Development of a liver viability index for transplantation

移植肝活力指数的制定

• 批准号: 9770638
• 负责人: Korkut Uygun
• 金额: $ 37.91万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-08-01 至 2023-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9770638
• 关键词: Adoption; Algorithm Design; Algorithms; Allografting; Biological Markers; Biopsy; Cadaver; Cardiac Death; Cessation of life; Charge; Clinical; Clinical Data; Clinical Research; Complement; Complex; Control Groups; Cryopreservation; Data; Development; Devices; Donor person; Energy Metabolism; Engineering; Ensure; Functional disorder; Funding; Goals; Graft Survival; Human; Ischemia; Least-Squares Analysis; Liver; Liver Cirrhosis; Liver diseases; Mass Spectrum Analysis; Measures; Metabolic; Methods; Modeling; Organ; Organ Donor; Organ Preservation; Organ Viability; Outcome; Patient-Focused Outcomes; Patients; Perfusion; Potential Energy; Process; Progress Reports; Protocols documentation; Rattus; Recovery; Regression Analysis; Research; Resuscitation; Risk; Science; Site; System; Technology; Testing; Time; Tissues; Training; Transaminases; Transplant Recipients; Transplantation; Transplantation Surgery; United Network for Organ Sharing; Validation; Waiting Lists; Work; base; body system; chronic liver disease; clinical predictors; clinical translation; design; graft failure; graft function; in vivo; indexing; liver function; liver metabolism; liver transplantation; metabolomics; outcome prediction; post-transplant; potential biomarker; preservation; public health relevance; scale up; success; survival prediction

ABSTRACT Chronic liver disease and cirrhosis causes up 60,000 deaths annually in the US, over 4,000 of which are directly due to lack of a donor liver available for transplant. These numbers could be reduced dramatically should the donor organ pool be expanded by rendering marginal cases, such as Donors obtained after Cardiac Death (DCD), transplantable. It is estimated that about 6,000 cadaveric livers/yr are only marginally damaged by ischemia post-cardiac death and could be resuscitated for transplantation. There is evidence from our lab and others that machine perfusion is a very promising approach for recovering cadaveric organs that would be otherwise rejected from the donor pool. However, safe and effective clinical realization of such a machine perfusion device requires sophisticated algorithms that ensure tight control of the system, maximize the viability of the organ and accurately assess if the liver is ready for transplantation at the end of perfusion. There is a significant gap of methods and algorithms designed for assessing organ viability for transplantation in a quantitative and objective manner, which is a major bottleneck in clinical translation of marginal organ recovery technologies and vertical advancement of the field. Our long-term goal is to maximize the use of donor organs while ensuring the graft success upon transplant. The objective of the proposed study is to develop and test a dynamic, online method to assess liver transplant success in a small clinical study. The central hypothesis to be tested here is that the liver survival post-transplantation is correlated to its energy state and energy metabolism during machine perfusion. The work described here is expected to create a dynamic, on-line liver viability score which can be used to assess the condition of the donor organs prior to transplantation surgery, ultimately reducing the guesswork involved in transplantation and consequently increasing the use of marginal donor organs reducing deaths due to graft failure. This development is anticipated to increase the pace of clinical adoption of machine perfusion preservation studies for the liver, as well as other organs. The results of this work will also have a positive impact on engineering science by establishing the basis for integration of process design & control of these complex, dynamic organ preservation systems.

摘要 慢性肝病和肝硬化在美国每年造成6万人死亡，其中4,000多人是 直接原因是缺乏可供移植的肝脏。这些数字可以大幅减少 是否应该通过提供边缘病例来扩大供体器官库，例如心脏移植后获得的供体 死亡（DCD），可移植。据估计，每年约有6，000例尸体肝脏仅轻微受损 心脏缺血后死亡，可以复苏移植。我们的实验室有证据表明 和其他人认为机器灌注是一种非常有前途的恢复尸体器官的方法， 否则就会被排除在捐赠者名单之外然而，这种机器的安全有效的临床实现 灌注设备需要复杂的算法，以确保系统的严格控制，最大限度地提高灌注设备的性能。 在灌注结束时，我们可以评估器官的存活能力，并准确评估肝脏是否准备好进行移植。那里 设计用于评估移植器官存活力的方法和算法的显著差距， 定量和客观的方式，这是一个主要的瓶颈，在临床翻译的边缘器官恢复 技术和该领域的垂直发展。 我们的长期目标是最大限度地利用供体器官，同时确保移植成功。 移植拟议研究的目的是开发和测试一种动态的在线方法来评估肝脏 在一项小型临床研究中获得了成功。这里要检验的中心假设是， 与其在机器灌注过程中的能量状态和能量代谢有关。 这里描述的工作预计将创建一个动态的在线肝脏活力评分，可用于 在移植手术前评估供体器官的状况，最终减少猜测 参与移植，从而增加了边缘供体器官的使用， 移植失败这一发展预计将加快机器灌注的临床采用步伐 肝脏和其他器官的保存研究。这项工作的结果也将产生积极的影响。 对工程科学的影响，建立了基础，为一体化的过程设计和控制这些 复杂动态的器官保存系统