REFERENCES
1. Eslam M, Newsome PN, Sarin SK, et al. A new definition for metabolic dysfunction-associated fatty liver disease: an international expert consensus statement. J Hepatol. 2020;73:202-9.
2. Eslam M, El-Serag HB, Francque S, et al. Metabolic (dysfunction)-associated fatty liver disease in individuals of normal weight. Nat Rev Gastroenterol Hepatol. 2022;19:638-51.
3. Ampuero J, Aller R, Gallego-Durán R, et al. ; HEPAmet Registry. The effects of metabolic status on non-alcoholic fatty liver disease-related outcomes, beyond the presence of obesity. Aliment Pharmacol Ther. 2018;48:1260-70.
4. 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;78:1966-86.
5. Cheah MCC, Crane H, George J. Global prevalence, metabolic characteristics, and outcomes of lean-MAFLD: a systematic review and meta-analysis. Hepatol Int. 2025;19:607-18.
6. Cheng YM, Kao JH, Wang CC. The metabolic profiles and body composition of lean metabolic associated fatty liver disease. Hepatol Int. 2021;15:405-12.
7. Gofton C, Clark-Dickson M, George J. Lean metabolic-associated fatty liver disease. Endocrinol Metab Clin North Am. 2023;52:431-44.
8. Choochuay K, Kunhapan P, Puangpetch A, et al. Associations of PNPLA3 and LEP genetic polymorphisms with metabolic-associated fatty liver disease in Thai people living with human immunodeficiency virus. World J Hepatol. 2024;16:366-78.
9. Souza M, Diaz I, Barchetta I, Mantovani A. Gastrointestinal cancers in lean individuals with non-alcoholic fatty liver disease: a systematic review and meta-analysis. Liver Int. 2024;44:6-14.
10. Moreno-Vedia J, Girona J, Ibarretxe D, Masana L, Rodríguez-Calvo R. Unveiling the role of the fatty acid binding protein 4 in the metabolic-associated fatty liver disease. Biomedicines. 2022;10:197.
11. Sethi JK, Vidal-Puig A. Visfatin: the missing link between intra-abdominal obesity and diabetes? Trends Mol Med 2005;11:344-7.
12. Després JP. Excess visceral adipose tissue/ectopic fat the missing link in the obesity paradox? J Am Coll Cardiol 2011;57:1887-9.
13. Virtue S, Vidal-Puig A. Adipose tissue expandability, lipotoxicity and the metabolic syndrome--an allostatic perspective. Biochim Biophys Acta. 2010;1801:338-49.
14. Kim HS, Lee J, Kim EH, et al. Association of myosteatosis with nonalcoholic fatty liver disease, severity, and liver fibrosis using visual muscular quality map in computed tomography. Diabetes Metab J. 2023;47:104-17.
15. Singh S, Allen AM, Wang Z, Prokop LJ, Murad MH, Loomba R. Fibrosis progression in nonalcoholic fatty liver vs nonalcoholic steatohepatitis: a systematic review and meta-analysis of paired-biopsy studies. Clin Gastroenterol Hepatol. 2015;13:643-54.e1-9.
16. Pezzino S, Sofia M, Faletra G, et al. Gut-liver axis and non-alcoholic fatty liver disease: a vicious circle of dysfunctions orchestrated by the gut microbiome. Biology. 2022;11:1622.
17. Guha S, Sesili S, Mir IH, Thirunavukkarasu C. Epigenetics and mitochondrial dysfunction insights into the impact of the progression of non-alcoholic fatty liver disease. Cell Biochem Funct. 2023;41:4-19.
18. Ramírez-Mejía MM, Jiménez-Gutiérrez C, Eslam M, George J, Méndez-Sánchez N. Breaking new ground: MASLD vs. MAFLD-which holds the key for risk stratification? Hepatol Int 2024;18:168-78.
19. Dallio M, Romeo M, Di Nardo F, et al. From “MAFLD” to “MASLD”: was this revolution worth it? A head-to-head comparison of MAFLD and MASLD criteria in estimating liver disease progression and cardiovascular risk in real life. Livers. 2025;5:58.
20. 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:e61-2.
