Sofosbuvir and Ribavirin for Treatment of Compensated Recurrent Hepatitis C Virus Infection After Liver Transplantation
Sofosbuvir and Ribavirin for Treatment of Compensated Recurrent Hepatitis C Virus Infection After Liver Transplantation
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DOI：
10.1053/j.gastro.2014.10.001
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发表时间：
2015-01-01
期刊：
影响因子：
29.4
通讯作者：
Terrault, Norah A.
中科院分区：
文献类型：
--
作者：
Charlton, Michael;Gane, Edward;Terrault, Norah A.
背景与目的：用于治疗肝移植术后复发性丙型肝炎病毒（HCV）感染的干扰素α为基础的方案耐受性差，与一般适度的疗效相关，并可能与免疫抑制剂相互作用。我们评估了核苷酸聚合酶抑制剂索非布韦联合利巴韦林24周无干扰素方案治疗移植后HCV感染的疗效和安全性。方法：在一项前瞻性、多中心、开放标签的初步研究中，我们招募了初次或二次肝移植后任何基因型的代偿性复发HCV感染患者。所有患者均接受24周的索非布韦400 mg/d和利巴韦林400 mg/d，根据肌酐清除率和血红蛋白值进行调整。主要终点是治疗后12周的持续病毒学应答。研究结果：在40例入组并接受治疗的患者中，78%为男性，85%为白色，83%为HCV基因型1，40%为肝硬化（基于活检），88%既往接受过干扰素治疗。治疗后12周，40例患者中有28例获得持续病毒学应答（70%; 90%置信区间：56%-82%）。复发占病毒学失败的所有病例。在治疗期间或治疗后，没有患者可检测到病毒耐药性。最常见的不良事件是疲劳（30%），腹泻（28%）和头痛（25%）。此外，20%的受试者发生贫血。2例患者因不良事件停止研究治疗，认为与研究治疗无关。无死亡、移植物丢失或排斥反应发生。未报告与任何伴随免疫抑制剂的相互作用。结论：索非布韦和利巴韦林联合治疗24周是一种有效且耐受性良好的无干扰素治疗移植后HCV感染的方法。EudraCT，编号：2012-002417-19; ClinicalTrials.gov，编号：NCT 01687270。
BACKGROUND & AIMS: Interferon alfa-based regimens used to treat recurrent hepatitis C virus (HCV) infection after liver transplantation are poorly tolerated, associated with generally modest efficacy, and can interact with immunosuppressive agents. We evaluated the efficacy and safety of an interferon-free regimen of the nucleotide polymerase inhibitor sofosbuvir combined with ribavirin for 24 weeks in treating post-transplantation HCV infection. METHODS: In a prospective, multicenter, open-label pilot study, we enrolled patients with compensated recurrent HCV infection of any genotype after a primary or secondary liver transplantation. All patients received 24 weeks of sofosbuvir 400 mg daily and ribavirin starting at 400 mg daily, which was adjusted according to creatinine clearance and hemoglobin values. The primary end point was sustained virologic response 12 weeks after treatment. RESULTS: Of the 40 patients enrolled and treated, 78% were male, 85% were white, 83% had HCV genotype 1, 40% had cirrhosis (based on biopsy), and 88% had been previously treated with interferon. Sustained virologic response 12 weeks after treatment was achieved by 28 of 40 patients (70%; 90% confidence interval: 56%-82%). Relapse accounted for all cases of virologic failure. No patients had detectable viral resistance during or after treatment. The most common adverse events were fatigue (30%), diarrhea (28%), and headache (25%). In addition, 20% of the subjects experienced anemia. Two patients discontinued study treatment because of adverse events, which were considered unrelated to study treatment. No deaths, graft losses, or episodes of rejection occurred. No interactions with any concomitant immunosuppressive agents were reported. CONCLUSIONS: Sofosbuvir and ribavirin combination therapy for 24 weeks is an effective and well-tolerated interferon-free treatment for post-transplantation HCV infection. EudraCT, Number: 2012-002417-19; ClinicalTrials.gov, Number: NCT01687270.