Determining the Influence of Clinicodemographic, Biologic and SDOH Factors in Racial and Ethnic Disparities in the Prognosis of Alcohol-Associated Liver Disease

确定临床人口统计学、生物和 SDOH 因素对酒精相关性肝病预后中种族和民族差异的影响

• 批准号: 10785492
• 负责人: Thomas Gerard Cotter
• 金额: $ 19.33万
• 依托单位: UT SOUTHWESTERN MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-20 至 2028-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10785492
• 关键词: AODR mortality; Accounting; Address; Affect; Age; Alcohol consumption; Alcoholic Hepatitis; Alcoholic Liver Diseases; Alcohols; American Indians; Award; Bilirubin; Biological; Black Populations; Black race; Case/Control Studies; Cause of Death; Cessation of life; Cirrhosis; Clinical; Clinical Research; Data; Development; Disease Outcome; Disease Progression; Disparity; Electronic Health Record; Ethnic Origin; Ethnic Population; Europe; European; Fibrosis; Funding; Future; Genes; Genetic; Genetic Diseases; Genetic Risk; Goals; Health; Health Services; Hispanic; Hispanic Populations; International; Intervention; Knowledge; Liver diseases; Logistic Regressions; Machine Learning; Mediation; Mediator; Mentors; Mentorship; Metabolic syndrome; Modeling; Monitor; Morbidity - disease rate; Natural History; Not Hispanic or Latino; Organ; Outcome; Patient Care; Patient-Focused Outcomes; Patients; Pattern; Population; Population Heterogeneity; Prevalence; Prognosis; Prognostic Factor; Prospective cohort; Psychological Impact; Psychosocial Factor; Public Health; Race; Regression Analysis; Research; Research Personnel; Risk; Risk Factors; Role; Sampling; Severity of illness; Single Nucleotide Polymorphism; Social Values; Socioeconomic Status; Steatohepatitis; Survey Methodology; Surveys; Talents; Time; Training; alcohol abstinence; alcohol use disorder; barrier to care; burden of illness; career; cohort; cultural values; disease natural history; disease prognosis; disparity reduction; ethnic difference; ethnic disparity; ethnic diversity; ethnic health disparity; ethnic minority; experience; genetic epidemiology; health disparity; improved; improved outcome; interest; liver transplantation; machine learning method; mortality; patient prognosis; prognostic; prospective; protective factors; racial difference; racial disparity; racial diversity; racial health disparity; racial minority; racial population; research study; risk prediction; risk stratification; sex; skills; social health determinants; socioeconomics; statistics; therapy development

PROJECT SUMMARY / ABSTRACT Alcohol-associated liver disease (ALD) is a major public health problem and the most common cause of death from cirrhosis in the US. ALD disproportionately impacts racial/ethnic minorities, with Hispanic and American Indian patients having increased morbidity and mortality compared with non-Hispanic White patients. Our understanding of these disparities is limited as most data on ALD natural history comes from Europe, while most prognostic studies focus on either risk of developing ALD among drinkers or short-term prognosis in severe ALD. Moreover, few studies have examined how clinicodemographic (e.g., metabolic syndrome) and social determinants of health (SDOH) factors impact patient prognosis in established ALD. Although the association of genetics (e.g., PNPLA3) with risk of developing ALD continues to garner interest, few studies have examined how genetics impact ALD prognosis. My central hypothesis is that unique clinicodemographic, biologic and SDOH factors drive differences in the prognosis and natural history of ALD among racial and ethnic groups, including risk factors leading to progression of ALD among Hispanics and AIs. Guided by an adapted Warnecke conceptual model, I will disentangle direct and indirect effects of clinicodemographic (e.g, Race/ethnicity), biologic (e.g., genetics), and SDOH (e.g. barriers to care) factors on ALD prognostication through the following specific aims in a racially, ethnically, and socioeconomically diverse cohort: 1) Define the role of clinicodemographic and SDOH factors with racial and ethnic differences in ALD severity; 2) Examine the association of genetic factors and ALD severity; 3) Derive a multilevel risk stratification model for ALD prognostication. These data will inform the most impactful interventions to reduce disparities in ALD. The PI is a clinical researcher and hepatologist at UT Southwestern, with a long-term vision of improving care for patients with ALD, including tackling disparities. The proposed training plan is integrated with the research aims and builds on his existing knowledge in clinical research whereby he will acquire new, advanced skills in advanced quantitative analysis, health disparities, genetics, cohort building, survey methods, machine learning in risk prediction. He has assembled an exceptionally talented interdisciplinary team of mentors with complementary expertise: Dr. Mack Mitchell, an experienced researcher and ALD content expert; Dr. Amit Singal, a world- renowned health services and disparities researcher; Dr. Helen Hobbs, an international expert in genetics and liver disease; Dr. King, an expert in AUD; Dr. Zhang, an expert statistician in quantitative analyses; Dr. Kozlitina, an expert in genetic statistics; and Dr. Sandikçi, an expert statistician in machine learning in risk prediction. The research studies in this proposal have significant public health impact as they will fill gaps in our understanding of the prognosis of ALD among racial/ethnic minorities. This award and training plan will provide the PI with the protected time, training, and mentorship, to build an independently-funded research career focused on improving ALD outcomes.

