ORCID
0000-0002-9236-9563 (Rehan), 0000-0003-3795-6084 (Benedict), 0000-0003-3086-8014 (Qayyum)
Document Type
Article
Publication Date
2026
DOI
10.1002/jgh3.70417
Publication Title
JGH Open
Volume
10
Issue
5
Pages
e70417
Abstract
Background and Aims
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.
Methods
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.
Results
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 (beta = -0.54 kPa; 95% CI: -0.86 to -0.22; p = 0.002) and higher CAP (beta = 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 (beta_indirect = 0.04; 95% CI: 0.02-0.07; p = 0.001) and a stronger negative direct association with fibrosis (beta_direct = -0.59 kPa; 95% CI: -0.90 to -0.27; p < 0.001). The total effect of selenium on fibrosis remained protective (beta_total = -0.54; 95% CI: -0.85 to -0.23; p = 0.001).
Conclusions
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.
Rights
© 2026 The Authors.
This is an open access article under the terms of the Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
Data Availability
Article states: "The data that support the findings of this study are available in NHANES Data at https://wwwn.cdc.gov/nchs/nhanes/default.aspx. These data were derived from the following resources available in the public domain: 2021–2023 data cycle: https://wwwn.cdc.gov/nchs/nhanes/continuousnhanes/default.aspx?Cycle=2021-2023 and 2017–20 220 data cycle: https://wwwn.cdc.gov/nchs/nhanes/continuousnhanes/default.aspx?Cycle=2017-2020."
Original Publication Citation
Rehan, N., Benedict, J., & Qayyum, R. (2026). Selenium and liver steatosis and fibrosis: Opposing direct and steatosis-mediated associations in a large cohort. JGH Open, 10(5), Article e70417. https://doi.org/10.1002/jgh3.70417
Repository Citation
Rehan, N., Benedict, J., & Qayyum, R. (2026). Selenium and liver steatosis and fibrosis: Opposing direct and steatosis-mediated associations in a large cohort. JGH Open, 10(5), Article e70417. https://doi.org/10.1002/jgh3.70417
Supporting Information
Included in
Diseases Commons, Epidemiology Commons, Hematology Commons, Physiology Commons