Meal Replacement Therapy for Metabolic Dysfunction-Associated Steatotic Liver Disease in Adolescents with Severe Obesity.

BACKGROUND

This clinical trial evaluated hepatic fat content and weight loss in adolescents with severe obesity and metabolic dysfunction-associated steatotic liver disease (MASLD) following short-term meal replacement therapy (MRT).

METHODS

Adolescents aged 12-17 years with severe obesity (BMI ≥1.2 × 95th percentile or ≥35 kg/m2) and magnetic resonance imaging-confirmed MASLD (hepatic fat fraction [HFF] ≥5%) completed a 4- to 8-week MRT program (∼500 kcal/day deficit) targeting ≥5% BMI reduction. Participants underwent 1H-magnetic resonance spectroscopy at baseline and at follow-up, along with 2-hour mixed-meal tolerance testing.

RESULTS

Seventeen adolescents [baseline mean (standard deviation or SD) BMI = 39.9 (4.1) kg/m2; age = 16.0 (1.6) years; 65% male; HFF = 15.6 (5.1)%] demonstrated a mean absolute decrease in BMI of 5.6% [-2.23 kg/m2; 95% confidence interval (CI): -2.45, -2.02; p < 0.001] and a 37.3% relative reduction (95% CI: 26.4%, 48.1%; p < 0.001) in HFF. Despite HFF reduction, 13 out of 17 had MASLD at study conclusion. Decrease in HFF corresponded to significant reductions in triglycerides [difference (95% CI): -5.8 mg/dL (-9.4, -2.1); p = 0.012], glucose area under the curve (AUC) [-2.2 mg/dL (-3.2, -1.3); p = 0.021], and leptin AUC [-40.5 pg/mL (-57.1, -23.9); p = 0.009]. No significant difference in alanine aminotransferase was observed.

CONCLUSIONS

Short-term MRT was associated with reductions in liver fat and improvements in metabolic biomarkers among adolescents with MASLD. Large-scale trials are needed to evaluate the implementation of MRT as part of a multimodal treatment strategy in this population. [Clinical Trial Registration: Enhancing Weight Loss Maintenance with GLP-1 RA (BYDUREON™) in Adolescents With Severe Obesity, NCT02496611, https://clinicaltrials.gov/study/NCT02496611].