Adult to Adult Living Donor Liver Transplantation Cohor*

成人对成人活体肝移植队列*

• 批准号: 7276277
• 负责人: JEAN C EMOND
• 金额: $ 3.11万
• 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/7276277
• 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)： 活体供体肝移植(LDLT)已被广泛接受用于儿童移植，在受者中取得了良好的效果，而且供者的安全性记录接近肾捐赠。面对身体捐赠者日益匮乏的情况，LDLT已扩大到成年人，并在过去4年中迅速扩大。这种手术需要更大范围的肝切除，因此增加了对供者的风险，这一点还没有得到充分的量化。不确定的捐赠者风险和不受控制的扩散共同导致了科学文献和非官方媒体的警示呼声。目前的研究将为这些关切提供一个有组织的回应，并提供一个机会来解决这一过程固有的有趣的生物学问题。 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。我们中心的肝脏移植计划从一开始就是为了期望LDLT将在我们的移植中占据相当大的比例，因为纽约州有大量的等待名单。目前，LDLT占我们中心成人移植手术的近三分之一；我们今年将完成30例，并在未来5年继续预期增长。我们的团队组成广泛，特别有能力解决与捐赠者结果的结构化健康评估、医学适应症和LDLT的应用以及外科和生物学问题有关的一系列问题。除了移植肝病和外科，我们在流行病学、病毒学和免疫学方面也有特别的优势。虽然我们认识到需要解决广泛的外科问题，但我们发现两个与同种异体移植物再生这一中心主题相关的特定于LDLT的问题最引人注目；第一，受体再生失败的病理生理学和可能的治疗方法，即。第二，在再生性肝移植中丙型肝炎早期和更严重复发的风险。再生的中心主题贯穿于LDLT，很可能取决于炎症性损伤。我们的合作伙伴，纽约长老会丙型肝炎研究中心的Charles Rice和移植医学计划中的Manikkan Suthan Than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验证我们的假设。