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  • Review Article
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Μetabolic dysfunction-associated steatotic liver disease: a condition of heterogeneous metabolic risk factors, mechanisms and comorbidities requiring holistic treatment

Nature Reviews Gastroenterology & Hepatology volume 22, pages 314–328 (2025)Cite this article

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An Author Correction to this article was published on 27 August 2025

An Author Correction to this article was published on 07 March 2025

This article has been updated

Abstract

Μetabolic dysfunction-associated steatotic liver disease (MASLD) comprises a heterogeneous condition in the presence of steatotic liver. There can be a hierarchy of metabolic risk factors contributing to the severity of metabolic dysfunction and, thereby, the associated risk of both liver and extrahepatic outcomes, but the precise ranking and combination of metabolic syndrome (MetS) traits that convey the highest risk of major adverse liver outcomes and extrahepatic disease complications remains uncertain. Insulin resistance, low-grade inflammation, atherogenic dyslipidaemia and hypertension are key to the mechanisms of liver and extrahepatic complications. The liver is pivotal in MetS progression as it regulates lipoprotein metabolism and secretes substances that affect insulin sensitivity and inflammation. MASLD affects the kidneys, heart and the vascular system, contributing to hypertension and oxidative stress. To address the global health burden of MASLD, intensified by obesity and type 2 diabetes mellitus epidemics, a holistic, multidisciplinary approach is essential. This approach should focus on both liver disease management and cardiometabolic risk factors. This Review examines the link between metabolic dysfunction and liver dysfunction and extrahepatic disease outcomes, the diverse mechanisms in MASLD due to metabolic dysfunction, and a comprehensive, personalized management model for patients with MASLD.

Key points

  • The new term metabolic dysfunction-associated steatotic liver disease (MASLD) comprises a heterogeneous condition with variable degrees of metabolic dysfunction underpinned by the presence of steatotic liver disease.

  • Metabolic syndrome (MetS) traits are vital in diagnosing MASLD as varying degrees of metabolic dysfunction, linked to different MetS traits, result in differential risks of hepatic and extrahepatic complications.

  • Individuals with MASLD and diverse metabolic co-factors are at higher risk of developing major adverse liver outcomes as well as cardiovascular or kidney disease outcomes.

  • A deeper understanding of the factors that affect the variability in MASLD phenotypes and their relationship with MetS traits can inform novel strategies to predict and positively influence liver health.

  • A care model for MASLD in the context of MetS traits should include screening, risk stratification and algorithmic management according to the specific risk factors and stage of fibrosis.

  • The variable severity of metabolic dysfunction and the heterogeneity of liver and extrahepatic outcomes highlight the need for a holistic approach to managing and treating MASLD as a multisystem disease.

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Fig. 1: MASLD diagnostic criteria, variable clinical phenotype and important clinical outcomes.
Fig. 2: Schematic figure illustrating how risk factors associated with MetS influence the pathogenesis of liver disease in MASLD.
Fig. 3: Strategies for non-invasive assessment of the risk of advanced fibrosis and liver-related outcomes in individuals with MASLD.

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References

  1. 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).

    Article  CAS  PubMed  Google Scholar 

  2. Angulo, P. et al. Liver fibrosis, but no other histologic features, is associated with long-term outcomes of patients with nonalcoholic fatty liver disease. Gastroenterology 149, 389–397.e310 (2015).

    Article  PubMed  Google Scholar 

  3. Byrne, C. D. & Targher, G. NAFLD: a multisystem disease. J. Hepatol. 62, S47–S64 (2015).

    Article  PubMed  Google Scholar 

  4. Targher, G., Tilg, H. & Byrne, C. D. Nonalcoholic fatty liver disease: a multisystem disease requiring a multidisciplinary and holistic approach. Lancet Gastroenterol. Hepatol. 6, 578–588 (2021).

    Article  PubMed  Google Scholar 

  5. Eslam, M. et al. A new definition for metabolic dysfunction-associated fatty liver disease: an international expert consensus statement. J. Hepatol. 73, 202–209 (2020).

    Article  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  7. Hagström, H., Vessby, J., Ekstedt, M. & Shang, Y. 99% of patients with NAFLD meet MASLD criteria and natural history is therefore identical. J. Hepatol. 80, e76–e77 (2024).

    Article  PubMed  Google Scholar 

  8. Fouad, Y., Barakat, S., Hashim, A. & Ghazinyan, H. Towards unifying fatty liver nomenclature: a voice from the Middle East and North Africa. Nat. Rev. Gastroenterol. Hepatol. 21, 297–298 (2024).

    Article  PubMed  Google Scholar 

  9. Fouad, Y. et al. Joint position statement from the Middle East and North Africa and sub-Saharan Africa on continuing to endorse the MAFLD definition. J. Hepatol. 80, e194–e197 (2024).

    Article  PubMed  Google Scholar 

  10. Byrne, C. D. & Targher, G. MASLD, MAFLD, or NAFLD criteria: have we re-created the confusion and acrimony surrounding metabolic syndrome? Metab. Target Organ Damage 4, 10 (2024).

    Article  CAS  Google Scholar 

  11. Younossi, Z. M. et al. Clinical profiles and mortality rates are similar for metabolic dysfunction-associated steatotic liver disease and nonalcoholic fatty liver disease. J. Hepatol. 80, 694–701 (2024).

    Article  CAS  PubMed  Google Scholar 

  12. Alberti, K. G. et al. Harmonizing the metabolic syndrome: a joint interim statement of the International Diabetes Federation Task Force on Epidemiology and Prevention; National Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; and International Association for the Study of Obesity. Circulation 120, 1640–1645 (2009).

