In a network meta-analysis of 9 trials, efruxifermin ranked highest for reversing liver fibrosis in MASH cirrhosis, while semaglutide and efruxifermin led for resolving the underlying liver inflammation.
Efruxifermin: only drug beating placebo for fibrosisAmong all tested treatments, only efruxifermin significantly reversed liver scarring in MASH cirrhosis patients
What the researchers found
Among 9 RCTs with 3,266 participants, efruxifermin was the only intervention significantly superior to placebo for fibrosis regression (≥1 stage improvement without MASH worsening), ranking highest (SUCRA 77.44), followed by cilofexor + firsocostat (SUCRA 72.38) and aldafermin (SUCRA 71.27).
For MASH resolution, three treatments were significantly superior to placebo: efruxifermin (SUCRA 81.38), semaglutide + cilofexor + firsocostat (SUCRA 74.07), and semaglutide alone (SUCRA 63.88).
Why it matters
MASH cirrhosis is rapidly becoming one of the most common causes of liver transplantation and liver-related death worldwide. Until recently, no drugs were approved for this condition. This analysis provides the first head-to-head ranking of emerging therapies, helping guide both clinical trial design and future treatment decisions as these drugs move toward approval.
How the study worked
Systematic review and network meta-analysis of randomized controlled trials from PubMed and Cochrane Library through May 2025. Included studies evaluated pharmacological treatments in biopsy-proven compensated MASH cirrhosis (F4c). SUCRA ranking analysis estimated the probability of each treatment being the most effective.
What this study cannot tell us
Network meta-analyses rely on indirect comparisons between trials with different designs, populations, and durations. The number of included trials (9) is relatively small, limiting the precision of rankings. SUCRA rankings do not represent absolute efficacy differences. Safety profiles were not compared. The analysis included only compensated cirrhosis, so results may not apply to decompensated disease.
How to read the evidence
This is a network meta-analysis of randomized controlled trials — among the highest levels of evidence. However, the relatively small number of included trials and indirect nature of most comparisons introduce some uncertainty into the rankings.
When this study was published
Published in 2026 with data through May 2025, this is the most current systematic comparison of MASH cirrhosis treatments available.
The bigger picture
The treatment landscape for MASH is evolving rapidly, with multiple peptide-based and small molecule drugs in late-stage development. Several of the top-ranked agents — efruxifermin (FGF21 analogue), aldafermin (FGF19 analogue), and semaglutide (GLP-1 agonist) — are peptide drugs, highlighting the central role of peptide therapeutics in addressing this global liver disease epidemic.
Questions still open
- Will efruxifermin's fibrosis improvement translate into reduced liver-related mortality and transplant need in longer trials?
- Could combining semaglutide with efruxifermin provide synergistic benefits for both fibrosis and MASH resolution?
- How do these treatments compare in terms of safety profiles and tolerability in cirrhosis patients?
Common questions
What is MASH cirrhosis and why is it important?
Are any of these drugs available for patients now?
Read the original research
Network Meta-Analysis: Comparison of Pharmacological Therapies in Compensated Metabolic Dysfunction-Associated Steatohepatitis Cirrhosis for Fibrosis Regression and MASH Resolution.
Alimentary pharmacology & therapeutics
Citation
Souza, Matheus; Al-Sharif, Lubna; Antunes, Vanio L J; Wong, Shi Yin; Huang, Daniel Q; Loomba, Rohit. (2026). Network Meta-Analysis: Comparison of Pharmacological Therapies in Compensated Metabolic Dysfunction-Associated Steatohepatitis Cirrhosis for Fibrosis Regression and MASH Resolution.. Alimentary pharmacology & therapeutics. https://doi.org/10.1111/apt.70565