Reddy Suresh, Sharma Raj Kumar, Mehrotra Sonia, Prasad Narayan, Gupta Amit, Kaul Anupma, Singh Bhadauria Dharmendra
Department of Nephrology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India.
Clin Kidney J. 2018 Jun;11(3):429-433. doi: 10.1093/ckj/sfx112. Epub 2017 Oct 30.
The objectives of this pilot study were to assess the efficacy and safety of an interferon-free sofosbuvir and ribavirin combination regimen to treat chronic hepatitis C virus (HCV) infection in kidney transplant recipients and to study the impact of sofosbuvir on calcineurin inhibitor (CNI) drug levels.
A total of 10 kidney transplant recipients with chronic HCV infection were included in the study. All received sofosbuvir and ribavirin combination therapy. The virological response to therapy and the adverse effects of the drugs were studied. The area under the curve (AUC) and pharmacokinetic data of levels of CNI were compared while the patients were receiving sofosbuvir and ribavirin drugs and when they were no longer on these drugs.
In all, 9 of 10 patients (90%) achieved rapid virological response (RVR) with undetectable HCV RNA at 4 weeks and the remaining patient achieved undetectable HCV RNA at 8 weeks. A sustained virological response was seen at 3, 6 and 12 months and was maintained in all 10 patients (100%). The important aspect of the study is the effect of treatment with the sofosbuvir-ribavirin combination regimen on the CNI AUC levels, which resulted in a reduction in the CNI AUC. While used as part of triple-drug immunosuppression, no change in the dose of CNI (tacrolimus and cyclosporine) was required based on measurement of C0 levels.
The sofosbuvir and ribavirin combination therapy is effective and safe to treat HCV infection in the post-renal transplant setting. There is a need for close CNI level monitoring while these patients are on sofosbuvir therapy. With therapy and viral clearance, there could be reduction in CNI levels due to increased clearance of CNI drugs, which is shown by the AUC measurements. This could be important for patients at high risk for rejection.
本初步研究的目的是评估不含干扰素的索磷布韦与利巴韦林联合治疗方案治疗肾移植受者慢性丙型肝炎病毒（HCV）感染的疗效和安全性，并研究索磷布韦对钙调神经磷酸酶抑制剂（CNI）药物水平的影响。
本研究共纳入10例慢性HCV感染的肾移植受者。所有患者均接受索磷布韦与利巴韦林联合治疗。研究了治疗的病毒学反应及药物的不良反应。比较了患者接受索磷布韦和利巴韦林治疗时以及停止使用这些药物后CNI水平的曲线下面积（AUC）和药代动力学数据。
总共10例患者中有9例（90%）在4周时实现快速病毒学应答（RVR），HCV RNA检测不到，其余1例患者在8周时HCV RNA检测不到。在3个月、6个月和12个月时均观察到持续病毒学应答，且10例患者（100%）均维持该应答。本研究的重要方面是索磷布韦-利巴韦林联合治疗方案对CNI AUC水平的影响，这导致CNI AUC降低。在作为三联药物免疫抑制的一部分使用时，根据C0水平的测量结果，无需调整CNI（他克莫司和环孢素）的剂量。
索磷布韦与利巴韦林联合治疗在肾移植后环境中治疗HCV感染是有效且安全的。在这些患者接受索磷布韦治疗期间，需要密切监测CNI水平。随着治疗和病毒清除，由于CNI药物清除增加，CNI水平可能会降低，AUC测量结果表明了这一点。这对于排斥反应高危患者可能很重要。
