Clinical Pharmacy, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi Arabia.
Tropical Medicine, Faculty of Medicine, Ain Shams Centre for Organ Transplantation (ASCOT), Ain Shams University, Cairo, Egypt.
J Clin Pharm Ther. 2019 Jun;44(3):447-453. doi: 10.1111/jcpt.12807. Epub 2019 Feb 3.
The influence of immunosuppression on the response to antiviral therapy (AVT) for recurrent hepatitis C virus (HCV) infection in liver transplant (LT) recipients remains controversial, especially for the rarely investigated genotype 4. This study aims to compare the effects of the two widely used calcineurin inhibitors (CNIs) (cyclosporine A (CsA) and tacrolimus (Tac)) on the therapeutic response to different AVT regimens.
A prospective, dual-centre, cohort study of 126 Egyptian living donor liver transplant (LDLT) recipients with recurrent HCV genotype 4 infection, who were categorized into three groups according to the AVT used. Group I received pegylated interferon (Peg-IFN-α 2a) plus ribavirin (RBV) (n = 44), group II received the direct antiviral agent (DAA) sofosbuvir plus RBV (n = 52) and group III received daclatasvir and sofosbuvir (also DAAs) plus RBV (n = 30). Each group was further subdivided according to the primary immunosuppression (CsA or Tac). The sustained virological response (SVR) and relapse rates were considered the primary therapeutic outcomes of AVT.
No significant intergroup differences were observed in the achievement of primary and secondary outcomes. SVR rates in the IFN-based regimen were 75% and 66.7% in CsA and Tac users and 81.2% and 83% in DAAs, respectively. Relapse rates in the IFN-based regimen were 10% and 16.7% in CsA and Tac users and 12.5% and 14.9% in DAAs, respectively.
Within the limitations of a relatively small study, CsA did not offer an advantage over Tac regarding the response to AVT after HCV genotype 4 recurrence in LDLT recipients.
免疫抑制对肝移植(LT)受者复发性丙型肝炎病毒(HCV)感染抗病毒治疗(AVT)反应的影响仍存在争议,特别是对于很少研究的基因型 4。本研究旨在比较两种广泛使用的钙调神经磷酸酶抑制剂(CNIs)(环孢素 A(CsA)和他克莫司(Tac))对不同 AVT 方案治疗反应的影响。
对 126 例埃及活体供肝移植(LDLT)受者复发性 HCV 基因型 4 感染进行前瞻性、双中心、队列研究,根据使用的 AVT 将受者分为三组。组 I 接受聚乙二醇干扰素(Peg-IFN-α 2a)加利巴韦林(RBV)(n=44),组 II 接受直接抗病毒药物(DAA)索磷布韦加 RBV(n=52),组 III 接受达拉他韦和索磷布韦(也是 DAA)加 RBV(n=30)。每组根据主要免疫抑制(CsA 或 Tac)进一步分为亚组。持续性病毒学应答(SVR)和复发率被认为是 AVT 的主要治疗结果。
各组间主要和次要治疗结果无显著差异。基于 IFN 的方案的 SVR 率在 CsA 和 Tac 使用者中分别为 75%和 66.7%,在 DAA 使用者中分别为 81.2%和 83%。基于 IFN 的方案的复发率在 CsA 和 Tac 使用者中分别为 10%和 16.7%,在 DAA 使用者中分别为 12.5%和 14.9%。
在一项相对较小的研究的局限性内,CsA 在 LDLT 受者 HCV 基因型 4 复发后对 AVT 反应方面并未优于 Tac。