REFERENCES

1. Akinyemiju T, Abera S, Ahmed M, Alam N, Alemayohu MA, et al; Global Burden of Disease Liver Cancer Collaboration. The burden of primary liver cancer and underlying etiologies from 1990 to 2015 at the global, regional, and national level: results from the global burden of disease study 2015. JAMA Oncol 2017;3:1683-91.

2. Blonski W, Kotlyar DS, Forde KA. Non-viral causes of hepatocellular carcinoma. World J Gastroenterol 2010;16:3603-15.

3. Bertot LC, Adams LA. Trends in hepatocellular carcinoma due to non-alcoholic fatty liver disease. Expert Rev Gastroenterol Hepatol 2019;13:179-87.

4. Swinburn BA, Sacks G, Hall KD, McPherson K, Finegood DT, et al. The global obesity pandemic: shaped by global drivers and local environments. Lancet 2011;378:804-14.

5. Younossi Z, Anstee QM, Marietti M, Hardy T, Henry L, et al. Global burden of NAFLD and NASH: trends, predictions, risk factors and prevention. Nat Rev Gastroenterol Hepatol 2018;15:11-20.

6. Bhaskaran K, Douglas I, Forbes H, dos-Santos-Silva I, Leon DA, et al. Body-mass index and risk of 22 specific cancers: a population-based cohort study of 5.24 million UK adults. Lancet 2014;384:755-65.

7. Milic S, Lulic D, Stimac D. Non-alcoholic fatty liver disease and obesity: biochemical, metabolic and clinical presentations. World J Gastroenterol 2014;20:9330-7.

8. Fan JG, Kim SU, Wong VW. New trends on obesity and NAFLD in Asia. J Hepatol 2017;67:862-73.

9. Petrucciani N, Gugenheim J. Molecular pathways between obesity, non-alcoholic steatohepatitis (NASH) and hepatocellular carcinoma (HCC). Hepatobiliary Surg Nutr 2019;8:395-7.

10. Xia MF, Bian H, Gao X. NAFLD and diabetes: two sides of the same coin? Rationale for gene-based personalized NAFLD treatment. Front Pharmacol 2019;10:877.

11. Masarone M, Rosato V, Aglitti A, Bucci T, Caruso R, et al. Liver biopsy in type 2 diabetes mellitus: steatohepatitis represents the sole feature of liver damage. PLoS One 2017;12:e0178473.

12. Bril F, Cusi K. Management of nonalcoholic fatty liver disease in patients with type 2 diabetes: a call to action. Diabetes Care 2017;40:419-30.

13. Mantovani A, Targher G. Type 2 diabetes mellitus and risk of hepatocellular carcinoma: spotlight on nonalcoholic fatty liver disease. Ann Transl Med 2017;5:270.

14. Agosti P, Sabba C, Mazzocca A. Emerging metabolic risk factors in hepatocellular carcinoma and their influence on the liver microenvironment. Biochim Biophys Acta Mol Basis Dis 2018;1864:607-17.

15. Yang JD, Ahmed F, Mara KC, Addissie BD, Allen AM, et al. Diabetes is associated with increased risk of hepatocellular carcinoma in cirrhosis patients with nonalcoholic fatty liver disease. Hepatology 2019. Epub ahead of print. doi: 10.1002/hep.30858

16. Margini C, Dufour JF. The story of HCC in NAFLD: from epidemiology, across pathogenesis, to prevention and treatment. Liver Int 2016;36:317-24.

17. Younossi Z, Stepanova M, Ong JP, Jacobson IM, Bugianesi E, et al. Nonalcoholic steatohepatitis is the fastest growing cause of hepatocellular carcinoma in liver transplant candidates. Clin Gastroenterol Hepatol 2019;17:748-55.e3.

18. Reig M, Gambato M, Man NK, Roberts JP, Victor D, et al. Should patients with NAFLD/NASH be surveyed for HCC? Transplantation 2019;103:39-44.

19. Sadler EM, Mehta N, Bhat M, Ghanekar A, Greig PD, et al. Liver transplantation for NASH-related hepatocellular carcinoma versus non-NASH etiologies of hepatocellular carcinoma. Transplantation 2018;102:640-7.

