ADLDT: An Opportunity to Expand the National Donor Pool

描述(由申请人提供)：本提案的总体目标是建立一个临床研究联盟来确定ALDLT的结果。我们提出以下具体目标来全面评估ALDLT的影响：1.核心研究：为成人LDLT和非ALDLT患者建立供受者核心信息数据库假设：ALDLT的短期生存结果，而不是并发症发生率，等同于完整身体和SLT移植。我们和其他人在非紧急患者中取得了良好的ALDLT短期生存结果，尽管受体并发症的发生率很高。为了充分评估ALDLT的益处，该技术将同时应用于紧急和非紧急受者，并将其结果与三组患者队列进行比较，其中包括：a)整个器官接受者，b)身体SLT接受者，以及c)最终未接受移植的候选人。活体捐赠者部分将比较活体捐赠者和未接受捐献的潜在捐赠者。主要终点决定了供者和受者在移植后1、2和3年的生存结果和并发症发生率。这将阐明ALDLT与整个身体、SLT和对照(未移植)患者在整个受者状态谱中的疗效，并确定与非移植非紧急对照的自然病史相比，ALDLT是否合理。次级终点评估技术变化对术后恢复的影响，捐献后的肝脏再生，活体捐献对身体捐赠者池的影响，并确定捐赠者排除标准。受者结局的临床研究方案：确定ALDLT对移植受者移植后丙型肝炎复发的影响假设：与全尸肝移植相比，ALDLT可能伴随着丙型肝炎病毒加速复发。在我们中心观察到，与整个器官移植患者相比，在ALDLT受者中观察到的快速和严重的丙型肝炎复发可能抵消了活体供者早期移植的好处。该方案比较了ALDLT和全器官移植受者在移植后6个月、1年、2年和3年的丙型肝炎复发时间。通过我们的次级终点研究对患者和移植物存活的影响，以及组织学疾病程度与丙型肝炎病毒RNA水平之间的相关性。捐赠者结局的临床研究方案：确定健康相关的生活质量结局和成人活体捐献的资源利用假说：活体捐赠者的HRQL在短期内受到影响，但不会影响ALDLT受者的长期HRQL，ALDLT后受者的HRQL可能会得到提高。供者和受者的HRQL将在ALDLT前以及移植后6个月和12个月通过通用和疾病特异性仪器进行比较。此外，还将进行卫生效用指数评估和卫生保健资源利用评估。

DESCRIPTION (provided by applicant):The overall objective of this proposal is to establish a Clinical Research Consortium to define the outcomes of ALDLT. We propose the following specific aims to fully evaluate the impact of ALDLT: 1. Core Study: Establish a Donor and Recipient Core Information Database for Adult LDLT and Non-ALDLT Patients Hypothesis: ALDLT short-term survival outcomes, but not complication rates, are equivalent to whole cadaveric and SLT transplantation. We and others, achieved excellent short-tem survival outcomes of ALDLT, despite a high rate of recipient complications, in non-urgent patients. To fully evaluate the benefits of ALDLT, the technique will be applied to both urgent and non-urgent recipients, and compare its outcomes to three sets of patient cohorts that include: a) whole organ recipients, b) cadaveric SLT recipients, and c) candidates who ultimately do not receive a transplant. The living donor section will compare living donors and potential donors who do not undergo donation. Primary endpoints define survival outcomes and complication rates in donors and recipients at 1, 2 and 3 years posttransplantation. This will elucidate the efficacy of ALDLT as compared to whole cadaveric, SLT, and control (untransplanted) patients in the entire spectrum of recipients' status, and determine if ALDLT is justified when compared to the natural history of non-transplanted non-urgent controls. Secondary endpoints assess the impact of technical variations on postoperative recovery, liver regeneration postdonation, impact of living donation on the cadaveric donor pool, and defines donor exclusion criteria.2. Clinical Research Protocol for Recipient Outcome: Determine the impact of ALDLT on Posttransplant HCV Recurrence in Transplant Recipients Hypothesis: ALDLT may be accompanied by accelerated recurrence of HCV versus whole cadaveric liver transplantation. Rapid and severe HCV recurrence observed, at our center, in ALDLT recipients compared to whole organ transplant patients, may offset the benefits of early transplantation with living donors. This protocol compares the time to histological recurrence of HCV in ALDLT and whole organ graft recipients at 6 months, 1, 2, and 3 years posttransplantation. The effects on patient and graft survival and the correlation between the degree of histological disease and HCV RNA levels are investigated by our secondary endpoints.3. Clinical Research Protocol for Donor Outcome: Determine Health-Related Quality of Life Outcomes and Resource Utilization of Adult Living Donation Hypothesis: HRQL of living donors is impacted in the short-, but not, the long-term and the HRQL of ALDLT recipients may be enhanced following ALDLT. HRQL in both donors and recipients will be compared before ALDLT and at 6 and 12 months posttransplantation through generic and disease-specific instruments. Additionally, health utility index assessments and evaluation of health care resource utilization will be conducted.