21. Pan Z, Khatry MA, Yu ML, et al. MAFLD: an ideal framework for understanding disease phenotype in individuals of normal weight. Ther Adv Endocrinol Metab. 2024;15:20420188241252543.
22. Kawaguchi T, Tsutsumi T, Nakano D, Eslam M, George J, Torimura T. MAFLD enhances clinical practice for liver disease in the Asia-Pacific region. Clin Mol Hepatol. 2022;28:150-63.
24. He N, Zhang XY, Lyu BB, Wang ZY, Hao S, Zhang FN. [Research progress on clinical characteristics and pathological mechanisms of lean metabolic-associated fatty liver disease]. Zhonghua Gan Zang Bing Za Zhi. 2025;33:811-6.
25. Chan KE, Koh TJL, Tang ASP, et al. Global prevalence and clinical characteristics of metabolic-associated fatty liver disease: a meta-analysis and systematic review of 10 739 607 individuals. J Clin Endocrinol Metab. 2022;107:2691-700.
26. Ye Q, Zou B, Yeo YH, et al. Global prevalence, incidence, and outcomes of non-obese or lean non-alcoholic fatty liver disease: a systematic review and meta-analysis. Lancet Gastroenterol Hepatol. 2020;5:739-52.
27. Ito T, Ishigami M, Zou B, et al. The epidemiology of NAFLD and lean NAFLD in Japan: a meta-analysis with individual and forecasting analysis, 1995-2040. Hepatol Int. 2021;15:366-79.
28. Tang A, Ng CH, Phang PH, et al. Comparative burden of metabolic dysfunction in lean NAFLD vs non-lean NAFLD - a systematic review and meta-analysis. Clin Gastroenterol Hepatol. 2023;21:1750-60.e12.
29. Younes R, Govaere O, Petta S, et al. Caucasian lean subjects with non-alcoholic fatty liver disease share long-term prognosis of non-lean: time for reappraisal of BMI-driven approach? Gut 2022;71:382-90.
30. Chen F, Esmaili S, Rogers GB, et al. Lean NAFLD: a distinct entity shaped by differential metabolic adaptation. Hepatology. 2020;71:1213-27.
31. Bhattacharya I, Maity DK, Kumar A, et al. Beyond obesity: lean metabolic dysfunction-associated steatohepatitis from unveiling molecular pathogenesis to therapeutic advancement. Naunyn Schmiedebergs Arch Pharmacol. 2025;398:13647-65.
32. Lim TS, Chun HS, Kim SS, et al. Fibrotic burden in the liver differs across metabolic dysfunction-associated fatty liver disease subtypes. Gut Liver. 2023;17:610-9.
33. 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;7:562.
34. Rastogi A, Shasthry SM, Agarwal A, et al. Non-alcoholic fatty liver disease - histological scoring systems: a large cohort single-center, evaluation study. APMIS. 2017;125:962-73.
35. Sookoian S, Pirola CJ. Systematic review with meta-analysis: the significance of histological disease severity in lean patients with nonalcoholic fatty liver disease. Aliment Pharmacol Ther. 2018;47:16-25.
36. Bandyopadhyay S, Samajdar SS, Chaudhuri S, Das S. An insight into the updated pharmacotherapy of metabolic-associated fatty liver disease (MAFLD) or metabolic dysfunction-associated steatohepatitis (MASH) in lean individuals: a review. Hosp Pract 2024;52:123-9.
37. Zhu R, Xu C, Jiang S, et al. Risk factor analysis and predictive model construction of lean MAFLD: a cross-sectional study of a health check-up population in China. Eur J Med Res. 2025;30:137.
38. Wang Q, You H, Ou X, et al. Non-obese histologically confirmed NASH patients with abnormal liver biochemistry have more advanced fibrosis. Hepatol Int. 2019;13:766-76.
39. Nabi O, Lapidus N, Boursier J, et al. Lean individuals with NAFLD have more severe liver disease and poorer clinical outcomes (NASH-CO Study). Hepatology. 2023;78:272-83.
