Project Lead 3: Hayley Treloar Padovano, PhD

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

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 study, 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.