REVIEW PAPER
Metabolic dysfunction-associated steatotic liver disease: Prevalence and progression in lean patients
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1
Department of Anesthesiology and Intensive Care, Gabriel Narutowicz Municipal Specialist Hospital,
Krakow, Poland, Poland
2
Jan Kochanowski University, Collegium Medicum, Poland
3
Department of Internal Medicine, Integrated Provincial Hospital, Poland
Submission date: 2025-02-06
Final revision date: 2025-04-04
Acceptance date: 2025-04-05
Online publication date: 2025-11-05
Corresponding author
Gerard Stupecki
Porucznika Halszki 24/9, 30-611 Kraków, Poland. Tel.: +48 666 397 509
KEYWORDS
TOPICS
ABSTRACT
Introduction:
Metabolic dysfunction-associated steatotic liver disease (MASLD), previously known as non-alcoholic fatty liver disease (NAFLD), is a common liver disease linked to metabolic dysfunction. While often associated with obesity, MASLD also affects lean individuals, raising questions about its underlying mechanisms and clinical implications.
Aim:
This paper aims to review the latest insights into MASLD, with a specific focus on lean individuals, exploring its prevalence, pathogenesis, cardiovascular risk and treatment strategies.
Material and methods:
A systematic review was conducted using PubMed and Google Scholar to examine recent studies on MASLD, particularly in lean patients. Key terms included ‘metabolic dysfunction-associated steatotic liver disease’ and ‘nonalcoholic fatty liver disease.’
Results and discussion:
Approximately 10%–20% of MASLD cases occur in lean individuals, who exhibit impaired glucose metabolism and visceral fat accumulation. Despite fewer metabolic comorbidities, lean MASLD patients show similar disease severity and poorer outcomes compared to obese patients. The condition is linked to insulin resistance, genetic factors, and alterations in the gut microbiome. Cardiovascular risk in lean MASLD patients is lower than in obese counterparts, but advanced age and hepatic fibrosis increase the likelihood of cardiovascular complications. Moreover, lean patients face higher overall mortality rates, with hepatocellular carcinoma more prevalent among them.
Conclusions:
Lean MASLD remains an under-recognized but significant condition. Early diagnosis, personalized treatment approaches, and further research are essential for improving outcomes. Future studies should focus on refining diagnostic tools, identifying biomarkers, and developing tailored therapies for lean patients.
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REFERENCES (27)
1.
Ng CH, Huang DQ, Nguyen MH. Nonalcoholic fatty liver disease versus metabolic-associated fatty liver disease: Prevalence, outcomes and implications of a change in name. Clin Mol Hepatol. 2022;28:790–801.
https://doi.org/10.3350/cmh.20....
2.
Wijarnpreecha K, Li F, Lundin SK, et al. Higher mortality among lean patients with non-alcoholic fatty liver disease despite fewer metabolic comorbidities. Aliment Pharmacol Ther. 2023;57(9):1014–1027.
https://doi.org/10.1111/apt.17....
3.
Sato-Espinoza K, Chotiprasidhi P, Huaman MR, Díaz-Ferrer J. Update in lean metabolic dysfunction-associated steatotic liver disease. World J Hepatol. 2024;16(3):452–464.
https://doi.org/10.4254/wjh.v1....
5.
Rinaldi R, De Nucci S, Donghia R, et al. Gender Differences in Liver Steatosis and Fibrosis in Overweight and Obese Patients with Metabolic Dysfunction-Associated Steatotic Liver Disease before and after 8 Weeks of Very Low-Calorie Ketogenic Diet. Nutrients. 2024;16(10):1408.
https://doi.org/10.3390/nu1610....
6.
Younossi ZM, Stepanova M, Negro F, et al. Nonalcoholic fatty liver disease in lean individuals in the United States. Medicine (Baltimore). 2012;91(6):319–327.
https://doi.org/10.1097/MD.0b0....
7.
Rinella ME, Lazarus JV, Ratziu V, et al. NAFLD Nomenclature consensus group. A multisociety Delphi consensus statement on new fatty liver disease nomenclature. Hepatology. 2023;78(6):1966–1986.
https://doi.org/10.1016/j.jhep....
8.
Long MT, Noureddin M, Lim JK. AGA Clinical Practice Update: Diagnosis and Management of Nonalcoholic Fatty Liver Disease in Lean Individuals: Expert Review. Gastroenterology. 2022;163(3):764–774.e1.
https://doi.org/10.1053/j.gast....
9.
De A, Bhagat N, Mehta M, Taneja S, Duseja A. Metabolic dysfunction- associated steatotic liver disease (MASLD) definition is better than MAFLD criteria for lean patients with NAFLD. J Hepatol. 2024;80(2):e61–e62.
https://doi.org/10.1016/j.jhep....
10.
Loomba R, Wong VW. Implications of the new nomenclature of steatotic liver disease and definition of metabolic dysfunction-associated steatotic liver disease. Aliment Pharmacol Ther. 2024;59(2):150–156.
https://doi.org/10.1111/apt.17....
