Association and diagnostic value of serum cardiometabolic biomarkers for metabolic-associated steatotic liver disease in children with obesity

Efficient non-invasive biomarkers for identifying children with obesity who have metabolic dysfunction-associated steatotic liver disease (MASLD) are still lacking. This study aimed to investigate the association of five novel cardiometabolic biomarkers with pediatric MASLD and evaluate their additional diagnostic value beyond established risk factors. We conducted a cross-sectional study of children with obesity at the Department of Pediatrics, Tongji Hospital, from January 2023 to September 2024. Anthropometric assessments were conducted, with parallel quantification of serum Cathepsin D (CTSD), leptin, adiponectin, insulin-like growth factor-1 (IGF-1), and growth differentiation factor-15 (GDF15) using enzyme-linked immunosorbent assay (ELISA). Hepatic steatosis was assessed using abdominal ultrasound. Odds ratios (ORs) and 95% confidence intervals (CI) were calculated after adjustment for established risk factors (age, sex, body mass index [BMI] z-score, and waist-to-height ratio [WHtR]). The additional diagnostic value of the biomarkers was assessed using the area under the curve (AUC) and continuous net reclassification improvement (NRI), and integrated discrimination improvement (IDI). This study included 84 children (53 boys, 31 girls) aged 6–14 years, of whom 43 (51.2%) were diagnosed with MASLD. Logarithmically transformed CTSD exhibited a positive, linear association with MASLD (Tertile [T]3 vs. T1: OR = 12.63, 95% CI: 2.57, 84.62), and GDF15 also showed a positive association (T3 vs. T1: OR = 4.86, 95% CI: 1.14, 23.57). Conversely, leptin showed an inverse U-shaped relationship with MASLD risk after full adjustment (T2 vs. T1: OR = 6.70, 95% CI: 1.46, 36.77; p for nonlinearity = 0.004). No significant independent associations were found for adiponectin or IGF-1 after full adjustment. While the individual addition of these novel biomarkers to the base model led to marginal, non-significant increases in the optimism-corrected AUC (e.g., ΔAUC = 0.047, p = 0.096 for CTSD), the integration of CTSD yielded the most prominent improvement in reclassification and risk discrimination, significantly enhancing both continuous NRI (1.147, 95% CI: 0.152, 1.657; p = 0.032) and IDI (0.142, 95% CI: 0.014, 0.339; p = 0.008). Significant reclassification improvements were also observed for leptin and IGF-1 (all p < 0.05). Serum CTSD, leptin, and GDF15 are independently associated with MASLD risk in children with obesity. Incorporating these biomarkers (especially CTSD and leptin) into conventional risk prediction models shows promising potential for enhancing non-invasive diagnostic performance and clinical risk stratification. However, given the limited sample size, these findings should be interpreted with caution and warrant further validation in larger, multicenter cohorts.‌‌.