项目概要/摘要 酒精相关性肝病（ALD）是一个主要的公共卫生问题，也是最常见的死亡原因 在美国，肝硬化对少数种族/族裔的影响尤为严重，其中包括西班牙裔和美国人。 与非西班牙裔白人患者相比，印度患者的发病率和死亡率有所增加。 对这些差异的理解是有限的，因为大多数关于 ALD 自然历史的数据来自欧洲，而大多数 预后研究的重点是饮酒者发生酒精性肝病的风险或严重酒精性肝病的短期预后。 此外，很少有研究探讨临床人口统计学（例如代谢综合征）和社会 健康决定因素 (SDOH) 因素影响已确诊的 ALD 患者的预后。 具有发生 ALD 风险的遗传学（例如 PNPLA3）继续引起人们的兴趣，但很少有研究对此进行检验 我的中心假设是，遗传学如何影响 ALD 预后。 SDOH 因素导致种族和族裔群体之间 ALD 的预后和自然史存在差异， 包括导致西班牙裔和人工智能中 ALD 进展的风险因素，由改编后的 Warnecke 指导。 概念模型，我将理清临床人口统计学的直接和间接影响（例如种族/民族）， 生物（例如遗传学）和 SDOH（例如护理障碍）因素通过以下方式影响 ALD 预后 种族、族裔和社会多元化群体中的具体目标： 1) 定义 临床人口统计学和 SDOH 因素与 ALD 严重程度存在种族和民族差异 2) 检查 3）推导ALD多级风险分层模型 这些数据将为减少 ALD 差异的最有效的干预措施提供信息。 UT Southwestern 的临床研究员和肝病学家，有着改​​善患者护理的长期愿景 与 ALD，包括谈判差异。拟议的培训计划与研究目标相结合。 建立在他现有的临床研究知识的基础上，他将获得先进的新技能 定量分析、健康差异、遗传学、队列建设、调查方法、风险机器学习 他组建了一支才华横溢、互补性强的跨学科导师团队。 专业知识：Mack Mitchell 博士，一位经验丰富的研究员和 ALD 内容专家；Amit Singal 博士，一位世界级的专家； 著名的健康服务和差异研究员海伦·霍布斯博士，国际遗传学专家 King 博士，AUD 专家；Zhang 博士，定量分析专家； 遗传统计学专家；Sandikçi 博士，风险预测机器学习专家统计学家。 该提案中的研究具有重大的公共卫生影响，因为它们将填补我们理解上的空白 该奖项和培训计划将为 PI 提供关于少数族裔 ALD 预后的信息。 受保护的时间、培训和指导，建立一个独立资助的研究职业，专注于提高 ALD 结果。