Key result
Male MAFLD patients with high BMI and uric acid levels exhibited worse cardiac remodelling, including increased left atrial diameter (β 2.07), while a female phenotype with high FIB-4 levels correlated with preserved cardiac function.
Why the study?
To identify novel, data-driven phenotypic clusters of MAFLD and investigate their associations with cardiac remodelling.
Are specific phenotypic clusters of metabolic dysfunction-associated fatty liver disease (MAFLD) associated with differences in cardiac remodelling?
Cross-Sectional (n=3,233)
No
Are specific phenotypic clusters of metabolic dysfunction-associated fatty liver disease (MAFLD) associated with differences in cardiac remodelling?
MAFLD exhibits sex-specific phenotypic clusters that are differentially associated with cardiac remodelling, with high BMI and uric acid male phenotypes showing worse remodelling and high FIB-4 female phenotypes showing preserved function.
OBJECTIVES: To identify novel, data-driven phenotypic clusters of metabolic dysfunction-associated fatty liver disease (MAFLD) and investigate their associations with cardiac remodelling. DESIGN: Cross-sectional study. SETTING: Secondary care; a single-centre study in China. PARTICIPANTS: A total of 3233 participants diagnosed with MAFLD were included in the study. The diagnosis was conducted in accordance with the established criteria for MAFLD. The exclusion criteria encompassed a history of significant cardiovascular or hepatic diseases, as well as excessive alcohol consumption. PRIMARY OUTCOME MEASURES: Echocardiographic parameters of cardiac structure and function. RESULTS: Four distinct clusters were identified. Cluster 1 (n=1381) comprised men with a normal metabolic state and low Fibrosis-4 Index (FIB-4) levels. Cluster 2 (n=453) included men with the highest body mass index (BMI) and uric acid levels. Cluster 3 (n=474) consisted of men with the most severe glucose and lipid metabolic disturbances. Cluster 4 (n=925) comprised women with the highest FIB-4 levels. Compared with Cluster 1, participants in Clusters 2 and 3 exhibited worse cardiac structure and function, including enlargement of the left atrium (LA), right atrium, left ventricular internal end-diastolic dimension, interventricular septum (IVS), left ventricular posterior wall (LVPW) thickness, right ventricular and reduced left ventricular ejection fraction. Conversely, participants in Cluster 4 had better cardiac structure and function compared with those in Cluster 1. After adjusting for confounders, Cluster 2 showed positive associations with the LA, IVS, LVPW, right atrium and right ventricular (all p<0.001), while Cluster 4 showed negative associations. CONCLUSIONS: The heterogeneity of MAFLD reveals sex-specific patterns of cardiac remodelling: male phenotypes with high BMI and uric acid levels are associated with worse remodelling, whereas a female phenotype characterised by high FIB-4 levels correlates with preserved cardiac function.
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Wang et al. (2025) conducted a cross-sectional in Metabolic (dysfunction)-associated fatty liver disease (MAFLD) (n=3,233). MAFLD phenotypic clusters (Cluster 2: high BMI and uric acid) vs. Cluster 1 (normal metabolic state and low FIB-4) was evaluated on Left atrium diameter (mm) (β 2.07, 95% CI 1.61-2.52, p=<0.001). Male MAFLD patients with high BMI and uric acid levels exhibited worse cardiac remodelling, including increased left atrial diameter (β 2.07), while a female phenotype with high FIB-4 levels correlated with preserved cardiac function.
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