Adult to Adult LDLT Cohort Study

成人至成人 LDLT 队列研究

• 批准号: 8330870
• 负责人: Kim Marie Olthoff
• 金额: $ 24万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-09-17 至 2014-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8330870
• 关键词: Acute; Adult; Adverse effects; Affect; Allografting; Ancillary Study; Antigens; Bile Acid Biosynthesis Pathway; Biological; Biological Markers; Biopsy; Blood; Blood Cells; Calcineurin inhibitor; Chimerism; Clinical; Clinical Trials Design; Cohort Studies; Collaborations; Collection; Colorado; Data; Databases; Development; Diagnosis; Diagnostic; Down-Regulation; Enrollment; Functional disorder; Gene Expression; Genetic; Genomics; Goals; Guidelines; Health; Hepatic Mass; Immune response; Immunobiology; Immunosuppression; Inflammatory Response; Intervention; Liver; Liver Function Tests; Liver Regeneration; Living Donors; Lobe; Lymphocyte; Messenger RNA; Metabolic; Methods; Mission; Molecular; Molecular Analysis; Molecular Profiling; Natural regeneration; Outcome; Outcome Study; Pathway interactions; Pattern; Peripheral; Personal Satisfaction; Physiological; Principal Investigator; Procedures; Process; Randomized; Randomized Clinical Trials; Recovery; Recovery of Function; Renal function; Research Design; Residual state; Risk; Safety; Severities; Specimen; Stem cells; Time; Transplantation; Universities; Ursodeoxycholic Acid; Withdrawal; allograft rejection; arm; design; experience; graft function; improved; innovation; interest; liver allograft; liver biopsy; liver function; meetings; pathogen; peripheral blood; prevent; prospective; psychosocial; public health relevance; response; restoration; standard of care; trafficking

DESCRIPTION (provided by applicant): The A2ALL study group was established with the aim to understand the physiological and psychosocial impact of living donor transplantation (LDLT) on the donor, explore methods to assure donor safety and outcomes, to study outcomes in the recipient, and to apply innovative mechanistic methods to better understand the processes of liver regeneration and immunobiology that are pertinent to this setting. The scientific explorations from the A2ALL consortium have resulted in significant contributions that have advanced our understanding of the procedure, established important guidelines for donor and recipient selection, and compiled pertinent information for a more informed decision. The aims of this application are to demonstrate our commitment to the ongoing A2ALL studies, describe established procedures to assure collection of prospective data that is the core mission of the A2ALL consortium, and propose scientific studies that will enhance our understanding of biological responses that are critical for the recovery and long term well being of the donor and recipient. Our concept proposals aim to investigate molecular pathways of regeneration that impact donor and recipient liver function and patterns of alloimmune response in LDLT recipients. 1. Donor Concept Proposal: This proposal will seek to identify molecular patterns of recovery in the donor liver remnant and peripheral blood that are indicative of, and predict, the eventual return of liver function and mass. This will be accomplished by correlating gene expression in the remnant lobe and in sequential peripheral blood mRNA profiles, with longitudinal assessment of donor liver regeneration and quantitative liver function testing. 2. Recipient Concept Proposal: Using a randomized clinical trial design, this proposal will investigate whether LDLT facilitates safe minimization of immunosuppression. In a parallel mechanistic study, we will investigate whether peripheral blood cell mRNA profiles offer a noninvasive means of predicting and diagnosing LDLT allograft rejection. The goals laid out in this proposal can be met within the time frame for the extension of A2ALL and take advantage of the existing clinical database, stored donor and recipient specimens that can be used for molecular analysis, and include in the prospective interventional studies recipients that are already enrolled in A2ALL and are eligible and willing to participate in immunosuppression minimization study. PUBLIC HEALTH RELEVANCE: As outcomes improve and more benefits are recognized, there is increased interest in living donor transplantation. Before significant expansion can occur, it is important to determine the consequences of the living donor procedure with regard to donor well-being and recipient outcomes. Potential interventions to improve liver function and regeneration in the donor, and efforts to prolong graft function and minimize side effects of immunosuppression in the recipient can have great impact on long-term outcomes.

描述（由申请人提供）：A2ALL研究组的成立旨在了解活体供体移植（LDLT）对供体的生理和心理社会影响，探索确保供体安全性和结局的方法，研究受体的结局，并应用创新的机制方法更好地了解与此相关的肝再生和免疫生物学过程。A2ALL联盟的科学探索做出了重大贡献，促进了我们对该程序的理解，为捐赠者和接受者的选择制定了重要的指导方针，并汇编了相关信息，以便做出更明智的决定。本申请的目的是证明我们对正在进行的A2 ALL研究的承诺，描述确保收集前瞻性数据（A2 ALL联合体的核心使命）的既定程序，并提出科学研究，以增强我们对生物反应的理解，这些生物反应对供体和受体的恢复和长期健康至关重要。我们的概念提案旨在研究影响供体和受体肝功能的再生分子途径以及LDLT受体的同种免疫反应模式。1.捐助者概念提案：该提案将寻求确定供体肝残体和外周血中恢复的分子模式，这些模式指示并预测肝功能和质量的最终恢复。这将通过将残叶和连续外周血mRNA谱中的基因表达与供体肝再生的纵向评估和定量肝功能测试相关联来实现。2.概念提案：使用随机临床试验设计，该提案将研究LDLT是否有助于安全地最大限度地减少免疫抑制。在一项平行的机制研究中，我们将研究外周血细胞mRNA谱是否提供了一种预测和诊断LDLT同种异体移植排斥反应的非侵入性方法。本提案中规定的目标可以在A2ALL扩展的时间范围内实现，并利用现有的临床数据库、可用于分子分析的储存供体和受体标本，并在前瞻性干预研究中纳入已入组A2ALL且有资格并愿意参加免疫抑制最小化研究的受体。 公共卫生相关性：随着结果的改善和更多的好处被认可，人们对活体移植的兴趣越来越大。在大规模扩大之前，重要的是要确定活体供体程序对供体福祉和受体结果的影响。改善供体肝功能和再生的潜在干预措施，以及延长移植物功能和最大限度地减少受体免疫抑制副作用的努力可能对长期结局产生重大影响。