    Article  CAS  PubMed  Google Scholar 

  13. Mottillo, S. et al. The metabolic syndrome and cardiovascular risk a systematic review and meta-analysis. J. Am. Coll. Cardiol. 56, 1113–1132 (2010).

    Article  PubMed  Google Scholar 

  14. Simon, T. G., Roelstraete, B., Khalili, H., Hagström, H. & Ludvigsson, J. F. Mortality in biopsy-confirmed nonalcoholic fatty liver disease: results from a nationwide cohort. Gut 70, 1375–1382 (2021).

    Article  PubMed  Google Scholar 

  15. Shang, Y. et al. Cause of death by fibrosis stage in 959 patients with biopsy-proven NAFLD. Gut 73, e30 (2024).

    Article  PubMed  Google Scholar 

  16. Sung, K. C., Cha, S. C., Sung, J. W., So, M. S. & Byrne, C. D. Metabolically healthy obese subjects are at risk of fatty liver but not of pre-clinical atherosclerosis. Nutr. Metab. Cardiovasc. Dis. 24, 256–262 (2014).

    Article  PubMed  Google Scholar 

  17. Jarvis, H. et al. Metabolic risk factors and incident advanced liver disease in nonalcoholic fatty liver disease (NAFLD): a systematic review and meta-analysis of population-based observational studies. PLoS Med. 17, e1003100 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Alexander, M. et al. Risks and clinical predictors of cirrhosis and hepatocellular carcinoma diagnoses in adults with diagnosed NAFLD: real-world study of 18 million patients in four European cohorts. BMC Med. 17, 95 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  19. Björkström, K. et al. Risk factors for severe liver disease in patients with type 2 diabetes. Clin. Gastroenterol. Hepatol. 17, 2769–2775.e2764 (2019).

    Article  PubMed  Google Scholar 

  20. Shang, Y. et al. Metabolic syndrome traits increase the risk of major adverse liver outcomes in type 2 diabetes. Diabetes Care 47, 978–985 (2024).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Alberti, K. G. & Zimmet, P. Z. Definition, diagnosis and classification of diabetes mellitus and its complications. Part 1: diagnosis and classification of diabetes mellitus provisional report of a WHO consultation. Diabet. Med. 15, 539–553 (1998).

    Article  CAS  PubMed  Google Scholar 

  22. Zaharia, O. P. et al. Risk of diabetes-associated diseases in subgroups of patients with recent-onset diabetes: a 5-year follow-up study. Lancet Diabetes Endocrinol. 7, 684–694 (2019).

    Article  PubMed  Google Scholar 

  23. Erman, H., Boyuk, B., Arslan, S., Akin, S. & Keskin, Ö. Noninvasive liver fibrosis indices as indicators of microvascular and macrovascular complications in type 2 diabetes. Metab. Syndr. Relat. Disord. 22, 619–625 (2024).

    Article  CAS  PubMed  Google Scholar 

  24. Sun, Y. et al. Fibrosis risk in nonalcoholic fatty liver disease is related to chronic kidney disease in older type 2 diabetes patients. J. Clin. Endocrinol. Metab. 107, e3661–e3669 (2022).

    Article  PubMed  Google Scholar 

  25. Ford, E. S. Risks for all-cause mortality, cardiovascular disease, and diabetes associated with the metabolic syndrome: a summary of the evidence. Diabetes Care 28, 1769–1778 (2005).

    Article  PubMed  Google Scholar 

  26. Guzder, R. N., Gatling, W., Mullee, M. A. & Byrne, C. D. Impact of metabolic syndrome criteria on cardiovascular disease risk in people with newly diagnosed type 2 diabetes. Diabetologia 49, 49–55 (2006).

    Article  CAS  PubMed  Google Scholar 

  27. Mantovani, A., Byrne, C. D., Bonora, E. & Targher, G. Nonalcoholic fatty liver disease and risk of incident type 2 diabetes: a meta-analysis. Diabetes Care 41, 372–382 (2018).

    Article  CAS  PubMed  Google Scholar 

  28. Mantovani, A. et al. Nonalcoholic fatty liver disease and risk of fatal and non-fatal cardiovascular events: an updated systematic review and meta-analysis. Lancet Gastroenterol. Hepatol. 6, 903–913 (2021).

    Article  PubMed  Google Scholar 

  29. Mantovani, A. et al. Nonalcoholic fatty liver disease and risk of incident chronic kidney disease: an updated meta-analysis. Gut 71, 156–162 (2022).

    Article  PubMed  Google Scholar 

  30. Mantovani, A. et al. Nonalcoholic fatty liver disease and risk of new-onset heart failure: an updated meta-analysis of about 11 million individuals. Gut 72, 372–380 (2023).

    Article  CAS  Google Scholar 

  31. Mantovani, A. et al. Nonalcoholic fatty liver disease and increased risk of incident extrahepatic cancers: a meta-analysis of observational cohort studies. Gut 71, 778–788 (2022).

    Article  PubMed  Google Scholar 

  32. Kim, K. S., Hong, S., Han, K. & Park, C. Y. Association of nonalcoholic fatty liver disease with cardiovascular disease and all cause death in patients with type 2 diabetes mellitus: nationwide population based study. BMJ 384, e076388 (2024).

    Article  PubMed  PubMed Central  Google Scholar 

  33. Sanyal, A. J. et al. Prospective study of outcomes in adults with nonalcoholic fatty liver disease. N. Engl. J. Med. 385, 1559–1569 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Lee, E., Korf, H. & Vidal-Puig, A. An adipocentric perspective on the development and progression of nonalcoholic fatty liver disease. J. Hepatol. 78, 1048–1062 (2023).

