New Therapies for Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD/MASH): Clinical Outcomes and Implementation Challenges
DOI:
https://doi.org/10.51987/Rev.Hosp.Ital.B.Aires.v46i3.1314Keywords:
MASH, MASLD, emerging therapies, liver fibrosis, FXR agonists, GLP-1Abstract
Introduction: metabolic dysfunction-associated fatty liver disease (MASLD) and its progressive inflammatory form, associated steatohepatitis (MASH), represent a growing challenge due to their high prevalence and potential progression to advanced fibrosis and cirrhosis. In recent years, the therapeutic approach has gone beyond lifestyle and dietary measures, driving the development of pharmacological alternatives aimed at modifying the natural history of the disease.
State of the art: recent research has focused on drugs that act on metabolic, inflammatory, and antifibrotic pathways involved in the pathophysiology of MASLD/MASH. Phase II and III clinical trials have shown promising results, notably glucagon-like peptide-1 (GLP-1) receptor agonists and selective thyroid hormone beta receptor agonists, which have shown improvement in the resolution of steatohepatitis and a decrease in the degree of liver fibrosis.
Discussion: despite the advances observed, therapeutic efficacy is not uniform among patients, suggesting pathophysiological heterogeneity and the need for personalized medicine strategies. Questions also remain regarding long-term safety, therapeutic adherence, and cost-benefit ratios in different healthcare settings, which are key aspects for their incorporation into routine clinical practice.
Conclusion: emerging drug therapies for MASLD and MASH represent a significant advance in the management of these conditions, offering significant clinical and histological benefits. However, optimizing their implementation requires further evidence on long-term safety, appropriate patient selection, and strategies to facilitate their effective integration into healthcare systems.
Downloads
References
Yadav P, Quadri K, Kadian R, et al. New approaches to the treatment of metabolic dysfunction-associated steatotic liver with natural products. ILIVER. 2024;3(4):100131.
Branković M, Dukić M, Gmizić T, et al. New therapeutic approaches for the treatment of patients with metabolic dysfunction-associated steatotic liver disease (MASLD) and increased cardiovascular risk. Diagnostics (Basel). 2024;14(2):229.
Patel P. Treatment landscape of metabolic-dysfunction-associated steatotic liver disease. J Clin Med. 2025;14(17):6060.
Vidal-Cevallos P, Sorroza-Martínez AP, Chávez-Tapia NC, et al. The relationship between pathogenesis and possible treatments for the MASLD-cirrhosis spectrum. Int J Mol Sci. 2024;25(8):4397.
Krintus M, Panteghini M. Detection of advanced liver fibrosis using blood noninvasive tests: a laboratory medicine perspective. Clin Chem. 2026;72(3):337-346.
Li Y, Sun W, Liu H, et al. Tirzepatide, a dual GIP/GLP-1 receptor agonist, alleviates metabolic dysfunction-associated steatotic liver disease by reducing the expression of CD36 and OBP2A. Genes Dis. 2025;12(6):101761.
Shakeel L, Shaukat A, Akilimali A. Resmetirom: a breakthrough in the treatment of metabolic dysfunction-associated steatotic liver disease (MASLD). Health Sci Rep. 2025;8(6):e70920.
Barb D, Kalavalapalli S, Godinez Leiva E, et al. Pan-PPAR agonist lanifibranor improves insulin resistance and hepatic steatosis in patients with T2D and MASLD. J Hepatol. 2025;82(6):979-991.
Choi R, Vemuri J, Poloju A, et al. Current and emerging treatments for metabolic associated steatotic liver disease and diabetes: a narrative review. Endocrines. 2025;6(2):27.
Vilarrasa N, Pellitero S. GLP-1-based therapies for obesity: impact on comorbidities or obesity-related diseases. Med Clin (Barc). 2025;165(6):107184.
Kamrul-Hasan ABM, Borozan S, Jena S, et al. Safety and efficacy of efruxifermin in metabolic dysfunction-associated steatohepatitis: a systematic review. World J Gastrointest Pharmacol Ther. 2025;16(3):1-15.
Cusi K, Abdelmalek MF, Apovian CM, et al. Metabolic dysfunction-associated steatotic liver disease (MASLD) in people with diabetes: the need for screening and early intervention. A consensus report of the American Diabetes Association. Diabetes Care. 2025;48(7):1057-1082.
Romero M. New molecules for treating metabolic-associated dysfunction steatotic liver disease (MASLD). Ann Hepatol. 2025;30(2):102157.
Drygalski K. Pharmacological treatment of MASLD: contemporary treatment and future perspectives. Int J Mol Sci. 2025;26(13):6518.
De la Hoz Gil L, Martínez-Echevarría SV, Lozano Estevan MDC. Enfermedad hepática esteatósica asociada a disfunción metabólica (MASLD) y fibrosis hepática. Propuesta de score APRI+FIB4+NFS. Nutr Hosp. 2025;42(3):1-6.
Srikanth P, Shaik KM, Patibandla V, et al. Significance of FXR agonists in MASLD treatment: a deep dive into lipid alteration by analytical techniques. Explor Endocr Metab Dis. 2025;2:1-24.
Zhou D, Fan J. Drug treatment for metabolic dysfunction-associated steatotic liver disease: progress and direction. Chin Med J (Engl). 2024;137(22):1-10.
Havranek B, Loh R, Torre B, et al. Glucagon-like peptide-1 receptor agonists improve metabolic dysfunction-associated steatotic liver disease outcomes. Sci Rep. 2025;15(1):1-11.
Suki M, Amer J, Milgrom Y, et al. Semaglutide in MASLD patients: improved survival and liver outcomes. Pharmaceuticals (Basel). 2025;18(7):1075.
Schwabe RF, Tacke F, Sugimoto A, et al.Antifibrotic therapies for metabolic dysfunction-associated steatotic liver disease. JHEP Rep. 2025;7(8):1-29.
Harrison SA, Rolph T, Knott M, et al. FGF21 agonists: an emerging therapeutic for metabolic dysfunction-associated steatohepatitis and beyond. J Hepatol. 2024;81(3):562-576.
Chiang JYL. New drug therapies for metabolic dysfunction-associated steatohepatitis. Liver Res. 2025;9(2):94-103.
Stefan N, Yki-Järvinen H, Neuschwander-Tetri BA. Metabolic dysfunction-associated steatotic liver disease: heterogeneous pathomechanisms and effectiveness of metabolism-based treatment. Lancet Diabetes Endocrinol. 2025;13(2):1-15.
Downloads
Published
Issue
Section
License
Copyright (c) 2026 Javier J. Flores, Elizabeth P. Aguilera

This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.










