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

实体器官移植的指导研究：使用丙型肝炎病毒感染的捐赠者的器官移植未感染的接受者的结果

• 批准号: 10427258
• 负责人: PETER PHILIP REESE
• 金额: $ 13.42万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-07-01 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10427258
• 关键词: Allografting; Antiviral Agents; Biopsy; Caregivers; Caring; Cessation of life; Cytomegalovirus; Cytomegalovirus Infections; Deterioration; Disease; Elderly; Glomerular Filtration Rate; Goals; Grant; Health; Heart; Heart Transplantation; Hepatitis C; Hepatitis C Therapy; Hepatitis C virus; Immunologics; Infection; Inflammatory; Informed Consent; Injury to Kidney; Interview; Kidney; Kidney Transplantation; Life; Lung; Lung Transplantation; Mentors; Methods; Organ; Organ Donor; Organ Transplantation; Outcome; Patient-Focused Outcomes; Patients; Perception; Persons; Predisposition; Process; Publishing; Qualitative Methods; Quality of life; Research; Risk; Science; Series; Solid; Structure; Surveys; Training; Transplant Recipients; Transplantation; Vascular Diseases; Virus Diseases; Waiting Lists; allograft rejection; donor-specific antibody; experience; graft failure; health related quality of life; high risk; improved; innovation; kidney allograft; organ transplant rejection; pilot trial; post-transplant; secondary analysis; side effect; social stigma; stem; training opportunity

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.

项目总结 使用肾脏、心脏或肺的实体器官移植延长了患者的生命并提高了患者的生活质量 患有终末期器官疾病。不幸的是，美国的等待名单超过了12万人。许多病人正在接受治疗 肾脏移植的等待名单必须等待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。健康状况大幅恶化或在等待中死亡 清单上列出的是需要心脏或肺移植的患者的常见结局。然而，超过800个肾脏和 数百名携带丙型肝炎病毒(丙型肝炎病毒)的已故捐赠者的存活心脏和肺被丢弃在 2016年；又有数百个器官从未获得，因为人们认为没有一个中心会接受它们。 不愿移植感染了丙型肝炎病毒的器官源于历史研究表明， 同种异体排斥反应。丙型肝炎病毒感染可能带来其他炎症后果，包括肾小球损伤 移植肾、血管病变或易受其他感染。此外，丙型肝炎病毒感染还具有社会影响 耻辱，这可能导致患者不愿接受器官。在这方面，新的直接演技 治愈率达95%且副作用少的抗病毒药物(DAA)改变了丙型肝炎病毒的治疗并促使 一些移植临床医生将被丢弃的感染丙型肝炎病毒的器官视为等待名单的宝贵机会 既有和不存在丙型肝炎病毒的患者。然而，目前尚不清楚DAA是否会完全减轻捐赠者- 衍生的丙型肝炎病毒。因此，移植领导者断言有必要进行高质量的研究来评估 将感染了丙型肝炎病毒的器官移植到丙型肝炎病毒阴性受体的结果。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科学研究，以更好地表征 接受丙型肝炎病毒感染的器官。这些努力为直接患者创造了大量机会 为里斯博士的受训者领导重要的患者结局分析的接触和经验。这个 首要目标是表征免疫学、感染性、同种异体移植的功能和生活质量结果 丙型肝炎病毒感染器官的丙型肝炎病毒阴性受体。具体地说，我们将确定与 丙型肝炎病毒阴性的器官，接受丙型肝炎病毒感染的器官的人1)器官结局的风险更高 排斥反应和供体特异性抗体；2)巨细胞病毒感染。我们还将确定收件人是否 与丙型肝炎病毒阴性的受者相比，感染丙型肝炎病毒的肾脏具有非劣质的同种异体移植功能。 最后，还将描述丙型肝炎病毒感染的器官接受者和照顾者使用 混合方法。这些目标不仅为导师提供了培训机会，而且还提供了宝贵的培训 并为各级学员提供研究经验。学员参与POR的机会 被提议和直接的患者接触使这个项目成为K-24支持的理想选择。