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

调查虚弱对在急症护理环境中接受肝移植的急性肝硬化患者的结局的作用

• 批准号: 10658726
• 负责人: Jennifer C. Lai
• 金额: $ 83.12万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-07-15 至 2028-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10658726
• 关键词: Acute; Address; American; Biological; Chronic; Cirrhosis; Clinical; Data; Decision Making; Equilibrium; Evaluation; Event; Extrahepatic; Eye; Goals; Hand; Hand Strength; Health; Healthcare Systems; Hepatology; Hospitalization; Hour; Individual; Inpatients; Intercept; Length of Stay; Liver; Machine Learning; Malnutrition; Measures; Modeling; Muscular Atrophy; Operative Surgical Procedures; Outcome; Outpatients; Patients; Personal Satisfaction; Physiological; Population; Population Dynamics; Portal Hypertension; Predictive Value; Recovery; Research; Role; Severities; Societies; Standardization; Surveys; Testing; Time; Transplant Recipients; Transplantation; Transplantation Surgery; Validation; acute care; clinical practice; clinical predictive model; cost; disability; frailty; functional disability; functional status; health care service utilization; health related quality of life; improved; indexing; liver function; liver transplantation; model building; mortality; novel; outcome prediction; post-transplant; recruit; stressor; theories; tool

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.

项目概要 对于肝硬化患者来说，肝移植是一种行之有效的治疗方法，可以恢复肝功能并恢复肝功能。 手术后数日至数周内即可逆转门脉高压，但肝硬化也会导致潜在的后果。 肝外效应，例如肌肉萎缩、营养不良和功能障碍，可能需要数月的时间才能缓解 逆转（如果有的话）可能会损害移植后的健康和福祉（“全球功能健康”）。 在门诊环境中，这些慢性肝硬化表现可以通过“虚弱”指标来捕捉，即 生理储备减少和对健康压力源的脆弱性增加的慢性生物状态，以及 使用肝脏衰弱指数 (LFI) 进行操作——我们的团队根据握力、椅子站立、 在动态环境中进行评估时，LFI 可以预测不良的健康结果，包括 住院率和死亡率现已成为肝病学/移植领域广为接受的概念：2019 年， 美国移植学会 (AST) 认可使用标准化的衰弱指标，包括 LFI，用于动态肝移植评估 然而，大约 1/3 的肝硬化患者进行了评估。 在移植前因急性疾病住院，其中病前、动态、虚弱指标 在这种情况下，移植手术在许多情况下都应用了这种结构。 在急症护理环境中为移植决策提供信息——通常通过“眼球测试”非正式地进行——尽管 与急性病患者不同，缺乏评估虚弱结构或测量虚弱工具的研究。 门诊环境中，虚弱代表了肝移植无法逆转的因素，单一的 急性环境下的虚弱评估可能只是反映急性肝脏相关失代偿的严重程度， 从理论上讲，新肝脏可以逆转这种情况；另一方面，虚弱的轨迹可能会提供信息。 患者恢复主要压力源（例如移植手术）的能力，因此应用虚弱作为轨迹 可能在临床上更合适，但在本提案中，我们尚未对这些假设进行测试。 将利用我们的 9 中心研究网络来开发和验证一种新型住院患者虚弱指数，该指数针对 对于这个重病人群，研究纳入单一和纵向虚弱评估的模型 预测移植后 1 年全球功能健康状况，并将住院患者虚弱评估与 1- 影响：我们的建议将产生一个务实、客观的工具， 标准化接受移植肝治疗的急性肝硬化患者的虚弱评估 临床预测模型指导使用单一和纵向的衰弱评估来做出移植决策 了解这一临床动态人群的精确关系。 和结果对于适当促进和系统实施移植中的衰弱至关重要。