Defining Phenotypes of Alcohol-Associated Liver Disease with Acute Hepatic Decompensation

项目摘要 在美国，饮酒量和酒精相关性肝病(ALD)的死亡率正在上升 ALD现在是肝移植的主要原因。阿尔茨海默病的自然历史与 肝病的其他病因，在表现时有更晚期的疾病，但也有机会 以恢复肝脏功能。对结果的准确预测仍然具有挑战性。拟议的研究将确立 一项前瞻性登记和生物信息库，将评估ALD和酒精使用患者的结果 因急性肝功能失代偿而住院的患者。这项研究将采取多方面的方法， 考虑到生物学和心理社会对临床结果的影响。患者将在 住院，并在门诊随访2年，纵向测量酒精使用情况 模式、血清生物标志物、放射学特征、营养、脆性/骨质疏松症和非侵入性评估 纤维化、炎症和脂肪变性。具体目标：(1)确定队列特征并优化留存 使用频繁沟通、附属联系和基于技术的资源的程序，(2)确定 用潜在类轨迹分析和轨迹分类预测因子区分ALD的轨迹， 以及(3)开发针对患者的风险预测模型来预测急性肝损伤后的肝脏恢复。 失代偿。这些项目目标将确定ALD和ALD患者的不同表型和预后预测因素 改进预测，以更好地针对干预措施并分配资源。首席调查员(PI)是 斯坦福大学肝病学家和临床研究人员，长期致力于改善对 ALD患者。她在结果研究方面的经验和她的临床研究和硕士学位 流行病学已经为她执行该项目的目标做好了充分的准备。拟议的研究和职业 发展计划得到了一个多学科指导团队和该机构的大力支持。私人侦探将 掌握纵向数据分析和机器学习方面的高级技能，以及 酒精研究，这将使她能够应用先进的统计技术来优化预测 与临床相关的ALD的转归。此外，她将有一个特征良好的ALD注册和 生物信息库作为未来翻译和多中心研究的平台。这一奖项将提供 PI有保障的时间、导师、培训和研究经验来发展独立的研究 在ALD的职业生涯，并提高我们对这种严重和普遍的疾病的认识。

Project Summary Alcohol consumption and mortality due to alcohol-associated liver disease (ALD) are increasing in the United States, and ALD is now the leading cause of liver transplantation. The natural history of ALD is distinct from other etiologies of liver disease, with more advanced disease at the time of presentation but also opportunity for hepatic recovery. Accurate prediction of outcome remains challenging. The proposed research will establish a prospective registry and biorepository that will evaluate the outcomes of patients with ALD and alcohol use disorder who are hospitalized with acute hepatic decompensation. This study will take a multifaceted approach, considering the biologic and psychosocial influences on clinical outcomes. Patients will be recruited during hospitalization and followed for 2 years in the outpatient clinics, with longitudinal measures of alcohol use patterns, serum biomarkers, radiographic features, nutrition, frailty/sarcopenia, and non-invasive assessments of fibrosis, inflammation, and steatosis. Specific Aims: (1) Characterize the cohort and optimize retention procedures using frequent communication, collateral contacts, and technology-based resources, (2) Identify distinct trajectories of ALD using latent class trajectory analysis and the predictors of trajectory classification, and (3) Develop a patient-specific risk prediction model to predict hepatic recovery after an acute hepatic decompensation. These project aims will identify distinct phenotypes and predictors of outcome in ALD and improve prognostication to better target interventions and allocate resources. The principal investigator (PI) is a hepatologist and clinical researcher at Stanford University, with a long-term vision of improving care for patients with ALD. Her experience with outcomes research and her Master’s in Clinical Research and Epidemiology have prepared her well to execute the project aims. The proposed research and career development plan are well-supported by a multi-disciplinary mentorship team and the institution. The PI will acquire advanced skills in longitudinal data analysis and machine learning, as well as content expertise in alcohol research, which will allow her to apply advanced statistical techniques to optimize prediction of outcome in ALD in a clinically relevant context. In addition, she will have a well-characterized ALD registry and biorepository to serve as a platform for future translational and multicenter studies. This award will provide the PI with the protected time, mentorship, training, and research experience to develop an independent research career in ALD and improve our understanding of this serious and prevalent condition.