REFERENCES
1. Younossi Z, Anstee QM, Marietti M, et al. Global burden of NAFLD and NASH: trends, predictions, risk factors and prevention. Nat Rev Gastroenterol Hepatol 2018;15:11-20.
2. Best CH, Hartroft WS, et al. Liver damage produced by feeding alcohol or sugar and its prevention by choline. Br Med J 1949;2:1002-6. pl
4. Ludwig J, Viggiano TR, McGill DB, Oh BJ. Nonalcoholic steatohepatitis: mayo clinic experiences with a hitherto unnamed disease. Mayo Clin Proc 1980;55:434-8.
6. Clark JM, Brancati FL, Diehl AM. Nonalcoholic fatty liver disease. Gastroenterology 2002;122:1649-57.
7. 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.
8. Machado MV, Cortez-Pinto H. Management of fatty liver disease with the metabolic syndrome. Expert Rev Gastroenterol Hepatol 2014;8:487-500.
9. Younossi ZM, Stepanova M, Younossi Y, et al. Epidemiology of chronic liver diseases in the USA in the past three decades. Gut 2020;69:564-8.
10. Chen CH, Huang MH, Yang JC, et al. Prevalence and risk factors of nonalcoholic fatty liver disease in an adult population of taiwan: metabolic significance of nonalcoholic fatty liver disease in nonobese adults. J Clin Gastroenterol 2006;40:745-52.
11. Younossi ZM, Stepanova M, Negro F, et al. Nonalcoholic fatty liver disease in lean individuals in the United States. Medicine (Baltimore) 2012;91:319-27.
12. Young S, Tariq R, Provenza J, et al. Prevalence and profile of nonalcoholic fatty liver disease in lean adults: systematic review and meta-analysis. Hepatol Commun 2020;4:953-72.
13. 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.
14. Das K, Das K, Mukherjee PS, et al. Nonobese population in a developing country has a high prevalence of nonalcoholic fatty liver and significant liver disease. Hepatology 2010;51:1593-602.
15. Machado MV, Cortez-Pinto H. Non-invasive diagnosis of non-alcoholic fatty liver disease. A critical appraisal. J Hepatol 2013;58:1007-19.
16. Weir CB, Jan A. BMI classification percentile and cut off points. StatPearls. Treasure Island (FL): StatPearls Publishing; 2020.
17. Consultation WHOE. Appropriate body-mass index for Asian populations and its implications for policy and intervention strategies. Lancet 2004;363:157-63.
18. Shi Y, Wang Q, Sun Y, et al. The prevalence of lean/nonobese nonalcoholic fatty liver disease: a systematic review and meta-analysis. J Clin Gastroenterol 2020;54:378-87.
19. Bellentani S, Saccoccio G, Masutti F, et al. Prevalence of and risk factors for hepatic steatosis in Northern Italy. Ann Intern Med 2000;132:112-7.
20. 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.
21. Nishioji K, Sumida Y, Kamaguchi M, et al. Prevalence of and risk factors for non-alcoholic fatty liver disease in a non-obese Japanese population, 2011-2012. J Gastroenterol 2015;50:95-108.
22. 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;110:1306-14. quiz 15
23. Kim SS, Cho HJ, Kim HJ, et al. Nonalcoholic fatty liver disease as a sentinel marker for the development of diabetes mellitus in non-obese subjects. Dig Liver Dis 2018;50:370-7.
24. Sinn DH, Kang D, Cho SJ, et al. Lean non-alcoholic fatty liver disease and development of diabetes: a cohort study. Eur J Endocrinol 2019;181:185-92.
25. Browning JD, Szczepaniak LS, Dobbins R, et al. Prevalence of hepatic steatosis in an urban population in the United States: impact of ethnicity. Hepatology 2004;40:1387-95.
26. Alberti KG, Zimmet P, Shaw J, Group IDFETFC. The metabolic syndrome--a new worldwide definition. Lancet 2005;366:1059-62.
27. Sookoian S, Pirola CJ. Systematic review with meta-analysis: risk factors for non-alcoholic fatty liver disease suggest a shared altered metabolic and cardiovascular profile between lean and obese patients. Aliment Pharmacol Ther 2017;46:85-95.
