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.

项目总结/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 肝硬化在美国ALD不成比例地影响种族/少数民族，西班牙裔和美国人 与非西班牙裔白色患者相比，印度裔患者的发病率和死亡率增加。我们 对这些差异的理解是有限的，因为大多数关于ALD自然史的数据来自欧洲，而大多数关于ALD自然史的数据来自欧洲。 预后研究集中在饮酒者发生ALD的风险或严重ALD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）影响已确定ALD患者的预后。虽然协会 遗传学（例如，PNPLA 3）与发展ALD的风险继续获得兴趣，很少有研究检查 遗传学如何影响ALD预后我的中心假设是，独特的临床人口统计学，生物学和 SDOH因素导致不同种族和民族之间ALD的预后和自然史的差异， 包括导致西班牙裔和人工智能患者酒精性肝脏病进展的风险因素。由一个经过改造的瓦内克人引导 概念模型，我将解开临床人口统计学（例如，种族/民族）的直接和间接影响， 生物的（例如，遗传学）和SDOH（例如，护理障碍）因素对ALD诊断的影响， 在一个种族，民族和社会经济多样化的群体中的具体目标：1）定义的作用 临床人口统计学和SDOH因素与ALD严重程度的种族和民族差异; 2）检查 遗传因素与ALD严重程度的相关性; 3）推导ALD的多水平危险分层模型 精确化。这些数据将为减少ALD差异的最有效干预措施提供信息。PI是一个 临床研究人员和德州西南肝病学家，具有改善患者护理的长期愿景 与ALD，包括解决差距。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，使他将获得新的，先进的技能，在先进的 定量分析，健康差距，遗传学，队列建设，调查方法，风险机器学习 预测.他组建了一支才华横溢的跨学科导师团队， 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 著名的卫生服务和差距研究员;海伦霍布斯博士，在遗传学和 肝病; King博士，AUD专家; Zhang博士，定量分析统计学专家; Kozlitina博士， 遗传统计学专家;以及风险预测机器学习专家统计学家Sandikçi博士。的 这项建议中的研究具有重大的公共卫生影响，因为它们将填补我们认识上的空白 在少数种族/民族中ALD的预后。该奖励和培训计划将为PI提供 保护时间，培训和导师，以建立一个独立资助的研究事业，重点是提高 ALD结果。