A Comparison of Novel Serum Markers of Liver Health in Adolescents With Metabolic Dysfunction-Associated Steatotic Liver Disease

Abstract

Several non-invasive biomarkers for paediatric metabolic dysfunction-associated steatotic liver disease (MASLD) have been reported, but no prior studies directly compared multiple protein or microRNA (miRNA) markers of liver health in adolescents with and without MASLD and determined which serum markers are associated with liver histopathological features. We measured 6 serum protein and 4 miRNA candidates in 3 groups of participants: 23 with obesity and biopsy-proven MASLD, 24 controls with obesity (Ob) and 24 controls with normal weight (NW). The MASLD group had higher median values for cytokeratin 18 (CK-18, 8.5 and 5.6-fold higher than NW and Ob, respectively), CK-18 fragments (2.6- and 2.6-fold), collagen IV (0.9- and 0.6-fold), miR-122 (16.9- and 10.7-fold) and miR-192 (9.7- and 12.0-fold). YKL-40 and N-terminal propeptide of type III procollagen were only higher in the MASLD group compared to the NW group. Serum AST, CK-18, CK-18 fragments, miR-122 and miR-192 were positively correlated with liver fibrosis stage. Area under the receiver operating curve for identifying MASLD for CK-18 (0.962), miR-192 (0.945) and miR-122 (0.944) was higher than ALT (0.935). miR-122 in serum and liver was inversely correlated in MASLD patients but neither was associated with putative mRNA targets AGPAT1 and DGAT1. These results show that CK-18, miR-122 and miR-192 are marginally better predictors of MASLD than ALT and correlated with fibrosis in this cohort, supporting further work to confirm these findings.