Introduction
Metabolic dysfunction-associated steatotic liver disease (MASLD) in children is driven by complex interactions between metabolic and inflammatory pathways [1, 2]. However, the role of severe external stressors in modulating these pathways remains poorly defined.
Aims & Methods
To assess the impact of war-related anxiety on serum markers of liver injury (cytokeratin-18, CK18), fibrogenesis (TGF-β1), inflammatory cytokines, and metabolic parameters in obese children with MASLD.
90 children aged 6–17 years were enrolled. Liver steatosis was assessed using transient elastography (FibroScan® 502 Touch, Echosens, France) with controlled attenuation parameter (CAP). Obesity was confirmed by bioimpedance analysis (TANITA MC-780MA, Japan). Anxiety disorders were evaluated using the Screen for Child Anxiety-Related Emotional Disorders (SCARED) questionnaire. Based on anxiety status, participants were divided into two groups: 1 group - 52 obese children with MASLD and anxiety, 2 group - 28 obese children with MASLD without anxiety. The control group consisted of 10 normal-weight children without anxiety. Serum TGF-β1, CK18, IL-6, IL-10, TNF-α, leptin, and insulin were measured using ELISA; the HOMA-IR index was calculated using standard methods.
Results
Serum CK18 levels were significantly elevated in children with MASLD, showing a 2.4-fold increase in 1 group and a 1.9-fold increase in 2 group compared to controls (p < 0.05), indicating enhanced hepatocyte apoptosis. No significant intergroup differences in TGF-β1 levels were observed; however, TGF-β1 positively correlated with CAP (r = +0.259; p < 0.01) and CK18 (r = +0.291; p < 0.05), suggesting its involvement in early fibrogenic remodeling. Children with MASLD and anxiety demonstrated markedly elevated TNF-α levels—6.1-fold higher than controls and 2.6-fold higher than non-anxious MASLD patients. TNF-α correlated positively with HOMA-IR (r = +0.348; p = 0.04) and leptin (r = +0.435; p < 0.05), indicating its role in insulin resistance and adipokine imbalance. HOMA-IR showed a positive correlation with IL-6 (r = +0.420; p < 0.05), further supporting the link between inflammation and metabolic dysfunction.
Overall, children with MASLD and anxiety exhibited the highest levels of IL-6, TNF-α, TNF-α/IL-10 ratio, insulin, HOMA-IR, and leptin, consistent with a pronounced pro-inflammatory and metabolically dysregulated phenotype under war-related stress conditions.
Conclusion
War-related anxiety identifies a distinct high-risk MASLD phenotype characterized by coordinated activation of inflammatory, metabolic, and hepatocellular injury pathways. These data provide evidence that psycho-emotional stress may act as a disease-modifying factor, amplifying liver injury signals independently of baseline metabolic burden. Integration of stress-related factors into pediatric MASLD risk stratification may improve early identification of children at risk of progressive liver disease.
References
1. Lefere S, Koot BGP, Mann JP, Bufler P, De Bruyne R, Hudert CA. Update in clinical science: MASLD in children and adolescents. J Hepatol. 2026 Feb 21:S0168-8278(26)00081-4. doi: 10.1016/j.jhep.2026.02.016.
2. Goyal NP, Xanthakos S, Schwimmer JB. Metabolic dysfunction-associated steatotic liver disease in children. Gut. 2025 Mar 6;74(4):669-677. doi: 10.1136/gutjnl-2023-331090.