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Background <p>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.</p> Methods <p>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.</p> Results <p>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%).</p> Conclusions <p>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.</p> Trial registration <p>The protocol of NMA was available at the Open Science Framework (OSF: <a href="https://doi.org/10.17605/OSF.IO/DM2NC">https://doi.org/10.17605/OSF.IO/DM2NC</a>).</p> Graphical Abstract <p></p>

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Efficacy of pharmacotherapies in improving liver fibrosis among patients with MASLD and fibrosis stages of F1-F3: systematic review and network meta-analysis

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年5月26日

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  • Xin-Yue Sun,
  • Hua-Ling Jiang,
  • Yu-Tong Ma,
  • Tian-Qi Xiong,
  • Xie-Yuan Leng,
  • Yi-Fan Zhao,
  • Xian-Feng Shen,
  • Chao Zhang,
  • Yi-Jun Tang

摘要

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).

Graphical Abstract