A comparison of plasma Tsukushi in adolescents with and without metabolic dysfunction-associated steatotic liver disease.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common liver disease in children and adolescents. Assessment of circulating biomarkers is needed to understand the underlying pathology, disease severity, and treatment options. The secreted hepatokine Tsukushi (TSK) is involved in lipid and carbohydrate metabolism. TSK is increased in adults with MASLD but has yet to be reported in adolescents. We hypothesized that plasma TSK is increased in adolescents with MASLD compared to peers without MASLD classified as obese (Ob) or normal weight (NW). We tested adolescents 10-20 years old with obesity and biopsy-confirmed MASLD (17F, 46 M), and controls without MASLD with either Ob (16F, 16 M) or NW (15F, 20 M). Fasting plasma TSK concentration was 27% higher (p < 0.05) in the MASLD group (median [interquartile range]: 188 [120, 418] ng/mL) than the NW group (148 [80, 241]), while the Ob group was intermediate (165 [84, 466]) and not different from the other two groups. TSK did not differ across histological grades of steatosis or fibrosis. Although TSK was increased in the MASLD group compared to NW controls, the lack of difference in TSK between the Ob and MASLD groups limits its value as a potential biomarker for MASLD.