    Article  CAS  PubMed  Google Scholar 

  35. Virtue, S. & Vidal-Puig, A. Adipose tissue expandability, lipotoxicity and the metabolic syndrome–an allostatic perspective. Biochim. Biophys. Acta 1801, 338–349 (2010).

    Article  CAS  PubMed  Google Scholar 

  36. Song, C., Long, X., He, J. & Huang, Y. Recent evaluation about inflammatory mechanisms in nonalcoholic fatty liver disease. Front. Pharmacol. 14, 1081334 (2023).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Ipsen, D. H., Lykkesfeldt, J. & Tveden-Nyborg, P. Molecular mechanisms of hepatic lipid accumulation in non-alcoholic fatty liver disease. Cell Mol. Life Sci. 18, 3313–3327 (2018).

    Article  Google Scholar 

  38. Palma, R. et al. The role of insulin resistance in fueling NAFLD pathogenesis: from molecular mechanisms to clinical implications. J. Clin. Med. 13, 3649 (2022).

    Article  Google Scholar 

  39. Yanai, H., Adachi, H., Hakoshima, M., Iida, S. & Katsuyama, H. Metabolic-dysfunction-associated steatotic liver disease-its pathophysiology, association with atherosclerosis and cardiovascular disease, and treatments. Int. J. Mol. Sci. 20, 15473 (2023).

    Article  Google Scholar 

  40. Allameh, A., Niayesh-Mehr, R., Aliarab, A., Sebastiani, G. & Pantopoulos, K. Oxidative stress in liver pathophysiology and disease. Antioxidants 12, 1653 (2023).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Shen, C. et al. The TLR4-IRE1α pathway activation contributes to palmitate-elicited lipotoxicity in hepatocytes. J. Cell. Mol. Med. 22, 3572–3581 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Prasun, P., Ginevic, I. & Oishi, K. Mitochondrial dysfunction in nonalcoholic fatty liver disease and alcohol related liver disease. Transl. Gastroenterol. Hepatol. 6, 4 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  43. Kuchay, M. S., Martínez-Montoro, J. I., Choudhary, N. S., Fernández-García, J. C. & Ramos-Molina, B. Non-alcoholic fatty liver disease in lean and non-obese individuals: current and future challenges. Biomedicines 9, 1346 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. González Hernández, M. A. et al. Identifying patient subgroups in MASLD and MASH-associated fibrosis: molecular profiles and implications for drug development. Sci. Rep. 14, 23362 (2024).

    Article  PubMed  PubMed Central  Google Scholar 

  45. Powell, E. E., Wong, V. W. & Rinella, M. Nonalcoholic fatty liver disease. Lancet 397, 2212–2224 (2021).

    Article  CAS  PubMed  Google Scholar 

  46. Loomba, R., Friedman, S. L. & Shulman, G. I. Mechanisms and disease consequences of nonalcoholic fatty liver disease. Cell 184, 2537–2564 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Mocciaro, G. et al. Nonalcoholic fatty liver disease is characterised by a reduced polyunsaturated fatty acid transport via free fatty acids and high-density lipoproteins (HDL). Mol. Metab. 73, 101728 (2023).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Sen, P. et al. Quantitative modeling of human liver reveals dysregulation of glycosphingolipid pathways in nonalcoholic fatty liver disease. iScience 25, 104949 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Azzu, V., Vacca, M., Virtue, S., Allison, M. & Vidal-Puig, A. Adipose tissue-liver cross talk in the control of whole-body metabolism: implications in nonalcoholic fatty liver disease. Gastroenterology 158, 1899–1912 (2020).

    Article  CAS  PubMed  Google Scholar 

  50. Vacca, M. et al. An unbiased ranking of murine dietary models based on their proximity to human metabolic dysfunction-associated steatotic liver disease (MASLD). Nat. Metab. 6, 1178–1196 (2024).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Medina-Gomez, G. et al. PPAR gamma 2 prevents lipotoxicity by controlling adipose tissue expandability and peripheral lipid metabolism. PLoS Genet. 3, e64 (2007).

    Article  PubMed  PubMed Central  Google Scholar 

  52. Monetti, M. et al. Dissociation of hepatic steatosis and insulin resistance in mice overexpressing DGAT in the liver. Cell Metab. 6, 69–78 (2007).

    Article  CAS  PubMed  Google Scholar 

  53. Matsusue, K. et al. Liver-specific disruption of PPARgamma in leptin-deficient mice improves fatty liver but aggravates diabetic phenotypes. J. Clin. Invest. 111, 737–747 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Shin, S., Kim, J., Lee, J. Y., Kim, J. & Oh, C. M. Mitochondrial quality control: its role in metabolic dysfunction-associated steatotic liver disease (MASLD). J. Obes. Metab. Syndr. 32, 289–302 (2023).

    Article  PubMed  PubMed Central  Google Scholar 

  55. Luukkonen, P. K. et al. The PNPLA3-I148M variant confers an antiatherogenic lipid profile in insulin-resistant patients. J. Clin. Endocrinol. Metab. 106, e300–e315 (2021).

    Article  PubMed  Google Scholar 

  56. Azzu, V. et al. Suppression of insulin-induced gene 1 (INSIG1) function promotes hepatic lipid remodelling and restrains NASH progression. Mol. Metab. 48, 101210 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Moessinger, C. et al. Two different pathways of phosphatidylcholine synthesis, the Kennedy Pathway and the Lands Cycle, differentially regulate cellular triacylglycerol storage. BMC Cell Biol. 15, 43 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  58. O’Donnell, V. B. New appreciation for an old pathway: the Lands Cycle moves into new arenas in health and disease. Biochem. Soc. Trans. 50, 1–11 (2022).

