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

项目摘要 饮酒是全球肝脏疾病的主要原因。重度酒精性肝炎（SAH），一种急性 酒精相关性肝病（ALD）的表现与短期生存率低下相关。不幸的是， 除了皮质类固醇外，几乎没有有效的药物治疗SAH，约40%的患者 难治的对于这些患者，肝移植（LT）是唯一可用的补救治疗。直到最近， 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，由于近期饮酒，SAH患者通常无法实现这一“6个月规则 短期死亡率高。欧洲和美国最近的几项研究支持这一概念 在这个高度脆弱的患者队列中，早期肝移植（ELT），尽管LT后酒精复发， 仍然存在诸如移植物损伤和肝硬化的不良后果。 到目前为止，在ALD中的最佳LT候选人选择标准上没有共识，这可能导致不均匀的 以及低于标准的肝移植后结果，包括酒精复发。这个项目将在几个方面推动我们的领域。 首先，它将定义ELT和戒酒对SAH自然史的影响。第二，它将发展 并在ALD中验证新的LT候选选择工具。项目结果将支持计划的多中心 试用和R01提交，用于候选人选择工具的外部评估。 这项拟议的工作代表了一个跨学科的方法，对优化和标准化， ALD中的LT候选人选择过程。为了进行这项研究，我将把自己融入研究中 NIAAA P50资助的约翰霍普金斯德尔塔酒精研究中心的社区，这将帮助我 建立一个酒精研究人员网络，以促进当前和未来的合作。我也会积极参与 生物统计学和成瘾科学的正式课程以及跨学科的职业发展 程序.通过职业发展计划，我将获得必要的技能和经验， 建立自己作为一个独立的临床研究者桥接肝病学，移植领域， 成瘾药物

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.