Adult to Adult Living Donor Liver Transplantation Cohor*

成人对成人活体肝移植队列*

• 批准号: 6651061
• 负责人: JEAN C EMOND
• 金额: $ 21.35万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-09-01 至 2009-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6651061
• 关键词: adult human (21+); clinical research; cooperative study; epidemiology; hepatitis C; human morbidity; human mortality; human subject; human therapy evaluation; immunotherapy; liver regeneration; liver transplantation; longitudinal human study; outcomes research; patient oriented research; quality of life; tissue donors; tumor necrosis factor alpha

DESCRIPTION (provided by applicant): Living donor liver transplantation (LDLT) has been widely accepted for the transplantation of children with excellent results in the recipient, and a track record of donor safety that approaches renal donation. In the face of a progressive scarcity of cadaver donors, LDLT has been extended to adults and proliferated rapidly over the last 4 years. This operation requires a more extensive hepatectomy and thus an increased risk to the donor which has not been adequately quantified. The combination of uncertain donor risk and unregulated proliferation has led to cries of alarm in both the scientific literature and the lay press. The current study will provide a structured response to these concerns and an opportunity to address fascinating biological questions inherent to this procedure. Our interest in LDLT spans nearly two decades across a broad range of surgical and medical issues. The liver transplant program in our center was constituted from the outset with the expectation that LDLT would be a significant proportion of our transplants because of the enormous waiting list in New York State. Currently LDLT accounts for nearly 1/3 of adult transplants in our center; we will perform 30 this year with continued anticipated growth in the next 5 years. Our team is broadly constituted and exceptionally capable of addressing a range of issues pertaining to structured health assessment of donor outcomes, medical indications and application of LDLT as well as surgical and biological questions. We have particular strength in epidemiology, virology, and immunology, in addition to transplant hepatology and surgery. While we recognize that a broad range of surgical questions will need to be addressed, we find two issues specific to LDLT related to the central theme of regeneration of the allograft most compelling; first, the pathophysiology and possible treatment of failure of regeneration in the recipient, ie. "small-for-size syndrome", and second, the risk of early and more severe recurrence of hepatitis C in a regenerating liver graft. The central theme of regeneration pervades LDLT, and likely hinges on inflammatory injury. Our collaborative partners, Charles Rice of the New York-Presbyterian Center for the Study of Hepatitis C and Manikkan Suthanthiran in the Transplantation Medicine program position us to test our hypotheses using novel techniques for the assessment of inflammatory cytokines and viral reinfection on the cellular level.

描述（由申请人提供）： 活体肝移植（LDLT）已被广泛接受用于儿童移植，在受体中具有良好的结果，并且供体安全性的跟踪记录接近肾脏捐献。面对尸体供体的逐渐稀缺，LDLT已扩展到成人，并在过去4年中迅速扩散。这种手术需要更广泛的肝切除术，因此对供体的风险增加，这还没有得到充分的量化。不确定的捐赠者风险和不受管制的扩散相结合，导致科学文献和非专业媒体发出警报。目前的研究将为这些问题提供一个结构化的回应，并有机会解决这一过程所固有的迷人的生物学问题。 我们对LDLT的兴趣跨越了近二十年，涉及广泛的外科和医疗问题。由于纽约州的等候名单庞大，我们中心的肝脏移植计划从一开始就期望LDLT将占我们移植的很大一部分。目前，LDLT占我们中心成人移植的近1/3;我们今年将进行30例，预计未来5年将继续增长。我们的团队组成广泛，特别能够解决与供体结果的结构化健康评估，医学适应症和LDLT的应用以及手术和生物学问题有关的一系列问题。我们在流行病学、病毒学和免疫学以及移植肝脏学和外科学方面具有特殊优势。虽然我们认识到，广泛的手术问题将需要解决，我们发现两个问题，具体到LDLT相关的移植物再生的中心主题最引人注目的;第一，病理生理学和可能的治疗失败的再生受体，即。第二，再生肝移植中丙型肝炎早期和更严重复发的风险。再生的中心主题遍及LDLT，并且可能取决于炎性损伤。我们的合作伙伴，纽约长老会丙型肝炎研究中心的Charles Rice和移植医学项目的Manikkan Suthanthiran使我们能够使用新技术在细胞水平上评估炎症细胞因子和病毒再感染来测试我们的假设。