Vol 75, No 3 (2024)
Review paper
Published online: 2024-06-26

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Metabolic-associated fatty liver disease and the role of hormones in its aetiopathogenesis

Szymon Suwała1, Roman Junik1
Pubmed: 38923899
Endokrynol Pol 2024;75(3):237-252.


Metabolic-associated fatty liver disease (MAFLD) is a newly coined term that links the presence of liver steatosis (characterised by the accumulation of lipids in at least 5% of liver cells) with a condition of overall systemic metabolic dysfunction. MAFLD impacts 24–36% of the global population. As per the official guidelines, a diagnosis of MAFLD can be made when hepatosteatosis is accompanied by type 2 diabetes mellitus, overweight, obesity, or at least 2 other specific metabolic abnormalities (increased waist circumference, hypertension, dyslipidaemia, prediabetes, elevated C-reactive protein level, or increased homeostasis model assessment of insulin resistance: HOMA-IR).

MAFLD is a heterogeneous illness associated with multiple diseases that impact various organs, particularly endocrine organs. Endocrinopathies can significantly influence the progression and severity of MAFLD. This paper provides a brief overview of the existing research on the connection between liver steatosis and the functioning of endocrine organs. The authors also propose dividing endocrine diseases into those having a possible, strong, and clear relationship with hepatosteatosis (for the purpose of preliminary recommendations regarding the need for monitoring the possible progression of MAFLD in these groups of patients).

