Optimal Older Donor and Recipient Matching to Enhance Liver Transplant Outcomes

 描述(由申请人提供)：肝移植(LT)是目前治疗终末期肝病(ESLD)患者的唯一确定的治疗方法。由于严重的器官短缺，每年有2000多人在等待LT时死亡。在过去的十年中，在LT等待名单上的ESLD患者和肝脏器官捐赠者的平均年龄都在增加。脑死亡后的捐赠是目前肝脏的最大来源。循环性死亡后供者(DCD)和其他扩展标准供者(ECD)越来越多地被用来扩大供体器官池。ECD器官通常是由年龄较大的人捐赠的，他们比年轻捐赠者的器官移植失败率更高。因此，大约65%来自65岁或以上捐赠者的捐赠肝脏被丢弃，因为纳入这些捐赠者可以扩大捐赠者的人才库，以挽救等待名单上垂死的生命。因此，确定可能从ECD肝脏和老年供者的肝脏中受益的最佳受体对于提高肝脏利用率和降低等待名单死亡率至关重要。医疗保险和医疗补助服务中心使用移植受者科学登记(SRTR)风险调整模型来认证移植中心的报销。美国移植外科学会(ASTS)已经确定了SRTR模型中没有考虑的几个重要因素，包括晚期冠状动脉疾病和其他与年龄相关的合并症。此外，捐赠者和接受者风险因素之间的一些交互作用已经被确定，但没有被纳入SRTR模型。该项目的总体目标是改善个人捐赠者和受赠者的匹配，以优化肝脏利用和 老年供者和受者的移植结局。为了实现这一目标，我们将使用先进的生物统计学方法，基于增强的供受者风险因素和结果数据进行二次数据分析，以改进个体供受者配型的风险预测模型，用于辅助以患者为中心的决策，改善移植中的器官分配。我们将合并机构(西北大学企业数据仓库[EDW])和国家(器官采购和移植网络[OPTN]、SRTR和大学医疗联盟[UHC])的数据源，以增强捐赠者和接受者的风险因素和结果数据，包括移植前和移植后的共病情况。然后，我们将追求两个具体目标：1)开发和验证统计模型，以预测个体供受者配型的短期和长期结果，并考虑供者和受者风险因素之间的相互作用。2)通过比较接受给定的供体肝脏与等待获得潜在更好的肝脏的风险和好处，帮助患者做出特定的决策。

 DESCRIPTION (provided by applicant): Liver transplantation (LT) is currently the only definitive treatment for patients with end stage liver disease (ESLD). Because of the critical organ shortage, more than 2,000 people die annually awaiting LT. The average ages of both patients with ESLD on LT waiting list and liver organ donors have been increasing over the past decade. Donation after brain death is currently the largest source of livers. Increasingly, donors after circulatory death (DCD), and other extended criteria donors (ECD) have been used to expand the pool of donor organs. ECD organs are often donated by older individuals, which have a higher rate of graft failure than organs from younger donors. Consequently, approximately 65% of donated livers from donors 65 years or older are discarded when their inclusion could expand the donor pool to save the lives dying on waiting list. Therefore, identifying the optimal recipients who might benefit from ECD livers and livers from older donors is of paramount importance to improve liver utilization and reduce waiting list mortality. The Scientific Registry of Transplant Recipients (SRTR) risk-adjustment models are used by the Centers for Medicare & Medicaid Services to certify transplant centers for reimbursement. The American Society of Transplant Surgeons (ASTS) has identified several important factors that are not considered in the SRTR models, including advanced coronary artery disease and other age-associated comorbidities. In addition, some interactions between donor and recipient risk factors have been identified but not incorporated in the SRTR model. The overall objective of this project is to improve individual donor-recipient matching for optimizing liver utilization and transplant outcomes of elderly donors and recipients. To accomplish the objective, we will use advanced biostatistical methods to conduct secondary data analysis based on enhanced donor and recipient risk factors and outcomes data to improve risk prediction models for individual donor-recipient matching, which can be used to assist patient-centered decision making and improve organ allocation in LT. We will merge institutional (Northwestern University Enterprise Data Warehouse [EDW]), and national (Organ Procurement and Transplant Network [OPTN], SRTR, and University Healthcare Consortium [UHC]) data sources to enhance donor and recipient risk factors and outcomes data including pre-transplant and post-transplant comorbidity conditions. We will then pursue the two Specific Aims: 1) To develop and validate statistical models for predicting short- and long-term outcomes for individual donor-recipient matching, considering interaction between donor and recipient risk factors. 2) To assist patient-specific decision making by comparing the risks and benefits of accepting a given donor liver vs. staying on the waiting list for a potential better liver.