs）比基于干扰素的治疗方案具有更好的疗效（持续病毒学应答[SVR]）和耐受性。近期的研究将这一突破性发现扩展到了慢性肾脏病（CKD）人群。 总结：估计肾小球滤过率（eGFR）>30 ml/min/1.73 m²的CKD患者可以使用任何已获批的DAAs治疗方案。在CKD 4 - 5期（主要是血液透析患者），每日一次口服的格佐普韦（100 mg）和艾尔巴韦（50 mg）组合，对基因1型和4型有活性，在近期的一项随机对照试验中诱导的SVR率>95%，耐受性与安慰剂相似。病例系列研究表明，其他DAAs治疗方案在血液透析患者中也非常有效且耐受性良好。在肾移植受者中，2个病例系列报告了基于索磷布韦的治疗方案具有100%的SVR且耐受性良好。重要的是，包括钙调神经磷酸酶抑制剂在内的几种DAAs存在药物相互作用的风险。最后，HCV阳性供体器官的使用可能显著缩短移植等待时间。 关键信息：（1）在eGFR>30的患者中，可以使用所有已获批的DAAs治疗方案。（2）在CKD 4 - 5期，包括透析患者以及肾移植受者中，HCV的治愈似乎即将实现。（3）CKD患者中DAAs治疗方案的选择应基于HCV基因型、病毒载量、eGFR、伴随用药、移植候选资格和合并症。（4）潜在肾移植候选者的治疗时机（移植前还是移植后）应与移植中心合作决定。（C）2017年，巴塞尔S. 卡尔格股份公司