Toshifumi Yodoshi, Nicholas J. Ollberding, Meghan McNeill, Sanita Ley, Shelley Kirk, David E. Kleiner, Ana Catalina Arce‐Clachar, Kristin Bramlage, Thomas H. Inge, M A Helmrath, Kim M. Cecil, Andrew T. Trout, Deborah A. Elder, Marialena Mouzaki, Stavra A. Xanthakos
BACKGROUND: Adolescents with severe obesity and metabolic dysfunction-associated steatotic liver disease (MASLD) lack prospective comparative evidence to select between bariatric surgery and intensive lifestyle intervention. AIMS: To compare 52-week histological and cardiometabolic outcomes of vertical sleeve gastrectomy (VSG) versus comprehensive lifestyle intervention (CLI). METHODS: Single-centre, prospective, parallel-arm study of adolescents aged 12-19 with severe obesity and biopsy-confirmed MASLD with NAFLD Activity Score (NAS) ≥ 3. The primary endpoint was NAS ≥ 2-point decrease without fibrosis worsening; secondary endpoints included MASH resolution, fibrosis regression, MRI proton density fat fraction (MRI-PDFF) and elastography (MRE). Overlap-weighted adjusted analysis addressed baseline imbalance. Conservative unadjusted intention-to-treat analogue analyses treated missing Week 52 histology as nonresponse and missing continuous outcomes as no change. RESULTS: Forty-two adolescents enrolled (VSG = 17; CLI = 25) and 27 (64%) completed paired Week 52 histology. In the adjusted analysis, VSG was associated with a higher probability of NAS improvement (risk difference [RD] 0.68, 95% CI 0.45-0.91), fibrosis improvement (RD 0.36, 95% CI 0.12-0.59) and complete MASLD resolution (RD 0.49, 95% CI 0.26-0.72) when compared to CLI. VSG produced greater reductions in percent weight (-19.6%, 95% CI -30.0 to -9.1), percentage of the 95th percentile BMI (-27.6%, 95% CI -42.6 to -12.7), ALT (-54.0 U/L, 95% CI -80.8 to -27.1) and MRI-PDFF (-8.0%, 95% CI -13.0 to -2.9). Findings were directionally consistent in conservative unadjusted intention-to-treat and paired-biopsy completer analyses. CONCLUSION: In this prospective cohort of adolescents with severe obesity and biopsy-confirmed MASLD, VSG achieved greater 52-week histological improvement, including steatosis and fibrosis, than CLI. TRIAL REGISTRATION: ClinicalTrials.gov identifier: (NCT02412540).