Candidate Selection for Liver Transplantation in Patients with Alcohol-related Liver Disease

酒精相关性肝病患者肝移植候选者的选择

• 批准号: 10166736
• 负责人: Po-Hung (Victor) Chen
• 金额: $ 19.82万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-07-01 至 2025-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10166736
• 关键词: Abstinence; Acute; Acute Alcoholic Hepatitis; Adrenal Cortex Hormones; Alcohol consumption; Alcoholic Hepatitis; Alcohols; Attenuated; Behavioral; Biological Markers; Biometry; Cessation of life; Chronic; Cirrhosis; Clinical Investigator; Cohort Studies; Collaborations; Communities; Consensus; Country; Data; Decision Making; Delphi Technique; Development; Development Plans; Europe; Evaluation; Event; Fostering; Funding; Future; Goals; Graft Rejection; Hepatitis C; Hepatology; Inferior; Injury; Intervention; Interview; Knowledge; Lead; Liver diseases; Medical; Medicine; Multicenter Trials; National Institute on Alcohol Abuse and Alcoholism; Natural History; Outcome; Patients; Pilot Projects; Predictive Analytics; Process; Program Development; Protocols documentation; Questionnaires; Refractory; Relapse; Reproducibility; Research; Research Personnel; Research Training; Risk; Risk Estimate; Science; Scientist; Selection Criteria; Social support; Standardization; Surveys; Transplant Recipients; Transplantation; United States; Universities; Validation; Work; addiction; adverse outcome; alcohol abstinence; alcohol abuse therapy; alcohol relapse; alcohol research; alcohol screening; base; candidate selection; career development; cohort; evidence base; experience; follow-up; improved; interdisciplinary approach; liver transplantation; member; mortality; mortality risk; non-alcoholic fatty liver disease; novel; post-transplant; predictive modeling; relapse risk; skills; sobriety; substance use; supportive environment; tool; transplant centers

PROJECT SUMMARY Alcohol consumption is a major cause of liver disease worldwide. Severe alcoholic hepatitis (SAH), an acute manifestation of alcohol-related liver disease (ALD), is associated with inferior short-term survival. Unfortunately, there are few effective medical therapies for SAH outside of corticosteroids, to which about 40% of patients are refractory. For these patients, liver transplantation (LT) is the only rescue treatment available. Until recently, most transplant centers mandated at least six months of continuous abstinence from alcohol before LT. Unfortunately, this “6-month rule” was(is) often unachievable for patients with SAH, due to recent alcohol use and high short-term mortality. Several recent studies from Europe and the United States championed the concept of early liver transplantation (ELT) in this highly vulnerable patient cohort, though post-LT alcohol relapse remained a concern with adverse consequences like graft injury and cirrhosis. To date, there is no consensus on the optimal LT candidate selection criteria in ALD, which can lead to uneven and substandard post-LT outcomes, including alcohol relapse. This project will advance our field in several ways. First, it will define the impacts of ELT and alcohol abstinence on the natural history of SAH. Second, it will develop and validate a novel LT candidate selection tool in ALD. The project findings will support a planned multicenter trial and R01 submission for the external evaluation of the candidate selection tool. This proposed work represents an interdisciplinary approach toward the optimization and the standardization of the LT candidate selection process in ALD. To conduct this study, I will integrate myself into the research community of the NIAAA P50-funded Johns Hopkins DELTA Center for Alcohol Research, which will help me establish a network of alcohol researchers for current and future collaboration. I will also actively engage in formal coursework in biostatistics and addiction science as well as interdisciplinary career development programs. Through the proposed career development plan, I will gain the necessary skills and experience to establish myself as an independent clinical investigator bridging the fields of hepatology, transplantation, and addiction medicine.

项目概要 饮酒是世界范围内导致严重酒精性肝炎（SAH）的主要原因。 不幸的是，酒精相关性肝病（ALD）的表现与短期生存率较低有关。 除了皮质类固醇外，对于 SAH 几乎没有有效的药物治疗方法，约 40% 的患者接受皮质类固醇治疗。 对于这些难治性的患者，肝移植（LT）是迄今为止唯一可用的挽救治疗方法。 大多数移植中心要求在 LT 之前至少连续戒酒六个月。 不幸的是，由于最近饮酒，这个“6 个月规则”对于 SAH 患者来说通常是无法实现的 欧洲和美国最近的几项研究支持了这一概念。 尽管 LT 后酒精复发，但早期肝移植 (ELT) 在这一高度脆弱的患者群体中的应用 仍然担心移植物损伤和肝硬化等不良后果。 迄今为止，对于 ALD 的最佳 LT 候选选择标准尚未达成共识，这可能导致不均匀 以及不合格的 LT 后结果，包括酒精复发。该项目将以多种方式推进我们的领域。 首先，它将定义 ELT 和戒酒对 SAH 自然史的影响。其次，它将发展。 并验证 ALD 中的新型 LT 候选者选择工具。该项目的研究结果将支持计划中的多中心计划。 试验和 R01 提交用于候选人筛选工具的外部评估。 这项拟议的工作代表了一种跨学科的方法来优化和标准化 ALD 中的 LT 候选人选择过程 为了进行这项研究，我将把自己融入到研究中。 NIAAA P50 资助的约翰霍普金斯 DELTA 酒精研究中心的社区，这将帮助我 我也将积极参与建立酒精研究人员网络以进行当前和未来的合作。 生物统计学和成瘾科学以及跨学科职业发展的正式课程 通过拟议的职业发展计划，我将获得必要的技能和经验。 使自己成为一名独立的临床研究者，在肝病学、移植和肝病学领域之间架起桥梁。 成瘾药。