    Article  PubMed  PubMed Central  Google Scholar 

  59. Alharthi, J. et al. A metabolic associated fatty liver disease risk variant in MBOAT7 regulates toll like receptor induced outcomes. Nat. Commun. 13, 7430 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Hall, Z. et al. Lipid zonation and phospholipid remodeling in nonalcoholic fatty liver disease. Hepatology 65, 1165–1180 (2017).

    Article  CAS  PubMed  Google Scholar 

  61. Venkatesan, N., Doskey, L. C. & Malhi, H. The role of endoplasmic reticulum in lipotoxicity during metabolic dysfunction-associated steatotic liver disease (MASLD) pathogenesis. Am. J. Pathol. 193, 1887–1899 (2023).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Xie, W. et al. Myocardial infarction accelerates the progression of MASH by triggering immunoinflammatory response and induction of periosti. Cell Metab. 36, 1269–1286.e9 (2024).

    Article  CAS  PubMed  Google Scholar 

  63. Reiter, F. P. et al. p70 ribosomal protein s6 kinase is a checkpoint of human hepatic stellate cell activation and liver fibrosis in mice. Cell. Mol. Gastroenterol. Hepatol. 13, 95–112 (2022).

    Article  CAS  PubMed  Google Scholar 

  64. Bae, E. J. et al. Liver-specific p70 S6 kinase depletion protects against hepatic steatosis and systemic insulin resistance. J. Biol. Chem. 287, 18769–18780 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Sinha, R. A. Autophagy: a cellular guardian against hepatic lipotoxicity. Genes 14, 553 (2023).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Ke, P. Y. Mitophagy in the pathogenesis of liver diseases. Cells 4, 831 (2020).

    Article  Google Scholar 

  67. Raza, S., Rajak, S., Yen, P. M. & Sinha, R. A. Autophagy and hepatic lipid metabolism: mechanistic insight and therapeutic potential for MASLD. NPJ Metab. Health Dis. 1, 19 (2024).

    Article  Google Scholar 

  68. Caussy, C. et al. Familial NAFLD Cirrhosis Research Consortium. Nonalcoholic fatty liver disease with cirrhosis increases familial risk for advanced fibrosis. J. Clin. Invest. 127, 2697–2704 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  69. Moore, M. P. et al. Low MBOAT7 expression, a genetic risk for MASH, promotes a profibrotic pathway involving hepatocyte TAZ upregulation. Hepatology 81, 576–590 (2024).

    Article  PubMed  Google Scholar 

  70. Trépo, E. & Valenti, L. Update on NAFLD genetics: from new variants to the clinic. J. Hepatol. 72, 1196–1209 (2020).

    Article  PubMed  Google Scholar 

  71. Stender, S. et al. Adiposity amplifies the genetic risk of fatty liver disease conferred by multiple loci. Nat. Genet. 49, 842–847 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Duan, Y. et al. Regulation of cholesterol homeostasis in health and diseases: from mechanisms to targeted therapeutics. Signal Transduct. Target. Ther. 1, 265 (2022).

    Article  Google Scholar 

  73. Caballero, F. et al. Enhanced free cholesterol, SREBP-2 and StAR expression in human NASH. J. Hepatol. 50, 789–796 (2009).

    Article  CAS  PubMed  Google Scholar 

  74. Van Rooyen, D. M. & Farrell, G. C. SREBP-2: a link between insulin resistance, hepatic cholesterol, and inflammation in NASH. J. Gastroenterol. Hepatol. 5, 789–792 (2011).

    Article  Google Scholar 

  75. Tzanaki, I., Agouridis, A. P. & Kostapanos, M. S. Is there a role of lipid-lowering therapies in the management of fatty liver disease? World J. Hepatol. 1, 119–139 (2022).

    Article  Google Scholar 

  76. Lai, J. et al. Alterations in circulating bile acids in metabolic dysfunction-associated steatotic liver disease: a systematic review and meta-analysis. Biomolecules 9, 1356 (2023).

    Article  Google Scholar 

  77. Jiao, N. et al. Suppressed hepatic bile acid signalling despite elevated production of primary and secondary bile acids in NAFLD. Gut 67, 1881–1891 (2018).

    Article  CAS  PubMed  Google Scholar 

  78. Zhuge, A. et al. Longitudinal 16S rRNA sequencing reveals relationships among alterations of gut microbiota and nonalcoholic fatty liver disease progression in mice. Microbiol. Spectr. 3, e0004722 (2022).

    Article  Google Scholar 

  79. Jasirwan, C. O. M., Muradi, A., Hasan, I., Simadibrata, M. & Rinaldi, I. Correlation of gut Firmicutes/Bacteroidetes ratio with fibrosis and steatosis stratified by body mass index in patients with non-alcoholic fatty liver disease. Biosci. Microbiota Food Health 1, 50–58 (2021).

    Article  Google Scholar 

  80. Monga Kravetz, A. et al. Effect of gut microbiota and PNPLA3 rs738409 variant on nonalcoholic fatty liver disease (NAFLD) in obese youth. J. Clin. Endocrinol. Metab. 105, e3575–e3585 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  81. Wang, G. et al. Bifidobacterium adolescentis and Lactobacillus rhamnosus alleviate non-alcoholic fatty liver disease induced by a high-fat, high-cholesterol diet through modulation of different gut microbiota-dependent pathways. Food Funct. 11, 6115–6127 (2020).

    Article  PubMed  Google Scholar 

  82. Kim, S. J. et al. Combination of Limosilactobacillus fermentum MG4231 and MG4244 attenuates lipid accumulation in high-fat diet-fed obese mice. Benef. Microbes 12, 479–491 (2021).