40. Ha J, Yim SY, Karagozian R. Mortality and liver-related events in lean versus non-lean nonalcoholic fatty liver disease: a systematic review and meta-analysis. Clin Gastroenterol Hepatol. 2023;21:2496-507.e5.
41. Alharthi J, Pan Z, Gloss BS, et al. Loss of metabolic adaptation in lean MAFLD is driven by endotoxemia leading to epigenetic reprogramming. Metabolism. 2023;144:155583.
42. Chahal D, Sharma D, Keshavarzi S, et al. Distinctive clinical and genetic features of lean vs overweight fatty liver disease using the UK Biobank. Hepatol Int. 2022;16:325-36.
43. Yoshida K, Yokota K, Kutsuwada Y, et al. Genome-wide association study of lean nonalcoholic fatty liver disease suggests human leukocyte antigen as a novel candidate locus. Hepatol Commun. 2020;4:1124-35.
44. Liu YL, Reeves HL, Burt AD, et al. TM6SF2 rs58542926 influences hepatic fibrosis progression in patients with non-alcoholic fatty liver disease. Nat Commun. 2014;5:4309.
45. Bale G, Vishnubhotla RV, Mitnala S, et al. Whole-exome sequencing identifies a variant in phosphatidylethanolamine N-methyltransferase gene to be associated with lean-nonalcoholic fatty liver disease. J Clin Exp Hepatol. 2019;9:561-8.
46. Longo M, Meroni M, Paolini E, et al. TM6SF2/PNPLA3/MBOAT7 loss-of-function genetic variants impact on NAFLD development and progression both in patients and in in vitro models. Cell Mol Gastroenterol Hepatol. 2022;13:759-88.
47. Ren G, Bai C, Yi S, Cong Q, Zhu Y. Mechanisms and therapeutic strategies for MAFLD targeting TLR4 signaling pathways. J Innate Immun. 2024;16:45-55.
48. Hagström H, Nasr P, Ekstedt M, et al. Risk for development of severe liver disease in lean patients with nonalcoholic fatty liver disease: a long-term follow-up study. Hepatol Commun. 2018;2:48-57.
49. 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;18:1396-415.
50. Alarabi M, Pan Z, Romero-Gómez M, George J, Eslam M. Telomere length and mortality in lean MAFLD: the other face of metabolic adaptation. Hepatol Int. 2024;18:1448-58.
51. Ochoa-Allemant P, Trivedi HD, Saberi B, Bonder A, Fricker ZP. Waitlist and posttransplantation outcomes of lean individuals with nonalcoholic fatty liver disease. Liver Transpl. 2023;29:145-56.
52. Jiao Q, Ren Y, Teng X, et al. Positive feedback between histone H4K16 lactylation and glycolysis promotes MAFLD progression. Hepatol Int. 2026;20:646-63.
53. Brion C, Hoang SA, Wang G, et al. MicroRNA isomiRs reveal novel pathways linked to disease activity and fibrosis in MASLD. Clin Mol Hepatol. 2026;32:706-20.
54. Xie F, Zheng W, Chen J, et al. Revisiting the causal impact of lipid traits on metabolic dysfunction-associated fatty liver disease: insights from a multidimensional plasma lipid profile. J Diabetes Investig. 2025;16:917-28.
55. Ren J, Wu M. Identification of novel therapeutic targets for MAFLD based on bioinformatics analysis combined with mendelian randomization. Int J Mol Sci. 2025;26:3166.
56. Kong J, Han X, Wei C. Causal relationship between metabolic dysfunction-associated fatty liver disease and endotoxin biomarkers: a Mendelian randomization study. Medicine. 2025;104:e42311.
57. Musso G, Gambino R, De Michieli F, et al. Dietary habits and their relations to insulin resistance and postprandial lipemia in nonalcoholic steatohepatitis. Hepatology. 2003;37:909-16.
58. Yasutake K, Nakamuta M, Shima Y, et al. Nutritional investigation of non-obese patients with non-alcoholic fatty liver disease: the significance of dietary cholesterol. Scand J Gastroenterol. 2009;44:471-7.
59. Enjoji M, Yasutake K, Kohjima M, Nakamuta M. Nutrition and nonalcoholic fatty liver disease: the significance of cholesterol. Int J Hepatol. 2012;2012:925807.
