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: 10666615
• 负责人: Hayley Treloar Padovano
• 金额: $ 8.26万
• 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/10666615
• 关键词: Alcohol consumption; Alcoholic Liver Diseases; 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; Hispanic Populations; Hospitals; Inflammation; Inflammatory; Intervention; 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; Risk; Sampling; Scientist; Testing; Universities; Woman; Work; addiction; alcohol abstinence; alcohol intervention; 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.

酒精相关性肝病（AALD）和酒精使用障碍（AUD）是交叉疾病，大大增加了全球疾病负担和死亡率。酒精相关性肝病是指慢性和过量饮酒引起的一系列肝组织损伤，可导致纤维化，随后出现以过度疤痕为特征的肝硬化，并最终导致肝衰竭。虽然戒酒是一个主要的治疗目标，但对于许多肝病患者来说，戒酒往往是无法实现的，因为潜在的AUD以渴望、负面影响和不顾危害寻求酒精为特征。大约三分之一的问题饮酒者发展为晚期AALD，在美国，由于有害饮酒的增加，肝脏疾病的死亡人数正在上升。特别值得关注的是，在过去十年中，对于那些AALD风险较高的人群，即女性和西班牙裔个体，澳元利率上升了50%。虽然有大量高质量的研究证明了短期社会心理干预对AUD的有效性，但只有五项对照试验测试了社会心理干预对减少AALD患者饮酒的有效性。这些研究的严谨性主要受到男性、非多样性样本和不同酒精相关医学病理的限制。这项提案，酒精使用障碍和酒精相关肝病的生物行为途径，联合了成瘾科学家和肝病学家团队，在COBRE成瘾和疾病风险加重中心，罗德岛医院的生命肝病诊所，普罗维登斯VA医疗中心和其他布朗大学网络之间建立了合作关系，并为未来测试AUD干预措施与AALD护理相结合的工作提供了一个平台。本提案的主要目的是证明实施与AALD医疗护理相结合的简短心理社会AUD干预的可行性。干预将包括来自肝功能生物标志物的个性化反馈，饮酒模式，以及通过智能手机报告日常生活中的渴望和负面影响的自我监测。过量饮酒者（n = 44）将从当地医院、诊所和更大的社区招募，在过去一个月里，女性/男性平均每天消耗bbbb24克/ bbbb36克。我们的参与者中有一半将患有晚期AALD和AUD，一半将患有AUD但没有AALD，各组的饮酒水平相匹配。招聘将以男女平等为目标，并对三分之一的西班牙裔进行抽样。该方案包括1周的筛查阶段，3周的干预阶段和3个月的随访。除了证明可行性之外，本项目旨在测试在临床试验中与酒精使用结果相关的行为内表型是否在AUD干预期间对患有AUD的AALD患者比仅患有AUD的AALD患者更不易改变。最终目的是探索炎症和免疫激活的生物标志物作为内表型持续的机制，特别是促炎细胞因子、趋化因子和其他与AALD发病机制有关的水平。