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

基于肝移植中移植前功能状态预测移植后死亡率和整体功能健康

• 批准号: 10221569
• 负责人: Jennifer C. Lai
• 金额: $ 66.72万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-06-15 至 2023-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10221569
• 关键词: Acute; Address; Ascites; Caregivers; Cessation of life; Characteristics; Cirrhosis; Clinical; Collaborations; Data; Decision Making; Elderly; Ensure; Extrahepatic; Future; Geriatrics; Goals; Habilitation; Hand Strength; Health; Hemorrhage; Hepatic; Icterus; Infrastructure; Intercept; Investigation; Knowledge; Liver; Liver diseases; Longitudinal Studies; Malnutrition; Measures; Modeling; Muscular Atrophy; Outcome; Outpatients; Patient Care; Patients; Performance; Peritonitis; Physical Function; Portal Hypertension; Preparation; Quality of life; Recovery of Function; Research; Risk; Standardization; Testing; Time; Transplant Recipients; Transplantation; Vulnerable Populations; Waiting Lists; Work; adverse outcome; balance testing; base; clinical decision-making; disability; experience; frailty; functional disability; functional status; health related quality of life; impaired functional status; improved; indexing; instrument; liver transplantation; mortality; mortality risk; post-transplant; prognostic model; shared decision making; stressor; tool; transplant centers

PROJECT SUMMARY The decision to proceed with liver transplantation in a patient with end-stage liver disease depends not just on the risk of death without transplant but the risk of adverse outcomes after it. The transplant clinician's assess- ment of a cirrhotic patient's global functional health – which we have conceptualized as his or her vulnerability to health stressors – is a critical factor (oftentimes the sole factor) in this decision. Yet at the current time, no standardized, objective criteria for poor global functional health exist to define who is “too frail for transplant”. Rather, assessment of functional status in transplant is subjective and is applied to decision-making ad hoc, resulting in unequal transplant access and potential denial of otherwise suitable candidates. To facilitate transplant decision-making, a precise understanding of how pre-transplant functional status impacts post- transplant outcomes is needed to inform prediction of who will not regain excellent global functional health after transplant. We have demonstrated that tools to quantify frailty and functional status in older adults have proven valuable to measure global functional health in cirrhotic patients and have developed an objective Liver Frailty Index, consisting of a composite of performance-based tests (grip strength, chairs stands, and balance testing), to capture longitudinal changes in functional status specifically for use in the pre- and post-transplant settings. Building logically upon this work, we propose to determine the impact of pre-transplant functional status on 1-year post-transplant mortality and global functional health and develop/validate clinical prediction rules for these outcomes that incorporate pre-transplant functional status. To accomplish these goals, we will leverage our existing Multi-center Functional Assessment in Liver Transplantation Study, consisting of 5 US liver transplant centers (UCSF, Johns Hopkins, Columbia, Baylor, and Duke) with a track record of collaboration and high-impact research to obtain data on a minimum of 1,300 liver transplant recipients with assessments of functional status pre-transplantation and assessments of global functional health (including the Liver Frailty Index, disability, and quality of life) 1-year post-transplantation. These data will be used to develop and validate clinical prediction rules that incorporate both pre-transplant functional status, patient and donor characteristics to predict death, functional status, disability, and quality of life 1-year after transplantation. This project will positively impact the field by expanding our ability to measure the benefit of transplant both by how long a recipient will live as well as by how well a recipient will live after liver transplantation. Importantly, this project will facilitate clinical decision-making for patients and their clinicians through the precise understanding of how functional status impacts outcomes and what patients can expect after liver transplantation with respect to functional recovery. Given that functional status is modifiable in cirrhotic patients, our data will also support future investigations to develop effective strategies to improve pre-transplant functional status with the goal of reducing mortality and optimizing post-transplant functional health.

项目概要 对终末期肝病患者进行肝移植的决定不仅取决于 不进行移植的死亡风险，以及移植临床医生评估后出现不良后果的风险。 肝硬化患者的整体功能健康状况——我们将其概念化为他或她的脆弱性 健康压力因素是这一决定的关键因素（通常是唯一因素），但目前还没有。 存在针对全球功能健康状况不佳的标准化、客观标准来定义谁“太虚弱而无法进行移植”。 相反，移植中功能状态的评估是主观的，并且应用于临时决策， 导致移植机会不平等，并可能拒绝其他合适的候选人。 移植决策，准确了解移植前功能状态如何影响移植后 需要移植结果来预测谁在移植后将无法恢复良好的整体功能健康 我们已经证明，量化老年人虚弱和功能状态的工具已经得到证实。 对于衡量肝硬化患者的整体功能健康状况很有价值，并制定了客观的肝脏衰弱指标 指数，由基于表现的测试（握力、椅子站立和平衡性）组成 测试），以捕获功能状态的纵向变化，专门用于移植前和移植后 根据这项工作的逻辑，我们建议确定移植前功能的影响。 移植后一年死亡率和全球功能健康状况并开发/验证临床预测 为了实现这些目标，我们将结合移植前的功能状态来制定这些结果的规则。 利用我们现有的肝移植研究多中心功能评估，包括 5 个美国 肝移植中心（加州大学旧金山分校、约翰霍普金斯大学、哥伦比亚大学、贝勒大学和杜克大学）拥有以下记录： 合作和高影响力的研究，以获得至少 1,300 名肝移植受者的数据 移植前功能状态评估和整体功能健康评估（包括 这些数据将用于制定移植后 1 年的肝脏衰弱指数、残疾和生活质量。 并验证结合移植前功能状态、患者和捐赠者的临床预测规则 预测移植后 1 年死亡、功能状态、残疾和生活质量的特征。 该项目将通过扩大我们衡量移植效益的能力来对该领域产生积极影响 重要的是，受者的生存时间以及受者在肝移植后的生存状况如何。 该项目将通过准确的理解促进患者及其追随者的临床决策 功能状态如何影响结果以及患者在肝移植后可以期待什么 鉴于肝硬化患者的功能状态是可以改变的，我们的数据也将支持这一点。 未来的研究旨在制定有效的策略来改善移植前的功能状态，目标是 降低死亡率并优化移植后的功能健康。