Sofosbuvir and Velpatasvir for HCV in Patients with Decompensated Cirrhosis
Sofosbuvir and Velpatasvir for HCV in Patients with Decompensated Cirrhosis
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DOI：
10.1056/nejmoa1512614
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发表时间：
2015-12-31
影响因子：
158.5
通讯作者：
Charlton, M.
中科院分区：
文献类型：
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作者：
Curry, M. P.;O'Leary, J. G.;Charlton, M.
背景随着丙型肝炎病毒 (HCV) 感染人群的老龄化，失代偿性肝硬化患者的数量预计将增加。 方法我们进行了一项 3 期开放标签研究，涉及先前接受过治疗和先前未接受治疗的感染 HCV 基因型 1 至 6 的失代偿性肝硬化患者（分类为 Child-Pugh-Turcotte B 级）。患者以 1:1:1 的比例随机分配接受核苷酸聚合酶抑制剂索磷布韦和 NS5A 抑制剂维帕他韦治疗，每天一次，持续 12 周，索磷布韦-维帕他韦加利巴韦林治疗 12 周，或索磷布韦-维帕他韦治疗 24 周。主要终点是治疗结束后 12 周出现持续病毒学应答。 结果 在接受治疗的 267 名患者中，78% 的 HCV 基因型为 1，4% 为基因型 2，15% 为基因型 3，3% 为基因型 4，不到 1% 为基因型 6；没有患者具有基因型 5。接受 12 周索磷布韦-维帕他韦治疗的患者中，持续病毒学应答总体率为 83%（95% 置信区间 [CI]，74 至 90）；接受 12 周索磷布韦-维帕他韦加利巴韦林治疗的患者中，持续病毒学缓解率为 94%（95% CI，87 至 98）；接受索磷布韦-维帕他韦联合利巴韦林治疗的患者中，持续病毒学缓解率为 86%（95% CI，77）。至 92）接受 24 周索磷布韦-维帕他韦治疗的患者。事后分析没有发现三个研究组之间持续病毒学应答率有任何显着差异。接受 12 周索磷布韦-维帕他韦治疗的患者中有 19% 发生严重不良事件，接受 12 周索磷布韦-维帕他韦加利巴韦林治疗的患者中有 16% 发生严重不良事件，而接受 24 周索磷布韦-维帕他韦治疗的患者中有 18% 发生严重不良事件。所有患者中最常见的不良事件为疲劳 (29%)、恶心 (23%) 和头痛 (22%)，而接受利巴韦林治疗的患者则为贫血 (31%)。结论：使用索磷布韦-维帕他韦联合或不联合利巴韦林治疗 12 周，以及使用索磷布韦-维帕他韦治疗 24 周，在 HCV 感染和代偿失调患者中，持续病毒学应答率较高。肝硬化。
BACKGROUNDAs the population that is infected with the hepatitis C virus (HCV) ages, the number of patients with decompensated cirrhosis is expected to increase.METHODSWe conducted a phase 3, open-label study involving both previously treated and previously untreated patients infected with HCV genotypes 1 through 6 who had decompensated cirrhosis (classified as Child-Pugh-Turcotte class B). Patients were randomly assigned in a 1: 1: 1 ratio to receive the nucleotide polymerase inhibitor sofosbuvir and the NS5A inhibitor velpatasvir once daily for 12 weeks, sofosbuvir-velpatasvir plus ribavirin for 12 weeks, or sofosbuvir-velpatasvir for 24 weeks. The primary end point was a sustained virologic response at 12 weeks after the end of therapy.RESULTSOf the 267 patients who received treatment, 78% had HCV genotype 1, 4% genotype 2, 15% genotype 3, 3% genotype 4, and less than 1% genotype 6; no patients had genotype 5. Overall rates of sustained virologic response were 83% (95% confidence interval [CI], 74 to 90) among patients who received 12 weeks of sofosbuvir-velpatasvir, 94% (95% CI, 87 to 98) among those who received 12 weeks of sofosbuvir-velpatasvir plus ribavirin, and 86% (95% CI, 77 to 92) among those who received 24 weeks of sofosbuvir-velpatasvir. Post hoc analysis did not detect any significant differences in rates of sustained virologic response among the three study groups. Serious adverse events occurred in 19% of patients who received 12 weeks of sofosbuvir-velpatasvir, 16% of those who received 12 weeks of sofosbuvir-velpatasvir plus ribavirin, and 18% of those who received 24 weeks of sofosbuvir-velpatasvir. The most common adverse events were fatigue (29%), nausea (23%), and headache (22%) in all patients and anemia (31%) in the patients receiving ribavirin.CONCLUSIONSTreatment with sofosbuvir-velpatasvir with or without ribavirin for 12 weeks and with sofosbuvir-velpatasvir for 24 weeks resulted in high rates of sustained virologic response in patients with HCV infection and decompensated cirrhosis.