Predicting post-transplant mortality and global functional health based on pre-transplant functional status in liver transplantation

项目总结 肝硬变导致肌肉萎缩和营养不良的潜伏性影响，这些已为人们所知 肝病学界“脆弱”，适应生理储备减少的老年结构 增加了对压力源的脆弱性。我们开发了新的肝脏脆弱指数(LFI)，使用了 2017年的身体功能(握力、椅子站立、平衡)，以规范对患者虚弱的评估 并证明了它在预测包括死亡、医疗保健在内的不良后果方面的价值 使用率和伤残。自从它发展以来，全球许多肝病/移植中心都采用了 LFI在他们对肝移植患者的面对面评估中。美国协会的国家指导方针 移植(2019)和美国肝病研究协会已正式认可 使用标准化指标，如LFI，对肝硬变患者进行常规的脆弱性评估。但在面对 冠状病毒病2019年(新冠肺炎)大流行，临床格局从面对面显著转变 访问远程医疗。慢性肝病患者中远程医疗的使用增加了4000% 在大流行的前两周内，98%的美国肝脏移植项目报告使用了 为移植护理的所有阶段提供远程医疗。远程医疗已被证明是双方都高度接受的 患者和临床医生表示，即使在疫情得到控制的情况下，面对面的访问仍在恢复， 远程医疗将继续补充-如果不是主导的话-在肝病提供的面对面护理。这就提高了 移植实践中新的(和未预见的)未得到满足的需求，用于开发标准化的易损工具 捕捉肝硬变患者的脆弱结构，可以完全虚拟地给药。在这 应用程序，我们的目标是通过派生出一种新的可管理的综合指数来解决这一未得到满足的需求 完全虚拟的，称为“TeLeFI”，并评估TeLeFI和临床结果之间的关联 包括住院治疗和等待死亡名单。我们将利用我们的多中心功能评估 肝移植(FrAILT)研究基础设施以评估脆弱性和脆弱性相关组件(例如， 身体功能、表现状态、残疾)虚拟地使用一组可以 然后进行评估，以纳入TeLeFI。这一目标正好符合父级的原始范围 奖项(R01 AG059183)，旨在调查虚弱与移植相关之间的联系 肝硬变患者的结果，但将实现一个新的研究目标，以得出这种虚拟的脆弱性 评估工具。这些目标将作为后续R01提案的基础：1)验证 TeLeFI用于预测足够强大的队列中的等待名单结果(使用我们现有的多中心 FrAILT研究基础设施)和2)调查TeLeFI与肝脏术后预后的关系 移植。

PROJECT SUMMARY Cirrhosis leads to the insidious effects of muscle wasting and malnutrition that have come to be known in the hepatology community as “frailty”, adapting the geriatric construct of a state of decreased physiological reserve and increased vulnerability to stressors. We developed the novel Liver Frailty Index (LFI) using tests of physical function (grip strength, chair stands, balance) in 2017 to standardize assessment of frailty in patients with cirrhosis and demonstrated its value in predicting adverse outcomes including death, healthcare utilization, and disability. Since its development, many hepatology/ transplant centers globally have adopted the LFI in their in-person evaluations of liver transplant patients. National guidelines by the American Society of Transplantation (2019) and American Association for the Study of Liver Diseases have formally endorsed routine frailty assessment in cirrhosis patients using standardized metrics, such as the LFI. But in the face of the coronavirus disease 2019 (COVID-19) pandemic, the clinical landscape shifted dramatically from in-person visits to telemedicine. Use of telemedicine increased by 4000% among patients with chronic liver diseases within the first 2 weeks of the pandemic, with 98% of U.S. liver transplant programs reporting using telemedicine for all phases of transplant care. Telemedicine has proven to be highly acceptable by both patients and clinicians, suggesting that even as in-person visits resume with control of the pandemic, telemedicine will continue to complement—if not dominate—in-person care provided in hepatology. This raises a new (and unforeseen) unmet need in transplant practice for the development of standardized frailty tools to capture the frailty construct in patients with cirrhosis that can be administered entirely virtually. In this application, we aim to address this unmet need by deriving a novel composite index that can be administered entirely virtually, called the “TeLeFI”, and evaluate the association between the TeLeFI and clinical outcomes including hospitalizations and waitlist mortality. We will leverage our multi-center Functional Assessment in Liver Transplantation (FrAILT) Study infrastructure to assess frailty and frailty-related components (e.g., physical function, performance status, disability) virtually using a battery of established instruments that can then be evaluated for inclusion in the TeLeFI. This objective fits squarely within the original scope of the parent award (R01 AG059183), which is to investigate the association between frailty and transplant-related outcomes in patients with cirrhosis, but will achieve a new research objective to derive this virtual frailty assessment tool. These aims will serve as the foundation for a subsequent R01 proposal to: 1) validate the TeLeFI for the prediction of waitlist outcomes in an adequately powered cohort (using our existing multi-center FrAILT Study infrastructure) and 2) investigate the association between TeLeFI and outcomes after liver transplantation.