    Article  CAS  PubMed  Google Scholar 

  83. Huo, Y. et al. Bifidobacterium animalis subsp. lactis A6 alleviates obesity associated with promoting mitochondrial biogenesis and function of adipose tissue in mice. Molecules 25, 1490 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Choi, K. J., Yoon, M. Y., Kim, J. E. & Yoon, S. S. Gut commensal Kineothrix alysoides mitigates liver dysfunction by restoring lipid metabolism and gut microbial balance. Sci. Rep. 13, 14668 (2023).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Kobyliak, N. et al. A multi-strain probiotic reduces the fatty liver index, cytokines and aminotransferase levels in NAFLD patients: evidence from a randomized clinical trial. J. Gastrointestin Liver Dis. 27, 41–49 (2018).

    Article  PubMed  Google Scholar 

  86. Lu, L., Finegold, M. J. & Johnson, R. L. Hippo pathway coactivators Yap and Taz are required to coordinate mammalian liver regeneration. Exp. Mol. Med. 50, e423 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  87. Lee, N. Y., Choi, M. G., Lee, E. J. & Koo, J. H. Interplay between YAP/TAZ and metabolic dysfunction-associated steatotic liver disease progression. Arch. Pharm. Res. 47, 558–570 (2024).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Vesković, M. et al. The interconnection between hepatic insulin resistance and metabolic dysfunction-associated steatotic liver disease-the transition from an adipocentric to liver-centric approach. Curr. Issues Mol. Biol. 45, 9084–9102 (2023).

    Article  PubMed  PubMed Central  Google Scholar 

  89. Mleczko, J. E. et al. Extracellular vesicles released by steatotic hepatocytes alter adipocyte metabolism. J. Extracell. Biol. 1, e32 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Li, J. et al. Pancreatic β cells control glucose homeostasis via the secretion of exosomal miR-29 family. J. Extracell. Vesicles 10, e12055 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Lee, E., Korf, H. & Vidal-Puig, A. Reply to: “Liver-adipose tissue crosstalk in nonalcoholic fatty liver disease: the emerging role of remnant cholesterol”: “BAT activation might improve NAFLD in patients, but this might require developing and/or maintaining functionally relevant levels of BAT mass.”. J. Hepatol. 80, e112–e114 (2024).

    Article  CAS  PubMed  Google Scholar 

  92. Fajkić, A., Jahić, R., Hadžović-Džuvo, A. & Lepara, O. Adipocytokines as predictors of metabolic dysfunction-associated steatotic liver disease (MASLD) development in type 2 diabetes mellitus patients. Cureus 16, e55673 (2024).

    PubMed  PubMed Central  Google Scholar 

  93. Wolfs, M. G. et al. Determining the association between adipokine expression in multiple tissues and phenotypic features of non-alcoholic fatty liver disease in obesity. Nutr. Diabetes 5, e146 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Li, J. et al. RNAkines are secreted messengers shaping health and disease. Trends Endocrinol. Metab. 35, 201–218 (2024).

    Article  PubMed  Google Scholar 

  95. Garcia-Martinez, I. et al. Saturated fatty acid-enriched small extracellular vesicles mediate a crosstalk inducing liver inflammation and hepatocyte insulin resistance. JHEP Rep. 5, 100756 (2023).

    Article  PubMed  PubMed Central  Google Scholar 

  96. Huang-Doran, I., Zhang, C. Y. & Vidal-Puig, A. Extracellular vesicles: novel mediators of cell communication in metabolic disease. Trends Endocrinol. Metab. 28, 3–18 (2017).

    Article  CAS  PubMed  Google Scholar 

  97. Wu, Z. et al. Extracellular vesicles originating from steatotic hepatocytes promote hepatic stellate cell senescence via AKT/mTOR signaling. Cell Biochem. Funct. 42, e4077 (2024).

    Article  CAS  PubMed  Google Scholar 

  98. Yki-Järvinen, H. Non-alcoholic fatty liver disease as a cause and a consequence of metabolic syndrome. Lancet Diabetes Endocrinol. 2, 901–910 (2014).

    Article  PubMed  Google Scholar 

  99. Milani, I. et al. Hepatokines and MASLD: the GLP1-Ras-FGF21-fetuin-A crosstalk as a therapeutic target. Int. J. Mol. Sci. 25, 107795 (2024).

    Article  Google Scholar 

  100. Wu, Y. et al. Lipid disorder and intrahepatic renin-angiotensin system activation synergistically contribute to nonalcoholic fatty liver disease. Liver Int. 36, 1525–1234 (2016).

    Article  CAS  PubMed  Google Scholar 

  101. Sironi, A. M., Sicari, R., Folli, F. & Gastaldelli, A. Ectopic fat storage, insulin resistance, and hypertension. Curr. Pharm. Des. 17, 3074–3080 (2011).

    Article  CAS  PubMed  Google Scholar 

  102. Reese-Petersen, A. L. et al. The sclerotic component of metabolic syndrome: fibroblast activities may be the central common denominator driving organ function loss and death. Diabetes Obes. Metab. 26, 2554–2566 (2024).

    Article  CAS  PubMed  Google Scholar 

  103. Åberg, F., Helenius-Hietala, J., Puukka, P., Färkkilä, M. & Jula, A. Interaction between alcohol consumption and metabolic syndrome in predicting severe liver disease in the general population. Hepatology 67, 2141–2149 (2018).

    Article  PubMed  Google Scholar 

  104. Marrero, J. A. et al. Alcohol, tobacco and obesity are synergistic risk factors for hepatocellular carcinoma. J. Hepatol. 42, 218–224 (2005).

