Metabolic associated fatty liver disease (MAFLD) is the commonest cause of chronic liver disease, which is associated with obesity and diabetes. However, it also occurs in lean individuals especially in Asian populations.
The participants of Tzu Chi MAFLD cohort (TCMC) including health controls or MAFLD patients were enrolled. MAFLD was defined as fatty liver in imaging without hepatitis B virus, hepatitis C virus infection, drug, alcohol or other known causes of chronic liver disease. Lean MAFLD was defined as MAFLD in lean subjects (BMI < 23 kg/m2).
A total of 880 subjects were included for final analysis. Of 394 MAFLD patients, 65 (16.5%) patients were diagnosed as lean MAFLD. Lean MAFLD patients were elder, higher percentage of female gender, lower ALT, diastolic blood pressure, triglyceride, and waist circumference but higher HDL than non-lean MAFLD patients. Using binary regression analysis, elder age and lower waist circumference were associated with lean MAFLD. Compared with lean healthy controls, lean MAFLD patients had higher BMI, waist circumference, and percentage of hypertension. In body composition, fatty tissue index (FTI), lean tissue index (LTI) ,and total body water (TBW) were lower in lean MAFLD than non-lean MAFLD patients; but they were comparable with lean healthy controls.
The prevalence of lean MAFLD was 16.5% in this study population and it was higher in elder age, especially of female subjects. Lean MAFLD patients had different metabolic profiles compared with lean healthy controls, but different body composition compared with non-lean MAFLD patients.
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The data that support the findings of this study are available from the corresponding author, upon reasonable request.
Eslam M, Sarin SK, Wong VW, Fan JG, Kawaguchi T, Ahn SH, et al. The Asian Pacific association for the study of the liver clinical practice guidelines for the diagnosis and management of metabolic associated fatty liver disease. Hepatol Int 2020.https://doi.org/10.1007/s12072-020-10094-2.
Eslam M, Sanyal AJ, George J. International consensus panel MAFLD: a consensus-driven proposed nomenclature for metabolic associated fatty liver disease. Gastroenterology 2020;158(7):1999–2014 (e1)
Eslam M, Newsome PN, Sarin SK, Anstee QM, Targher G, Romero-Gomez M, et al. A new definition for metabolic dysfunction-associated fatty liver disease: an international expert consensus statement. J Hepatol 2020;73(1):202–209
Younossi Z, Anstee QM, MariettiM HT, HenryL E, et al. Global burden of NAFLD and NASH: trends, predictions, risk factors and prevention. Nat Rev Gastroenterol Hepatol 2018;15:11–20
Golabi P, Paik JM, Arshad T, Younossi Y, Mishra A, Younossi ZM. Mortality of NAFLD according to the body composition and presence of metabolic abnormalities. Hepatol Commun 2020;4(8):1136–1148
Kumar R, Rastogi A, Sharma MK, Bhatia V, Garg H, Bihari C, et al. Clinicopathological characteristics and metabolic profiles of non-alcoholic fatty liver disease in Indian patients with normal body mass index: do they differ from obese or overweight non-alcoholic fatty liver disease? Indian J Endocrinol Metab 2013;17:665–671
Hl Z, Wang NJ, Han B, Li Q, Chen Y, Zhu CF, et al. Low vitamin D levels and non-alcoholic fatty liver disease, evidence for their independent association in men in East China: a cross-sectional study [Survey on Prevalence in East China for metabolic diseases and risk factors (SPECT-China)]. Br J Nutr 2016;115:1352–1359
Cichoż-Lach H, Michalak A. A comprehensive review of bioelectrical impedance analysis and other methods in the assessment of nutritional status in patients with liver cirrhosis. Gastroenterol Res Pract 2017;2017:6765856
Feldman A, Eder SK, Felder TK, Kedenko L, Paulweber B, Stadlmayr A, et al. Clinical and metabolic characterization of lean caucasian subjects with non-alcoholic fatty liver. Am J Gastroenterol 2017;112:102–110
Shah P, Rathi P, Mandot A, Pal A, Ahire D. Study and comparison of metabolic profile of lean and obese subjects with non alcoholic fatty liver disease. J Assoc Physicians India 2020;68(8):51–54
