Pellicelli Adriano M, Montalbano Marzia, Lionetti Raffaella, Durand Christine, Ferenci Peter, D'Offizi Gianpiero, Knop Viola, Telese Andrea, Lenci Ilaria, Andreoli Arnaldo, Zeuzem Stefan, Angelico Mario
Liver Unit, San Camillo Forlanini Hospital, Rome, Italy.
Liver Unit, Istituto Nazionale Malattie Infettive Spallanzani, Rome, Italy.
Dig Liver Dis. 2014 Oct;46(10):923-7. doi: 10.1016/j.dld.2014.06.004. Epub 2014 Jul 3.
We evaluated efficacy and safety of sofosbuvir and daclatasvir±ribavirin in liver transplant recipients with severe recurrent hepatitis C.
Patients included in an international compassionate use programme for treatment with sofosbuvir and daclatasvir±ribavirin for 24 weeks were prospectively studied. Serum hepatitis C virus RNA was measured at treatment weeks 4, 12, and 24 and during follow-up at weeks 4, 8, and 12.
Twelve patients (3 with fibrosing cholestatic hepatitis and 9 with cirrhosis; median model for end-stage liver disease score 20) received sofosbuvir 400mg/day+daclatasvir 60mg/day, and 6 patients (50%) also received ribavirin 200-800mg/day. Nine patients completed 24 weeks of treatment (75%), and all had undetectable hepatitis C virus RNA at week 24; 3 patients died (25%, liver failure, gastrointestinal bleeding and sepsis); 4 patients experienced severe liver disease-related adverse events. Post-treatment hepatitis C virus RNA was available for 5 patients (week 8, n=2; week 4, n=3) and was undetectable in all cases. Mean Child-Pugh score and albumin level improved significantly at week 24. No changes in immunosuppressant doses were needed.
All-oral sofosbuvir plus daclatasvir combination shows high virological efficacy in liver transplant recipients and does not interact with immunosuppressants. All adverse events were unrelated to study drugs. These data strongly suggest that this combination must be initiated before decompensation.
我们评估了索磷布韦和达卡他韦±利巴韦林在患有严重复发性丙型肝炎的肝移植受者中的疗效和安全性。
对纳入一项国际同情用药计划、接受索磷布韦和达卡他韦±利巴韦林治疗24周的患者进行前瞻性研究。在治疗第4、12和24周以及随访第4、8和12周时检测血清丙型肝炎病毒RNA。
12例患者（3例为纤维化胆汁淤积性肝炎，9例为肝硬化；终末期肝病模型评分中位数为20）接受索磷布韦400mg/天+达卡他韦60mg/天治疗，6例患者（50%）还接受了利巴韦林200 - 800mg/天治疗。9例患者完成了24周治疗（75%），且所有患者在第24周时丙型肝炎病毒RNA检测不到；3例患者死亡（25%，死于肝衰竭、胃肠道出血和脓毒症）；4例患者发生了严重的肝病相关不良事件。5例患者有治疗后丙型肝炎病毒RNA检测结果（第8周，n = 2；第4周，n = 3），所有病例均检测不到。第24周时Child-Pugh评分均值和白蛋白水平显著改善。无需调整免疫抑制剂剂量。
全口服索磷布韦加达卡他韦联合方案在肝移植受者中显示出高病毒学疗效，且不与免疫抑制剂相互作用。所有不良事件均与研究药物无关。这些数据强烈表明，应在失代偿前开始使用该联合方案。
