Hepatic Steatosis and Stiffness in Adolescent Obesity are Linked to Androgenemia, Insulin Sensitivity, and Inflammation.

Abstract

Introduction: Metabolic dysfunction-associated steatotic liver disease (MASLD) is driven by obesity and is common among girls with polycystic ovary syndrome (PCOS). Higher testosterone concentrations are associated with more severe histological MASLD features in girls, but less severe in boys. This proof-of-concept study tested the hypotheses that MRI-based hepatic fat and stiffness are higher among girls with PCOS versus girls without PCOS but not boys and are associated with testosterone concentration (differing by sex), insulin sensitivity, and inflammation.

Methods: This proof-of-concept cross-sectional study at an academic pediatric center included pubertal girls (n=25; 10 without PCOS, 15 with PCOS) and boys (n=10) with obesity, ages 12-18 years. Outcomes were (primary) MRI hepatic fat fraction (HFF %) and stiffness and (secondary) insulin sensitivity index (ISI), 2-hour OGTT and inflammatory markers.

Results: HFF was higher in girls with PCOS versus those without but not different from boys. Stiffness did not differ by group. HFF and stiffness were both directly associated with OGTT 2-hour glucose and inversely with ISI. Stiffness was directly associated with testosterone (total, free) in girls without PCOS and with interleukin (IL)-6 and IL-18 in the full cohort.

Conclusions: HFF was higher in girls with PCOS versus those without, but not different from boys. While stiffness did not differ by group, its association with testosterone concentrations in girls without PCOS may be an additional risk biomarker for MASLD in addition to inflammation and insulin resistance. Future larger, longitudinal studies should determine if addressing these alterations, separately or collectively, in youth with obesity could improve hepatic outcomes.