Metabolic dysfunction‐associated fatty liver disease and atherosclerotic cardiovascular disease risk: Dual aetiology or metabolic dysfunction?

We read with interest the paper by Pan et al. demonstrating that metabolic dysfunction-associated fatty liver disease (MAFLD) predicted the atherosclerotic cardiovascular disease (ASCVD) risk better than metabolic dysfunction-associated steatotic liver disease (MASLD); this higher predictive ability was attributed to metabolic dysfunction rather than alcohol consumption.1 The authors stated MAFLD-only patients are more likely to have a worse metabolic profile than MASLD-only patients. However, if considering only metabolic risk factors, these patients with worse metabolic profile should also meet the looser diagnostic criteria for MASLD.2, 3 Their exclusion from the overlapping group may be due to the presence of other aetiologies of liver disease, such as excess alcohol consumption or viral hepatitis, but does not imply inferiority of their metabolic profile. In the study by Pan et al. "MetALD" and "MASLD with other combination causes" were defined, but the ASCVD risk associated with these classifications was not computed. To further elucidate the role of overlapping aetiology and metabolic disorders in the high ASCVD risk related to fatty liver, we conducted a cross-sectional study with a similar design among a 10 365-person physical examination population aged 18–85 years during 2018–2023 in Dalian, China, using the Chinese 10-year ASCVD risk prediction model.4 A total of 5392 and 5658 individuals met the diagnostic criteria for MASLD and MAFLD, respectively, with 4987 in the overlapping group. Among the MAFLD-only patients, 296 had a history of heavy alcohol consumption (MetALD group), 369 had concomitant viral hepatitis (MASLD-Viral group) and 6 had cryptogenic steatotic liver disease (SLD) according to the SLD nomenclature system.2 Figure 1 illustrates the ASCVD risk distribution across different fatty liver categories. Multiple logistic regression analysis adjusted for age, sex, liver enzymes and alcohol intake showed that MAFLD (odds ratio [OR] 2.46, 95% confidence interval [CI] 1.82–3.48) had a slightly higher independent association with high ASCVD risk than MASLD (OR 2.35, 95% CI 1.73–3.34) compared to the respective ascendence of condition. MetALD and MASLD-Viral were very strongly associated with a high risk of ASCVD (OR 4.96, 95% CI 2.67–9.87; OR 4.73, 95% CI 2.34–9.13, respectively). After excluding patients with overlapping aetiologies, the ASCVD risk did not differ significantly between MAFLD and MASLD (p > .05). Our findings suggest that the stronger association between MAFLD and high ASCVD risk may be due to inclusion of patients with dual aetiologies rather than metabolic dysfunction. We believe this determines the strategies to be prioritized when treating these patients. Tianyi Ma wrote the manuscript draft. Huawei Yuan and Zhanfang Guo edited and revised the manuscript. No acknowledgments. No external funding received. The authors do not have any disclosures to report. This study was approved by the Ethics Committee of Central Hospital of Dalian University of Technology (Approval Number: 2023-042-09). The datasets used and/or analysed during the current study are available from the corresponding author ([email protected]) on reasonable request.