Alcohol Use Disorder With Metabolic Dysfunction Is Associated With Adverse Health Impacts in a United States Clinical Setting

Abstract

The combined disease burden of excessive alcohol consumption and metabolic dysfunction (MD) is an escalating global concern. Although it is well established that both factors adversely impact health, the biological characteristics and comorbidities of their overlap remain understudied in the United States. The present study investigated whether concurrent MD and alcohol use disorder (AUD) is associated with worse liver-related and psychiatric health. A total of 1220 participants were recruited through the Natural History Protocol at the National Institutes of Health (NIH) and categorized into the following four groups: healthy controls (HC), individuals with MD (metHC), individuals with current AUD without MD (AUD) and those with both current AUD and MD (metAUD). Sociodemographic and clinical biomarkers, liver injury indices (Fibrosis-4 [FIB-4], LiverRisk, NAFLD fibrosis score [NFS]), liver enzymes and inflammatory markers (GGT, AST, ALT, CRP), liver function tests (albumin, bilirubin, PT-INR), psychiatric and substance use comorbidities as well as current smoking were assessed in the four groups using analysis of covariance (ANCOVA). In addition, the clinical biomarkers were compared across three groups: mild (< 3 MD criteria) and severe (≥ 3) metAUD, as well as AUD only. Liver enzymes, noninvasive liver fibrosis scores and liver function tests showed additive effects across metHC, AUD and metAUD compared to HC, with the largest effects in metAUD for GGT, AST, ALT, CRP, albumin, direct bilirubin, FIB-4, LiverRisk and NFS (p < 0.001). Psychiatric disorders also exhibited the most significant association with metAUD (p < 0.001). Within AUD, greater MD severity was associated with higher GGT, ALT, CRP, NFS and any DSM anxiety disorders (p < 0.05). These findings suggest that MD in the context of AUD is associated with greater liver dysfunction and psychiatric burden, supporting MD-targeted treatment strategies in clinical care for AUD.