60. Kwak JH, Jun DW, Lee SM, et al. Lifestyle predictors of obese and non-obese patients with nonalcoholic fatty liver disease: a cross-sectional study. Clin Nutr. 2018;37:1550-7.
61. Viswanath A, Fouda S, Fernandez CJ, Pappachan JM. Metabolic-associated fatty liver disease and sarcopenia: a double whammy. World J Hepatol. 2024;16:152-63.
62. Cinque F, Cespiati A, Lombardi R, Guaraldi G, Sebastiani G. Nutritional and lifestyle therapy for NAFLD in people with HIV. Nutrients. 2023;15:1990.
63. Zhao Q, Yin Y, Deng Y. Metabolic associated fatty liver disease and sarcopenia additively increase mortality: a real-world study. Nutr Diabetes. 2023;13:21.
64. Keating SE, Chawla Y, De A, George ES. Lifestyle intervention for metabolic dysfunction-associated fatty liver disease: a 24-h integrated behavior perspective. Hepatol Int. 2024;18:959-76.
65. Beygi M, Ahi S, Zolghadri S, Stanek A. Management of metabolic-associated fatty liver disease/metabolic dysfunction-associated steatotic liver disease: from medication therapy to nutritional interventions. Nutrients. 2024;16:2220.
66. Eslam M, Fan JG, Yu ML, et al. The Asian Pacific association for the study of the liver clinical practice guidelines for the diagnosis and management of metabolic dysfunction-associated fatty liver disease. Hepatol Int. 2025;19:261-301.
67. Yun Y, Kim HN, Lee EJ, et al. Fecal and blood microbiota profiles and presence of nonalcoholic fatty liver disease in obese versus lean subjects. PLoS One. 2019;14:e0213692.
68. Dey P. Gut microbial signatures associated with the Indian lean MASLD phenotype. Front Nutr. 2025;12:1673517.
69. Colella M, Notaristefano R, Tragni M, Mandorino M. Gut microbiota in NAFLD/MASLD: functional dysbiosis and the gut-liver axis in disease progression. Livers. 2026;6:93.
70. Semmler G, Wernly S, Bachmayer S, et al. Nonalcoholic fatty liver disease in lean subjects: associations with metabolic dysregulation and cardiovascular risk-a single-center cross-sectional study. Clin Transl Gastroenterol. 2021;12:e00326.
71. Lakhdhir F, Muhammad AS, Qureshi AN, et al. Assessing mortality disparities among non-alcoholic fatty liver disease metabolic dysfunction fatty liver disease and metabolic dysfunction-associated liver disease: a comprehensive meta-analysis. Cureus. 2024;16:e71639.
72. Azimi A, Jolfayi AG, Rezayifar V, et al. The association between metabolic-associated fatty liver diseases and risk of colorectal polyps, neoplasia, and cancer: a systematic review and meta-analysis of over 56 million individuals. Clin Res Hepatol Gastroenterol. 2025;49:102652.
73. Shin HK, Park JH, Yu JH, et al. ; Korean Nonalcoholic Fatty Liver Study Group (KNSG). Association between telomere length and hepatic fibrosis in non-alcoholic fatty liver disease. Sci Rep. 2021;11:18004.
74. Abbaszadeh M, Hosseinpanah F, Tohidi M, Karimpour Reyhan S, Mahdavi M, Valizadeh M. Sex-specific impact of metabolic dysfunction-associated fatty liver disease on incident cardiovascular diseases and mortality. Endocrinol Diabetes Metab. 2025;8:e70035.
75. Moran-Salvador E, Mann J. Epigenetics and liver fibrosis. Cell Mol Gastroenterol Hepatol. 2017;4:125-34.
76. Sergi CM, Kehar M, Jimenez-Rivera C. Liver biopsy handling of metabolic-associated fatty liver disease (MAFLD): the Children’s Hospital of Eastern Ontario grossing protocol. Ther Adv Endocrinol Metab. 2024;15:20420188241227766.