    Article  CAS  PubMed  Google Scholar 

  105. Dunnm, W. et al. Modest alcohol consumption is associated with decreased prevalence of steatohepatitis in patients with non-alcoholic fatty liver disease (NAFLD). J. Hepatol. 57, 384–391 (2012).

    Article  Google Scholar 

  106. Jarvis, H. et al. Does moderate alcohol consumption accelerate the progression of liver disease in NAFLD? A systematic review and narrative synthesis. BMJ Open 12, e049767 (2022).

    Article  PubMed  PubMed Central  Google Scholar 

  107. Marti-Aguado, D. et al. Low-to-moderate alcohol consumption is associated with increased fibrosis in individuals with metabolic dysfunction-associated steatotic liver disease. J. Hepatol. 81, 930–940 (2024).

    Article  CAS  PubMed  Google Scholar 

  108. EASL–EASD–EASO. EASL–EASD–EASO Clinical Practice Guidelines on the management of metabolic dysfunction-associated steatotic liver disease (MASLD). J. Hepatol. 81, 492–542 (2024).

    Article  Google Scholar 

  109. daSilva-deAbreu, A., Alhafez, B. A., Lavie, C. J., Milani, R. V. & Ventura, H. O. Interactions of hypertension, obesity, left ventricular hypertrophy, and heart failure. Curr. Opin. Cardiol. 36, 453–460 (2021).

    Article  PubMed  Google Scholar 

  110. Younes, R. et al. Caucasian lean subjects with nonalcoholic fatty liver disease share long-term prognosis of non-lean: time for reappraisal of BMI-driven approach? Gut 71, 382–390 (2022).

    Article  CAS  PubMed  Google Scholar 

  111. Karlsen, T. H. et al. The EASL–Lancet liver commission: protecting the next generation of Europeans against liver disease complications and premature mortality. Lancet 399, 61–116 (2022).

    Article  PubMed  Google Scholar 

  112. Sperling, L. S. et al. The CardioMetabolic Health Alliance: working toward a new care model for the metabolic syndrome. J. Am. Coll. Cardiol. 66, 1050–1067 (2015).

    Article  PubMed  Google Scholar 

  113. Thiele, M. et al. Screening for liver fibrosis: lessons from colorectal and lung cancer screening. Nat. Rev. Gastroenterol. Hepatol. 21, 517–527 (2024).

    Article  PubMed  Google Scholar 

  114. Kanwal et al. Clinical care pathway for the risk stratification and management of patients with nonalcoholic fatty liver disease. Gastroenterology 161, 1657–1669 (2021).

    Article  CAS  PubMed  Google Scholar 

  115. Rinella, M. E. et al. AASLD Practice Guidance on the clinical assessment and management of nonalcoholic fatty liver disease. Hepatology 77, 1797–1835 (2023).

    Article  PubMed  Google Scholar 

  116. Wattacheril, J. J., Abdelmalek, M. F., Lim, J. K. & Sanyal, A. J. AGA clinical practice update on the role of noninvasive biomarkers in the evaluation and management of nonalcoholic fatty liver disease: Expert Review. Gastroenterology 165, 1080–1088 (2023).

    Article  CAS  PubMed  Google Scholar 

  117. Gawrieh, S. et al. Increases and decreases in liver stiffness measurement are independently associated with the risk of liver-related events in NAFLD. J. Hepatol. 81, 600–608 (2024).

    Article  PubMed  Google Scholar 

  118. Lin, H. et al. Vibration-controlled transient elastography scores to predict liver-related events in steatotic liver disease. JAMA 331, 1287–1297 (2024).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  119. Catapano, A. L. et al. 2016 ESC/EAS guidelines for the management of dyslipidaemias: the task force for the management of dyslipidaemias of the European Society of Cardiology (ESC) and European Atherosclerosis Society (EAS) Developed with the special contribution of the European Assocciation for Cardiovascular Prevention & Rehabilitation (EACPR). Atherosclerosis 253, 281–344 (2016).

    Article  CAS  PubMed  Google Scholar 

  120. Loomba, R., Ratziu, V. & Harrison, S. A. Expert panel review to compare FDA and EMA guidance on drug development and endpoints in nonalcoholic steatohepatitis. Gastroenterology 162, 680–688 (2022).

    Article  CAS  PubMed  Google Scholar 

  121. Harrison, S. A., Allen, A. M., Dubourg, J., Noureddin, M. & Alkhouri, N. Challenges and opportunities in NASH drug development. Nat. Med. 29, 562–573 (2023).

    Article  CAS  PubMed  Google Scholar 

  122. Sinha, R. A., Singh, B. K. & Yen, P. M. Direct effects of thyroid hormones on hepatic lipid metabolism. Nat. Rev. Endocrinol. 14, 259–269 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  123. Kelly, M. J. et al. Discovery of 2-[3,5-dichloro-4-(5-isopropyl-6-oxo-1,6-dihydropyridazin-3-yloxy)phenyl]-3,5-dioxo-2,3,4,5-tetrahydro[1,2,4]triazine-6-carbonitrile (MGL-3196), a highly selective thyroid hormone receptor β agonist in clinical trials for the treatment of dyslipidemia. J. Med. Chem. 57, 3912–3923 (2014).

    Article  CAS  PubMed  Google Scholar 

  124. Alonso-Merino, E. et al. Thyroid hormones inhibit TGF-β signaling and attenuate fibrotic responses. Proc. Natl Acad. Sci. USA 113, E3451–E3460 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  125. Harrison, S. A. et al. A phase 3, randomized, controlled trial of resmetirom in NASH with liver fibrosis. N. Engl. J. Med. 390, 497–509 (2024).

