TABLE 1

Landmark studies of therapeutic options for MASH fibrosis regression

Intervention (year)Study typePopulation, criteriaFibrosis regressionMean total body weight loss
Semaglutide (2025)15Phase 3 randomized controlled trial800 adults MASH, fibrosis stage 2 or 336.8% improved ≥ 1 stage (vs 22.4% placebo)10.5% at 72 weeks
Tirzepatide (2024)19Phase 2 randomized controlled trial190 adults MASH, fibrosis stage 2 or 344% in 5-mg group improved ≥ 1 stage (vs 30% placebo)11%–16% at 52 weeks
Resmetirom (2021,22 202423)Phase 3 randomized controlled trial966 adults MASH, fibrosis stage 2 or 324%–26% improved ≥ 1 stage (vs 14% placebo)No clinically meaningful weight loss observed
Roux-en-Y gastric bypass (2023)31Randomized controlled trial288 adults MASH, obesity, noncirrhotic37% improved ≥ 1 fibrosis stage; 56% had MASH resolution (vs 16% lifestyle modification)32% at 1 year
Laparoscopic sleeve gastrectomy (2020)32Prospective cohort94 adults MASH, obesity42% had MASH resolution with significant fibrosis improvement25%–30% at 1 year
Endoscopic sleeve gastroplasty (2021)38Prospective cohort118 adults Obesity, MASH20% improved from fibrosis stage 3 or 4 or indeterminate to stage 0–216% at 2 years
Intragastric balloon (2021)39Prospective cohort21 adults Radiologically proven steatosis and fibrosis, obesity50% improved ≥ 1 fibrosis stage11.7% at 6 months
Duodenal-jejunal bypass liner (2022)41Randomized controlled trial32 adults Obesity, MASHMean FibroScan-AST score reduced by 0.21 (P < .001, surrogate for fibrosis or MASH)11% at 48 weeks
Transoral outlet reduction (2023)43Retrospective cohort40 adults MASLD or fibrosis after Roux-en-Y gastric bypass and weight regainFibrosis-4 index score decreased from 1.56 ± 0.46 to 1.24 ± 0.58 (P = .05)8.5% at 1 year, 8.8% at 5 years

  • MASH = metabolic dysfunction–associated steatohepatitis, MASLD = metabolic dysfunction–associated steatotic liver disease