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

项目总结 对终末期肝病患者进行肝移植的决定不仅取决于 没有移植的死亡风险，但移植后不良后果的风险。移植临床医生的评估- 肝硬变患者的整体功能健康状况--我们将其定义为患者的脆弱性 对健康的压力--是这个决定中的一个关键因素(往往是唯一的因素)。然而，就目前而言，没有 全球功能健康状况差的标准、客观标准已经存在，用来定义谁“太虚弱而不能移植”。 相反，对移植功能状态的评估是主观的，适用于特别的决策， 导致不平等的移植机会和潜在的拒绝其他合适的候选人。为了方便 移植决策，准确了解移植前的功能状态对移植后的影响 需要移植结果来预测谁将不会在术后恢复良好的全球功能健康 移植。我们已经证明，量化老年人的虚弱和功能状态的工具已经证明 对测量肝硬变患者的整体功能健康有价值，并已发展为客观的肝功能脆弱 指数，由基于性能的测试(握力、座椅支架和平衡)组成 测试)，以捕捉专门用于移植前和移植后的功能状态的纵向变化 设置。根据这项工作的逻辑，我们建议确定移植前功能 移植后1年死亡率和全球功能健康状况，并制定/验证临床预测 这些结果的规则包含了移植前的功能状态。为了实现这些目标，我们将 在肝移植研究中利用我们现有的多中心功能评估，由5个US组成 肝脏移植中心(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) 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全球功能健康评估(包括 肝脏脆弱指数、残疾和生活质量)移植后1年。这些数据将用于开发 并验证包含移植前功能状态、患者和供者的临床预测规则 预测移植后1年内死亡、功能状态、残疾和生活质量的特征。这 该项目将通过扩展我们的能力来衡量移植的好处，从而对该领域产生积极影响 受者的寿命取决于受者在肝移植后的生存状况。重要的是，这 项目将通过对患者及其临床医生的精确了解，促进临床决策 功能状态如何影响结果以及患者在尊重的情况下接受肝移植后的期望 为功能恢复干杯。鉴于肝硬变患者的功能状态是可以改变的，我们的数据也将支持 未来的研究，以制定有效的战略，以改善移植前的功能状态，目标是 降低死亡率和优化移植后的功能健康。

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.