    Article  PubMed  Google Scholar 

  126. US National Library of Medicine. ClinicalTrials.gov https://clinicaltrials.gov/study/NCT03900429 (2024).

  127. Francque, S. M. et al. A randomised, controlled trial of the pan-PPAR agonist lanifibranor in NASH. N. Engl. J. Med. 385, 1547–1558 (2021).

    Article  CAS  PubMed  Google Scholar 

  128. US National Library of Medicine. ClinicalTrials.gov https://clinicaltrials.gov/study/NCT04849728 (2024).

  129. Davies, M. J. et al. Management of hyperglycaemia in type 2 diabetes, 2022. A consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetologia 65, 1925–1966 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  130. Brandt, S. J., Kleinert, M., Tschöp, M. H. & Müller, T. D. Are peptide conjugates the golden therapy against obesity? J. Endocrinol. 238, R109–R119 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  131. Newsome, P. N. et al. A placebo-controlled trial of subcutaneous semaglutide in nonalcoholic steatohepatitis. N. Engl. J. Med. 384, 1113–1124 (2021).

    Article  CAS  PubMed  Google Scholar 

  132. Newsome, P. et al. Phase 3 ESSENCE trial: Semaglutide in metabolic dysfunction-associated steatohepatitis. AASLD 2024, Hepatology (Late Breaking Abstract Supplement) 30–32 Abstr. 5018. https://www.aasld.org/sites/default/files/2024-11/TLM2024LBA_20241115A.pdf (2024).

  133. US National Library of Medicine. ClinicalTrials.gov https://clinicaltrials.gov/study/NCT04822181 (2025).

  134. Wester, A., Shang, Y., Toresson Grip, E., Matthews, A. A. & Hagström, H. Glucagon-like peptide-1 receptor agonists and risk of major adverse liver outcomes in patients with chronic liver disease and type 2 diabetes. Gut 73, 835–843 (2024).

    Article  CAS  PubMed  Google Scholar 

  135. Kanwal, F. et al. GLP-1 receptor agonists and risk for cirrhosis and related complications in patients with metabolic dysfunction-associated steatotic liver disease. JAMA Intern. Med. 184, 1314–1323 (2024).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  136. Loomba, R. et al. Tirzepatide for metabolic dysfunction-associated steatohepatitis with liver fibrosis. N. Engl. J. Med. 391, 299–310 (2024).

    Article  CAS  PubMed  Google Scholar 

  137. Sanyal, A. J. et al. A phase 2 randomised trial of survodutide in MASH and fibrosis. N. Engl. J. Med. 391, 311–319 (2024).

    Article  CAS  PubMed  Google Scholar 

  138. Nahra, R. et al. Effects of cotadutide on metabolic and hepatic parameters in adults with overweight or obesity and type 2 diabetes: a 54-week randomised phase 2b study. Diabetes Care 44, 1433–1442 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  139. Romero-Gómez, M. et al. A phase IIa active-comparator-controlled study to evaluate the efficacy and safety of efinopegdutide in patients with nonalcoholic fatty liver disease. J. Hepatol. 79, 888–897 (2023).

    Article  PubMed  Google Scholar 

  140. Sanyal, A. J. et al. Triple hormone receptor agonist retatrutide for metabolic dysfunction-associated steatotic liver disease: a randomized phase 2a trial. Nat. Med. 30, 2037–2048 (2024).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  141. Loomba, R. et al. Semaglutide 2.4 mg once weekly in patients with non-alcoholic steatohepatitis-related cirrhosis: a randomised, placebo-controlled phase 2 trial. Lancet Gastroenterol. Hepatol. 8, 511–522 (2023).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  142. Lawitz, E. J. et al. Efficacy, tolerability and pharmacokinetics of survodutide, a glucagon/glucagon-like peptide-1 receptor dual agonist, in cirrhosis. J. Hepatol. 81, 837–846 (2024).

    Article  CAS  PubMed  Google Scholar 

  143. Brown, E., Heerspink, H. J. L., Cuthbertson, D. J. & Wilding, J. P. H. SGLT2 inhibitors and GLP-1 receptor agonists: established and emerging indications. Lancet 389, 262–276 (2021).

    Article  Google Scholar 

  144. Kuchay, M. S. et al. Effect of empagliflozin on liver fat in patients with type 2 diabetes and nonalcoholic fatty liver disease: a randomized controlled trial (E-LIFT Trial). Diabetes Care 41, 1801–1808 (2018).

    Article  CAS  PubMed  Google Scholar 

  145. Kahl, S. et al. Empagliflozin effectively lowers liver fat content in well-controlled type 2 diabetes: a randomized, double-blind, phase 4, placebo-controlled trial. Diabetes Care 43, 298–305 (2020).

    Article  CAS  PubMed  Google Scholar 

  146. Latva-Rasku, A. et al. The SGLT2 inhibitor dapagliflozin reduces liver fat but does not affect tissue insulin sensitivity: a randomized, double-blind, placebo-controlled study with 8-week treatment in type 2 diabetes patients. Diabetes Care 42, 931–937 (2019).

    Article  CAS  PubMed  Google Scholar 

  147. Harrison, S. A. et al. Licogliflozin for nonalcoholic steatohepatitis: a randomized, double-blind, placebo-controlled, phase 2a study. Nat. Med. 28, 1432–1438 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  148. van der Aart-van der Beek, A. B., de Boer, R. A. & Heerspink, H. J. L. Kidney and heart failure outcomes associated with SGLT2 inhibitor use. Nat. Rev. Nephrol. 18, 294–306 (2022).