28. Feldman A, Eder SK, Felder TK, et al. Clinical and metabolic characterization of lean caucasian subjects with non-alcoholic fatty liver. Am J Gastroenterol 2017;112:102-10.
29. 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.
30. Kumar R, Rastogi A, Sharma MK, 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;17:665-71.
31. Kwon YM, Oh SW, Hwang SS, Lee C, Kwon H, Chung GE. Association of nonalcoholic fatty liver disease with components of metabolic syndrome according to body mass index in Korean adults. Am J Gastroenterol 2012;107:1852-8.
32. Xu C, Yu C, Ma H, Xu L, Miao M, Li Y. Prevalence and risk factors for the development of nonalcoholic fatty liver disease in a nonobese Chinese population: the Zhejiang Zhenhai Study. Am J Gastroenterol 2013;108:1299-304.
33. Kim NH, Kim JH, Kim YJ, et al. Clinical and metabolic factors associated with development and regression of nonalcoholic fatty liver disease in nonobese subjects. Liver Int 2014;34:604-11.
34. Wong VW, Wong GL, Yeung DK, et al. Incidence of non-alcoholic fatty liver disease in Hong Kong: a population study with paired proton-magnetic resonance spectroscopy. J Hepatol 2015;62:182-9.
35. Niriella MA, Kasturiratne A, Pathmeswaran A, et al. Lean non-alcoholic fatty liver disease (lean NAFLD): characteristics, metabolic outcomes and risk factors from a 7-year prospective, community cohort study from Sri Lanka. Hepatol Int 2019;13:314-22.
36. Li L, Liu DW, Yan HY, Wang ZY, Zhao SH, Wang B. Obesity is an independent risk factor for non-alcoholic fatty liver disease: evidence from a meta-analysis of 21 cohort studies. Obes Rev 2016;17:510-9.
37. Kumar R, Mohan S. Non-alcoholic fatty liver disease in lean subjects: characteristics and implications. J Clin Transl Hepatol 2017;5:216-23.
38. Bernhardt P, Kratzer W, Schmidberger J, Graeter T, Gruener B, Group ES. Laboratory parameters in lean NAFLD: comparison of subjects with lean NAFLD with obese subjects without hepatic steatosis. BMC Res Notes 2018;11:101.
40. Trepo E, Valenti L. Update on NAFLD genetics: from new variants to the clinic. J Hepatol 2020;72:1196-209.
41. Adams LC, Lubbe F, Bressem K, Wagner M, Hamm B, Makowski MR. Non-alcoholic fatty liver disease in underweight patients with inflammatory bowel disease: a case-control study. PLoS One 2018;13:e0206450.
42. Buchman AL, Naini BV, Spilker B. The differentiation of intestinal-failure-associated liver disease from nonalcoholic fatty liver and nonalcoholic steatohepatitis. Semin Liver Dis 2017;37:33-44.
43. Duarte SMB, Stefano JT, Miele L, 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;28:369-84.
44. Yildiz Y, Sivri HS. Inborn errors of metabolism in the differential diagnosis of fatty liver disease. Turk J Gastroenterol 2020;31:3-16.
45. Machado MV, Diehl AM. Pathogenesis of nonalcoholic steatohepatitis. Gastroenterology 2016;150:1769-77.
46. Ruderman NB, Schneider SH, Berchtold P. The “metabolically-obese” normal-weight individual. Am J Clin Nutr 1981;34:1617-21.
47. Stefan N, Schick F, Haring HU. Causes, characteristics, and consequences of metabolically unhealthy normal weight in humans. Cell Metab 2017;26:292-300.
48. Kramer CK, Zinman B, Retnakaran R. Are metabolically healthy overweight and obesity benign conditions? A systematic review and meta-analysis. Ann Intern Med 2013;159:758-69.
49. Rothman KJ. BMI-related errors in the measurement of obesity. Int J Obes (Lond) 2008;32 Suppl 3:S56-9.
50. Gujral UP, Vittinghoff E, Mongraw-Chaffin M, et al. Cardiometabolic abnormalities among normal-weight persons from five racial/Ethnic Groups in the United States: a cross-sectional analysis of two cohort studies. Ann Intern Med 2017;166:628-36.