20. Olofson AM, Gonzalo DH, Chang M, Liu X. Steatohepatitic variant of hepatocellular carcinoma: a focused review. Gastroenterology Res 2018;11:391-6.

21. Kanwal F, Kramer JR, Mapakshi S, Natarajan Y, Chayanupatkul M, et al. Risk of hepatocellular cancer in patients with non-alcoholic fatty liver disease. Gastroenterology 2018;155:1828-37.e2.

22. Estes C, Anstee QM, Arias-Loste MT, Bantel H, Bellentani S, et al. Modeling NAFLD disease burden in China, France, Germany, Italy, Japan, Spain, United Kingdom, and United States for the period 2016-2030. J Hepatol 2018;69:896-904.

23. Uygun A. Is that possible to stop or cease the NASH to turn into HCC? J Gastrointest Cancer 2017;48:250-5.

24. Yopp AC, Choti MA. Non-alcoholic steatohepatitis-related hepatocellular carcinoma: a growing epidemic? Dig Dis 2015;33:642-7.

25. Weinmann A, Alt Y, Koch S, Nelles C, Duber C, et al. Treatment and survival of non-alcoholic steatohepatitis associated hepatocellular carcinoma. BMC Cancer 2015;15:210.

26. Oda K, Uto H, Mawatari S, Ido A. Clinical features of hepatocellular carcinoma associated with nonalcoholic fatty liver disease: a review of human studies. Clin J Gastroenterol 2015;8:1-9.

27. Page JM, Harrison SA. NASH and HCC. Clin Liver Dis 2009;13:631-47.

28. Zen Y, Katayanagi K, Tsuneyama K, Harada K, Araki I, et al. Hepatocellular carcinoma arising in non-alcoholic steatohepatitis. Pathol Int 2001;51:127-31.

29. Gawrieh S, Dakhoul L, Miller E, Scanga A, deLemos A, et al. Characteristics, aetiologies and trends of hepatocellular carcinoma in patients without cirrhosis: a United States multicentre study. Aliment Pharmacol Ther 2019;50:809-21.

30. Grohmann M, Wiede F, Dodd GT, Gurzov EN, Ooi GJ, et al. Obesity drives STAT-1-dependent NASH and STAT-3-dependent HCC. Cell 2018;175:1289-306.e20.

31. Younossi ZM, Otgonsuren M, Henry L, Venkatesan C, Mishra A, et al. Association of nonalcoholic fatty liver disease (NAFLD) with hepatocellular carcinoma (HCC) in the United States from 2004 to 2009. Hepatology 2015;62:1723-30.

32. Piscaglia F, Svegliati-Baroni G, Barchetti A, Pecorelli A, Marinelli S, et al. Clinical patterns of hepatocellular carcinoma in nonalcoholic fatty liver disease: a multicenter prospective study. Hepatology 2016;63:827-38.

33. Yasui K, Hashimoto E, Komorizono Y, Koike K, Arii S, et al. Characteristics of patients with nonalcoholic steatohepatitis who develop hepatocellular carcinoma. Clin Gastroenterol Hepatol 2011;9:428-33.

34. Ertle J, Dechene A, Sowa JP, Penndorf V, Herzer K, et al. Non-alcoholic fatty liver disease progresses to hepatocellular carcinoma in the absence of apparent cirrhosis. Int J Cancer 2011;128:2436-43.

35. Chen K, Ma J, Jia X, Ai W, Ma Z, et al. Advancing the understanding of NAFLD to hepatocellular carcinoma development: From experimental models to humans. Biochim Biophys Acta Rev Cancer 2019;1871:117-25.

36. Anstee QM, Day CP. The genetics of nonalcoholic fatty liver disease: spotlight on PNPLA3 and TM6SF2. Semin Liver Dis 2015;35:270-90.

37. Buzzetti E, Pinzani M, Tsochatzis EA. The multiple-hit pathogenesis of non-alcoholic fatty liver disease (NAFLD). Metabolism 2016;65:1038-48.

