A branched-chain amino acid-based metabolic score can predict liver fat in children and adolescents with severe obesity

Background Eighty percent of adolescents with severe obesity suffer from non-alcoholic fatty liver disease (NAFLD). Non-invasive prediction models have been tested in adults, however, they performed poorly in paediatric populations. Objective This study aimed to investigate novel biomarkers for NAFLD and to develop a score that predicts liver fat in youth with severe obesity. Methods From a population with a BMI >97th percentile aged 9-19 years (n= 68), clinically thoroughly characterized including MRI-derived proton density fat fraction (MRI-PDFF), amino acids and acylcarnitines were measured by HPLC-MS. Results In children with NAFLD, higher levels of plasma branched-chain amino acids (BCAA) were determined. BCAAs correlated with MRI-PDFF (R= 0.46,p < .01). We identified a linear regression model adjusted for age, sex and pubertal stage consisting of BCAAs, ALT, GGT, ferritin and insulin that predicted MRI-PDFF (R= 0.75,p < .01). ROC analysis of this model revealed AUCs of 0.85, 0.85 and 0.92 for the detection of any, moderate and severe steatosis, respectively, thus markedly outperforming previously published scores. Conclusion BCAAs could be an important link between obesity and other metabolic pathways. A BCAA-based metabolic score can predict steatosis grade in high-risk children and adolescents and may provide a feasible alternative to sophisticated methods like MRI or biopsy in the future.