11.
Buzova D, Maugeri A, Liguori A, et al. Circulating histone signature of human lean metabolic-associated fatty liver disease (MAFLD). Clin Epigenetics. 2020;12(1):126.
https://doi.org/10.1186/s13148....
13.
Denkmayr L, Feldman A, Stechemesser L, et al. Lean Patients with Non-Alcoholic Fatty Liver Disease Have a Severe Histological Phenotype Similar to Obese Patients. J Clin Med. 2018;7(12):562.
https://doi.org/10.3390/jcm712....
14.
Zeng J, Yang RX, Sun C, el al. Prevalence, clinical characteristics, risk factors, and indicators for lean Chinese adults with nonalcoholic fatty liver disease. World J Gastroenterol. 2020;26(15):1792–1804.
https://doi.org/10.3748/wjg.v2....
15.
Wei JL, Leung JC, Loong TC, et al. Prevalence and Severity of Nonalcoholic Fatty Liver Disease in Non-Obese Patients: A Population Study Using Proton-Magnetic Resonance Spectroscopy. Am J Gastroenterol. 2015;110(9):1306–14; quiz 1315.
https://doi.org/10.1038/ajg.20....
16.
Shen J, Wong GL, Chan HL, el al. PNPLA3 gene polymorphism accounts for fatty liver in community subjects without metabolic syndrome. Aliment Pharmacol Ther. 2014;39(5):532–9.
https://doi.org/10.1111/apt.12....
17.
Souza M, Diaz I, Al-Sharif L. Liver and cardiovascular outcomes in lean non-alcoholic fatty liver disease: an updated systematic review and meta-analysis of about 1 million individuals. Hepatol Int. 2024;18(5):1396–1415.
https://doi.org/10.1007/s12072....
18.
Nso N, Mergen D, Ikram M, et al. Cardiovascular morbidity and mortality in lean vs. non-lean MASLD: A comprehensive meta-analysis. Curr Probl Cardiol. 2024;49(6):102569.
https://doi.org/10.1016/j.cpca....
19.
Danpanichkul P, Suparan K, Prasitsumrit V, Ahmed A, Wijarnpreecha K, Kim D. Long-term Outcomes and Risk Modifiers of MASLD Between Lean and Non-Lean Populations. Clin Mol Hepatol. 2024.
https://doi.org/10.3350/cmh.20....
20.
Semmler, G, Wernly, S, Bachmayer, S, et al. Nonalcoholic fatty liver disease in lean subjects: associations with metabolic dysregulation and cardiovascular riska single-center cross-sectional study. Clin Transl Gastroenterol. 2021;12:e00326.
https://doi.org/10.14309/ctg.0....
21.
Ciardullo S, Muraca E, Vergani M, Invernizzi P, Perseghin G. Advancements in pharmacological treatment of NAFLD/MASLD: a focus on metabolic and liver- targeted interventions. Gastroenterol Rep (Oxf). 2024;12:goae029.
https://doi.org/10.1093/gastro....
22.
Njei B, Ameyaw P, Al-Ajlouni Y, Njei LP, Boateng S. Diagnosis and Management of Lean Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD): A Systematic Review. Cureus. 2024;16(10):e71451.
https://doi.org/10.7759/cureus....
23.
European Association for the Study of the Liver (EASL); European Association for the Study of Diabetes (EASD); European Association for the Study of Obesity (EASO). EASL-EASD-EASO Clinical Practice Guidelines on the management of metabolic dysfunction-associated steatotic liver disease (MASLD). J Hepatol. 2024;81(3):492–542.
https://doi.org/10.1016/j.jhep....
24.
Wang W, Ren J, Zhou W, et al. Lean non-alcoholic fatty liver disease (Lean-NAFLD) and the development of metabolic syndrome: a retrospective study. Sci Rep. 2022;12(1):10977.
https://doi.org/10.1038/s41598....
25.
Sun W, Lv Y, Wang L, et al. Comparison of Risk Factors Between Lean and Nonlean Metabolic Dysfunction-Associated Steatotic Liver Disease in Individuals With Type 2 Diabetes: A Multicenter Study. Endocr Pract. 2024;30(12):1171–1179.
https://doi.org/10.1016/j.epra....
26.
Almomani A, Kumar P, Onwuzo S, et al. Epidemiology and prevalence of lean nonalcoholic fatty liver disease and associated cirrhosis, hepatocellular carcinoma, and cardiovascular outcomes in the United States: a population-based study and review of literature. J Gastroenterol Hepatol. 2023;38(2):269–273.
https://doi.org/10.1111/jgh.16....
27.
Lee Y, Cho EJ, Choe EK, et al. Author Correction: Genome-wide association study of metabolic dysfunctionassociated fatty liver disease in a Korean population. Sci Rep. 2024;14(1):11030.
https://doi.org/10.1038/s41598....