51. Wang B, Zhuang R, Luo X, et al. Prevalence of metabolically healthy obese and metabolically obese but normal weight in adults worldwide: a meta-analysis. Horm Metab Res 2015;47:839-45.
52. Taylor R, Holman RR. Normal weight individuals who develop type 2 diabetes: the personal fat threshold. Clin Sci (Lond) 2015;128:405-10.
53. Du T, Yu X, Zhang J, Sun X. Lipid accumulation product and visceral adiposity index are effective markers for identifying the metabolically obese normal-weight phenotype. Acta Diabetol 2015;52:855-63.
54. Neeland IJ, Ross R, Despres JP, et al. Visceral and ectopic fat, atherosclerosis, and cardiometabolic disease: a position statement. Lancet Diabetes Endocrinol 2019;7:715-25.
55. Zierath JR, Livingston JN, Thorne A, et al. Regional difference in insulin inhibition of non-esterified fatty acid release from human adipocytes: relation to insulin receptor phosphorylation and intracellular signalling through the insulin receptor substrate-1 pathway. Diabetologia 1998;41:1343-54.
56. Nielsen S, Guo Z, Johnson CM, Hensrud DD, Jensen MD. Splanchnic lipolysis in human obesity. J Clin Invest 2004;113:1582-8.
57. Feng R, Luo C, Li C, et al. Free fatty acids profile among lean, overweight and obese non-alcoholic fatty liver disease patients: a case - control study. Lipids Health Dis 2017;16:165.
58. Tchernof A, Despres JP. Pathophysiology of human visceral obesity: an update. Physiol Rev 2013;93:359-404.
59. Wensveen FM, Valentic S, Sestan M, Turk Wensveen T, Polic B. The “Big Bang” in obese fat: events initiating obesity-induced adipose tissue inflammation. Eur J Immunol 2015;45:2446-56.
60. Hamaguchi M, Kojima T, Itoh Y, et al. The severity of ultrasonographic findings in nonalcoholic fatty liver disease reflects the metabolic syndrome and visceral fat accumulation. Am J Gastroenterol 2007;102:2708-15.
61. Park BJ, Kim YJ, Kim DH, et al. Visceral adipose tissue area is an independent risk factor for hepatic steatosis. J Gastroenterol Hepatol 2008;23:900-7.
62. Chung GE, Kim D, Kwark MS, et al. Visceral adipose tissue area as an independent risk factor for elevated liver enzyme in nonalcoholic fatty liver disease. Medicine (Baltimore) 2015;94:e573.
63. Yu SJ, Kim W, Kim D, et al. Visceral obesity predicts significant fibrosis in patients with nonalcoholic fatty liver disease. Medicine (Baltimore) 2015;94:e2159.
64. Choe EY, Lee YH, Choi YJ, et al. Waist-to-calf circumstance ratio is an independent predictor of hepatic steatosis and fibrosis in patients with type 2 diabetes. J Gastroenterol Hepatol 2018;33:1082-91.
65. Kure T, Mawatari S, Imamura Y, et al. Nonalcoholic fatty liver disease is associated with both subcutaneous and visceral adiposity: a cross-sectional study. Medicine (Baltimore) 2019;98:e17879.
66. Kim D, Chung GE, Kwak MS, et al. Body fat distribution and risk of incident and regressed nonalcoholic fatty liver disease. Clin Gastroenterol Hepatol 2016;14:132-8.e4.
67. Kim HJ, Kim HJ, Lee KE, et al. Metabolic significance of nonalcoholic fatty liver disease in nonobese, nondiabetic adults. Arch Intern Med 2004;164:2169-75.
68. 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.
69. Shida T, Oshida N, Suzuki H, et al. Clinical and anthropometric characteristics of non-obese non-alcoholic fatty liver disease subjects in Japan. Hepatol Res 2020; doi: 10.1111/hepr.13543.
70. Nakamuta M, Kohjima M, Higuchi N, et al. The significance of differences in fatty acid metabolism between obese and non-obese patients with non-alcoholic fatty liver disease. Int J Mol Med 2008;22:663-7.
