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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。

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）

Serum biomarkers of liver fibrosis identify globus pallidus vulnerability.

DOI：
10.1016/j.nicl.2023.103333
发表时间：
2023
期刊：
NEUROIMAGE-CLINICAL
影响因子：
4.2
作者：
Kwong, Allison J.;Zahr, Natalie M.
通讯作者：
Zahr, Natalie M.

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：
10.1002/hep.32770
发表时间：
2023
期刊：
Hepatology (Baltimore, Md.)
影响因子：
0
作者：
Kim,WRay;Mannalithara,Ajitha;Kwo,PaulY;Bonham,CAndrew;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：
10.1097/tp.0000000000004291
发表时间：
2023
期刊：
Transplantation
影响因子：
6.2
作者：
Kwong,AllisonJ;Kim,WRay;Lake,John;Stock,PeterG;Wang,ConnieJ;Wetmore,JamesB;Melcher,MarcL;Wey,Andrew;Salkowski,Nicholas;Snyder,JonJ;Israni,AjayK
通讯作者：
Israni,AjayK

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：
10.1002/hep.32545
发表时间：
2023
期刊：
Hepatology (Baltimore, Md.)
影响因子：
0
作者：
Sripongpun,Pimsiri;Kim,WRay;Mannalithara,Ajitha;Charu,Vivek;Vidovszky,Anna;Asch,Steven;Desai,Manisha;Kim,SunH;Kwong,AllisonJ
通讯作者：
Kwong,AllisonJ

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。