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

项目总结 饮酒是世界范围内肝病的主要原因。重症酒精性肝炎(SAH)，急性 酒精相关性肝病(ALD)的表现与较差的短期存活率有关。不幸的是， 除了皮质类固醇外，治疗SAH的有效药物很少，约40%的患者对其有效 耐火材料。对于这些患者，肝移植(LT)是唯一可用的抢救治疗。直到最近， 大多数移植中心要求在肝移植前至少连续戒酒六个月。 不幸的是，由于最近酗酒，SAH患者通常无法实现这一“6个月规则”。 以及高短期死亡率。最近来自欧洲和美国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)的可能性，尽管LT后酒精复发 仍然是一个令人担忧的不良后果，如移植物损伤和肝硬变。 到目前为止，对于ALD中的最佳LT候选选择标准还没有达成共识，这可能会导致不平衡 以及不符合标准的肝移植后结果，包括酗酒复发。这个项目将在几个方面推进我们的领域。 首先，它将定义ELT和戒酒对SAH自然历史的影响。第二，它将发展 并在ALD中验证了一种新的LT候选选择工具。项目调查结果将支持规划中的多中心 试用和R01提交，用于候选人遴选工具的外部评估。 这项拟议的工作代表了一种跨学科的方法，用于优化和标准化 ALD中LT候选者的选择过程。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·霍普金斯三角洲酒精研究中心的社区，这将帮助我 为当前和未来的合作建立酒精研究人员网络。我还将积极参与 生物统计学和成瘾科学以及跨学科职业发展方面的正式课程 程序。通过拟议的职业发展计划，我将获得必要的技能和经验，以 将我自己确立为一名独立的临床研究员，在肝病、移植和 成瘾药。

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.