71. Karpe F, Pinnick KE. Biology of upper-body and lower-body adipose tissue--link to whole-body phenotypes. Nat Rev Endocrinol 2015;11:90-100.
72. Sahakyan KR, Somers VK, Rodriguez-Escudero JP, et al. Normal-weight central obesity: implications for total and cardiovascular mortality. Ann Intern Med 2015;163:827-35.
73. Snijder MB, Zimmet PZ, Visser M, Dekker JM, Seidell JC, Shaw JE. Independent and opposite associations of waist and hip circumferences with diabetes, hypertension and dyslipidemia: the AusDiab Study. Int J Obes Relat Metab Disord 2004;28:402-9.
74. Yusuf S, Hawken S, Ounpuu S, et al. Obesity and the risk of myocardial infarction in 27,000 participants from 52 countries: a case-control study. Lancet 2005;366:1640-9.
75. Tchoukalova YD, Votruba SB, Tchkonia T, Giorgadze N, Kirkland JL, Jensen MD. Regional differences in cellular mechanisms of adipose tissue gain with overfeeding. Proc Natl Acad Sci U S A 2010;107:18226-31.
76. Pinnick KE, Nicholson G, Manolopoulos KN, et al. Distinct developmental profile of lower-body adipose tissue defines resistance against obesity-associated metabolic complications. Diabetes 2014;63:3785-97.
77. Lotta LA, Gulati P, Day FR, et al. Integrative genomic analysis implicates limited peripheral adipose storage capacity in the pathogenesis of human insulin resistance. Nat Genet 2017;49:17-26.
78. Zheng RD, Chen ZR, Chen JN, Lu YH, Chen J. Role of body mass index, waist-to-height and waist-to-hip ratio in prediction of nonalcoholic fatty liver disease. Gastroenterol Res Pract 2012;2012:362147.
79. Lee YH, Kim SU, Song K, et al. Sarcopenia is associated with significant liver fibrosis independently of obesity and insulin resistance in nonalcoholic fatty liver disease: nationwide surveys (KNHANES 2008-2011). Hepatology 2016;63:776-86.
80. Hong HC, Hwang SY, Choi HY, et al. Relationship between sarcopenia and nonalcoholic fatty liver disease: the Korean sarcopenic obesity study. Hepatology 2014;59:1772-8.
81. Issa D, Alkhouri N, Tsien C, et al. Presence of sarcopenia (muscle wasting) in patients with nonalcoholic steatohepatitis. Hepatology 2014;60:428-9.
82. Koo BK, Kim D, Joo SK, et al. Sarcopenia is an independent risk factor for non-alcoholic steatohepatitis and significant fibrosis. J Hepatol 2017;66:123-31.
83. Petta S, Ciminnisi S, Di Marco V, et al. Sarcopenia is associated with severe liver fibrosis in patients with non-alcoholic fatty liver disease. Aliment Pharmacol Ther 2017;45:510-8.
84. 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.
85. Cai C, Song X, Chen Y, Chen X, Yu C. Relationship between relative skeletal muscle mass and nonalcoholic fatty liver disease: a systematic review and meta-analysis. Hepatol Int 2020;14:115-26.
86. Tobari M, Hashimoto E, Taniai M, et al. Characteristics of non-alcoholic steatohepatitis among lean patients in Japan: Not uncommon and not always benign. J Gastroenterol Hepatol 2019;34:1404-10.
87. Machado MV, Ferreira DM, Castro RE, et al. Liver and muscle in morbid obesity: the interplay of fatty liver and insulin resistance. PLoS One 2012;7:e31738.
88. Bhanji RA, Narayanan P, Allen AM, Malhi H, Watt KD. Sarcopenia in hiding: the risk and consequence of underestimating muscle dysfunction in nonalcoholic steatohepatitis. Hepatology 2017;66:2055-65.
89. Kalyani RR, Corriere M, Ferrucci L. Age-related and disease-related muscle loss: the effect of diabetes, obesity, and other diseases. Lancet Diabetes Endocrinol 2014;2:819-29.
