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

• 批准号: 10560558
• 负责人: ANDREW M. CAMERON
• 金额: $ 33.64万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-02-01 至 2025-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10560558
• 关键词: Abstinence; Accounting; Address; Agreement; Alcoholic Hepatitis; Alcoholic Liver Diseases; Caring; Clinical; Cohort Analysis; 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; Knowledge; Leadership; Life; Link; Liver; Longitudinal Studies; Modeling; 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; Selection Criteria; Specialized Center; Standardization; Steroids; Survival Rate; Transplant Recipients; Transplantation; United States; Vertebral column; Work; alcohol research; 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; organ allocation; patient subsets; post-transplant; prospective; recidivism; sobriety; transplant centers; transplant registry

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.

项目摘要 酒精性肝病（ALD）占美国每年肝移植（LT）的26%。 States.考虑到移植后复发的担忧和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）的患者对积极的基于类固醇的治疗难治。为 这些令人难以置信的病人，3个月的死亡率是70-80%，没有LT，排除了6个月的可能性。 清醒规则早期LT（ELT）是这些患者唯一可用的挽救生命的治疗方法，然而， 仍然是罕见的和有争议的，因为在大多数中心的标准6个月清醒期是一个 移植候选人资格要求。 尽管全世界很少有移植中心对SAH进行ELT，但有几组患者表现出了良好的效果。 短期存活率和类似的再犯率。我们最近进行了一项试点研究， SAH的ELT接受者，表现出极好的总生存率和相似的LT后复发率 对于那些接受LT治疗ALD且清醒时间>6个月的患者，我们建立了三角洲中心 （提供早期肝移植治疗酒精性肝炎）在JHU作为一个专门的酒精研究中心， 监督这项工作的进展 ELT在适当选择的SAH候选人中的生存益处必须量化并支持 为了推进SAH的ELT，必须从公众和移植界获得。为了 建立适当的候选人选择所需的知识基础， 的ELT为SAH，并确定公众对这种做法的意见，我们建议：1）量化后ELT SAH的死亡率，并比较其他适应症与LT的结局; 2）量化ELT的生存获益 3）根据SAH的意见，为考虑SAH的ELT创建伦理框架 患者，移植提供者和公众对这种做法，从而产生了一个新的理性 关于SAH的ELT的国家政策。 本研究将代表世界上规模最大的SAH LT前瞻性队列研究。我们 研究结果将对美国SAH的ELT实践产生直接和直接的影响， 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。鲁棒 量化与ELT治疗SAH相关的风险和生存获益是新颖的， 在伦理约束和移植界的关注范围内的实践。更好地了解 这种新兴的治疗方法对于改善SAH患者的护理至关重要， 用于SAH的ELT的可行性、可用性和质量可能为患者提供新型、挽救生命的治疗 SAH在美国。