Selenium and Liver Steatosis and Fibrosis: Opposing Direct and Steatosis-Mediated Associations in a Large Cohort

Epidemiologic studies have reported conflicting associations between selenium exposure and liver disease. Whether selenium exerts opposing direct and steatosis-mediated effects on liver fibrosis is unknown. To evaluate the associations of blood selenium with elastography-defined hepatic steatosis and fibrosis and to determine whether hepatic steatosis mediates the relationship between selenium and fibrosis.

We conducted a cross-sectional analysis of adults aged ≥ 18 years in NHANES 2017-2023. Hepatic steatosis was assessed using the controlled attenuation parameter (CAP) and fibrosis using liver stiffness measurement (LSM). Blood selenium was categorized into quartiles. Survey-weighted multivariable linear regression and structural equation modeling were used, adjusting for demographic, behavioral, and metabolic covariates.

Among 13 241 adults (52.4% women; mean age 51.3 years), higher selenium was associated with lower liver stiffness and greater hepatic steatosis. In fully adjusted models, participants in the highest selenium quartile had lower LSM compared with the lowest quartile (β = -0.54 kPa; 95% CI: -0.86 to -0.22; p = 0.002) and higher CAP (β = 9.17 dB/m; 95% CI: 5.87-12.47; p < 0.001). Mediation analysis demonstrated a positive indirect effect of selenium on fibrosis through steatosis (β_indirect = 0.04; 95% CI: 0.02-0.07; p = 0.001) and a stronger negative direct association with fibrosis (β_direct = -0.59 kPa; 95% CI: -0.90 to -0.27; p < 0.001). The total effect of selenium on fibrosis remained protective (β_total = -0.54; 95% CI: -0.85 to -0.23; p = 0.001).

Higher blood selenium is associated with increased hepatic steatosis yet lower liver stiffness, reflecting opposing steatosis-mediated and direct antifibrotic pathways. Longitudinal studies are needed to clarify causal mechanisms and define optimal selenium exposure in metabolic liver disease.