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: 10356013
• 负责人: ANDREW M. CAMERON
• 金额: $ 34.88万
• 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 2024-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10356013
• 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

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)占美国每年进行的肝移植的26% 各州。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，大多数中心需要在LT之前记录6个月的戒酒情况。然而，一个子集 患有严重酒精性肝炎(SAH)的患者对激进的基于类固醇的治疗无效。为 这些病情严重的患者，在没有肝移植的情况下，3个月的死亡率是70%-80%，排除了6个月的可能性 戒酒规则。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，它 仍然是罕见和有争议的，因为在大多数中心，标准的6个月戒酒期是 移植候选资格要求。 尽管全世界很少有移植中心为蛛网膜下腔出血进行ELT，但有几个小组表现出色 短期存活率和可比的再犯罪率。我们最近进行了一项试验性研究，这是 接受ELT治疗SAH的患者，总体存活率很高，移植后复发情况相似 对那些戒酒6个月的ALD患者进行LT的比率。我们已经建立了Delta中心 (酒精性肝炎的早期肝移植)作为专门的酒精研究中心在JHU 监督这项工作向前推进。 ELT在适当选择的SAH候选者中的生存益处必须被量化和支持 为了推进蛛网膜下腔出血的ELT，必须从公众和移植社区获得。为了 建立合适的候选人选择所需的知识库，加深对临床的理解 ，并确定公众对这一做法的意见，我们建议：1)量化后英语教学 SAH的死亡率，以及在其他适应症上与LT的结果比较；2)量化ELT的生存益处 为SAH；以及3)根据SAH的意见，创建一个考虑SAH的ELT的伦理框架 患者、移植提供者和普通公众对这种做法的看法，从而导致了一种新的理性 关于SAH英语教学的国家政策。 这项研究将是世界上最大规模的蛛网膜下腔出血肝移植前瞻性队列研究。我们的 研究结果将对美国SAH的ELT实践产生直接和直接的影响， 向候选人选择、知情同意、肝移植后护理和国家政策等关键方面提供信息。健壮 量化ELT治疗SAH的风险和生存益处是新的，也是推广所必需的 在移植社区的道德约束和关注的范围内的实践。更好地理解 这种新出现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SAH的可行性、有效性和质量有望为患者提供新的挽救生命的治疗方法 在美国的SAH。