38. Bessone F, Razori MV, Roma MG. Molecular pathways of nonalcoholic fatty liver disease development and progression. Cell Mol Life Sci 2019;76:99-128.

39. Spahis S, Delvin E, Borys JM, Levy E. Oxidative stress as a critical factor in nonalcoholic fatty liver disease pathogenesis. Antioxid Redox Signal 2017;26:519-41.

40. Zhang XQ, Xu CF, Yu CH, Chen WX, Li YM. Role of endoplasmic reticulum stress in the pathogenesis of nonalcoholic fatty liver disease. World J Gastroenterol 2014;20:1768-76.

41. Gadd VL, Skoien R, Powell EE, Fagan KJ, Winterford C, et al. The portal inflammatory infiltrate and ductular reaction in human nonalcoholic fatty liver disease. Hepatology 2014;59:1393-405.

42. Krenkel O, Puengel T, Govaere O, Abdallah AT, Mossanen JC, et al. Therapeutic inhibition of inflammatory monocyte recruitment reduces steatohepatitis and liver fibrosis. Hepatology 2018;67:1270-83.

43. 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.

44. Singal AG, Manjunath H, Yopp AC, Beg MS, Marrero JA, et al. The effect of PNPLA3 on fibrosis progression and development of hepatocellular carcinoma: a meta-analysis. Am J Gastroenterol 2014;109:325-34.

45. Liu YL, Patman GL, Leathart JB, Piguet AC, Burt AD, 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.

46. Kozlitina J, Smagris E, Stender S, Nordestgaard BG, Zhou HH, et al. Exome-wide association study identifies a TM6SF2 variant that confers susceptibility to nonalcoholic fatty liver disease. Nat Genet 2014;46:352-6.

47. Chen LZ, Xia HH, Xin YN, Lin ZH, Xuan SY. TM6SF2 E167K variant, a novel genetic susceptibility variant, contributing to nonalcoholic fatty liver disease. J Clin Transl Hepatol 2015;3:265-70.

48. Donati B, Dongiovanni P, Romeo S, Meroni M, McCain M, et al. MBOAT7 rs641738 variant and hepatocellular carcinoma in non-cirrhotic individuals. Sci Rep 2017;7:4492.

49. Schulze K, Imbeaud S, Letouze E, Alexandrov LB, Calderaro J, et al. Exome sequencing of hepatocellular carcinomas identifies new mutational signatures and potential therapeutic targets. Nat Genet 2015;47:505-11.

50. Tryndyak VP, Han T, Muskhelishvili L, Fuscoe JC, Ross SA, et al. Coupling global methylation and gene expression profiles reveal key pathophysiological events in liver injury induced by a methyl-deficient diet. Mol Nutr Food Res 2011;55:411-8.

51. Liu F, Li H, Chang H, Wang J, Lu J. Identification of hepatocellular carcinoma-associated hub genes and pathways by integrated microarray analysis. Tumori 2015;101:206-14.

52. Erstad DJ, Fuchs BC, Tanabe KK. Molecular signatures in hepatocellular carcinoma: a step toward rationally designed cancer therapy. Cancer 2018;124:3084-104.

53. de Conti A, Ortega JF, Tryndyak V, Dreval K, Moreno FS, et al. MicroRNA deregulation in nonalcoholic steatohepatitis-associated liver carcinogenesis. Oncotarget 2017;8:88517-28.

54. Xu Z, Hu J, Cao H, Pilo MG, Cigliano A, et al. Loss of Pten synergizes with c-Met to promote hepatocellular carcinoma development via mTORC2 pathway. Exp Mol Med 2018;50:e417.

55. Tessitore A, Cicciarelli G, Del Vecchio F, Gaggiano A, Verzella D, et al. MicroRNA expression analysis in high fat diet-induced NAFLD-NASH-HCC progression: study on C57BL/6J mice. BMC Cancer 2016;16:3.

56. Takakura K, Oikawa T, Nakano M, Saeki C, Torisu Y, et al. Recent insights into the multiple pathways driving non-alcoholic steatohepatitis-derived hepatocellular carcinoma. Front Oncol 2019;9:762.