77. Yan T, Zhang X, Wong T, Cheung R, Nguyen MH. Sex differences in adverse liver and nonliver outcomes in steatotic liver disease. JAMA Netw Open. 2024;7:e2448946.
78. Ekstedt M, Hagström H, Nasr P, et al. Fibrosis stage is the strongest predictor for disease-specific mortality in NAFLD after up to 33 years of follow-up. Hepatology. 2015;61:1547-54.
79. Jiang H, Li M, Yu H, et al. Body mass index and waist-to-height ratio effect on mortality in non-alcoholic fatty liver: revisiting the obesity paradox. Front Endocrinol. 2024;15:1419715.
80. Mostafa AM, Fouad Y, Gaber Y, Alem SA, Pan Z, Eslam M. Differential risk factors of fibrosis between lean and obese MAFLD. Clin Exp Med. 2025;25:211.
81. Somnay K, Wadgaonkar P, Sridhar N, Roshni P, Rao N, Wadgaonkar R. Liver fibrosis leading to cirrhosis: basic mechanisms and clinical perspectives. Biomedicines. 2024;12:2229.
82. Nusrat S, Khan MS, Fazili J, Madhoun MF. Cirrhosis and its complications: evidence based treatment. World J Gastroenterol. 2014;20:5442-60.
83. Orci LA, Sanduzzi-Zamparelli M, Caballol B, et al. Incidence of hepatocellular carcinoma in patients with nonalcoholic fatty liver disease: a systematic review, meta-analysis, and meta-regression. Clin Gastroenterol Hepatol. 2022;20:283-92.e10.
84. 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;49:102569.
85. Wakabayashi SI, Tamaki N, Kimura T, Umemura T, Kurosaki M, Izumi N. Natural history of lean and non-lean metabolic dysfunction-associated steatotic liver disease. J Gastroenterol. 2024;59:494-503.
86. Danpanichkul P, Suparan K, Prasitsumrit V, Ahmed A, Wijarnpreecha K, Kim D. Long-term outcomes and risk modifiers of metabolic dysfunction-associated steatotic liver disease between lean and non-lean populations. Clin Mol Hepatol. 2025;31:74-89.
87. Clayton-Chubb D, Kemp WW, Majeed A, et al. Steatotic liver disease in older adults: clinical implications and unmet needs. Nutrients. 2025;17:2189.
88. Lee H, Lim TS, Kim SU, Kim HC. Long-term cardiovascular outcomes differ across metabolic dysfunction-associated fatty liver disease subtypes among middle-aged population. Hepatol Int. 2022;16:1308-17.
89. Ezeani C, Omaliko C, Al-Ajlouni YA, Njei B. Mortality, hepatic decompensation, and cardiovascular- and renal-related outcomes in lean versus non-lean patients hospitalized with metabolic dysfunction-associated steatohepatitis (MASH). Cureus. 2024;16:e60968.
90. Mantovani A, Lombardi R, Cattazzo F, Zusi C, Cappelli D, Dalbeni A. MAFLD and CKD: an updated narrative review. Int J Mol Sci. 2022;23:7007.
91. Fukunaga S, Nakano D, Kawaguchi T, et al. Non-obese MAFLD is associated with colorectal adenoma in health check examinees: a multicenter retrospective study. Int J Mol Sci. 2021;22:5462.
92. Fukunaga S, Mukasa M, Nakane T, et al. Impact of non-obese metabolic dysfunction-associated fatty liver disease on risk factors for the recurrence of esophageal squamous cell carcinoma treated with endoscopic submucosal dissection: a multicenter study. Hepatol Res. 2024;54:201-12.
93. Xu M, Gong R, Xie J, Xu S, Wang S. Clinical characteristics of lean and non-lean non-alcoholic fatty liver disease: a cross-sectional study. Nutr Metab. 2025;22:40.
94. Feng RN, Du SS, Wang C, et al. Lean-non-alcoholic fatty liver disease increases risk for metabolic disorders in a normal weight Chinese population. World J Gastroenterol. 2014;20:17932-40.
95. Mapouka M, Ndemazie NB, Ikedum I. S2326 outcomes of liver and cardiovascular metabolic diseases among lean vs non-lean individuals with dysfunction-associated steatotic liver disease: a meta-analysis. Am J Gastroenterol. 2025;120:S500.
