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

• 批准号: 10191957
• 负责人: Allison Kwong
• 金额: $ 19.35万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 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/10191957
• 关键词: Abstinence; Academic Medical Centers; Acute; Alcohol Phenotype; Alcohol consumption; Alcohols; 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; Development Plans; Diagnostic radiologic examination; 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; Pharmacology; Phenotype; Principal Investigator; Procedures; Process; Psychosocial Influences; Public Health; Recovery; Registries; Research; Research Personnel; Resources; Risk; Serum; Severity of illness; Signal Transduction; Subgroup; Susceptibility Gene; Techniques; Technology; Testing; Time; Training; Translating; Transplant Recipients; Transplantation; United States; Universities; Vision; Visit; Woman; advanced disease; age group; alcohol abstinence; alcohol research; alcohol use disorder; base; biobank; biomarker identification; career; career development; chemokine; clinical epidemiology; clinically relevant; cohort; cost; cytokine; demographics; disease heterogeneity; disease phenotype; disease registry; ethnic minority population; experience; fibrogenesis; follow-up; frailty; genetic variant; hepatocyte injury; high risk; improved; lipidome; liver transplantation; microbiome; mortality; mortality risk; multidisciplinary; nutrition; outcome prediction; preclinical study; prognostic; programs; prospective; recruit; research and development; risk prediction model; risk variant; sarcopenia; skills; sobriety; sociodemographic factors; transcriptome; translational study; urinary

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，酒精消费和酒精相关性肝病（ALD）的死亡率正在增加。 美国，酒精性肝脏病现在是肝移植的主要原因。ALD的自然史不同于 肝病的其他病因，在出现时疾病更晚期，但也有机会 用于肝脏恢复准确预测结果仍然具有挑战性。该研究将建立 一项前瞻性登记和生物储存库，将评估ALD和酒精使用患者的结局 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学对临床结果的影响。患者将在 住院治疗，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、影像学特征、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。具体目标：（1）描述队列并优化保留 使用频繁的沟通、间接联系人和基于技术的资源的程序，（2）识别 使用潜在类别轨迹分析和轨迹分类的预测器的ALD的不同轨迹， 和（3）开发患者特异性风险预测模型以预测急性肝损伤后的肝脏恢复。 代偿失调这些项目的目标将确定不同的表型和ALD结果的预测因子， 改进对更有针对性的干预措施和资源分配的说明。主要研究者（PI）是 他是斯坦福大学的肝病学家和临床研究人员，长期致力于改善 酒精性痴呆患者。她在成果研究方面的经验和她的临床研究硕士学位， 流行病学使她做好了充分的准备来实现项目目标。建议的研究和职业 发展计划得到多专业导师团队和院校的大力支持。PI将 获得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，以优化预测 在临床相关背景下的ALD结果。此外，她将有一个特征良好的ALD登记， 生物储存库作为未来转化和多中心研究的平台。该奖项将提供 PI具有受保护的时间，导师，培训和研究经验，以开发独立的研究 职业生涯在ALD和提高我们对这种严重和普遍的条件的理解。