90. Hernandez-Alvarez MI, Thabit H, Burns N, et al. Subjects with early-onset type 2 diabetes show defective activation of the skeletal muscle PGC-1{alpha}/Mitofusin-2 regulatory pathway in response to physical activity. Diabetes Care 2010;33:645-51.
91. Phillips T, Leeuwenburgh C. Muscle fiber specific apoptosis and TNF-alpha signaling in sarcopenia are attenuated by life-long calorie restriction. FASEB J 2005;19:668-70.
92. Rubio-Ruiz ME, Guarner-Lans V, Perez-Torres I, Soto ME. Mechanisms underlying metabolic syndrome-related sarcopenia and possible therapeutic measures. Int J Mol Sci 2019;20:647.
93. Defronzo RA. Banting Lecture. From the triumvirate to the ominous octet: a new paradigm for the treatment of type 2 diabetes mellitus. Diabetes 2009;58:773-95.
94. Kim TN, Yang SJ, Yoo HJ, et al. Prevalence of sarcopenia and sarcopenic obesity in Korean adults: the Korean sarcopenic obesity study. Int J Obes (Lond) 2009;33:885-92.
95. Bostrom P, Wu J, Jedrychowski MP, et al. A PGC1-alpha-dependent myokine that drives brown-fat-like development of white fat and thermogenesis. Nature 2012;481:463-8.
96. Zhang HJ, Zhang XF, Ma ZM, et al. Irisin is inversely associated with intrahepatic triglyceride contents in obese adults. J Hepatol 2013;59:557-62.
97. Huh JY. The role of exercise-induced myokines in regulating metabolism. Arch Pharm Res 2018;41:14-29.
98. Han HQ, Zhou X, Mitch WE, Goldberg AL. Myostatin/activin pathway antagonism: molecular basis and therapeutic potential. Int J Biochem Cell Biol 2013;45:2333-47.
99. Li F, Li Y, Duan Y, Hu CA, Tang Y, Yin Y. Myokines and adipokines: Involvement in the crosstalk between skeletal muscle and adipose tissue. Cytokine Growth Factor Rev 2017;33:73-82.
100. Konopka AR, Wolff CA, Suer MK, Harber MP. Relationship between intermuscular adipose tissue infiltration and myostatin before and after aerobic exercise training. Am J Physiol Regul Integr Comp Physiol 2018;315:R461-8.
101. Delogu W, Caligiuri A, Provenzano A, et al. Myostatin regulates the fibrogenic phenotype of hepatic stellate cells via c-jun N-terminal kinase activation. Dig Liver Dis 2019;51:1400-8.
102. Garcia PS, Cabbabe A, Kambadur R, Nicholas G, Csete M. Brief-reports: elevated myostatin levels in patients with liver disease: a potential contributor to skeletal muscle wasting. Anesth Analg 2010;111:707-9.
103. Nishikawa H, Enomoto H, Ishii A, et al. Elevated serum myostatin level is associated with worse survival in patients with liver cirrhosis. J Cachexia Sarcopenia Muscle 2017;8:915-25.
104. Shida T, Oshida N, Oh S, Okada K, Shoda J. Progressive reduction in skeletal muscle mass to visceral fat area ratio is associated with a worsening of the hepatic conditions of non-alcoholic fatty liver disease. Diabetes Metab Syndr Obes 2019;12:495-503.
105. Romeo S, Kozlitina J, Xing C, et al. Genetic variation in PNPLA3 confers susceptibility to nonalcoholic fatty liver disease. Nat Genet 2008;40:1461-5.
106. Speliotes EK, Butler JL, Palmer CD, et al. PNPLA3 variants specifically confer increased risk for histologic nonalcoholic fatty liver disease but not metabolic disease. Hepatology 2010;52:904-12.
107. Rotman Y, Koh C, Zmuda JM, Kleiner DE, Liang TJ, Nash CRN. The association of genetic variability in patatin-like phospholipase domain-containing protein 3 (PNPLA3) with histological severity of nonalcoholic fatty liver disease. Hepatology 2010;52:894-903.
