AP-HP Hôpital Paul-Brousse, Centre Hépato-Biliaire, Villejuif F-94800, France; Université Paris-Sud, UMR-S 785, Villejuif F-94800, France; Inserm, Unité 785, Villejuif F-94800, France; Hepatinov, Villejuif F-94800, France.
Hôpital Edouard Herriot, Unité de transplantation hépatique, Lyon F-69400, France.
J Hepatol. 2014 Jan;60(1):78-86. doi: 10.1016/j.jhep.2013.08.018. Epub 2013 Aug 29.
BACKGROUND & AIMS: Protease inhibitors (PI) with peginterferon/ribavirin have significantly improved SVR rates in HCV G1 patients. Their use to treat HCV recurrence after liver transplantation (LT) is a challenge.
This cohort study included 37 liver transplant recipients (male, 92%, age 57 ± 11 years), treated with boceprevir (n=18) or telaprevir (n=19). The indication for therapy was HCV recurrence (fibrosis stage ≥F2 (n=31, 83%) or fibrosing cholestatic hepatitis (n=6, 16%).
Eighteen patients were treatment-naive, five were relapsers and fourteen were non-responders to dual therapy after LT. Twenty-two patients received cyclosporine and fifteen tacrolimus. After 12 weeks of PI therapy, a complete virological response was obtained in 89% of patients treated with boceprevir, and 58% with telaprevir (p=0.06). The end of treatment virological response rate was 72% (13/18) in the boceprevir group and 40% (4/10) in the telaprevir group (p=0.125). A sustained virological response 12 weeks after treatment discontinuation was observed in 20% (1/5) and 71% (5/7) of patients in the telaprevir and boceprevir groups, respectively (p=0.24). Treatment was discontinued in sixteen patients (treatment failures (n=11), adverse events (n=5)). Infections occurred in ten patients (27%), with three fatal outcomes (8%). The most common adverse effect was anemia (n=34, 92%), treated with erythropoietin and/or a ribavirin dose reduction; thirteen patients (35%) received red blood cell transfusions. The cyclosporine dose was reduced by 1.8 ± 1.1-fold and 3.4 ± 1.0-fold with boceprevir and telaprevir, respectively. The tacrolimus dose was reduced by 5.2 ± 1.5-fold with boceprevir and 23.8±18.2-fold with telaprevir.
Our results suggest that triple therapy is effective in LT recipients, particularly those experiencing a severe recurrence. The occurrence of anemia and drug-drug interactions, and the risk of infections require close monitoring.
聚乙二醇干扰素/利巴韦林联合蛋白酶抑制剂（PI）显著提高了 HCV G1 患者的 SVR 率。将其用于治疗肝移植（LT）后 HCV 复发是一个挑战。
本队列研究纳入了 37 名接受过治疗的肝移植受者（男性，92%，年龄 57±11 岁），其中 18 名接受博赛泼维治疗，19 名接受特拉泼维治疗。治疗的指征是 HCV 复发（纤维化分期≥F2（n=31，83%）或纤维性胆汁性肝炎（n=6，16%））。
18 名患者为初治患者，5 名患者为 LT 后复发患者，14 名患者为双重治疗无应答患者。22 名患者接受环孢素治疗，15 名患者接受他克莫司治疗。PI 治疗 12 周后，博赛泼维组 89%的患者获得完全病毒学应答，特拉泼维组 58%的患者获得完全病毒学应答（p=0.06）。博赛泼维组的治疗结束病毒学应答率为 72%（13/18），特拉泼维组为 40%（4/10）（p=0.125）。停药 12 周后，特拉泼维组和博赛泼维组分别有 20%（1/5）和 71%（5/7）的患者获得持续病毒学应答（p=0.24）。16 名患者（治疗失败（n=11），不良反应（n=5））停止治疗。10 名患者（27%）发生感染，其中 3 例死亡（8%）。最常见的不良反应是贫血（n=34，92%），用促红细胞生成素和/或减少利巴韦林剂量治疗；13 名患者（35%）接受了红细胞输注。博赛泼维和特拉泼维分别使环孢素剂量减少 1.8±1.1 倍和 3.4±1.0 倍。博赛泼维使他克莫司剂量减少 5.2±1.5 倍，特拉泼维使他克莫司剂量减少 23.8±18.2 倍。
我们的研究结果表明，三联疗法在 LT 受者中是有效的，特别是那些严重复发的患者。贫血和药物相互作用的发生以及感染的风险需要密切监测。
