Background and Aims: Metabolic dysfunction-associated steatohepatitis (MASH) is a leading cause of liver disease. Dynamic changes in magnetic resonance imaging (MRI) proton-density-fat fraction (PDFF) are associated with MASH resolution. We aimed to determine the relative efficacy of therapeutic agents for reducing hepatic fat, assessed by magnetic resonance imaging (MRI) proton-density-fat fraction (PDFF). Approach and results: In this systematic review and network meta-analysis, we searched MEDLINE and Embase from inception until Dec 26, 2023, for published randomized-controlled trials (RCTs) comparing pharmacological interventions in patients with MASH that assessed changes in MRI-PDFF. The primary outcome was the absolute change in MRI-PDFF. The secondary outcome was a ≥30% decline in MRI-PDFF. A surface under-the-curve cumulative ranking probabilities (SUCRA) analysis was performed. Of 1550 records, a total of 39 RCTs (3311 participants) met the inclusion criteria. For MRI-PDFF decline at 24 weeks, aldafermin (SUCRA: 83.65), pegozafermin (SUCRA: 83.46), and pioglitazone (SUCRA: 71.67) were ranked the most effective interventions. At 24-weeks, efinopegdutide (SUCRA: 67.02), semaglutide + firsocostat (SUCRA: 62.43), and pegbelfermin (SUCRA: 61.68) were ranked the most effective interventions for achieving a ≥30% decline in MRI-PDFF. Conclusions: This study provides an updated, relative rank-order efficacy of therapies for MASH in reducing hepatic fat. These data may help inform the design and sample size calculation of future clinical trials and assist selection of combination therapy.

中文翻译：

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MASH 药物治疗降低肝脏脂肪含量的疗效比较：系统评价和网络荟萃分析


背景和目的：代谢功能障碍相关脂肪性肝炎（MASH）是肝病的主要原因。磁共振成像 (MRI) 质子密度脂肪分数 (PDFF) 的动态变化与 MASH 分辨率相关。我们的目的是通过磁共振成像（MRI）质子密度脂肪分数（PDFF）评估治疗药物减少肝脂肪的相对功效。方法和结果：在这项系统评价和网络荟萃分析中，我们搜索了 MEDLINE 和 Embase 从开始到 2023 年 12 月 26 日期间已发表的随机对照试验 (RCT)，这些试验比较了 MASH 患者的药物干预措施，并评估了 MRI-PDFF 的变化。这主要结局是 MRI-PDFF 的绝对变化。次要结果是 MRI-PDFF 下降 ≥30%。进行了表面曲线下累积排名概率（SUCRA）分析。在 1550 条记录中，共有 39 条随机对照试验（3311 名受试者）符合纳入标准。对于 24 周时 MRI-PDFF 下降，aldafermin (SUCRA: 83.65)、pegozafermin (SUCRA: 83.46) 和 pioglitazone (SUCRA: 71.67) 被列为最有效的干预措施。 24 周时，efinopegdutide (SUCRA: 67.02)、semaglutide + firsocostat (SUCRA: 62.43) 和 pegbelfermin (SUCRA: 61.68) 被列为实现 MRI-PDFF 下降 ≥30% 的最有效干预措施。结论：本研究提供了 MASH 疗法在减少肝脂肪方面的更新的相对排序功效。这些数据可能有助于为未来临床试验的设计和样本量计算提供信息，并帮助选择联合治疗。