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Molecular mechanisms and pathogenesis of MASH

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Why This Matters

The recent consensus on MASLD (metabolic dysfunction-associated steatotic liver disease) highlights its complex molecular mechanisms and diverse subtypes, emphasizing the importance of personalized diagnosis and treatment strategies. This advancement is crucial for the tech industry as it drives innovation in diagnostic tools, data analytics, and targeted therapies, ultimately improving patient outcomes and reducing healthcare costs.

Key Takeaways

Rinella, M. E. et al. A multisociety Delphi consensus statement on new fatty liver disease nomenclature. J. Hepatol. 79, 1542–1556 (2023). International consensus statement providing the new nomenclature for MASLD.

Ludwig, J., Viggiano, T. R., McGill, D. B. & Oh, B. J. Nonalcoholic steatohepatitis: Mayo Clinic experiences with a hitherto unnamed disease. Mayo Clin. Proc. 55, 434–438 (1980). The initial publication describing the disease NASH.

Huang, D. Q., El-Serag, H. B. & Loomba, R. Global epidemiology of NAFLD-related HCC: trends, predictions, risk factors and prevention. Nat. Rev. Gastroenterol. Hepatol. 18, 223–238 (2021).

Younossi, Z. M., Kalligeros, M. & Henry, L. Epidemiology of metabolic dysfunction-associated steatotic liver disease. Clin. Mol. Hepatol. 31, S32–S50 (2025).

Zhou, X. D. et al. Global burden of disease attributable to metabolic risk factors in adolescents and young adults aged 15-39, 1990-2021. Clin. Nutr. 43, 391–404 (2024).

Stroes, A. R., Vos, M., Benninga, M. A. & Koot, B. G. P. Pediatric MASLD: current understanding and practical approach. Eur. J. Pediatr. 184, 29 (2024).

Lefere, S. et al. Update in clinical science: MASLD in children and adolescents. J. Hepatol. https://doi.org/10.1016/j.jhep.2026.02.016 (2026).

Ding, J. et al. Integrative multiomic analysis identifies distinct molecular subtypes of NAFLD in a Chinese population. Sci. Transl. Med. 16, eadh9940 (2024).

Jamialahmadi, O. et al. Partitioned polygenic risk scores identify distinct types of metabolic dysfunction-associated steatotic liver disease. Nat. Med. 30, 3614–3623 (2024). The authors identified that MASLD comprises of at least two subgroups: liver-centric and cardiometabolic centric.

Raverdy, V. et al. Data-driven cluster analysis identifies distinct types of metabolic dysfunction-associated steatotic liver disease. Nat. Med. 30, 3624–3633 (2024). The authors identified MASLD as comprising at least 2 subgroups: liver-centric and cardiometabolic centric.

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