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

项目摘要 肝硬化会导致肌肉萎缩和营养不良的潜在影响，这在医学界已经众所周知。 肝病学社区作为“脆弱”，适应老年人生理储备减少的状态 和对压力的脆弱性增加。我们开发了新的肝功能脆弱指数（LFI）， 2017年身体功能（握力、椅子站立、平衡），以标准化患者虚弱评估 并证明了其在预测不良结局（包括死亡、医疗保健）方面的价值 使用和残疾。自其发展以来，全球许多肝病/移植中心已采用 LFI对肝移植患者的亲自评估。美国社会的国家指导方针 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）对肝硬化患者进行常规虚弱评估。但面对 2019年冠状病毒病（COVID-19）大流行，临床格局从面对面的 远程医疗访问。慢性肝病患者中远程医疗的使用增加了4000% 在大流行的前2周内，98%的美国肝移植项目报告使用 移植护理各个阶段的远程医疗。远程医疗已被证明是高度可接受的， 病人和临床医生，这表明，即使在亲自访问恢复与控制流行病， 远程医疗将继续补充-如果不是占主导地位-肝病学提供的现场护理。这就提出 移植实践中一个新的（和不可预见的）未满足的需求，即开发标准化的脆弱性工具， 捕获肝硬化患者的脆弱结构，可以完全虚拟地施用。在这 应用程序，我们的目标是解决这一未满足的需要，通过推导出一种新的复合指数，可以管理 完全虚拟，称为“TeLeFI”，并评估TeLeFI和临床结果之间的关联 包括住院和候补名单死亡率。我们将利用多中心功能评估， 肝移植（FrAILT）评估虚弱和虚弱相关成分的研究基础设施（例如， 身体功能、性能状态、残疾），虚拟地使用一组已建立的仪器， 然后进行评估，以纳入TeLeFI。这一目标完全符合母公司的原始范围 Award（R 01 AG 059183），旨在调查虚弱与移植相关性之间的关系。 肝硬化患者的结果，但将实现一个新的研究目标，以获得这种虚拟的脆弱性 评估工具。这些目标将作为后续R 01提案的基础，以：1）验证 TeLeFI用于预测充分把握度队列中的等待名单结局（使用我们现有的多中心 FrAILT研究基础设施）和2）研究TeLeFI与肝脏移植后结局之间的相关性 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.