108. Valenti L, Al-Serri A, Daly AK, et al. Homozygosity for the patatin-like phospholipase-3/adiponutrin I148M polymorphism influences liver fibrosis in patients with nonalcoholic fatty liver disease. Hepatology 2010;51:1209-17.
109. Sookoian S, Pirola CJ. Meta-analysis of the influence of I148M variant of patatin-like phospholipase domain containing 3 gene (PNPLA3) on the susceptibility and histological severity of nonalcoholic fatty liver disease. Hepatology 2011;53:1883-94.
110. Liu YL, Patman GL, Leathart JB, et al. Carriage of the PNPLA3 rs738409 C >G polymorphism confers an increased risk of non-alcoholic fatty liver disease associated hepatocellular carcinoma. J Hepatol 2014;61:75-81.
111. Dubuquoy C, Robichon C, Lasnier F, et al. Distinct regulation of adiponutrin/PNPLA3 gene expression by the transcription factors ChREBP and SREBP1c in mouse and human hepatocytes. J Hepatol 2011;55:145-53.
112. Huang Y, He S, Li JZ, et al. A feed-forward loop amplifies nutritional regulation of PNPLA3. Proc Natl Acad Sci U S A 2010;107:7892-7.
113. Hao L, Ito K, Huang KH, Sae-tan S, Lambert JD, Ross AC. Shifts in dietary carbohydrate-lipid exposure regulate expression of the non-alcoholic fatty liver disease-associated gene PNPLA3/adiponutrin in mouse liver and HepG2 human liver cells. Metabolism 2014;63:1352-62.
114. BasuRay S, Smagris E, Cohen JC, Hobbs HH. The PNPLA3 variant associated with fatty liver disease (I148M) accumulates on lipid droplets by evading ubiquitylation. Hepatology 2017;66:1111-24.
115. Nishioji K, Mochizuki N, Kobayashi M, et al. The impact of PNPLA3 rs738409 genetic polymorphism and weight gain >/=10 kg after age 20 on non-alcoholic fatty liver disease in non-obese japanese individuals. PLoS One 2015;10:e0140427.
116. Honda Y, Yoneda M, Kessoku T, et al. Characteristics of non-obese non-alcoholic fatty liver disease: Effect of genetic and environmental factors. Hepatol Res 2016;46:1011-8.
117. Leung JC, Loong TC, Wei JL, et al. Histological severity and clinical outcomes of nonalcoholic fatty liver disease in nonobese patients. Hepatology 2017;65:54-64.
118. Fracanzani AL, Petta S, Lombardi R, et al. Liver and cardiovascular damage in patients with lean nonalcoholic fatty liver disease, and association with visceral obesity. Clin Gastroenterol Hepatol 2017;15:1604-11.e1.
119. Younossi ZM. Non-alcoholic fatty liver disease - a global public health perspective. J Hepatol 2019;70:531-44.
120. Fan Y, Lu H, Guo Y, et al. Hepatic transmembrane 6 superfamily member 2 regulates cholesterol metabolism in mice. Gastroenterology 2016;150:1208-18.
121. Kozlitina J, Smagris E, Stender S, et al. Exome-wide association study identifies a TM6SF2 variant that confers susceptibility to nonalcoholic fatty liver disease. Nat Genet 2014;46:352-6.
122. 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.
123. Goffredo M, Caprio S, Feldstein AE, et al. Role of TM6SF2 rs58542926 in the pathogenesis of nonalcoholic pediatric fatty liver disease: a multiethnic study. Hepatology 2016;63:117-25.
124. Chen X, Zhou P, De L, Li B, Su S. The roles of transmembrane 6 superfamily member 2 rs58542926 polymorphism in chronic liver disease: a meta-analysis of 24,147 subjects. Mol Genet Genomic Med 2019;7:e824.
125. Dongiovanni P, Petta S, Maglio C, et al. Transmembrane 6 superfamily member 2 gene variant disentangles nonalcoholic steatohepatitis from cardiovascular disease. Hepatology 2015;61:506-14.
126. Chen F, Esmaili S, Rogers GB, et al. Lean NAFLD: a distinct entity shaped by differential metabolic adaptation. Hepatology 2020;71:1213-27.