57. Anstee QM, Reeves HL, Kotsiliti E, Govaere O, Heikenwalder M. From NASH to HCC: current concepts and future challenges. Nat Rev Gastroenterol Hepatol 2019;16:411-28.

58. Grattagliano I, de Bari O, Bernardo TC, Oliveira PJ, Wang DQ, et al. Role of mitochondria in nonalcoholic fatty liver disease - from origin to propagation. Clin Biochem 2012;45:610-8.

59. Donnelly KL, Smith CI, Schwarzenberg SJ, Jessurun J, Boldt MD, et al. Sources of fatty acids stored in liver and secreted via lipoproteins in patients with nonalcoholic fatty liver disease. J Clin Invest 2005;115:1343-51.

60. Nakagawa H, Hayata Y, Kawamura S, Yamada T, Fujiwara N, et al. Lipid metabolic reprogramming in hepatocellular carcinoma. Cancers (Basel) 2018;10:E447.

61. Hirsova P, Ibrahim SH, Gores GJ, Malhi H. Lipotoxic lethal and sublethal stress signaling in hepatocytes: relevance to NASH pathogenesis. J Lipid Res 2016;57:1758-70.

62. Garcia-Ruiz C, Fernandez-Checa JC. Mitochondrial oxidative stress and antioxidants balance in fatty liver disease. Hepatol Commun 2018;2:1425-39.

63. Masarone M, Rosato V, Dallio M, Gravina AG, Aglitti A, et al. Role of oxidative stress in pathophysiology of nonalcoholic fatty liver disease. Oxid Med Cell Longev 2018;2018:9547613.

64. Fu Y, Chung FL. Oxidative stress and hepatocarcinogenesis. Hepatoma Res 2018;4.

65. Nishida N, Yada N, Hagiwara S, Sakurai T, Kitano M, et al. Unique features associated with hepatic oxidative DNA damage and DNA methylation in non-alcoholic fatty liver disease. J Gastroenterol Hepatol 2016;31:1646-53.

66. Song MJ, Malhi H. The unfolded protein response and hepatic lipid metabolism in non alcoholic fatty liver disease. Pharmacol Ther 2019;203:107401.

67. Nakagawa H, Umemura A, Taniguchi K, Font-Burgada J, Dhar D, et al. ER stress cooperates with hypernutrition to trigger TNF-dependent spontaneous HCC development. Cancer Cell 2014;26:331-43.

68. Wu WKK, Zhang L, Chan MTV. Autophagy, NAFLD and NAFLD-related HCC. Adv Exp Med Biol 2018;1061:127-38.

69. Tian Y, Yang B, Qiu W, Hao Y, Zhang Z, et al. ER-residential Nogo-B accelerates NAFLD-associated HCC mediated by metabolic reprogramming of oxLDL lipophagy. Nat Commun 2019;10:3391.

70. Ichimura Y, Waguri S, Sou YS, Kageyama S, Hasegawa J, et al. Phosphorylation of p62 activates the Keap1-Nrf2 pathway during selective autophagy. Mol Cell 2013;51:618-31.

71. Sinha RA, Singh BK, Zhou J, Wu Y, Farah BL, et al. Thyroid hormone induction of mitochondrial activity is coupled to mitophagy via ROS-AMPK-ULK1 signaling. Autophagy 2015;11:1341-57.

72. Sun K, Xu L, Jing Y, Han Z, Chen X, et al. Autophagy-deficient Kupffer cells promote tumorigenesis by enhancing mtROS-NF-kappaB-IL1alpha/beta-dependent inflammation and fibrosis during the preneoplastic stage of hepatocarcinogenesis. Cancer Lett 2017;388:198-207.

73. Kanno M, Kawaguchi K, Honda M, Horii R, Takatori H, et al. Serum aldo-keto reductase family 1 member B10 predicts advanced liver fibrosis and fatal complications of nonalcoholic steatohepatitis. J Gastroenterol 2019;54:549-57.

