Safety and Effectiveness of Ledipasvir and Sofosbuvir, With or Without Ribavirin, in Treatment-Experienced Patients With Genotype 1 Hepatitis C Virus Infection and Cirrhosis.
Safety and Effectiveness of Ledipasvir and Sofosbuvir, With or Without Ribavirin, in Treatment-Experienced Patients With Genotype 1 Hepatitis C Virus Infection and Cirrhosis.
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Ledipasvir 和 Sofosbuvir（联合或不联合利巴韦林）在经历过治疗的基因 1 型丙型肝炎病毒感染和肝硬化患者中的安全性和有效性。
DOI：
10.1016/j.cgh.2017.12.037
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发表时间：
2018
期刊：
影响因子：
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通讯作者：
Michael,Larr
中科院分区：
文献类型：
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作者：
Lim,JosephK;Liapakis,AnnMarie;Shiffman,MitchellL;Lok,AnnaS;Zeuzem,Stefan;Terrault,NorahA;Park,JamesS;Landis,CharlesS;Hassan,Mohamed;Gallant,Joel;Kuo,Alexander;Pockros,PaulJ;Vainorius,Monika;Akushevich,Lucy;Michael,Larr
背景和目的我们的目的是在常规临床实践中评估雷迪帕韦和索磷布韦联合或不联合利巴韦林治疗 12 或 24 周对于有治疗经验的丙型肝炎病毒 (HCV) 基因型 1 感染和肝硬化患者的安全性和有效性。在一项多中心、前瞻性、观察性队列研究 (HCV-TARGET) 中对患者进行了随访。方法我们收集了 667 名经历过治疗的慢性基因 1 型 HCV 感染成人的数据，他们从 2011 年到 2016 年 9 月 15 日开始接受雷迪帕韦和索磷布韦治疗，无论是否联合利巴韦林，根据地区护理标准，在学术机构 (n = 39) 和社区 (n) = 18) 位于美国、加拿大、德国和以色列的中心。从医疗记录中收集信息并抽象到一个独特的集中数据核心中。独立监察员系统地审查数据输入的完整性和准确性。在治疗期间和随访期间每 12 周收集一次人口统计学、临床、不良事件和病毒学数据。主要疗效终点是持续病毒学应答，定义为治疗结束后至少 64 天 HCV RNA 水平低于定量下限或检测不到 (SVR12)。符合方案人群 (n = 610) 仅限于完成 12 或 24 周（±2 周）治疗并具有最终病毒学结果的患者。结果符合方案分析显示，579 名患者 (93.8%) 实现了 SVR12，其中 50/51 名患者接受了雷迪帕韦和索磷布韦治疗 12 周 (98%)，384/408 名患者接受了雷迪帕韦 和索磷布韦治疗 24 周 (94.1%)，68/70 名患者接受雷迪帕韦和索磷布韦联合利巴韦林治疗 12 周 (97.1%)，57/60 名患者接受雷迪帕韦和索磷布韦联合利巴韦林治疗 24 周 (95%)。多变量分析显示，治疗持续时间和利巴韦林的添加均与 SVR12 无关。代偿性肝硬化（比值比 [OR] 与失代偿性肝硬化相比，2.41；95% CI，1.16-5.02），白蛋白 ≥ 3.5 g/dL（OR，3.15；95% CI 1.46–6.80），或总胆红素 ≤ 1.2 mg/dL（OR 3.34；95%） CI，1.59–7.00）与 SVR12. 结论在对 HCV-TARGET 研究的安全性和有效性数据进行分析时，我们发现雷迪帕韦和索磷布韦治疗（无论是否联合利巴韦林）均有效，并且对于经历过治疗的基因 1 型 HCV 感染和代偿性肝硬化患者来说，治疗效果良好且耐受性良好。在使用雷迪帕韦和索磷布韦治疗 12 周或 24 周（联合或不联合利巴韦林）的患者中，SVR12 率没有显着差异。失代偿性肝硬化患者似乎受益于加用利巴韦林或将雷迪帕韦和索磷布韦治疗延长至 24 周。 ClinicalTrials.gov 编号：NCT10474811。
Background & AimsWe aimed to evaluate the safety and effectiveness of 12 or 24 weeks treatment with ledipasvir and sofosbuvir, with or without ribavirin, in treatment-experienced patients with hepatitis C virus (HCV) genotype 1 infection and cirrhosis in routine clinical practice. Patients were followed in a multi-center, prospective, observational cohort study (HCV-TARGET).MethodsWe collected data from 667 treatment-experienced adults with chronic genotype 1 HCV infection who began treatment with ledipasvir and sofosbuvir, with or without ribavirin, from 2011 through September 15, 2016, according to the regional standards of care, at academic (n = 39) and community (n = 18) centers in the United States, Canada, Germany, and Israel. Information was collected from medical records and abstracted into a unique centralized data core. Independent monitors systematically reviewed data entries for completeness and accuracy. Demographic, clinical, adverse event, and virologic data were collected every 12 weeks during treatment and during the follow-up period. The primary efficacy endpoint was sustained virologic response, defined as a level of HCV RNA below the lower limit of quantification or undetectable at a minimum 64 days after the end of treatment (SVR12). The per-protocol population (n = 610) was restricted to patients who completed 12 or 24 weeks of treatment (±2 weeks) and had final virologic outcomes available.ResultsThe per-protocol analysis revealed that 579 patients (93.8%) achieved an SVR12, including 50/51 patients who received ledipasvir and sofosbuvir for 12 weeks (98%), 384/408 patients who received ledipasvir and sofosbuvir for 24 weeks (94.1%), 68/70 patients who received ledipasvir and sofosbuvir with ribavirin for 12 weeks (97.1%), and 57/60 patients who received ledipasvir and sofosbuvir with ribavirin for 24 weeks (95%). On multivariate analysis, neither treatment duration nor the addition of ribavirin was associated with SVR12. Compensated cirrhosis (odds ratio [OR] compared to decompensated cirrhosis, 2.41; 95% CI, 1.16-5.02), albumin ≥ 3.5 g/dL (OR, 3.15; 95% CI 1.46–6.80), or total bilirubin ≤ 1.2 mg/dL (OR 3.34; 95% CI, 1.59–7.00) were associated with SVR12.ConclusionsIn an analysis of safety and effectiveness data from the HCV-TARGET study, we found treatment with ledipasvir and sofosbuvir, with or without ribavirin, to be effective and well tolerated by treatment-experienced patients with genotype 1 HCV infection and compensated cirrhosis. There were no significant differences in rate of SVR12 among patients treated with ledipasvir and sofosbuvir for 12 or 24 weeks, with or without ribavirin. Patients with decompensated cirrhosis appear to benefit from the addition of ribavirin or extension of ledipasvir and sofosbuvir treatment to 24 weeks. ClinicalTrials.gov no: NCT10474811.