Adult to Adult LDLT Cohort Study

描述（由申请人提供）：A2ALL研究组的建立旨在了解活体供体移植（LDLT）对供体的生理和社会心理影响，探索确保供体安全和结果的方法，研究受体的结果，并应用创新的机制方法来更好地了解与此相关的肝脏再生过程和免疫生物学。来自A2ALL联盟的科学探索已经产生了重大的贡献，提高了我们对程序的理解，建立了重要的供体和受体选择指南，并为更明智的决定汇编了相关信息。本申请的目的是展示我们对正在进行的A2ALL研究的承诺，描述既定的程序，以确保收集前瞻性数据，这是A2ALL联盟的核心任务，并提出科学研究，以增强我们对生物反应的理解，这些反应对供体和受体的恢复和长期健康至关重要。我们的概念建议旨在研究影响供体和受体肝功能的再生分子途径以及LDLT受体同种免疫反应的模式。1. 供体概念建议：该建议将寻求确定供体肝脏残余物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肿块的最终恢复。这将通过将残叶和外周血mRNA序列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. 接受者概念提案：采用随机临床试验设计，该提案将研究LDLT是否有助于安全最小化免疫抑制。在一项平行的机制研究中，我们将研究外周血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。本提案所提出的目标可以在A2ALL扩展的时间框架内实现，并利用现有的临床数据库、储存的可用于分子分析的供体和受体标本，并将已经入组A2ALL且符合条件并愿意参与最小化免疫抑制研究的受者纳入前瞻性介入研究。

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.