74. Arendt BM, Teterina A, Pettinelli P, Comelli EM, Ma DWL, et al. Cancer-related gene expression is associated with disease severity and modifiable lifestyle factors in non-alcoholic fatty liver disease. Nutrition 2019;62:100-7.

75. Torres-Mena JE, Salazar-Villegas KN, Sanchez-Rodriguez R, Lopez-Gabino B, Del Pozo-Yauner L, et al. Aldo-Keto reductases as early biomarkers of hepatocellular carcinoma: a comparison between animal models and human HCC. Dig Dis Sci 2018;63:934-44.

76. Nikolaou N, Gathercole LL, Marchand L, Althari S, Dempster NJ, et al. AKR1D1 is a novel regulator of metabolic phenotype in human hepatocytes and is dysregulated in non-alcoholic fatty liver disease. Metabolism 2019;99:67-80.

77. Marra F, Svegliati-Baroni G. Lipotoxicity and the gut-liver axis in NASH pathogenesis. J Hepatol 2018;68:280-95.

78. Iannucci LF, Sun J, Singh BK, Zhou J, Kaddai VA, et al. Short chain fatty acids induce UCP2-mediated autophagy in hepatic cells. Biochem Biophys Res Commun 2016;480:461-7.

79. Koopman N, Molinaro A, Nieuwdorp M, Holleboom AG. Review article: can bugs be drugs? The potential of probiotics and prebiotics as treatment for non-alcoholic fatty liver disease. Aliment Pharmacol Ther 2019;50:628-39.

80. Jandhyala SM, Talukdar R, Subramanyam C, Vuyyuru H, Sasikala M, et al. Role of the normal gut microbiota. World J Gastroenterol 2015;21:8787-803.

81. Mouries J, Brescia P, Silvestri A, Spadoni I, Sorribas M, et al. Microbiota-driven gut vascular barrier disruption is a prerequisite for non-alcoholic steatohepatitis development. J Hepatol 2019;71:1216-28.

82. Liu Q, Liu S, Chen L, Zhao Z, Du S, et al. Role and effective therapeutic target of gut microbiota in NAFLD/NASH. Exp Ther Med 2019;18:1935-44.

83. Kim HN, Joo EJ, Cheong HS, Kim Y, Kim HL, et al. Gut microbiota and risk of persistent nonalcoholic fatty liver diseases. J Clin Med 2019;8:E1089.

84. Jasirwan COM, Lesmana CRA, Hasan I, Sulaiman AS, Gani RA. The role of gut microbiota in non-alcoholic fatty liver disease: pathways of mechanisms. Biosci Microbiota Food Health 2019;38:81-8.

85. Leung C, Rivera L, Furness JB, Angus PW. The role of the gut microbiota in NAFLD. Nat Rev Gastroenterol Hepatol 2016;13:412-25.

86. Ezzaidi N, Zhang X, Coker OO, Yu J. New insights and therapeutic implication of gut microbiota in non-alcoholic fatty liver disease and its associated liver cancer. Cancer Lett 2019;459:186-91.

87. Yoshimoto S, Loo TM, Atarashi K, Kanda H, Sato S, et al. Obesity-induced gut microbial metabolite promotes liver cancer through senescence secretome. Nature 2013;499:97-101.

88. Dapito DH, Mencin A, Gwak GY, Pradere JP, Jang MK, et al. Promotion of hepatocellular carcinoma by the intestinal microbiota and TLR4. Cancer Cell 2012;21:504-16.

89. Chu H, Williams B, Schnabl B. Gut microbiota, fatty liver disease, and hepatocellular carcinoma. Liver Res 2018;2:43-51.

90. Nguyen J, Jiao J, Smoot K, Watt GP, Zhao C, et al. Toll-like receptor 4: a target for chemoprevention of hepatocellular carcinoma in obesity and steatohepatitis. Oncotarget 2018;9:29495-507.

91. Liu Y, Yan W, Tohme S, Chen M, Fu Y, et al. Hypoxia induced HMGB1 and mitochondrial DNA interactions mediate tumor growth in hepatocellular carcinoma through Toll-like receptor 9. J Hepatol 2015;63:114-21.

