索磷布韦维帕他韦片治疗失代偿期肝硬化的丙型肝炎病毒感染。
Sofosbuvir and Velpatasvir for HCV in Patients with Decompensated Cirrhosis.
机构信息
From the Beth Israel Deaconess Medical Center, Boston (M.P.C.); Baylor University Medical Center, Dallas (J.G.O.), and Texas Liver Institute, University of Texas Health Science Center, San Antonio (E.L.) - both in Texas; Ochsner Medical Center, New Orleans (N.B.); Duke University, Durham (A.J.M.), and School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill (M.F.) - both in North Carolina; Washington University School of Medicine, St. Louis (K.M.K.); Thomas Jefferson University (J.M.F.) and University of Pennsylvania School of Medicine (K.R.R.) - both in Philadelphia; Northwestern University, Chicago (S.L.F.); Mount Sinai Hospital (T.S.), New York University School of Medicine (L.T.), and Weill Cornell Medical College (R.S.B.) - all in New York; University of Michigan, Ann Arbor (R.F.); University of Miami, Miami (E.S.); Gilead Sciences, Foster City, CA (B.D., D.A., J.M., A.O., D.M.B., J.G.M.); and Intermountain Medical Center, Salt Lake City (M.C.).
出版信息
N Engl J Med. 2015 Dec 31;373(27):2618-28. doi: 10.1056/NEJMoa1512614. Epub 2015 Nov 16.
BACKGROUND
As the population that is infected with the hepatitis C virus (HCV) ages, the number of patients with decompensated cirrhosis is expected to increase.
METHODS
We 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.
RESULTS
Of 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.
CONCLUSIONS
Treatment 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. (Funded by Gilead Sciences; ASTRAL-4 ClinicalTrials.gov number, NCT02201901.).
背景
随着感染丙型肝炎病毒（HCV）的人群年龄增长，失代偿性肝硬化患者的数量预计将会增加。
方法
我们开展了一项 3 期、开放标签研究，纳入了先前接受过治疗和未接受过治疗的感染 HCV 基因型 1-6 且患有失代偿性肝硬化（分为 Child-Pugh-Turcotte 分级 B）的患者。患者以 1:1:1 的比例随机分配，分别接受核苷酸聚合酶抑制剂索磷布韦和 NS5A 抑制剂维帕他韦每日 1 次，持续 12 周，索磷布韦-维帕他韦联合利巴韦林治疗 12 周，或索磷布韦-维帕他韦治疗 24 周。主要终点为治疗结束后 12 周时的持续病毒学应答。
结果
在接受治疗的 267 例患者中，78%为 HCV 基因型 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；无基因型 5 的患者。接受 12 周索磷布韦-维帕他韦治疗的患者持续病毒学应答率为 83%（95%置信区间[CI]，74%至 90%），接受 12 周索磷布韦-维帕他韦联合利巴韦林治疗的患者为 94%（95%CI，87%至 98%），接受 24 周索磷布韦-维帕他韦治疗的患者为 86%（95%CI，77%至 92%）。事后分析未发现三组研究中持续病毒学应答率有任何显著差异。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-维帕他韦联合利巴韦林治疗的患者中有 16%，接受 24 周索磷布韦-维帕他韦治疗的患者中有 18%。所有患者中最常见的不良事件为疲劳（29%）、恶心（23%）和头痛（22%），接受利巴韦林治疗的患者中最常见的不良事件为贫血（31%）。
结论
索磷布韦-维帕他韦联合或不联合利巴韦林治疗 12 周，以及索磷布韦-维帕他韦治疗 24 周，可使 HCV 感染和失代偿性肝硬化患者获得较高的持续病毒学应答率。（由吉利德科学公司资助；ASTRAL-4 ClinicalTrials.gov 编号，NCT02201901。）
Zotero 插件