AccScience Publishing / EJMO / Online First / DOI: 10.36922/EJMO025330348
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ORIGINAL RESEARCH ARTICLE

Mediating role of systemic inflammation in heavy metal-induced metabolic dysfunction-associated steatotic liver disease: Insights from NHANES 2017 to 2020

Hui Liu1* ,  Somchai Bovornkitti1 ,  Sarisak Soontornchai1* ,  Xiaoqiang Qiu2 ,  Wenjie Shi3
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1 Public Health Program, Graduate School, Suan Sunandha Rajabhat University, Bangkok, Thailand
2 Department of Epidemiology and Health Statistics, School of Public Health, Guangxi Medical University, Nanning, Guangxi, China
3 General, Visceral, Vascular and Transplantation Surgery Clinic, Faculty of Medicine, University Hospital Magdeburg, OttovonGuericke University, Magdeburg, Saxony-Anhalt, Germany
EJMO, 025330348 https://doi.org/10.36922/EJMO025330348
Received: 13 August 2025 | Revised: 23 October 2025 | Accepted: 27 October 2025 | Published online: 18 November 2025
© 2025 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution -Noncommercial 4.0 International License (CC-by the license) ( https://creativecommons.org/licenses/by-nc/4.0/ )
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Abstract

Introduction: Inflammatory responses play an essential role in metabolic dysfunction-associated steatotic liver disease (MASLD).

Objective: This study investigates the mediating role of systemic inflammation in the pathophysiology of heavy metal-induced MASLD.

Methods: We employed data from the National Health and Nutrition Examination Survey from 2017 to 2020 to examine the relationship between 16 heavy metals and MASLD. Vibration-controlled transient elastography was used to evaluate hepatic steatosis and determine the Systemic Immune Inflammation Index (SII) and Systemic Inflammatory Response Index (SIRI). Data analysis was conducted using linear or logistic regressions, weighted quantile sum regression (WQS), restricted cubic spline, and mediation effect models.

Results: The study involved 2,934 patients, with an average age of 44.86 ± 20.58 years, of whom 50.23% were female. Urinary cadmium (Cd), lead (Pb), arsenic, mercury, and tungsten were all positively associated with MASLD risk. The WQS model showed a strong positive correlation between a high amount of urea-metal mixtures and higher SII, SIRI, and MASLD (p<0.01). Mediation analysis found that systemic inflammation mediated the effects of single metals (Cd, cesium [Cs], and Pb) on MASLD risk. The mediation proportions of urinary metal mixtures on MASLD risk, mediated by SII and SIRI, were 57.84% and 65.21%, respectively.

Conclusion: Based on the findings, systemic inflammation partially mediates the association between metals such as Cd, Cs, and Pb—and their combined effects—and metabolic dysfunction and steatosis. Hence, reducing systemic inflammation could help prevent and treat metal-related steatohepatitis caused by environmental exposure.

Keywords
Metabolically-dysfunction-associated steatotic liver disease
Heavy metals
Mediation analysis
Systemic inflammation
National Health and Nutrition Examination Survey
Funding
None.
Conflict of interest
The authors declare that they have no competing interests.
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Eurasian Journal of Medicine and Oncology, Electronic ISSN: 2587-196X Print ISSN: 2587-2400, Published by AccScience Publishing
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