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; 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）占联合每年进行的肝移植（LTS）的26％ 状态。考虑到移植后累犯和移植前临床改善的可能性 戒酒时，大多数中心都需要在LT之前进行6个月的清醒记录。但是，一个子集 患者患有严重的酒精性肝炎（SAH）对基于类固醇的侵袭性治疗的难治性。为了 这些令人难以置信的病患者，3个月的死亡率为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救生治疗方法，但是 仍然很罕见且引起争议，因为大多数中心是标准的6个月清醒期是一个 移植候选人护理。 尽管全世界很少有移植中心在SAH上表现出ELT，但几个组表现出了极好的表现 短期生存和可比的累犯率。我们最近进行了一项试点研究，这是最大的队列 SAH的ELT接收者，表现出极好的总体生存率和类似的LT累犯 率先为6个月清醒的ALD的人的利率。我们已经建立了三角洲中心 （在酒精性肝炎中提供早期肝移植）在JHU担任专门的酒精研究中心 监督这项工作的前进。 必须量化ELT在适当选择的SAH候选人中的生存益处并支持 必须从公共和移植社区获得，以便推进SAH的ELT。为了 建立适当候选人选择所需的知识基础，建立临床理解 SAH的ELT，并确定公众对这种做法的看法，我们建议：1）量化邮政 SAH的死亡率，并将结果与​​其他适应症的LT进行比较； 2）量化ELT的生存益处 对于SAH； 3）创建一个道德框架，以根据SAH的意见考虑SAH的ELT 患者，移植提供者和公众对这种做法，从而导致了新的理性 关于SAH的ELT的国家政策。 这项研究将代表世界上SAH中最大的前瞻性队列研究。我们的 调查结果将对美国SAH的ELT实践产生直接而直接的影响， 告知候选人选择，知情同意，LT护理和国家政策的关键方面。强壮的 与SAH的ELT相关的风险和生存益处的数量是新颖的，并且需要扩展 移植社区的道德约束和关注点内的实践。更好地理解 这种新兴治疗对于改善SAH患者的护理至关重要，将有助于改善 SAH的可行性，可用性和ELT的质量可能为患者提供新颖的救生治疗 与SAH一起在美国。