92. Brandi G, De Lorenzo S, Candela M, Pantaleo MA, Bellentani S, et al. Microbiota, NASH, HCC and the potential role of probiotics. Carcinogenesis 2017;38:231-40.

93. Takahashi S, Tanaka N, Fukami T, Xie C, Yagai T, et al. Role of farnesoid X receptor and bile acids in hepatic tumor development. Hepatol Commun 2018;2:1567-82.

94. He G, Karin M. NF-kappa B and STAT3 - key players in liver inflammation and cancer. Cell Res 2011;21:159-68.

95. Park EJ, Lee JH, Yu GY, He G, Ali SR, et al. Dietary and genetic obesity promote liver inflammation and tumorigenesis by enhancing IL-6 and TNF expression. Cell 2010;140:197-208.

96. Min HK, Mirshahi F, Verdianelli A, Pacana T, Patel V, et al. Activation of the GP130-STAT3 axis and its potential implications in nonalcoholic fatty liver disease. Am J Physiol Gastrointest Liver Physiol 2015;308:G794-803.

97. Widjaja AA, Singh BK, Adami E, Viswanathan S, Dong J, et al. Inhibiting interleukin 11 signaling reduces hepatocyte death and liver fibrosis, inflammation, and steatosis in mouse models of nonalcoholic steatohepatitis. Gastroenterology 2019;157:777-92.e14.

98. Zheng H, Yang Y, Han J, Jiang WH, Chen C, et al. TMED3 promotes hepatocellular carcinoma progression via IL-11/STAT3 signaling. Sci Rep 2016;6:37070.

99. Gomes AL, Teijeiro A, Buren S, Tummala KS, Yilmaz M, et al. Metabolic inflammation-associated IL-17A causes non-alcoholic steatohepatitis and hepatocellular carcinoma. Cancer Cell 2016;30:161-75.

100. Syn WK, Choi SS, Liaskou E, Karaca GF, Agboola KM, et al. Osteopontin is induced by hedgehog pathway activation and promotes fibrosis progression in nonalcoholic steatohepatitis. Hepatology 2011;53:106-15.

101. Chung SI, Moon H, Ju HL, Cho KJ, Kim DY, et al. Hepatic expression of sonic hedgehog induces liver fibrosis and promotes hepatocarcinogenesis in a transgenic mouse model. J Hepatol 2016;64:618-27.

102. Chen J, Gingold JA, Su X. Immunomodulatory TGF-beta signaling in hepatocellular carcinoma. Trends Mol Med 2019;25:1010-23.

103. Yang L, Roh YS, Song J, Zhang B, Liu C, et al. Transforming growth factor beta signaling in hepatocytes participates in steatohepatitis through regulation of cell death and lipid metabolism in mice. Hepatology 2014;59:483-95.

104. Jin Z, Lei L, Lin D, Liu Y, Song Y, et al. IL-33 released in the liver inhibits tumor growth via promotion of CD4(+) and CD8(+) T cell responses in hepatocellular carcinoma. J Immunol 2018;201:3770-9.

105. Ma C, Kesarwala AH, Eggert T, Medina-Echeverz J, Kleiner DE, et al. NAFLD causes selective CD4(+) T lymphocyte loss and promotes hepatocarcinogenesis. Nature 2016;531:253-7.

106. Malehmir M, Pfister D, Gallage S, Szydlowska M, Inverso D, et al. Platelet GPIbalpha is a mediator and potential interventional target for NASH and subsequent liver cancer. Nat Med 2019;25:641-55.

107. de Oliveira S, Houseright RA, Graves AL, Golenberg N, Korte BG, et al. Metformin modulates innate immune-mediated inflammation and early progression of NAFLD-associated hepatocellular carcinoma in zebrafish. J Hepatol 2019;70:710-21.

108. Bril F, Lomonaco R, Orsak B, Ortiz-Lopez C, Webb A, et al. Relationship between disease severity, hyperinsulinemia, and impaired insulin clearance in patients with nonalcoholic steatohepatitis. Hepatology 2014;59:2178-87.

