The SHELTER Trial of Transplanting Hepatitis C Virus-Infected Lungs Into Uninfected Recipients.
The SHELTER Trial of Transplanting Hepatitis C Virus-Infected Lungs Into Uninfected Recipients.
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DOI：
10.1097/txd.0000000000001504
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发表时间：
2023-07
影响因子：
2.3
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中科院分区：
文献类型：
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SHELTER是一项将已故丙型肝炎病毒（HCV）感染供者的肺移植到丙型肝炎阴性候选人体内的试验（赞助商：默克公司；NCT03724149）。很少有试验报告了使用HCV-RNA+供体的胸部器官的结果，也没有研究报告生活质量（QOL）。这项研究是在单一中心进行的10例肺移植的单臂试验。患者年龄在18岁到67岁之间，并在等待肺移植。排除有肝脏疾病证据的患者。主要终点是HCV治愈（完成抗病毒治疗后12周的持续病毒学应答）。受试者使用经过验证的RAND-36仪器纵向报告生活质量。我们还采用先进的方法在同一中心以1:3的比例匹配HCV-RNA+肺受体和hcv -阴性肺受体。在2018年11月至2020年11月期间，18名患者同意并选择在分配系统中接受HCV-RNA+肺治疗。中位数为37 d（四分位间距[IQR]， 6-373）后，10名参与者接受了双肺移植。中位受者年龄为57岁（IQR, 44-67）， 7名受者（70%）患有慢性阻塞性肺疾病。移植时肺分配评分中位数为34.3 （IQR, 32.7-86.9）。移植后，5名受者在第2天或第3天出现原发性移植物功能障碍3级，尽管没有人需要体外膜氧合。9名患者接受elbasvir/grazoprevir治疗，1名患者接受sofosbuvir/velpatasvir治疗。所有10例HCV患者均治愈并存活至1年（相比之下，匹配比较者的1年生存率为83%）。未发现与HCV或治疗相关的严重不良事件。RAND-36评分显示身体生活质量有明显改善，精神生活质量有一定改善。我们还检查了1的用力呼气量-移植后最重要的肺功能参数。我们发现HCV-RNA+肺受体与匹配比较组在1 s内的用力呼气量没有临床上重要的差异。SHELTER为将HCV-RNA+肺移植到未感染受体的安全性提供了重要证据，并表明生活质量改善。
SHELTER is a trial of transplanting lungs from deceased donors with hepatitis C virus (HCV) infection into HCV-negative candidates (sponsor: Merck; NCT03724149). Few trials have reported outcomes using thoracic organs from HCV-RNA+ donors and none have reported quality of life (QOL). This study is a single-arm trial of 10 lung transplants at a single center. Patients were included who were between 18 and 67 y of age and waitlisted for lung-only transplant. Patients were excluded who had evidence of liver disease. Primary outcome was HCV cure (sustained virologic response 12 wk after completing antiviral therapy). Recipients longitudinally reported QOL using the validated RAND-36 instrument. We also applied advanced methods to match HCV-RNA+ lung recipients to HCV-negative lung recipients in a 1:3 ratio at the same center. Between November 2018 and November 2020, 18 patients were consented and opted-in for HCV-RNA+ lung offers in the allocation system. After a median of 37 d (interquartile range [IQR], 6–373) from opt-in, 10 participants received double lung transplants. The median recipient age was 57 y (IQR, 44–67), and 7 recipients (70%) had chronic obstructive pulmonary disease. The median lung allocation score at transplant was 34.3 (IQR, 32.7–86.9). Posttransplant, 5 recipients developed primary graft dysfunction grade 3 on day 2 or 3, although none required extracorporeal membrane oxygenation. Nine patients received elbasvir/grazoprevir, whereas 1 patient received sofosbuvir/velpatasvir. All 10 patients were cured of HCV and survived to 1 y (versus 83% 1-y survival among matched comparators). No serious adverse events were found to be related to HCV or treatment. RAND-36 scores showed substantial improvement in physical QOL and some improvement in mental QOL. We also examined forced expiratory volume in 1 s—the most important lung function parameter after transplantation. We detected no clinically important differences in forced expiratory volume in 1 s between the HCV-RNA+ lung recipients versus matched comparators. SHELTER adds important evidence regarding the safety of transplanting HCV-RNA+ lungs into uninfected recipients and suggests QOL benefits.