    Article  PubMed  Google Scholar 

  149. Cusi, K. et al. Long-term pioglitazone treatment for patients with nonalcoholic steatohepatitis and prediabetes or type 2 diabetes mellitus: a randomised trial. Ann. Intern. Med. 165, 305–315 (2016).

    Article  PubMed  Google Scholar 

  150. Loomba, R. et al. Denifanstat for the treatment of metabolic dysfunction-associated steatohepatitis: a multicentre, double-blind, randomised, placebo-controlled, phase 2b trial. Lancet Gastroenterol. Hepatol. 9, 1090–1100 (2024).

    Article  CAS  PubMed  Google Scholar 

  151. Harrison, S. A., Rolph, T., Knot, M. & Dubourg, J. FGF21 agonists: an emerging therapeutic for metabolic dysfunction-associated steatohepatitis and beyond. J. Hepatol. 81, 562–576 (2024).

    Article  CAS  PubMed  Google Scholar 

  152. Harrison, S. A. et al. Safety and efficacy of once-weekly efruxifermin versus placebo in nonalcoholic steatohepatitis (HARMONY): a multicentre, randomised, double-blind, placebo-controlled, phase 2b trial. Lancet Gastroenterol. Hepatol. 8, 1080–1093 (2023).

    Article  CAS  PubMed  Google Scholar 

  153. Loomba, R. et al. Randomised, controlled trial of the FGF21 analogue pegozafermin in NASH. N. Engl. J. Med. 389, 998–1008 (2023).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  154. US National Library of Medicine. ClinicalTrials.gov https://clinicaltrials.gov/study/NCT06161571 (2025).

  155. US National Library of Medicine. ClinicalTrials.gov https://clinicaltrials.gov/study/NCT06215716 (2025).

  156. US National Library of Medicine. ClinicalTrials.gov https://clinicaltrials.gov/study/NCT06419374 (2025).

  157. Husain, M. et al. Semaglutide (SUSTAIN and PIONEER) reduces cardiovascular events in type 2 diabetes across varying cardiovascular risk. Diabetes Obes. Metab. 22, 442–451 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  158. Lincoff, A. M. et al. Semaglutide and cardiovascular outcomes in obesity without diabetes. N. Engl. J. Med. 389, 2221–2232 (2023).

    Article  CAS  PubMed  Google Scholar 

  159. Butler, J. et al. Semaglutide versus placebo in people with obesity-related heart failure with preserved ejection fraction: a pooled analysis of the STEP-HFpEF and STEP-HFpEF DM randomised trials. Lancet 403, 1635–1648 (2024).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  160. Perkovic, V. et al. Effects of semaglutide on chronic kidney disease in patients with type 2 diabetes. N. Engl. J. Med. 391, 109–121 (2024).

    Article  CAS  PubMed  Google Scholar 

  161. Zannad, F. et al. MASLD and MASH at the crossroads of hepatology trials and cardiorenal metabolic trials. J. Intern. Med. 296, 24–38 (2024).

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

C.D.B. is funded in part by the Southampton National Institute for Health and Care Research, Biomedical Research Centre (NIHR 203319). E.B. is funded by the Italian Ministry for Education, University and Research (MIUR) under the programme ‘Dipartimenti di Eccellenza 2018-2022’ Project code D15D18000410001 and Precision medicine to stratify disease severity and outcomes of patients with nonalcoholic fatty liver disease by using artificial intelligence – Next Generation EU – grant number 2022L273C9. E.B. and A.A. are funded by PNRR ‘D3 4 Health – Digital Driven Diagnostics, prognostics and therapeutics for sustainable Health care’, Piano Nazionale per gli investimenti Complementari (PNC) al Piano Nazionale di Ripresa e Resilienza – Decreto di Concessione n. 1986 del 9 dicembre 2022, Codice progetto MUR: PNC0000001 – CUP ENTE: B53C22006110001. A.V.-P. and E.B. are funded by IMI Litmus, MRC Programme grant MC_UU_00014/2, BHF programme grant RG/18/7/33636. Caixa Foundation and Spanish Government ATRAE Programme.

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Authors and Affiliations

  1. National Institute for Health and Care Research, Southampton Biomedical Research Centre, University Hospital Southampton and University of Southampton, Southampton, UK

    Christopher D. Byrne

  2. Division of Gastroenterology and Hepatology, Department of Medical Sciences, University of Turin, Turin, Italy

    Angelo Armandi & Elisabetta Bugianesi

  3. Institute of Metabolic Science, MRC MDU Unit, University of Cambridge, Cambridge, UK

    Vanessa Pellegrinelli & Antonio Vidal-Puig

  4. Centro de Investigacion Principe Felipe, Valencia, Spain

    Vanessa Pellegrinelli & Antonio Vidal-Puig

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All authors researched data for the article. E.B., C.D.B. and A.V.-P. contributed substantially to discussion of the content. All authors wrote the article. E.B., C.D.B. and A.V.-P. reviewed and/or edited the manuscript before submission.

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Correspondence to Elisabetta Bugianesi.

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C.D.B. has received research grant funding from Echosens (France). E.B. served as a consultant for Boehringer, MSD, Novo Nordisk and Pfizer; and a speaker for MSD, Novo Nordisk and Madrigal. She received research grants from Gilead Sciences. The other authors declare no competing interests.

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Byrne, C.D., Armandi, A., Pellegrinelli, V. et al. Μetabolic dysfunction-associated steatotic liver disease: a condition of heterogeneous metabolic risk factors, mechanisms and comorbidities requiring holistic treatment. Nat Rev Gastroenterol Hepatol 22, 314–328 (2025). https://doi.org/10.1038/s41575-025-01045-z

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