Sterling RK, Lissen E, Clumeck N, Sola R, Correa MC, Montaner J, et al. Development of a simple noninvasive index to predict significant fibrosis in patients with HIV/HCV coinfection. Hepatology 2006;43:1317–1325
Wang C-C, Liu C-H, Lin C-L, Wang P-C, Tseng T-C, Lin HH, et al. Fibrosis index based on four factors better predicts advanced fibrosis or cirrhosis than aspartate aminotransferase/platelet ratio index in chronic hepatitis C patients. J Formos Med Assoc 2015;114:923–928
Wang YW, Lin TY, Peng CH, Huang JL, Hung SC. Factors associated with decreased lean tissue index in patients with chronic kidney disease. Nutrients 2017;9:434
Hung SC, Kuo KL, Peng CH, Wu CH, Lien YC, Wang YC, et al. Volume overload correlates with cardiovascular risk factors in patients with chronic kidney disease. Kidney Int 2014;85(3):703–709
Young S, Tariq R, Provenza J, Satapathy SK, Faisal K, Choudhry A, et al. Prevalence and profile of nonalcoholic fatty liver disease in lean adults: systematic review and meta-analysis. Hepatol Commun 2020;4(7):953–972
Shi Y, Wang Q, Sun Y, Zhao X, Kong Y, Ou X, et al. The prevalence of lean/nonobese nonalcoholic fatty liver disease: a systematic review and meta-analysis. J Clin Gastroenterol 2020;54(4):378–387
Ye Q, Zou B, Yeo YH, Li J, Huang DQ, Wu Y, 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(8):739–752
Wong VW, Hui AY, Tsang SW, Chan JLY, Wong GLH, Chan AWH, et al. Prevalence of undiagnosed diabetes and postchallenge hyperglycaemia in Chinese patients with non-alcoholic fatty liver disease. Aliment Pharmacol Ther 2006;24:1215–1222
Lu FB, Zheng KI, Rios RS, Targher G, Byrne CD, Zheng MH. Global epidemiology of lean non-alcoholic fatty liver disease: a systematic review and meta-analysis. J Gastroenterol Hepatol 2020 https://doi.org/10.1111/jgh.15156.
Younossi ZM, Stepanova M, Negro F, Hallaji S, Younossi Y, Lam B, et al. Nonalcoholic fatty liver disease in lean individuals in the United States. Med (Baltim) 2012;91:319–327
Honda Y, Yoneda M, Kessoku T, Ogawa Y, Tomeno W, Imajo K, et al. Characteristics of non-obese non-alcoholic fatty liver disease: effect of genetic and environmental factors. Hepatol Res 2016;46:1011–1018
Feng RN, Du SS, Wang C, Li YC, Liu LY, Guo FC, et al. Lean-non-alcoholic fatty liver disease increases risk for metabolic disorders in a normal weight Chinese population. World J Gastroenterol 2014;20:17932–17940
Alam S, Gupta UD, Alam M, Kabir J, Chowdhury ZR, Alam AK. Clinical, anthropometric, biochemical, and histological characteristics of nonobese nonalcoholic fatty liver disease patients of Bangladesh. Indian J Gastroenterol 2014;33:452–457
Leung JC, Loong TC, Wei JL, Wong GL, Chan AW, Choi PC, et al. Histological severity and clinical outcomes of nonalcoholic fatty liver disease in nonobese patients. Hepatology 2017;65:54–64
Kim HJ, Kim HJ, Lee KE, Kim DJ, Kim SK, Ahn CW, et al. Metabolic significance of nonalcoholic fatty liver disease in nonobese, nondiabetic adults. Arch Intern Med 2004;164:2169–2175
Akyuz U, Yesil A, Yilmaz Y. Characterization of lean patients with nonalcoholic fatty liver disease: potential role of high hemoglobin levels. Scand J Gastroenterol 2015;50:341–346
Margariti E, Deutsch M, Manolakopoulos S, Papatheodoridis GV. Non-alcoholic fatty liver disease may develop in individuals with normal body mass index. Ann Gastroenterol 2012;25:45–51
Eslam M, Hashem AM, Leung R, Romero-Gomez M, Berg T, Dore GJ, International Hepatitis C Genetics Consortium (IHCGC), et al. Interferon-λ rs12979860 genotype and liver fibrosis in viral and non-viral chronic liver disease. Nat Commun 2015;6:6422
Petta S, Valenti L, Tuttolomondo A, Dongiovanni P, Pipitone RM, Cammà C, et al. Interferon lambda 4 rs368234815 TT>δG variant is associated with liver damage in patients with nonalcoholic fatty liver disease. Hepatology 2017;66(6):1885–1893
Trépo E, Romeo S, Zucman-Rossi J, Nahon P. PNPLA3 gene in liver diseases. J Hepatol 2016;65(2):399–412
Eslam M, Valenti L, Romeo S. Genetics and epigenetics of NAFLD and NASH: clinical impact. J Hepatol 2018;68(2):268–279
Valenti LVC, Baselli GA. Genetics of nonalcoholic fatty liver disease: a 2018 update. Curr Pharm Des 2018;24(38):4566–4573
