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. 2024 Jul 19:10.1097/HEP.0000000000001028.
doi: 10.1097/HEP.0000000000001028. Online ahead of print.

Comparative efficacy of pharmacologic therapies for MASH in reducing liver fat content: Systematic review and network meta-analysis

Benjamin Koh  1 , Jieling Xiao  1 , Cheng Han Ng  2   3 , Michelle Law  1 , Shyna Zhuoying Gunalan  1 , Pojsakorn Danpanichkul  4 , Vijay Ramadoss  2 , Benedix Kuan Loon Sim  1 , En Ying Tan  2 , Chong Boon Teo  1 , Benjamin Nah  2 , Margaret Teng  1 , Karn Wijarnpreecha  5 , Yuya Seko  6 , Mei Chin Lim  7 , Hirokazu Takahashi  8 , Atsushi Nakajima  9 , Mazen Noureddin  10 , Mark Muthiah  2 , Daniel Q Huang  1   2   11   12 , Rohit Loomba  12   13
Affiliations

Comparative efficacy of pharmacologic therapies for MASH in reducing liver fat content: Systematic review and network meta-analysis

Benjamin Koh et al. Hepatology. .

Abstract

Background and aims: Metabolic dysfunction-associated steatohepatitis (MASH) is a leading cause of liver disease. Dynamic changes in 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 MRI-PDFF.

Approach and results: In this systematic review and network meta-analysis, we searched MEDLINE and Embase from inception until December 26, 2023, for published randomized controlled trials 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 randomized controlled trials (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 in the selection of combination therapy.

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Conflict of interest statement

Conflicts of Interests

Cheng Han Ng consults for Boxer Capital. Mazen Noureddin advises and received grants from Boehringer Ingelheim, Gilead, GlaxoSmithKline, Madrigal, Novo Nordisk, Pfizer, Takeda, and Terns. He advises 89bio, Altimmune, Blade, CohBar, CytoDyn, Echosens, Fractyl, Intercept, Merck, NorthSea, Roche, and Siemens. He received grants from Allergan, Akero, Boehringer Ingelheim, Bristol Myers Squibb, Conatus, Corcept, Enanta, Galectin, Galmed, GENFIT, Novartis, Shire, Viking, and Zydus. He owns stock in Anaetos, ChronWell, CytoDyn, Rivus, and Viking. Daniel Q. Huang consults for Gilead and Roche. Rohit Loomba consults and received grants from Arrowhead, AstraZeneca, Bristol Myers Squibb, Eli Lilly, Galmed, Gilead, Intercept, Inventiva, Ionis, Janssen, Madrigal, Merck, NGM Bio, Novo Nordisk, Pfizer, and Terns. He consults and owns stock in Sagimet. He consults for 89bio, Aardvark, Altimmune, Alnylam/Regeneron, Amgen, Cascade, CohBar, Glympse Bio, HighTide, Inipharm, Lipidio, Metacrine, NeuroBo, Novartis, Takeda, Theratechnologies, and Viking. He received grants from Boehringer Ingelheim, Galectin, Hanmi, and Sonic Incytes. He has other interests with LipoNexus. The remaining authors have no conflicts to report.

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