Across 92 adults with obesity and MASLD followed for 72 weeks, sleeve gastrectomy produced the largest absolute reductions in hepatic steatosis (CAP: −83.7 dB/m) and liver stiffness (LSM: −4.9 kPa), while semaglutide (1.0 mg/week) delivered meaningful intermediate improvements (CAP: −46.0 dB/m; LSM: −2.8 kPa) versus lifestyle alone (CAP: −17.9 dB/m; LSM: −0.8 kPa). Critically, after adjusting for the dramatic weight differential (−31.6% surgery vs. −10.7% semaglutide), relative LSM reduction did not differ significantly between the two active treatment arms (p = 0.428). Surgery's fibrosis benefit was weight-dependent, while semaglutide's was not.
The weight-independent liver benefit of semaglutide is the most provocative signal here. GLP-1 receptor agonists likely act directly on hepatic stellate cells and through suppression of inflammatory cascades — mechanisms now gaining experimental support — beyond simply offloading lipotoxic stress through caloric deficit. The modest FIB-4 rise post-surgery (+0.29) likely reflects transient hepatic stress rather than true fibrosis progression, but warrants monitoring. Limitations are real: observational design, single center, 92 patients, non-invasive markers substituting for biopsy, and non-randomized group allocation introduce confounding. Still, this is a clinically meaningful hypothesis-generator: for patients unsuitable for surgery, semaglutide may deliver disproportionate hepatic protection relative to weight lost — an incremental but directionally important finding for MASLD management.