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从HCV感染供者至未感染受者的心肺移植
Heart and Lung Transplants from HCV-Infected Donors to Uninfected Recipients


Ann E. Woolley ... 其他 • 2019.04.25
相关阅读
• 丙型肝炎病毒感染供者的心肺被安全移植到HCV阴性受者体内 • glecaprevir和pibrentasvir复方药用于治疗丙型肝炎病毒感染合并重度肾功能损害患者 • 用glecaprevir-pibrentasvir 8周对慢性HCV基因型1或3感染有效

摘要


背景

如果供者患丙型肝炎病毒血症,其心肺通常不会用于移植。治疗丙型肝炎病毒(HCV)感染的直接抗病毒药出现之后,使得感染HCV的供者的心肺能够移植到未感染HCV的受者体内,从而有可能显著扩大供者器官捐献库。

 

方法

我们开展了一项试验,将患丙型肝炎病毒血症(不考虑HCV基因型)的供者的心肺移植到未感染HCV的成人患者体内。从移植后数小时内开始,对器官受者进行4周索磷布韦-维帕他韦(全基因型直接抗病毒治疗方案)超前用药,以阻断病毒复制。主要结局是由以下两项构成的复合结局:完成针对HCV的抗病毒治疗后12周时的持续病毒学应答,以及移植后6个月时移植物存活。

 

结果

本试验共纳入了44例患者:36例接受了肺移植,8例接受了心脏移植。HCV感染供者的中位病毒载量为890,000 IU/ml(四分位距,276,000~4,630,000)。HCV基因型包括基因型1(61%的供者)、基因型2(17%的供者)、基因型3(17%的供者)和不确定(5%的供者)。在44名受者中,共有42名(95%)的丙型肝炎病毒载量在移植后即刻可测,中位病毒载量为1,800 IU/mL(四分位距,800~6,180)。本试验纳入的前35例患者已完成6个月随访,在移植后6个月时,全部35例患者(100%;精确95%置信区间,90~100)均存活,移植物功能优异,并且丙型肝炎病毒载量不可测;病毒载量在移植后约2周内变得不可测,之后所有患者均保持病毒载量不可测。未发现与治疗相关的严重不良事件。与接受HCV未感染供者肺移植的患者队列相比,在感染HCV的肺移植受者中,有治疗指征的急性细胞排斥反应病例较多。在对可能的混杂因素进行校正后,这一差异不显著。

 

结论

未感染HCV的患者从患丙型肝炎病毒血症的供者接受心脏或肺移植后,在移植后数小时内开始的4周抗病毒治疗预防了HCV感染的发生(由美国Mendez国立移植研究所基金会[Mendez National Institute of Transplantation Foundation]等资助;DONATE HCV在ClinicalTrials.gov注册号为NCT03086044)。





作者信息

Ann E. Woolley, M.D., Steve K. Singh, M.D., Hilary J. Goldberg, M.D., Hari R. Mallidi, M.D., Michael M. Givertz, M.D., Mandeep R. Mehra, M.D., Antonio Coppolino, M.D., Amanda E. Kusztos, B.S., Megan E. Johnson, B.A., Kaiwen Chen, B.S., Esther A. Haddad, M.D., John Fanikos, R.Ph., David P. Harrington, Ph.D., Phillip C. Camp, M.D., and Lindsey R. Baden, M.D. for the DONATE HCV Trial Team*
From the Divisions of Infectious Diseases (A.E.W., A.E.K., M.E.J., K.C., E.A.H., L.R.B.), Cardiac Surgery (S.K.S., H.R.M.), Thoracic Surgery (S.K.S., H.R.M., A.C., P.C.C.), Pulmonary and Critical Care Medicine (H.J.G.), and Cardiovascular Medicine (M.M.G., M.R.M.), and the Department of Pharmacy (J.F.), Brigham and Women’s Hospital, Harvard Medical School (A.E.W., S.K.S., H.J.G., H.R.M., M.M.G., M.R.M., A.C., E.A.H., P.C.C., L.R.B.), Massachusetts College of Pharmacy and Health Sciences (J.F.), the Department of Biostatistics and Computational Biology, Dana–Farber Cancer Institute (D.P.H.), and Harvard T.H. Chan School of Public Health (D.P.H.) — all in Boston. Address reprint requests to Dr. Woolley at the Division of Infectious Diseases, Brigham and Women’s Hospital, 75 Francis St., Boston, MA 02115, or at awoolley@bwh.harvard.edu. *A complete list of the members of the DONATE HCV Trial Team is provided in the Supplementary Appendix, available at NEJM.org.

 

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