109. De Minicis S, Agostinelli L, Rychlicki C, Sorice GP, Saccomanno S, et al. HCC development is associated to peripheral insulin resistance in a mouse model of NASH. PLoS One 2014;9:e97136.

110. Kudo Y, Tanaka Y, Tateishi K, Yamamoto K, Yamamoto S, et al. Altered composition of fatty acids exacerbates hepatotumorigenesis during activation of the phosphatidylinositol 3-kinase pathway. J Hepatol 2011;55:1400-8.

111. Jeong SH, Kim HB, Kim MC, Lee JM, Lee JH, et al. Hippo-mediated suppression of IRS2/AKT signaling prevents hepatic steatosis and liver cancer. J Clin Invest 2018;128:1010-25.

112. Chettouh H, Lequoy M, Fartoux L, Vigouroux C, Desbois-Mouthon C. Hyperinsulinaemia and insulin signalling in the pathogenesis and the clinical course of hepatocellular carcinoma. Liver Int 2015;35:2203-17.

113. Polyzos SA, Aronis KN, Kountouras J, Raptis DD, Vasiloglou MF, et al. Circulating leptin in non-alcoholic fatty liver disease: a systematic review and meta-analysis. Diabetologia 2016;59:30-43.

114. Jiang N, Sun R, Sun Q. Leptin signaling molecular actions and drug target in hepatocellular carcinoma. Drug Des Devel Ther 2014;8:2295-302.

115. Stefanou N, Papanikolaou V, Furukawa Y, Nakamura Y, Tsezou A. Leptin as a critical regulator of hepatocellular carcinoma development through modulation of human telomerase reverse transcriptase. BMC Cancer 2010;10:442.

116. Bruinstroop E, Dalan R, Cao Y, Bee YM, Chandran K, et al. Low-dose levothyroxine reduces intrahepatic lipid content in patients with type 2 diabetes mellitus and NAFLD. J Clin Endocrinol Metab 2018;103:2698-706.

117. Pinter M, Haupt L, Hucke F, Bota S, Bucsics T, et al. The impact of thyroid hormones on patients with hepatocellular carcinoma. PLoS One 2017;12:e0181878.

118. Lonardo A, Ballestri S, Mantovani A, Nascimbeni F, Lugari S, et al. Pathogenesis of hypothyroidism-induced NAFLD: evidence for a distinct disease entity? Dig Liver Dis 2019;51:462-70.

119. Sinha RA, Bruinstroop E, Singh BK, Yen PM. Nonalcoholic fatty liver disease and hypercholesterolemia: roles of thyroid hormones, metabolites, and agonists. Thyroid 2019;29:1173-91.

120. Ali MA, Lacin S, Abdel-Wahab R, Uemura M, Hassan M, et al. Nonalcoholic steatohepatitis-related hepatocellular carcinoma: is there a role for the androgen receptor pathway? Onco Targets Ther 2017;10:1403-12.

121. Wu EM, Wong LL, Hernandez BY, Ji JF, Jia W, et al. Gender differences in hepatocellular cancer: disparities in nonalcoholic fatty liver disease/steatohepatitis and liver transplantation. Hepatoma Res 2018;4.

122. Bosch FX, Ribes J, Diaz M, Cleries R. Primary liver cancer: worldwide incidence and trends. Gastroenterology 2004;127:S5-16.

123. Gan L, Chitturi S, Farrell GC. Mechanisms and implications of age-related changes in the liver: nonalcoholic fatty liver disease in the elderly. Curr Gerontol Geriatr Res 2011;2011:831536.

124. Hashimoto E, Tokushige K. Prevalence, gender, ethnic variations, and prognosis of NASH. J Gastroenterol 2011;46 Suppl 1:63-9.

125. Iyer JK, Kalra M, Kaul A, Payton ME, Kaul R. Estrogen receptor expression in chronic hepatitis C and hepatocellular carcinoma pathogenesis. World J Gastroenterol 2017;23:6802-16.

126. Kettner NM, Voicu H, Finegold MJ, Coarfa C, Sreekumar A, et al. Circadian homeostasis of liver metabolism suppresses hepatocarcinogenesis. Cancer Cell 2016;30:909-24.

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