The risk of cardiovascular events in metabolic dysfunction–associated steatotic liver disease according to fibrosis stage and diabetes status: A cohort study

Background: Atherosclerotic cardiovascular disease (ASCVD) is a major cause of morbidity and mortality in metabolic dysfunction–associated steatotic liver disease (MASLD). We investigated whether fibrosis severity assessed using guideline-recommended noninvasive liver fibrosis pathways was associated with incident ASCVD across different glycemic states. Methods: This retrospective cohort study included subjects with MASLD. Fibrosis severity was classified using the Korean Association for the Study of the Liver/European Association for the Study of the Liver (KASL/EASL) and American Gastroenterological Association (AGA) sequential pathways, based on fibrosis-4 followed by vibration-controlled transient elastography. Incident ASCVD was analyzed using Fine-Gray subdistribution hazard models, with death treated as a competing event. Results: Among 6519 subjects with MASLD who had both fibrosis-4 and vibration-controlled transient elastography data, 3243 had normoglycemia, 2369 had prediabetes, and 907 had diabetes; 3221 were included in the survival analysis cohort. Baseline 10-year ASCVD risk increased with worsening glycemic status. In the longitudinal analysis, the association between fibrosis severity and incident ASCVD differed by glycemic status. In patients with prediabetes, the highest fibrosis tier was associated with higher incident ASCVD risk (adjusted subdistribution hazard ratio: 2.62, p =0.024). This association was also more apparent in younger individuals. In patients with diabetes, 5-year cumulative ASCVD incidence was high across fibrosis tiers (15.2%–18.5%), without a significant increase by fibrosis severity. Conclusions: Higher liver fibrosis severity assessed by noninvasive tests was associated with incident ASCVD outcomes in selected MASLD subgroups, particularly patients with prediabetes and younger individuals. Fibrosis assessment may help identify patients who warrant closer cardiometabolic evaluation when interpreted alongside established ASCVD risk prediction tools.