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

Background and Aims: 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. Methods: 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. Results: 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. Conclusion: 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.