127. Adams LA, Marsh JA, Ayonrinde OT, et al. Cholesteryl ester transfer protein gene polymorphisms increase the risk of fatty liver in females independent of adiposity. J Gastroenterol Hepatol 2012;27:1520-7.
128. Musso G, Cassader M, Bo S, De Michieli F, Gambino R. Sterol regulatory element-binding factor 2 (SREBF-2) predicts 7-year NAFLD incidence and severity of liver disease and lipoprotein and glucose dysmetabolism. Diabetes 2013;62:1109-20.
129. 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.
130. Dong H, Wang J, Li C, et al. The phosphatidylethanolamine N-methyltransferase gene V175M single nucleotide polymorphism confers the susceptibility to NASH in Japanese population. J Hepatol 2007;46:915-20.
131. Song J, da Costa KA, Fischer LM, et al. Polymorphism of the PEMT gene and susceptibility to nonalcoholic fatty liver disease (NAFLD). FASEB J 2005;19:1266-71.
132. Nakatsuka A, Matsuyama M, Yamaguchi S, et al. Insufficiency of phosphatidylethanolamine N-methyltransferase is risk for lean non-alcoholic steatohepatitis. Sci Rep 2016;6:21721.
133. 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.
134. Machado MV, Cortez-Pinto H. Diet, microbiota, obesity, and NAFLD: a dangerous quartet. Int J Mol Sci 2016;17:481.
135. Ponziani FR, Bhoori S, Castelli C, et al. Hepatocellular carcinoma is associated with gut microbiota profile and inflammation in nonalcoholic fatty liver disease. Hepatology 2019;69:107-20.
136. Elshaghabee FMF, Bockelmann W, Meske D, et al. Ethanol production by selected intestinal microorganisms and lactic acid bacteria growing under different nutritional conditions. Front Microbiol 2016;7:47.
137. Elshaghabee FMF, Ghadimi D, Habermann D, et al. Effect of oral administration of weissella confusa on fecal and plasma ethanol concentrations, lipids and glucose metabolism in wistar rats fed high fructose and fat diet. Hepat Med 2020;12:93-106.
138. Koutnikova H, Genser B, Monteiro-Sepulveda M, et al. Impact of bacterial probiotics on obesity, diabetes and non-alcoholic fatty liver disease related variables: a systematic review and meta-analysis of randomised controlled trials. BMJ Open 2019;9:e017995.
139. 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.
140. Assy N, Nasser G, Kamayse I, et al. Soft drink consumption linked with fatty liver in the absence of traditional risk factors. Can J Gastroenterol 2008;22:811-6.
141. 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.
142. Bardella MT, Valenti L, Pagliari C, et al. Searching for coeliac disease in patients with non-alcoholic fatty liver disease. Dig Liver Dis 2004;36:333-6.
143. Emami MH, Hashemi M, Kouhestani S, Taheri H, Karimi S. Should we look for celiac disease among all patients with liver function test abnormalities? Int J Prev Med 2012;3:167-72.
144. Bakhshipour A, Kaykhaei MA, Moulaei N, Mashhadi MA. Prevalence of coeliac disease in patients with non-alcoholic fatty liver disease. Arab J Gastroenterol 2013;14:113-5.
145. Rahimi AR, Daryani NE, Ghofrani H, et al. The prevalence of celiac disease among patients with non-alcoholic fatty liver disease in Iran. Turk J Gastroenterol 2011;22:300-4.
146. Bargiggia S, Maconi G, Elli M, et al. Sonographic prevalence of liver steatosis and biliary tract stones in patients with inflammatory bowel disease: study of 511 subjects at a single center. J Clin Gastroenterol 2003;36:417-20.
147. Tovoli F, Negrini G, Fari R, et al. Increased risk of nonalcoholic fatty liver disease in patients with coeliac disease on a gluten-free diet: beyond traditional metabolic factors. Aliment Pharmacol Ther 2018;48:538-46.
148. Reilly NR, Lebwohl B, Hultcrantz R, Green PH, Ludvigsson JF. Increased risk of non-alcoholic fatty liver disease after diagnosis of celiac disease. J Hepatol 2015;62:1405-11.
