The Association between Hepatic Fibrosis Indicators and Subclinical Carotid Atherosclerosis in the Population with Metabolic Dysfunction-associated Steatotic Liver Disease: A Dual-Center Cross-Sectional Study

Objective Metabolic Dysfunction-associated Steatotic Liver Disease (MASLD) and subclinical carotid atherosclerosis (SCA) are both closely related to systemic inflammation and metabolic disorders. Liver fibrosis can effectively reflect the inflammatory and metabolic disorder status of MASLD patients. However, the relationship between liver fibrosis and SCA remains unclear. This study aims to explore the relationship between biomarkers related to inflammation, metabolism, and liver fibrosis and the prevalence of SCA in MASLD patients, and to identify potential indicators for SCA epidemiological studies in this population. Methods This study included 14,567 MASLD patients as the study cohort, all of whom underwent physical examinations at Northern Jiangsu People's Hospital. Additionally, 4,731 MASLD patients from the First Affiliated Hospital of Soochow University were included as the validation cohort. The patients were divided into SCA and non-SCA groups.The study employed Least Absolute Shrinkage and Selection Operator (LASSO) regression and Boruta algorithm for variable selection. It also utilized multivariate logistic regression analysis, Restricted Cubic Spline(RCS) analysis, subgroup analysis, Receiver Operating Characteristic(ROC) curve, and mediation analysis to explore the associations between these indicators and the risk of SCA in MASLD patients. Results LASSO regression, Boruta algorithm, and multivariate logistic regression analysis in both the study cohort and validation cohort all indicated that elevated levels of NAFLD Fibrosis Score (NFS) and Fibrosis-4 (FIB-4) are independent risk factors for SCA in patients with MASLD (P for trend < 0.001).RCS analysis showed significant positive non-linear associations between NFS/FIB-4 and SCA ( P for non-linear < 0.001). Subgroup analysis revealed significant interaction effects between age and the associations of NFS and FIB-4 with SCA ( P for interaction < 0.05). The area under the ROC curve (AUC) in both the study cohort and validation cohort further confirmed that NFS and FIB-4 have excellent predictive value. Mediation analysis showed that NFS and FIB-4 have significant indirect effects on the prevalence of SCA through Red Cell Distribution Width to Albumin Ratio (RAR), with the mediation effect accounting for 28.6–44.6% of the total effect( P  < 0.05). Conclusion In patients with MASLD, NFS and FIB-4 exhibit an inverse L-shaped positive correlation with the prevalence of SCA, particularly in those aged < 50 years, and may serve as potential epidemiological predictive indicators. The RAR index may act as a mediator in the associations between NFS/FIB-4 and SCA. Interventions targeting the RAR index may help to mitigate the impact of NFS and FIB-4 on SCA.