Project 1-Cohort and Ethical Analysis of Patients undergoing Early Liver Transplant for Severe Alcoholic Hepatitis

项目1-严重酒精性肝炎早期肝移植患者的队列和伦理分析

基本信息

批准号：
10093986
负责人：
ANDREW M. CAMERON
金额：
$ 34.53万
依托单位：
JOHNS HOPKINS UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-02-01 至 2024-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10093986
关键词：
Abstinence Accounting Address Alcoholic Hepatitis Alcoholic Liver Diseases Caring Clinical Cohort Studies Communities Consensus Data Disease Enrollment Ensure Ethical Analysis Ethical Issues Ethics General Population Graft Survival Health Personnel Health Professional Hybrids Infection Informed Consent Institutes Knowledge Lead Leadership Life Link Liver Longitudinal Studies Modeling Organ Organ Donations Outcome Patient Care Patients Pattern Phenotype Pilot Projects Policies Probability Process Prospective cohort study Provider Public Opinion Qualitative Research Reaction Refractory Registries Research Methodology Risk Savings Selection Criteria Specialized Center Standardization Steroids Survival Rate Transplant Recipients Transplantation United States Vertebral column Work alcohol research base candidate selection care providers clinical center cohort data registry evidence based guidelines graft function hospital readmission improved interdisciplinary approach knowledge base liver transplantation markov model medication compliance mortality novel patient subsets post-transplant prospective recidivism sobriety transplant centers transplant registry

项目摘要

Project Summary Alcoholic liver disease (ALD) accounts for 26% of liver transplants (LTs) performed annually in the United States. Given concerns of post-transplant recidivism and the possibility for pre-transplant clinical improvement with abstinence, most centers require 6 months of documented sobriety prior to LT. However, a subset of patients present with severe alcoholic hepatitis (SAH) refractory to aggressive steroid-based treatment. For these incredibly sick patients, 3-month mortality is 70-80% without LT, precluding the possibility of a 6-month sobriety rule. Early LT (ELT) is the only life-saving treatment available for these patients, however, it remains rare and controversial, because at most centers the standard 6-month sobriety period is a transplant candidacy requirement. Although few transplant centers worldwide perform ELT for SAH, several groups have shown excellent short-term survival and comparable recidivism rates. We recently conducted a pilot study, the largest cohort of ELT recipients for SAH, which demonstrated excellent overall survival rates and similar post-LT recidivism rates to those undergoing LT for ALD with >6 months of sobriety. We have established the DELTA Center (Delivery of Early Liver Transplant for Alcoholic Hepatitis) at JHU as a specialized alcohol research center to oversee this work moving forward. The survival benefit of ELT in appropriately selected SAH candidates must be quantified and support from the public and transplant community must be gained in order to advance ELT for SAH. In order to establish the knowledge base necessary for appropriate candidate selection, develop a clinical understanding of ELT for SAH, and identify the public’s opinion regarding this practice, we propose: 1) To quantify post-ELT mortality for SAH and compare outcomes to LT for other indications; 2) To quantify the survival benefit of ELT for SAH; and 3) To create an ethical framework for considering ELT for SAH based on the opinions of SAH patients, transplant providers, and the general public about this practice, thus resulting in a new rational national policy on ELT for SAH. This study will represent the largest prospective cohort study of LT for SAH in the world. Our findings will have an immediate and direct impact on the practice of ELT for SAH in the United States, informing critical aspects of candidate selection, informed consent, post-LT care and national policy. Robust quantification of the risk and survival benefit associated with ELT for SAH is novel and necessary to expand the practice within the ethical constraints and concerns of the transplant community. A better understanding of this emerging treatment is essential for improving care of patients with SAH and will help improve the feasibility, availability and quality of ELT for SAH potentially providing novel, lifesaving treatment for patients with SAH in the United States.

项目概要在美国，酒精性肝病 (ALD) 占每年进行的肝移植 (LT) 的 26% 考虑到移植后累犯的担忧以及移植前临床改善的可能性。对于禁欲，大多数中心要求在 LT 之前有 6 个月的清醒记录。患有严重酒精性肝炎（SAH）且对积极的类固醇治疗无效的患者。这些病情严重的患者，如果不进行 LT，3 个月的死亡率为 70-80%，排除了 6 个月的可能性早期 LT (ELT) 是这些患者唯一可以挽救生命的治疗方法。仍然很少见且有争议，因为在大多数中心，标准的 6 个月清醒期是移植候选资格要求。尽管世界范围内很少有移植中心对 SAH 进行 ELT，但一些研究小组已经表现出了出色的表现我们最近进行了一项试点研究，这是最大的队列研究。 SAH 的 ELT 接受者表现出出色的总体生存率和类似的 LT 后累犯率清醒状态超过 6 个月且接受 LT 的 ALD 患者的费用我们建立了 DELTA 中心。（针对酒精性肝炎的早期肝移植）在约翰霍普金斯大学作为专门的酒精研究中心监督这项工作的进展。必须量化并支持 ELT 对适当选择的 SAH 候选人的生存益处为了推进 SAH 的 ELT，必须获得公众和移植界的支持。建立适当候选人选择所需的知识库，培养临床理解为了了解 SAH 的 ELT 的效果，并确定公众对此做法的看法，我们建议： 1) 量化 ELT 后的效果 SAH 的死亡率并将其他适应症的结果与 LT 进行比较 2) 量化 ELT 的生存获益； 3) 根据 SAH 的意见，建立考虑针对 SAH 进行 ELT 的道德框架患者、移植提供者和公众对这种做法的关注，从而产生了一种新的理性针对 SAH 的 ELT 国家政策。这项研究将成为世界上最大的 LT 治疗 SAH 的前瞻性队列研究。研究结果将对美国 SAH 的 ELT 实践产生直接影响，告知候选人选择、知情同意、LT 后护理和国家政策的关键方面。与 ELT 治疗 SAH 相关的风险和生存获益的量化是新颖的，有必要进行扩展更好地理解移植界的道德约束和关注范围内的实践。这种新兴的治疗方法对于改善 SAH 患者的护理至关重要，并将有助于改善 ELT 治疗蛛网膜下腔出血的可行性、可用性和质量可能为患者提供新颖的救生治疗方法与美国 SAH 一起。