149. Abenavoli L, Milic N, De Lorenzo A, Luzza F. A pathogenetic link between non-alcoholic fatty liver disease and celiac disease. Endocrine 2013;43:65-7.
150. van Zutphen T, Ciapaite J, Bloks VW, et al. Malnutrition-associated liver steatosis and ATP depletion is caused by peroxisomal and mitochondrial dysfunction. J Hepatol 2016;65:1198-208.
151. Machado MV, Cortez-Pinto H. Insulin resistance and steatosis in chronic hepatitis C. Ann Hepatol 2009;8 Suppl 1:S67-75.
152. HH AK. Lysosomal acid lipase deficiency: a form of non-obese fatty liver disease (NOFLD). Expert Rev Gastroenterol Hepatol 2017;11:911-24.
153. Reynolds TM, Mewies C, Hamilton J, Wierzbicki AS, group PPC. Identification of rare diseases by screening a population selected on the basis of routine pathology results-the PATHFINDER project: lysosomal acid lipase/cholesteryl ester storage disease substudy. J Clin Pathol 2018;71:608-13.
154. Khoury J, Zohar Y, Shehadeh N, Saadi T. Glycogenic hepatopathy. Hepatobiliary Pancreat Dis Int 2018;17:113-8.
155. Welty FK. Hypobetalipoproteinemia and abetalipoproteinemia: liver disease and cardiovascular disease. Curr Opin Lipidol 2020;31:49-55.
156. Noto D, Arca M, Tarugi P, Cefalu AB, Barbagallo CM, Averna MR. Association between familial hypobetalipoproteinemia and the risk of diabetes. Is this the other side of the cholesterol-diabetes connection? A systematic review of literature. Acta Diabetol 2017;54:111-22.
157. Pelusi S, Baselli G, Pietrelli A, et al. Rare pathogenic variants predispose to hepatocellular carcinoma in nonalcoholic fatty liver disease. Sci Rep 2019;9:3682.
158. Dela Cruz ACD, Bugianesi E, George J, et al. Characteristics and long-term prognosis of lean patients with nonalcoholic fatty liver disease: international follow up study. Gastroenterology 2014;146:A379.
159. Shao C, Ye J, Li F, Feng S, Wang W, Zhong B. Different predictors of steatosis and fibrosis severity among lean, overweight and obese patients with nonalcoholic fatty liver disease. Dig Liver Dis 2019;51:1392-9.
160. Hagstrom 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.
161. 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;33:452-7.
162. 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.
163. 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;50:341-6.
164. Yilmaz Y, Senates E, Ayyildiz T, et al. Characterization of nonalcoholic fatty liver disease unrelated to the metabolic syndrome. Eur J Clin Invest 2012;42:411-8.
165. Fukuda T, Hamaguchi M, Kojima T, et al. The impact of non-alcoholic fatty liver disease on incident type 2 diabetes mellitus in non-overweight individuals. Liver Int 2016;36:275-83.
166. Golabi P, Paik J, Fukui N, Locklear CT, de Avilla L, Younossi ZM. Patients with lean nonalcoholic fatty liver disease are metabolically abnormal and have a higher risk for mortality. Clin Diabetes 2019;37:65-72.
167. European Association for the Study of the L, European Association for the Study of D, European Association for the Study of O. EASL-EASD-EASO Clinical Practice Guidelines for the management of non-alcoholic fatty liver disease. J Hepatol 2016;64:1388-402.
168. Alam S, Jahid Hasan M, Khan MAS, Alam M, Hasan N. Effect of weight reduction on histological activity and fibrosis of lean nonalcoholic steatohepatitis patient. J Transl Int Med 2019;7:106-14.
169. Albu JB, Heilbronn LK, Kelley DE, et al. Metabolic changes following a 1-year diet and exercise intervention in patients with type 2 diabetes. Diabetes 2010;59:627-33.
170. Ohkawara K, Tanaka S, Miyachi M, Ishikawa-Takata K, Tabata I. A dose-response relation between aerobic exercise and visceral fat reduction: systematic review of clinical trials. Int J Obes (Lond) 2007;31:1786-97.
