Luis Antonio Díaz

Introduction: Although the role of cardiometabolic risk factors (CMRF) has been characterized in steatotic liver disease, their role in the severity of alcohol-associated hepatitis (AH) remains unclear. We aimed to evaluate the impact of CMRF on mortality. Methods: Multinational prospective cohort study (2015–2024) including hospitalized patients with severe AH across 32 centers in 14 countries. Diagnosis of AH was made using the NIAAA criteria. Analyses included adjusted competing-risk models by age, sex, ethnicity, history of cirrhosis, CMRF, corticosteroid use, MELD, and ACLF grade, with liver transplantation as a competing risk. Results: 936 participants were included; mean age 48±11.2 years, and 88.9% were male. At least one CMRF was present in 46.6%; median body mass index (BMI) was 24.2 kg/m ² [IQR: 22.8–28.2], prevalence of diabetes 17.6%, hypertension 16.5%, and dyslipidemia 5.8%. Median MELD was 24.4 [19.3–31.4], 86.7% had severe AH, and 180-day survival was 72.9%. Survival did not differ by CMRF status (log-rank p =0.453). In adjusted competing-risk models, higher age (sHR 1.02; 95%CI:1.01–1.04), greater alcohol intake (per g/day; sHR 1.001; 95%CI:1.000–1.002), MELD (sHR 1.04; 95%CI:1.01–1.06), and ACLF grade 2–3 (sHR 2.34 and 4.34) predicted mortality. However, no individual CMRF independently increased mortality. A prespecified non-linear BMI analysis showed modestly lower mortality between 25–40 kg/m², with a higher risk above 40 kg/m². Conclusion: Among patients with severe AH, metabolic dysfunction was not associated with increased mortality. Although a higher BMI was associated with slightly lower mortality in AH, this may reflect better nutritional status rather than a true protective effect.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a leading global cause of chronic liver disease and is strongly linked to cardiovascular disease (CVD), which remains the primary cause of death in affected individuals. This narrative review summarizes contemporary evidence on the MASLD–CVD interface and outlines a practical framework for cardiovascular risk assessment and comorbidity management. We discuss how liver disease severity can inform cardiovascular risk stratification beyond traditional scores, including cardiovascular imaging, biomarkers of myocyte injury and stress, inflammation markers, proteomics, lipidomics, and lipid profiles. Lifestyle interventions - dietary optimization, weight loss, and increased physical activity - remain foundational and improve hepatic steatosis and key cardiometabolic parameters. Pharmacotherapies with relevance to MASLD and cardiometabolic disease - including β-selective thyromimetics, incretin-based therapies, sodium–glucose cotransporter 2 inhibitors, and pioglitazone - offer benefits across weight, glycemic control, and metabolic risk, while statins remain the cornerstone of dyslipidemia management and CVD prevention in MASLD. For patients who do not achieve lipid targets or are statin-intolerant, non-statin therapies such as proprotein convertase subtilisin/kexin type 9 inhibitors and bempedoic acid provide additional risk-reduction options. Bariatric surgery can achieve durable weight loss and meaningful improvements in steatohepatitis and fibrosis in carefully selected patients. Finally, we emphasize the need for integrated, multidisciplinary care pathways that coordinate hepatology, cardiology, endocrinology, and primary care to identify high-risk individuals early, tailor intensity of preventive therapies, and address the concurrent liver and CVD burden.