The Optimal Timing of Transplantation in Pediatric Acute Liver Failure

小儿急性肝衰竭移植的最佳时机

• 批准号: 7867830
• 负责人: MARK Stenius ROBERTS
• 金额: $ 19.38万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-07-01 至 2011-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7867830
• 关键词: Acute Liver Failure; Address; Adult; Area; Cessation of life; Characteristics; Child; Childhood; Chronic; Clinical; Collaborations; Complex; Data; Databases; Decision Modeling; Diabetes Mellitus; Disease; Disease Outcome; Disease Progression; Donor person; Ensure; Etiology; Event; Face; Family; Family member; Foundations; Funding; Goals; Kidney Diseases; Life; Life Expectancy; Liver; Liver diseases; Living Donors; Lobe; Medical; Modeling; Natural History; Obesity; Operative Surgical Procedures; Organ; Organ Donor; Organ Model; Organ Transplantation; Outcome; Parents; Patients; Policies; Principal Investigator; Procedures; Process; Quality of life; Registries; Research; Risk; Statistical Models; Surgeon; System; Techniques; Testing; Time; Transplantation; United States National Institutes of Health; Waiting Lists; Work; acute liver disease; base; clinical decision-making; experience; high risk; improved; innovation; liver transplantation; longitudinal database; loved ones; mathematical model; models and simulation; organ allocation; organ procurement transplantation network; outcome forecast; public health relevance; simulation; statistics

DESCRIPTION (provided by applicant): Pediatric acute liver failure (PALF) is a complex disease that has multiple causes and is associated with a high risk of death. For a child with PALF, liver transplantation can be a lifesaving procedure. However, there are two primary reasons that the decision to pursue transplantation is difficult for the child's clinicians and family members. First, there is a very real chance that the child's liver will recover on its own if the child is able to survive for enough time without a transplant. Second, in nearly 50% of cases of PALF, the cause of the disease is unknown, and this makes it very difficult to predict the outcomes for these patients in the absence of transplantation. Clinicians are faced with the dilemma of whether to place a child on the list to receive a liver from a deceased donor or whether to wait for the child to recover. A child's family member must decide whether to become a living donor, as occurs in over 14% of cases in which patients receive transplants for acute liver failure. There is some concern that transplantation may be pursued "too early," when waiting may allow the damaged liver to recover without surgery. To address this problem, the proposed study will use data from the PALF registry, which is the largest and most clinically detailed longitudinal database of PALF patients in the world. The study will be a collaborative effort of two research groups that are uniquely suited to evaluate factors influencing when to pursue transplantation. The Principal Investigator's modeling group has extensive experience in mathematically modeling the progression of liver disease, applying simulation models to organ allocation policies, and representing complex medical decisions. The overall goals of the study are to improve clinical decision making in cases of PALF by (1) developing quantitative models of prognosis and disease progression and (2) using these models to calibrate optimization models of the transplant decision. These goals will be accomplished through two specific aims. Aim 1 is to characterize and quantitatively describe the short-term natural history of children with PALF. This will require estimating statistical models of pretransplant and post transplant survival, as well as developing quantitative models of disease progression. Aim 2 is to construct a proof-of-concept model evaluating the optimal timing of liver transplantation for children with PALF, including the possibility of transplanting an organ from a living donor. We will modify our existing simulation model of the US organ allocation system to include PALF, will validate the model to ensure that it represents the time course of PALF, and will use the model to examine transplant timing practices in children with PALF. PUBLIC HEALTH RELEVANCE: Acute liver failure in children is a devastating, often fatal condition for which one of the potential treatments is liver transplantation. However, the decision to choose to treat a child with a transplant is difficult, because even if a child is very ill, there is a chance that the child's liver would recover on its own, without surgery, and that the transplant would therefore be unnecessary. The best strategy for deciding when to wait a little longer or when to undertake transplantation is not known with certainty. The research we describe here will use statistics and mathematical models to better predict how fast liver disease will progress in children. The goal of the research is to improve decisions regarding the use of liver transplantation for young patients with acute liver disease.

描述（由申请人提供）：儿科急性肝衰竭（PALF）是一种复杂的疾病，有多种原因，并与高死亡风险相关。对于患有PALF的儿童来说，肝移植可能是一种挽救生命的手术。然而，有两个主要原因，决定追求移植是困难的儿童的临床医生和家庭成员。首先，如果孩子能够在没有移植的情况下存活足够长的时间，那么孩子的肝脏有真实的机会自行恢复。其次，在近50%的PALF病例中，疾病的原因是未知的，这使得在没有移植的情况下很难预测这些患者的结果。临床医生面临着两难的境地，是把一个孩子放在名单上接受已故捐赠者的肝脏，还是等待孩子康复。儿童的家庭成员必须决定是否成为活体捐赠者，因为超过14%的患者因急性肝衰竭接受移植。有人担心移植可能会“过早”进行，等待可能会使受损的肝脏在没有手术的情况下恢复。为了解决这个问题，拟议的研究将使用来自PALF登记处的数据，这是世界上最大和最详细的PALF患者纵向数据库。这项研究将是两个研究小组的合作努力，这两个研究小组非常适合评估影响何时进行移植的因素。主要研究者的建模团队在对肝脏疾病的进展进行数学建模、将模拟模型应用于器官分配政策以及代表复杂的医疗决策方面拥有丰富的经验。该研究的总体目标是通过（1）开发预后和疾病进展的定量模型和（2）使用这些模型校准移植决策的优化模型来改善PALF病例的临床决策。这些目标将通过两个具体目标来实现。目的1是描述和定量描述儿童PALF的短期自然史。这将需要估计移植前和移植后存活率的统计模型，以及开发疾病进展的定量模型。目的2是构建一个概念验证模型，评估PALF儿童肝移植的最佳时机，包括移植活体供体器官的可能性。我们将修改我们现有的美国器官分配系统的模拟模型，以包括PALF，将验证模型，以确保它代表PALF的时间过程，并将使用该模型来检查PALF儿童的移植时机的做法。公共卫生相关性：儿童急性肝衰竭是一种毁灭性的，往往是致命的条件，其中一个潜在的治疗是肝移植。然而，选择用移植治疗儿童的决定是困难的，因为即使孩子病得很重，孩子的肝脏也有可能自行恢复，而不需要手术，因此移植是不必要的。决定何时再等待一段时间或何时进行移植的最佳策略并不确定。我们在这里描述的研究将使用统计学和数学模型来更好地预测儿童肝脏疾病的进展速度。这项研究的目的是改善急性肝病年轻患者肝移植的决策。