Efficacy of pharmacotherapies in improving liver fibrosis among patients with MASLD and fibrosis stages of F1-F3: systematic review and network meta-analysis.
This systematic review and network meta-analysis (NMA) evaluated the comparative efficacy of pharmacological interventions—at specific dosages—for improving liver fibrosis in adults with metabolism-associated steatotic liver disease (MASLD) and fibrosis stages F1–F3. Researchers searched three databases through July 2025, identifying 13 randomized controlled trials encompassing 3,871 patients and 12 distinct drug regimens. Using both direct comparisons and network meta-analysis, the study found that six interventions—resmetirom (two doses), survodutide, and tirzepatide (three doses)—were significantly more effective than placebo at achieving NASH resolution without worsening fibrosis. Surface Under the Cumulative Ranking (SUCRA) analysis ranked survodutide 6 mg/week highest, followed by tirzepatide 15 mg/week; emricasan 10 mg/day ranked lowest. The authors concluded that survodutide, efruxiferimin, resmetirom, and denifanstat showed the most promise for this population, while emricasan was not supported. Limitations include the moderate number of included trials, potential heterogeneity across study populations and outcome definitions, and the indirect nature of many NMA comparisons, which may limit the precision of the relative effect estimates.
Why this grade: Although based on RCTs in humans, the conclusions rely partly on indirect network comparisons across only 13 trials, which limits the certainty of effect estimates for individual drug-dose combinations.
Background Metabolism-associated steatotic liver disease (MASLD) is one of the most prevalent chronic liver diseases worldwide. In recent years, although a network meta-analysis evaluated the efficacy of different drugs for patients with MASLD, it did not provide the specific dosage of the drugs and could not be accurately applied to the specific population for MASLD and fibrosis stages F1-F3, which greatly affected the extensibility and accuracy of the evidence. Therefore, this study aimed to evaluate the efficacy of various pharmacotherapies with different dosages in improving liver fibrosis among MASLD patients with fibrosis stages F1-F3 through a network meta-analysis. Methods Randomized controlled trials involving adults with MASLD and fibrosis stages of F1-F3 who received pharmacological interventions for improving liver fibrosis from three databases were identified from inception to July 21, 2025. Results Thirteen RCTs involving 3,871 patients with 12 pharmacological interventions were involved. Compared with placebo in this network meta-analysis, 6 active pharmacological interventions, including resmetirom 80 mg/day (RR = 2.56, 95%CI: 1.09, 6.02), resmetirom 100 mg/day (RR = 3.07, 95%CI: 1.31, 7.16), survodutide 6 mg/week (RR = 7.25, 95%CI: 2.07, 25.36), tirzepatide 5 mg/week (RR = 4.29, 95%CI: 1.33, 13.82), tirzepatide 10 mg/week (RR = 5.31, 95%CI: 1.67, 16.85), and tirzepatide 15 mg/week (RR = 6.00, 95%CI: 1.91, 18.89), were significantly more effective for achieving NASH resolution without worsening of fibrosis. In direct comparisons, 6 active interventions, including resmetirom 80 mg/day (RR = 1.70, 95%CI: 1.22, 2.37), survodutide 6 mg/week (RR = 7.25, 95%CI: 2.68, 19.60), tirzepatide 5 mg/week (RR = 4.29, 95%CI: 1.76, 10.43), tirzepatide 10 mg/week (RR = 5.31, 95%CI: 2.23, 12.66), tirzepatide 15 mg/week (RR = 6.00, 95%CI: 2.54, 14.15), and denifanstat 50 mg/day (RR = 2.46, 95%CI: 1.18, 5.13), were significantly more effective than placebo. The ranking based SUCRA showed that survodutide 6 mg/week (92.0%) demonstrated the best efficacy, followed by tirzepatide 15 mg/week (89.9%), whereas emricasan 10 mg/day had the poorest efficacy (8.1%). Conclusions This study supported the use of survodutide (4.8 mg/week), efruxiferimin (28 mg/week), resmetirom (80 mg/day), and denifanstat (50 mg/day) as an recommended regimen in adults with MASLD and fibrosis stages of F1-F3. However, these findings did not support the clinical use of emricasan because of its poor efficacy. Concurrently, multiple pharmacological agents also exhibited efficacy at other relevant clinical endpoints. Trial registration The protocol of NMA was available at the Open Science Framework (OSF: https://doi.org/10.17605/OSF.IO/DM2NC).
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