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.

项目总结