Liver, Cardiovascular and Infectious Outcomes in Alcohol-Associated Liver Disease With Cardiometabolic Risk Factors

Cardiometabolic risk factors (CMRF) are common in alcohol-associated liver disease (ALD), but their impact on clinical outcomes is unclear. We evaluated whether CMRF identifies a higher-risk phenotype among adults with ALD.

We performed a multicenter retrospective cohort study within the TriNetX research network, including adults with ALD (ICD-10 K70) from 2010 to 2019. CMRFs were defined by overweight/obesity, dysglycemia, hypertension or dyslipidemia using the steatotic liver disease framework. Individuals with other liver diseases, cancer, prior liver transplantation or pregnancy were excluded. After 1:1 propensity score matching (PSM) on demographics, comorbidities, laboratory indices and medications, we compared ALD with versus without CMRF using Cox models, overall and stratified by cirrhosis.

After matching, 2942 adults with ALD were included (ALD with CMRF, n = 1471; without CMRF, n = 1471). Five-year all-cause mortality was similar between groups (Hazard Ratio [HR]: 1.01, 95% CI 0.83-1.23). In contrast, ALD patients with CMRF had higher risks of alcohol-associated hepatitis (HR 2.12, 95% CI 1.62-2.79) and a numerically higher risk of major adverse liver outcomes (HR 1.14, 95% CI 0.98-1.32). Cardiovascular complications were markedly increased, including major adverse cardiovascular events (HR 3.07, 95% CI 2.14-4.39), arrhythmia (12.4% vs. 4.8%, HR 2.24, 95% CI 1.70-2.94) and heart failure (HR 3.70, 95% CI 2.11-6.47). Infectious events were also more frequent among CMRF patients, including sepsis, urinary tract infection and pneumonia. Associations were generally stronger among patients with cirrhosis.

Among individuals with ALD, CMRF does not increase short- to intermediate-term mortality but identifies a phenotype with substantially higher liver, cardiovascular and infectious morbidity. Systematic detection and intensive management of CMRF should be integrated into ALD care pathways.