Review

Reversing fibrosis in metabolic dysfunction–associated steatohepatitis—beyond telling patients to lose weight

Leandro Sierra, MD, Lily Liu, MD, Akash Khurana, MD, Roma Patel, MD, Arjun Chatterjee, MD, Stephen Firkins, MD and Roberto Simons-Linares, MD
Cleveland Clinic Journal of Medicine May 2026, 93 (5) 279-286; DOI: https://doi.org/10.3949/ccjm.93a.25082

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  • 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

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