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

定义酒精相关性肝病急性肝功能失代偿的表型

基本信息

批准号：
10659203
负责人：
Allison Kwong
金额：
$ 19.35万
依托单位：
STANFORD UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-06-10 至 2026-05-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10659203
关键词：
Abstinence Academic Medical Centers Acute Alcohol Phenotype Alcohol consumption Alcoholic Hepatitis Alcoholic Liver Diseases Ambulatory Care Facilities Apoptotic Ascites Award Bacterial DNA Bilirubin Biological Biological Markers Cessation of life Characteristics Classification Clinical Clinical Investigator Clinical Research Communication Communities Complex Creatinine Cytokeratin-18 Staining Method Data Data Analyses Dedications Development Plans Disease Progression Etiology Feces Fibrosis Foundations Future Genetic Risk Hemorrhage Hepatic Hepatitis Hospitalization Hospitals Image Immunoassay Inflammation Inflammatory Institution Intervention Laboratories Lipopolysaccharides Liver Liver diseases Machine Learning Measures Mentorship MicroRNAs Morbidity - disease rate Multicenter Studies Natural History Outcome Outcomes Research Pathway interactions Patient Care Patient-Focused Outcomes Patients Pattern Phenotype Principal Investigator Procedures Process Psychosocial Influences Public Health Recovery Registries Relaxation Research Research Personnel Resource Allocation Resources Risk Serum Severity of illness Signal Transduction Subgroup Susceptibility Gene Techniques Technology Testing Time Training Translating Transplant Recipients Transplantation United States Universities Visit Woman advanced disease age group alcohol abstinence alcohol research alcohol use disorder biobank career career development chemokine clinical epidemiology clinically relevant cohort cost cytokine demographics disease heterogeneity disease phenotype disease registry ethnic minority experience fibrogenesis follow-up frailty genetic variant hepatocyte injury high risk improved lipidome liver transplantation microbiome mortality mortality risk multidisciplinary nutrition outcome prediction pharmacologic preclinical study prognostication programs prospective radiological imaging recruit research and development risk prediction model risk variant sarcopenia skills sobriety sociodemographic factors transcriptome translational study urinary

项目摘要

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.

项目概要在美国，酒精消耗量和酒精相关性肝病 (ALD) 导致的死亡率正在增加目前，ALD 是肝移植的主要原因。ALD 的自然病程与此不同。肝病的其他病因，在就诊时患有更晚期的疾病，但也有机会对于肝脏恢复的准确预测仍然具有挑战性。前瞻性登记和生物储存库，将评估 ALD 和饮酒患者的结果因急性肝代偿失调而住院的疾病这项研究将采取多方面的方法，考虑到对临床结果的生物学和社会心理影响。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、虚弱/肌肉减少症和非侵入性评估纤维化、炎症和脂肪变性的具体目标：(1) 表征队列并优化保留。使用频繁沟通、间接联系和基于技术的资源的程序，(2) 识别使用潜在类轨迹分析和轨迹分类的预测因子来确定 ALD 的不同轨迹， (3) 开发患者特异性风险预测模型来预测急性肝病后的肝脏恢复情况这些项目的目标将确定 ALD 和失代偿的不同表型和结果预测因子。改善预后以更好地进行针对性干预并分配资源。斯坦福大学的肝病学家和临床研究员，有着改善患者护理的长期愿景她在结果研究方面的经验以及她的临床研究硕士学位和流行病学为她执行拟议的研究和职业目标做好了充分的准备。发展计划得到多学科指导团队和机构的大力支持。获得纵向数据分析和机器学习方面的高级技能，以及以下方面的内容专业知识酒精研究，这将使她能够应用先进的统计技术来优化对酒精的预测此外，她还将拥有一个特征明确的 ALD 登记和临床相关的 ALD 治疗结果。生物储存库作为未来转化和多中心研究的平台。 PI 拥有受保护的时间、指导、培训和研究经验来开展独立研究从事 ALD 事业并提高我们对这种严重而普遍的疾病的了解。

项目成果

期刊论文数量（7）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

MELD 3.0 for adolescent liver transplant candidates.

MELD 3.0 适用于青少年肝移植候选人。

DOI：
发表时间：
2023-08-01
期刊：
影响因子：
0
作者：
Kwong, Allison J;Zhang, Ke;Ebel, Noelle;Mannalithara, Ajitha;Kim, W Ray
通讯作者：
Kim, W Ray

Decreased Urgency Among Liver Transplantation Candidates With Hepatocellular Carcinoma in the United States.

美国患有肝细胞癌的肝移植候选人的紧迫性降低。

DOI：
发表时间：
2022-04
期刊：
影响因子：
0
作者：
Kwong, Allison J;Ghaziani, T Tara;Mehta, Neil
通讯作者：
Mehta, Neil

Mortality in patients with end-stage liver disease above model for end-stage liver disease 3.0 of 40.

终末期肝病模型3.0以上的终末期肝病患者死亡率为40。

DOI：
发表时间：
2023-03-01
期刊：
影响因子：
0
作者：
Kim, W Ray;Mannalithara, Ajitha;Kwo, Paul Y;Bonham, C Andrew;Kwong, Allison
通讯作者：
Kwong, Allison

Impact of Donor Liver Macrovesicular Steatosis on Deceased Donor Yield and Posttransplant Outcome.

供体肝脏大泡脂肪变性对已故供体产量和移植后结果的影响。

DOI：
发表时间：
2023-02-01
期刊：
影响因子：
6.2
作者：
Kwong, Allison J;Kim, W Ray;Lake, John;Stock, Peter G;Wang, Connie J;Wetmore, James B;Melcher, Marc L;Wey, Andrew;Salkowski, Nicholas;Snyder, Jon J;Israni, Ajay K
通讯作者：
Israni, Ajay K

The steatosis-associated fibrosis estimator (SAFE) score: A tool to detect low-risk NAFLD in primary care.

脂肪变性相关纤维化估计器 (SAFE) 评分：初级保健中检测低风险 NAFLD 的工具。

DOI：
发表时间：
2023-01-01
期刊：
影响因子：
0
作者：
Sripongpun, Pimsiri;Kim, W Ray;Mannalithara, Ajitha;Charu, Vivek;Vidovszky, Anna;Asch, Steven;Desai, Manisha;Kim, Sun H;Kwong, Allison J
通讯作者：
Kwong, Allison J