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丙型肝炎病毒复发的肝移植受者中 boceprevir 和免疫抑制治疗的实用管理。

Practical management of boceprevir and immunosuppressive therapy in liver transplant recipients with hepatitis C virus recurrence.

机构信息

AP-HP, Hôpital Paul Brousse, Centre Hépato-Biliaire, Villejuif, France.

出版信息

Antimicrob Agents Chemother. 2012 Nov;56(11):5728-34. doi: 10.1128/AAC.01151-12. Epub 2012 Aug 20.

Abstract

Hepatitis C virus (HCV) recurrence is the most important complication in HCV liver transplant patients. Boceprevir with pegylated interferon and ribavirin (PegIFN/RBV) enabled improvement in sustained virological response rates of patients with genotype 1 HCV. Boceprevir interacts with immunosuppressive therapy (IT) by inhibiting the cytochrome P450 3A enzyme. Our aim was to study interactions and assess the safety of boceprevir in the context of HCV recurrence. Boceprevir (800 mg three times a day) initiated after a 4-week lead-in phase was associated with cyclosporine (three patients), tacrolimus (two patients), and everolimus (one patient) in five liver transplant patients with genotype 1 HCV infection who experienced HCV recurrence. The mean follow-up period after HCV therapy was 14.8 ± 3.1 weeks. Estimated oral clearances of IT decreased on average by 50%, requiring reduced dosing regimens. Anemia occurred in all patients, with a mean fall in hemoglobin levels between baseline and week 12 of 3.12 ± 2.27 g/dl. All patients required administration of β-erythropoietin (n = 5), three needed ribavirin dose reduction, and one needed a blood transfusion. A virological response was observed in all patients (mean HCV viral load [HVL] decrease at week 12, 6.64 ± 0.35 log(10) IU/ml). These preliminary results in liver transplant patients with HCV recurrence demonstrate the feasibility and safety of coadministration of boceprevir and IT.

摘要

丙型肝炎病毒 (HCV) 复发是 HCV 肝移植患者最重要的并发症。波西普韦联合聚乙二醇干扰素和利巴韦林(PegIFN/RBV)可提高基因型 1 HCV 患者的持续病毒学应答率。波西普韦通过抑制细胞色素 P450 3A 酶与免疫抑制治疗(IT)相互作用。我们的目的是研究波西普韦在 HCV 复发背景下的相互作用和安全性。在 5 例基因型 1 HCV 感染、HCV 复发的肝移植患者中,在 4 周导入期后开始使用 800 mg 每日 3 次的波西普韦,同时合用环孢素(3 例)、他克莫司(2 例)和依维莫司(1 例)。HCV 治疗后平均随访 14.8 ± 3.1 周。IT 的口服清除率平均降低 50%,需要减少剂量方案。所有患者均发生贫血,血红蛋白水平从基线至第 12 周平均下降 3.12 ± 2.27 g/dl。所有患者均需要使用促红细胞生成素(n = 5),3 例需要减少利巴韦林剂量,1 例需要输血。所有患者均观察到病毒学应答(第 12 周平均 HCV 病毒载量[HVL]下降 6.64 ± 0.35 log(10) IU/ml)。这些在 HCV 复发的肝移植患者中的初步结果表明,波西普韦与 IT 联合应用具有可行性和安全性。

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