Mentored research in solid organ transplantation: outcomes using organs from Hepatitis C virus infected donors for uninfected recipients

项目摘要 使用肾脏、心脏或肺的实体器官移植可延长患者的生命并提高其生活质量 晚期器官疾病不幸的是，美国的等待名单超过12万人。许多患者在 肾移植等待名单必须等待5年以上才能获得器官。对于老年人和其他一些患者群体， 等待名单上的死亡比移植更有可能。健康状况严重恶化或等待死亡 这些是需要心脏或肺移植的患者的常见结果。然而，超过800个肾脏和 数百个来自患有丙型肝炎病毒（HCV）的已故捐赠者的可存活心脏和肺被丢弃， 2016年;数百个器官从未被采购，因为人们认为没有中心会接受它们。 不愿移植HCV感染的器官源于历史研究表明， 同种异体移植排斥反应。HCV感染还可能导致其他炎症反应，包括肾小球损伤， 肾移植、血管病变或易受其他感染。此外，HCV感染携带社会 耻辱，这可能导致病人不愿意接受器官。在这方面，新的直接行动 治愈率>95%且副作用少的抗病毒药物（DAA）改变了HCV治疗， 一些移植临床医生将被丢弃的HCV感染器官视为等待名单的宝贵机会， 有和没有预先存在的HCV的患者。然而，目前尚不清楚DAA是否会完全减轻供体的风险。 衍生的HCV。因此，移植领导者断言需要高质量的研究来评估 HCV感染的器官移植到HCV阴性的受者身上时的结果。里斯博士的研究 该小组领导了一系列高度创新的试验和相关的科学研究，以更好地描述 HCV感染器官的接受者这些努力创造了大量的机会，直接病人 接触和领导的经验，为里斯博士的学员的患者结果的重要分析。的 总体目标是表征免疫学、感染、同种异体移植物功能和生活质量结果， HCV感染器官的HCV阴性受体。具体来说，我们将确定，与接受者相比， HCV阴性器官，HCV感染器官的接受者经历1）器官结局的风险更高 2）巨细胞病毒感染。我们还将确定， HCV感染的肾脏与HCV阴性的肾脏相比，具有非劣效的移植物功能。 最后，还将描述HCV感染的器官接受者和照顾者使用 混合方法这些目标不仅为指导者提供了培训机会， 和研究经验的学员在所有级别。学员参与POR的机会 被提议和直接的患者接触使该项目成为K-24支持的理想选择。

PROJECT SUMMARY Solid organ transplantation using kidneys, hearts or lungs extends life and improves quality of life for patients with end-stage organ disease. Unfortunately, the US waiting list exceeds 120,000 people. Many patients on the kidney transplant wait-list must wait over 5 years for an organ. For the elderly and some other patient groups, death on the waiting list is more likely than transplant. Substantial health deterioration or death on the waiting list are common outcomes for patients in need of a heart or lung transplant. Yet, over 800 kidneys and hundreds of viable hearts and lungs from deceased donors with hepatitis C virus (HCV) were discarded in 2016; hundreds more organs were never procured because of the perception that no center will accept them. The reluctance to transplant HCV-infected organs stems from historical studies showing elevated rates of allograft rejection. HCVinfection may carry other inflammatory consequences, includingglomerular injury to the kidney allograft, vasculopathy, or susceptibility to other infections. Additionally, HCV-infection carries social stigma, which may contribute to reluctance from patients to accept the organs. In this context, new direct acting antivirals (DAAs) with cure rates of >95% and few side effects have transformed HCV treatment and prompted some transplant clinicians to view discarded HCV-infected organs as a valuable opportunity for waitlisted patients with and without pre-existing HCV. However, it is unknown if DAAs will fully mitigate the risks of donor- derived HCV. As a result, transplant leaders have asserted the need for high quality studies to assess outcomes when HCV-infected organs are transplanted into HCV-negative recipients. Dr. Reese's research group leads a series of highly innovative trials and related scientific studies to better characterize outcomes for recipients of HCV-infected organs. These endeavors have created substantial opportunities for direct patient contact and the experience of leading important analyses of patient outcomes for Dr. Reese's mentees. The overarching goal is to characterize immunologic, infectious, allograft function and quality of life outcomes of HCV-negative recipients of HCV-infected organs. Specifically, we will determine if, compared to recipients of HCV-negative organs, recipients of HCV-infected organs experience a higher risk of the outcomes of 1) organ rejection and donor specific antibody and 2) cytomegalovirus infection. We will also determine if recipients of HCV-infected kidneys have non-inferior allograft function compared to recipients of HCV-negative kidneys. Finally, will also describe the experience and concerns of HCV-infected organ recipients and caregivers using mixed-methods. These aims provide not only training opportunities for the mentor, but also valuable training and research experiences for mentees at all levels. The opportunities for mentee involvement in the POR being proposed and direct patient contact make this project ideal for K-24 support.