Biobehavioral Pathways Underlying Alcohol Use Disorder and Alcohol-associated Liver Disease

酒精使用障碍和酒精相关性肝病的生物行为途径

• 批准号: 10335094
• 负责人: Hayley Treloar Padovano
• 金额: $ 20.24万
• 依托单位: BROWN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-08-01 至 2024-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10335094
• 关键词: Alcohol consumption; Alcohols; Behavioral; Biological Markers; Caring; Cellular Phone; Centers of Research Excellence; Cessation of life; Chronic; Cicatrix; Cirrhosis; Clinic; Clinical Trials; Communities; Consumption; Disease; Effectiveness; Ethnic Origin; Feedback; Fibrosis; Future; Goals; Hepatology; Hispanics; Hospitals; Individual; Inflammation; Inflammatory; Intervention; Lead; Life; Liver; Liver Failure; Liver diseases; Longevity; Matched Group; Medical; Medical center; Monitor; Outcome; Participant; Pathogenesis; Pathology; Pathway interactions; Patients; Pattern; Phase; Protocols documentation; Reporting; Resistance; Rhode Island; Sampling; Scientist; Testing; Universities; Woman; Work; addiction; alcohol abstinence; alcohol intervention; alcohol risk; alcohol seeking behavior; alcohol testing; alcohol use disorder; biobehavior; burden of illness; chemokine; craving; cytokine; disorder risk; drinking; efficacy testing; endophenotype; follow-up; immune activation; liver function; male; men; mortality; negative affect; problem drinker; psychosocial; recruit; screening; tissue injury

Alcohol-associated liver disease (AALD) and alcohol use disorder (AUD) are intersecting diseases that add substantially to the global burden of disease and mortality. Alcohol-associated liver disease refers to a spectrum of liver tissue injury caused by chronic and excessive alcohol use, which can lead to fibrosis, followed by cirrhosis characterized by excessive scarring, and eventually, liver failure. Although alcohol abstinence is a main treatment goal, stopping drinking is often unachievable for many liver disease patients due to an underlying AUD characterized by craving, negative affect, and alcohol seeking despite harms. Approximately 1/3 of problem drinkers develop advanced AALD, and deaths from liver diseases are rising in the U.S., driven largely by increases in harmful drinking. Of particular concern, AUD rates have risen 50% in the past decade for those at greater risk of AALD, i.e., women and individuals of Hispanic ethnicity. While numerous, high-quality studies demonstrate effectiveness of brief psychosocial interventions for AUD, only five controlled trials have tested the efficacy of psychosocial interventions to reduce drinking in AALD patients. The rigor of these studies is limited by primarily male, nondiverse samples with varied alcohol-related medical pathology. This proposal, Biobehavioral Pathways Underlying Alcohol Use Disorder and Alcohol-associated Liver Disease, unites a team of addiction scientists and hepatologists for a partnership between the COBRE Center for Addiction and Disease Risk Exacerbation, Lifespan Hepatology Clinic at Rhode Island Hospital, Providence VA Medical Center, and other Brown University networks, and provides a platform for future work testing AUD interventions integrated with AALD care. The primary aim of this proposal is to demonstrate the feasibility of implementing a brief psychosocial AUD intervention integrated with AALD medical care. The intervention will include personalized feedback from biomarkers of liver function, drinking patterns, and self-monitoring of craving and negative affect via smartphone reports in daily life. Excessive drinkers (n = 44) consuming >24g/>36g per day, on average, for women/men in the past month, will be recruited from local hospitals, clinics, and the greater community. Half of our participants will have advanced AALD and AUD, and half will have AUD without AALD, with groups matched on drinking level. Recruitment will target equal representation of men and women and oversample for 1/3 individuals of Hispanic ethnicity. The protocol includes a 1-week screening phase, 3-week intervention phase, and 3-month follow-up. In addition to demonstrating feasibility, this project aims to test whether behavioral endophenotypes associated with alcohol-use outcomes in clinical trials are more resistant to change during AUD intervention for AALD patients with AUD relative to those with AUD only. A final aim is to explore biomarkers of inflammation and immune activation as mechanisms of persistence of endophenotypes, specifically levels of pro-inflammatory cytokines, chemokines, and others implicated in the pathogenesis of AALD.

酒精相关的肝病（AALD）和酒精使用障碍（AUD）是相交的疾病，这些疾病大大增加了疾病和死亡率的负担。酒精相关的肝病是指由慢性和饮酒过量引起的一系列肝组织损伤，这可能导致纤维化，其次是肝硬化，其特征是过度疤痕，最终是肝衰竭。尽管戒酒是一个主要的治疗目标，但由于渴望，负面影响和寻求酒精的特征，对于许多肝病患者来说，停止饮酒通常是无法实现的。大约有1/3的问题饮酒者发展为高级AALD，在美国，肝病的死亡人数正在增加，这在很大程度上是由于有害饮酒的增加而驱动的。特别令人担忧的是，在过去的十年中，AUD率上升了50％，即ALD风险更大的人，即西班牙裔种族的妇女和个人。尽管许多高质量的研究证明了对AUD的简短社会心理干预措施的有效性，但只有五项对照试验测试了社会心理干预措施减少AALD患者饮酒的功效。这些研究的严谨受到主要是与酒精相关的医学病理不同的男性非弗弗弗弗弗弗弗弗弗斯特（Drigr）的限制。这项建议，酒精使用障碍和与酒精相关的肝病所基于的生物行为途径，将成瘾科学家和肝病学家团队团结起来，与柯布雷成瘾和疾病风险加剧中心之间的合作关系，在罗德岛州医院，普罗维登斯·弗朗（Rhode Island Hospital），Providence VA Medical Centers，以及其他驾驶范围内的驾驶范围内，以及其他审计培训培训，并提供了一名未来的工作，并提供了审计培养基。该提案的主要目的是证明实施与AALD医疗护理集成的简短社会心理干预的可行性。干预措施将包括来自肝功能生物标志物的个性化反馈，饮酒方式以及对日常生活中智能手机报告对渴望和负面影响的自我监控。过量的饮酒者（n = 44），在过去一个月中，平均而言，每天食用> 24g/> 36克，将从当地的医院，诊所和更大的社区中招募。我们的一半参与者将提高Aald和Aud，一半将没有AALD，而小组的饮酒水平则相符。招聘将针对男性和女人的平等代表，并为1/3个西班牙裔种族的人过度按样品进行过言。该协议包括一个1周的筛查阶段，3周的干预阶段和3个月的随访。除了证明可行性外，该项目旨在测试临床试验中与酒精使用结果相关的行为内表型是否在AUD干预期间对AALD AUD患者的抗拒性更大。最终的目的是探索炎症和免疫激活的生物标志物，作为内跨表型持续性的机制，特别是促炎性细胞因子，趋化因子，趋化因子和其他与AALD发病机理有关的水平。