Phenotyping of Adolescents With Metabolic Dysfunction-Associated Steatotic Liver Disease

Objectives: Metabolic dysfunction-associated steatotic liver disease (MASLD) is well characterized in adults, but much less is known about the disease severity in the pediatric population. Thus, we sought to characterize MASLD and its associated comorbidities in an adolescent cohort. Methods: In this cross-sectional study, we phenotyped 4 groups of adolescents, ages 11-20y, with varying levels of fitness, body composition, and liver health. Groups comprised 1) normal weight with adequate fitness based on published thresholds for metabolic health (NW-Fit, n=13); 2) normal weight with low fitness (NW-Low, n=25); 3) obese with low fitness without MASLD (Ob, n=21); and 4) obese with low fitness and biopsy-confirmed MASLD (MASLD, n=44). Results: Relative to NW-Fit, NW-Low, OB, and MASLD had higher body fat (21.8±7.0%, 29.5±7.6%, 44.2±7.0%, 46.5±5.9%, respectively; p< 0.001 for each) and trunk fat (19.3±6.6%, 28.1±7.8%, 46.1±7.2%, 49.9±5.9%; p< 0.001 for each). Trunk fat was higher in MASLD than OB (p=0.004). Total lean mass (LBM) was similar in NW-Fit, OB, and MASLD, but lower in NW-Low than NW-Fit (36.5±9.0 kg vs. 42.5±11.4 kg, p=0.035). Daily step totals, measured by accelerometry, did not differ amongst the groups. Compared to NW-Fit, VO2peak (adjusted for LBM), was lower in NW-Low, OB, and MASLD (2491±309, 1942±249, 1960±331, 1768±369; p< 0.001 for each comparison). Moreover, VO2peak was lower in MASLD compared to OB (p=0.011). While mean HbA1c was within the normal range for all groups, insulin resistance (HOMA1-IR) differed among all groups (all p< 0.01), increasing from group 1 to 4. HOMA1-IR was indicative of insulin resistance in both OB and MASLD. Energy expenditure (adjusted for LBM) was similar between NW-Fit (1509±150 kcal/d) and NW-Low (1581±215 kcal/d), but higher in OB (1677±247 kcal/d, p=0.003) and MASLD (1760±214, p< 0.001). Within the MASLD group, liver biopsy confirmed that 2 had simple steatosis, 28 had MASH (including 10 with fibrosis), and 1 had cirrhosis. Conclusions: Our data suggest adolescents with MASLD have a metabolic burden beyond that which is imparted by obesity alone. Especially striking is the severity of liver disease in such a young cohort. Funding Sources: Funding agencies include the National Institutes of Health, the Presbyterian Health Foundation, the Children's Health Foundation, and the Harold Hamm Diabetes Center.