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: 10424443
• 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/10424443
• 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; 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; 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; prognostication; programs; prospective; radiological imaging; 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 曼联的饮酒和死亡率正在增加 国家和ALD现在是肝移植的主要原因。 ALD的自然历史与 肝病的其他病因，出现时患有更晚期疾病，但也有机会 用于肝恢复。准确预测结果仍然是挑战。拟议的研究将建立 一种预期的注册表和生物座席，将评估ALD和酒精使用的患者的结果 患有急性肝功能补偿的疾病。这项研究将采用多方面的方法， 考虑生物学和社会心理影响对临床结果的影响。将在 住院并在门诊诊所进行了2年，并采用了酒精饮酒的措施 图案，血清生物标志物，射线照相特征，营养，脆弱/肌肉减少症和非侵入性评估 纤维化，感染和脂肪变性。具体目的：（1）表征同类并优化保留率 使用经常通信，附带联系和基于技术的资源的程序，（2）确定 使用潜在类轨迹分析和轨迹分类的预测指标，ALD的不同轨迹， （3）开发一种患者特异性的风险预测模型，以预测急性肝后的肝恢复 代偿性。这些项目的目的将确定ALD和 改善预后，以更好地靶向干预措施并分配资源。首席研究员（PI）是 斯坦福大学的肝病学家和临床研究人员，长期愿景可以改善护理 ALD患者。她在结果研究和临床研究硕士和硕士学位方面的经验和 流行病学已经为执行该项目的目标做好了准备。拟议的研究和职业 发展计划由一个多学科的心态团队和机构良好支持。 PI会 在纵向数据分析和机器学习方面获得高级技能，以及内容专业知识 酒精研究将使她能够采用先进的统计技术来优化预测 在临床相关的环境中ALD的结果。此外，她将拥有一个符合特征的ALD注册表，并且 生物座席是将来翻译和多中心研究的平台。该奖项将提供 PI具有受保护的时间，指导，培训和研究经验，以开发独立研究 在ALD领域的职业，并提高我们对这种严重和普遍状况的理解。