Eslam M, George J. Genetic contributions to NAFLD: leveraging shared genetics to uncover systems biology. Nat Rev Gastroenterol Hepatol 2020;17:40–52
Yasutake K, Nakamuta M, Shima Y, Ohyama A, Masuda K, Haruta N, et al. Nutritional investigation of non-obese patients with non-alcoholic fatty liver disease: the significance of dietary cholesterol. Scand J Gastroenterol 2009;44(4):471–477
Duarte SMB, Stefano JT, Miele L, Ponziani FR, Souza-Basqueira M, Okada LSRR, et al. Gut microbiome composition in lean patients with NASH is associated with liver damage independent of caloric intake: a prospective pilot study. Nutr Metab Cardiovasc Dis 2018;28(4):369–384
Chen F, Esmaili S, Rogers GB, Bugianesi E, Petta S, Marchesini G, et al. Lean NAFLD: a distinct entity shaped by differential metabolic adaptation. Hepatology 2020;71(4):1213–1227
Yun Y, Kim HN, Lee EJ, Ryu S, Chang Y, Shin H, et al. Fecal and blood microbiota profiles and presence of nonalcoholic fatty liver disease in obese versus lean subjects. PLoS ONE 2019;14(3):e0213692
Ampuero J, Aller R, Gallego-Durán R, Banales JM, Crespo J, García-Monzón C, et al. The effects of metabolic status on non-alcoholic fatty liver disease-related outcomes, beyond the presence of obesity. Aliment Pharmacol Ther 2018;48(11–12):1260–1270
Eslam M, Fan JG, Mendez-Sanchez N. Non-alcoholic fatty liver disease in non-obese individuals: the impact of metabolic health. Lancet Gastroenterol Hepatol 2020;5(8):713–715
Park YW, Zhu S, Heshka S, Carnethon MR, Heymsfield SB. The metabolic syndrome: prevalence and associated risk factor findings in the US population from the third national health and nutrition examination survey, 1988–1994. Arch Intern Med 2003;163:427–446
Golabi P, Paik JM, Arshad T, Younossi Y, Mishra A, Younossi ZM. Mortality of NAFLD according to the body composition and presence of metabolic abnormalities. Hepatol Commun 2020;4:1136–1148
Wattacheril J, Sanyal AJ. Lean NAFLD: an underrecognized outlier. Curr Hepatol Rep 2016;15(2):134–139
Volpi E, Nazemi R, Fujita S. Muscle tissue changes with aging. Curr Opin Clin Nutr Metab Care 2004;7(4):405–410
Pacifico L, Perla FM, Chiesa C. Sarcopenia and nonalcoholic fatty liver disease: a causal relationship. HepatoBil Surg Nutr 2019;8:2
Yu R, Shi Q, Liu L, Chen L. Relationship of sarcopenia with steatohepatitis and advanced liver fibrosis in non-alcoholic fatty liver disease: a meta-analysis. BMC Gastroenterol 2018;18:51
Wong VW, Wong GL, Chan RS, Shu SS, Cheung BH, Li LS, et al. Beneficial effects of lifestyle intervention in non-obese patients with non-alcoholic fatty liver disease. J Hepatol 2018;69(6):1349–1356
Jin YJ, Kim KM, Hwang S, Lee SG, Ha TY, Song GW, et al. Exercise and diet modification in non-obese non-alcoholic fatty liver disease: analysis of biopsies of living liver donors. J Gastroenterol Hepatol 2012;27:1341–1347
Petroni ML, Caletti MT, Dalle Grave R, Bazzocchi A, Aparisi Gómez MP, Marchesini G. Prevention and treatment of sarcopenic obesity in women. Nutrients 2019;11(6):1302
Wei JL, Leung JC, Loong TC, Wong GL, Yeung DK, Chan RS, 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;110:1306–1314
This work was supported by grants (No: TCRD-TPE-108-2) from Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation and the Taiwan Liver Disease Consortium (109-2321-B-002 -034), Ministry of Science and Technology, Taiwan.
Conflict and interest
Yu-Ming Cheng, Jia-Horng Kao and Chia-Chi Wang authors declare no conflict and interest.
The study was performed in accordance with the principles of the 1975 Declaration of Helsinki and approved by the Ethical Committee of Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation with waived informed consent.
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Cheng, YM., Kao, JH. & Wang, CC. The metabolic profiles and body composition of lean metabolic associated fatty liver disease. Hepatol Int (2021). https://doi.org/10.1007/s12072-021-10147-0
- Metabolic profiles
- Waist circumference
- Body composition
- Bioelectrical impedance analysis
- Fatty tissue index
- Lean tissue index
- Sarcopenic obesity