96. Zhang Z, Lu J, Chen M, et al. Cause-specific mortality in lean individuals with metabolic dysfunction-associated steatotic liver disease. Lipids Health Dis. 2025;25:6.
97. Kechagias S, Ekstedt M, Simonsson C, Nasr P. Non-invasive diagnosis and staging of non-alcoholic fatty liver disease. Hormones. 2022;21:349-68.
98. Shao CX, Ye J, Dong Z, et al. Steatosis grading consistency between controlled attenuation parameter and MRI-PDFF in monitoring metabolic associated fatty liver disease. Ther Adv Chronic Dis. 2021;12:20406223211033119.
99. Eddowes PJ, Sasso M, Allison M, et al. Accuracy of fibroscan controlled attenuation parameter and liver stiffness measurement in assessing steatosis and fibrosis in patients with nonalcoholic fatty liver disease. Gastroenterology. 2019;156:1717-30.
100. Mózes FE, Lee JA, Selvaraj EA, et al. ; LITMUS Investigators. Diagnostic accuracy of non-invasive tests for advanced fibrosis in patients with NAFLD: an individual patient data meta-analysis. Gut. 2022;71:1006-19.
101. Hirose S, Matsumoto K, Tatemichi M, et al. Nineteen-year prognosis in Japanese patients with biopsy-proven nonalcoholic fatty liver disease: lean versus overweight patients. PLoS One. 2020;15:e0241770.
102. Feng Z, Zhao F, Wang Z, Tang X, Xie Y, Qiu L. The relationship between sarcopenia and metabolic dysfunction-associated fatty liver disease among the young and middle-aged populations. BMC Gastroenterol. 2024;24:111.
103. Li AA, Ahmed A, Kim D. Impact of sarcopenia on the progression of nonalcoholic fatty liver disease: a frequently forgotten association. Hepatobiliary Surg Nutr. 2019;8:260-1.
104. Chalasani N, Younossi Z, Lavine JE, et al. The diagnosis and management of nonalcoholic fatty liver disease: practice guidance from the American Association for the Study of Liver Diseases. Hepatology. 2018;67:328-57.
105. Hao X, Song H, Su X, et al. Prophylactic effects of nutrition, dietary strategies, exercise, lifestyle and environment on nonalcoholic fatty liver disease. Ann Med. 2025;57:2464223.
106. Rinella ME, Neuschwander-Tetri BA, Siddiqui MS, et al. AASLD Practice Guidance on the clinical assessment and management of nonalcoholic fatty liver disease. Hepatology. 2023;77:1797-835.
107. Sato-Espinoza K, Chotiprasidhi P, Huaman MR, Díaz-Ferrer J. Update in lean metabolic dysfunction-associated steatotic liver disease. World J Hepatol. 2024;16:452-64.
108. Chai XN, Zhou BQ, Ning N, et al. Effects of lifestyle intervention on adults with metabolic associated fatty liver disease: a systematic review and meta-analysis. Front Endocrinol. 2023;14:1081096.
109. Noureddin M, Rinella M, Taub R, et al. Effects of resmetirom on metabolic-dysfunction associated steatohepatitis in patients with weight loss and/or diabetes taking glucagon-like peptide-1 receptor agonists and other diabetes therapies: a secondary analysis of the MAESTRO-NASH trial. Aliment Pharmacol Ther. 2025;62:1089-99.
110. Fouad Y, Elwakil R, Sanai FM, et al. The African Middle East Association of Gastroenterology (AMAGE) clinical practice guidelines for the diagnosis and management of metabolic dysfunction associated fatty liver disease. Ann Hepatol. 2026;31:102180.
111. Mousa AM, Mahmoud M, AlShuraiaan GM. Resmetirom: the first disease-specific treatment for MASH. Int J Endocrinol. 2025;2025:6430023.
112. Schwabe RF, Tacke F, Sugimoto A, Friedman SL. Antifibrotic therapies for metabolic dysfunction-associated steatotic liver disease. JHEP Rep. 2025;7:101421.






