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定义ALDLT的结果。为了全面评估ALDLT的影响，我们提出以下具体目标：核心研究：建立成人LDLT和非ALDLT患者的供体和受体核心信息数据库假设：ALDLT的短期生存结果，但不并发症发生率，与全尸和SLT移植相当。我们和其他人在非紧急患者中，尽管受体并发症发生率很高，但仍获得了良好的ALDLT短期生存结果。为了充分评估ALDLT的益处，该技术将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，包括：a)全器官受者，b)尸体SLT受者，c)最终不接受移植的候选者。活体捐赠者部分将比较活体捐赠者和不接受捐赠的潜在捐赠者。主要终点确定移植后1年、2年和3年供体和受体的生存结局和并发症发生率。这将阐明与全尸体、SLT和对照（未移植）患者相比，在整个受体状态范围内，ALDLT的疗效，并确定与非移植非紧急对照的自然史相比，ALDLT是否合理。次要终点评估技术变化对术后恢复、捐赠后肝脏再生的影响，活体捐赠对尸体供体池的影响，并确定供体排除标准。受体结局的临床研究方案：确定ALDLT对移植受者移植后HCV复发的影响假设：与全尸肝移植相比，ALDLT可能伴随HCV加速复发。在我们的中心，与全器官移植患者相比，在ALDLT受者中观察到的快速和严重的HCV复发可能抵消了活体供者早期移植的益处。该方案比较了移植后6个月、1年、2年和3年，全肝移植和全肝移植受者HCV的组织学复发时间。我们通过次要终点研究了对患者和移植物存活的影响以及组织学疾病程度与HCV RNA水平之间的相关性。假设：活体供者的HRQL在短期内受到影响，但在长期内不会受到影响，而接受活体移植的患者的HRQL可能在接受活体移植后得到提高。将通过通用和疾病特异性仪器比较供体和受体在ALDLT前和移植后6个月和12个月的HRQL。开展卫生效用指标评价和卫生资源利用评价。

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.