Investigating the role of frailty on outcomes in acutely ill patients with cirrhosis undergoing liver transplantation in the acute care setting

项目摘要 对于肝硬化患者，肝移植是一种成熟的治疗方法，可以恢复肝功能， 在手术后几天到几周内逆转门脉高压。但肝硬化也会导致 肝外效应，如肌肉萎缩、营养不良和功能障碍，可能需要数月才能 逆转，如果有的话，这可能会损害移植后的健康和福祉（“整体功能健康”）。 在门诊环境中，这些慢性肝硬化表现可以通过测量“虚弱”来捕获， 生理储备减少和对健康应激源的脆弱性增加的慢性生物状态，以及 使用肝脏虚弱指数（LFI）进行操作-我们的团队从握力，椅子站立， 和平衡。当在门诊环境中进行评估时，LFI预测不良健康结局，包括 住院和死亡率。虚弱现在是肝病学/移植中一个广为接受的概念：2019年， 美国移植学会（AST）支持使用标准化的虚弱指标，包括 LFI，用于动态肝移植评估。然而，大约1/3的肝硬化患者 移植前即刻因急性疾病住院，其中发病前、可走动、虚弱指标 可能无法使用。在这种情况下，移植临床医生，在许多情况下， 在急性护理环境中，通常通过“眼球测试”非正式地告知移植决策， 缺乏评估虚弱结构的研究或测量急性病患者虚弱的工具。不像在 在非卧床环境中，虚弱代表肝移植不会逆转的因素， 急性环境中的虚弱评估可以简单地反映急性肝脏相关的代偿失调的严重性， 从理论上讲，移植新的肝脏可以逆转这种情况另一方面，虚弱轨迹可以提供关于患者的健康状况的信息。 病人的恢复能力是一个主要的压力源，如移植手术，所以应用脆弱作为一个轨迹 在临床上可能更合适但这些假设的测试尚未完成。在本提案中，我们 将利用我们的9个中心的研究网络，开发和验证一种新的住院虚弱指数， 这个急性病的人群，调查模型，包括单一和纵向评估的脆弱性， 预测移植后1年的整体功能健康状况，并将住院患者虚弱评估与1- 移植后一年的医疗保健利用率。影响：我们的提案将产生一个务实、客观的工具， 肝硬化急性期肝移植患者虚弱标准化评估 临床预测模型，以指导使用单一和纵向评估的脆弱性移植决策- 在这个临床动态人群中。了解急性护理脆弱与 和结果是至关重要的，以促进适当的和系统的实施移植的脆弱性。

PROJECT SUMMARY For patients with cirrhosis, liver transplantation is a well-established therapy, restoring liver function and reversing portal hypertension within days to weeks of the surgery itself. But cirrhosis also leads to insidious extra-hepatic effects such as muscle wasting, malnutrition, and functional impairment that may take months to reverse, if at all, which can compromise health and wellbeing (“global functional health”) after transplantation. In the ambulatory setting, these chronic cirrhosis manifestations can be captured by measures of “frailty”, the chronic biological state of decreased physiological reserve and increased vulnerability to health stressors, and operationalized using the Liver Frailty Index (LFI)—which our team developed from grip strength, chair stands, and balance. When assessed in the ambulatory setting, LFI predicts adverse health outcomes including hospitalizations and mortality. Frailty is now a well-accepted construct in hepatology/transplantation: in 2019, the American Society of Transplantation (AST) endorsed the use of standardized frailty metrics, including the LFI, for ambulatory liver transplant evaluation. However, approximately 1/3 of cirrhosis patients are hospitalized with acute illness immediately prior to transplant, in whom pre-morbid, ambulatory, frailty metrics may not be available. In this setting, transplant clinicians have, in many instances, been applying this construct in the acute care setting to inform transplant decisions—often informally through an “eyeball test”—despite a lack of studies evaluating the construct of frailty or tools to measure frailty in acutely ill patients. Unlike in the ambulatory setting where frailty represents factors that would not reverse with liver transplantation, a single frailty assessment in the acute setting may simply reflect the severity of acute liver-related decompensation, which, in theory, could reverse with a new liver. On the other hand, frailty trajectories may be informative of a patient’s ability to recovery a major stressor such as transplant surgery, so application of frailty as a trajectory may be more clinically appropriate. But testing of these hypotheses has not yet been done. In this proposal, we will leverage our 9-center research network to develop and validate a novel inpatient frailty index optimized for this acutely ill population, investigate models incorporating single and longitudinal assessments of frailty for the prediction of 1-year post-transplant global functional health, and associate inpatient frailty assessments with 1- year post-transplant healthcare utilization. Impact: Our proposal will result in a pragmatic, objective tool to standardize assessment of frailty in acutely ill patients with cirrhosis undergoing liver transplantation and clinical prediction models to guide use of single and longitudinal assessments of frailty for transplant decision- making in this clinically dynamic population. Understanding the precise relationship between acute care frailty and outcomes is essential to facilitate appropriate and systematic implementation of frailty in transplantation.