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  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(1): 202–209.
  2. Dobrowolski P, Prejbisz A, Kuryłowicz A, et al. Metabolic syndrome - a new definition and management guidelines: A joint position paper by the Polish Society of Hypertension, Polish Society for the Treatment of Obesity, Polish Lipid Association, Polish Association for Study of Liver, Polish Society of Family Medicine, Polish Society of Lifestyle Medicine, Division of Prevention and Epidemiology Polish Cardiac Society, "Club 30" Polish Cardiac Society, and Division of Metabolic and Bariatric Surgery Society of Polish Surgeons. Arch Med Sci. 2022; 18(5): 1133–1156.
  3. Shiha G, Korenjak M, Eskridge W, et al. Redefining fatty liver disease: an international patient perspective. Lancet Gastroenterol Hepatol. 2021; 6(1): 73–79.
  4. Mantovani A. MAFLD vs NAFLD: Where are we? Dig Liver Dis. 2021; 53(10): 1368–1372.
  5. Michaelidou M, Pappachan JM, Jeeyavudeen MS. Management of diabesity: Current concepts. World J Diabetes. 2023; 14(4): 396–411.
  6. Suwała S, Białczyk A, Koperska K, et al. Prevalence and Crucial Parameters in Diabesity-Related Liver Fibrosis: A Preliminary Study. J Clin Med. 2023; 12(24).
  7. Yamamura S, Eslam M, Kawaguchi T, et al. MAFLD identifies patients with significant hepatic fibrosis better than NAFLD. Liver Int. 2020; 40(12): 3018–3030.
  8. Kim SH, Park MJ. Effects of growth hormone on glucose metabolism and insulin resistance in human. Ann Pediatr Endocrinol Metab. 2017; 22(3): 145–152.
  9. Hutchison AL, Tavaglione F, Romeo S, et al. Endocrine aspects of metabolic dysfunction-associated steatotic liver disease (MASLD): Beyond insulin resistance. J Hepatol. 2023; 79(6): 1524–1541.
  10. Lewiński A, Smyczyńska J, Stawerska R, et al. National Program of Severe Growth Hormone Deficiency Treatment in Adults and Adolescents after Completion of Growth Promoting Therapy. Endokrynol Pol. 2018; 69(5): 468–524.
  11. Adams LA, Feldstein A, Lindor KD, et al. Nonalcoholic fatty liver disease among patients with hypothalamic and pituitary dysfunction. Hepatology. 2004; 39(4): 909–914.
  12. Hong JW, Kim JY, Kim YE, et al. Metabolic parameters and nonalcoholic fatty liver disease in hypopituitary men. Horm Metab Res. 2011; 43(1): 48–54.
  13. Xu L, Xu C, Yu C, et al. Association between serum growth hormone levels and nonalcoholic fatty liver disease: a cross-sectional study. PLoS One. 2012; 7(8): e44136.
  14. Mosca A, Della Volpe L, Alisi A, et al. The Role of the GH/IGF1 Axis on the Development of MAFLD in Pediatric Patients with Obesity. Metabolites. 2022; 12(12).
  15. Takahashi Y, Iida K, Takahashi K, et al. Growth hormone reverses nonalcoholic steatohepatitis in a patient with adult growth hormone deficiency. Gastroenterology. 2007; 132(3): 938–943.
  16. Nishizawa H, Iguchi G, Murawaki A, et al. Nonalcoholic fatty liver disease in adult hypopituitary patients with GH deficiency and the impact of GH replacement therapy. Eur J Endocrinol. 2012; 167(1): 67–74.
  17. Stanley TL, Fourman LT, Feldpausch MN, et al. Effects of tesamorelin on non-alcoholic fatty liver disease in HIV: a randomised, double-blind, multicentre trial. Lancet HIV. 2019; 6(12): e821–e830.
  18. Pan CS, Weiss JJ, Fourman LT, et al. Effect of recombinant human growth hormone on liver fat content in young adults with nonalcoholic fatty liver disease. Clin Endocrinol (Oxf). 2021; 94(2): 183–192.
  19. Bettini S, Bombonato G, Dassie F, et al. Liver Fibrosis and Steatosis in Alström Syndrome: A Genetic Model for Metabolic Syndrome. Diagnostics (Basel). 2021; 11(5).
  20. Fan Y, Fang X, Tajima A, et al. Evolution of hepatic steatosis to fibrosis and adenoma formation in liver-specific growth hormone receptor knockout mice. Front Endocrinol (Lausanne). 2014; 5: 218.
  21. Rufinatscha K, Ress C, Folie S, et al. Metabolic effects of reduced growth hormone action in fatty liver disease. Hepatol Int. 2018; 12(5): 474–481.
  22. Fellinger P, Wolf P, Pfleger L, et al. Increased ATP synthesis might counteract hepatic lipid accumulation in acromegaly. JCI Insight. 2020; 5(5).
  23. Møller N, Jørgensen JO. Effects of growth hormone on glucose, lipid, and protein metabolism in human subjects. Endocr Rev. 2009; 30(2): 152–177.
  24. Rogowicz-Frontczak A, Majchrzak A, Zozulińska-Ziółkiewicz D. Insulin resistance in endocrine disorders - treatment options. Endokrynol Pol. 2017; 68(3): 334–351.
  25. Winhofer Y, Wolf P, Krššák M, et al. No evidence of ectopic lipid accumulation in the pathophysiology of the acromegalic cardiomyopathy. J Clin Endocrinol Metab. 2014; 99(11): 4299–4306.
  26. Bredella MA, Schorr M, Dichtel LE, et al. Body Composition and Ectopic Lipid Changes With Biochemical Control of Acromegaly. J Clin Endocrinol Metab. 2017; 102(11): 4218–4225.
  27. Arlien-Søborg MC, Madsen MA, Dal J, et al. Ectopic lipid deposition and insulin resistance in patients with GH disorders before and after treatment. Eur J Endocrinol. 2023; 188(1).
  28. Ciresi A, Guarnotta V, Campo D, et al. Hepatic Steatosis Index in Acromegaly: Correlation with Insulin Resistance Regardless of the Disease Control. Int J Endocrinol. 2018; 2018: 5421961.
  29. Eroğlu İ, Iremli BG, Idilman IS, et al. Nonalcoholic Fatty Liver Disease, Liver Fibrosis, and Utility of Noninvasive Scores in Patients With Acromegaly. J Clin Endocrinol Metab. 2023; 109(1): e119–e129.
  30. Gierach M, Bruska-Sikorska M, Rojek M, et al. Hyperprolactinemia and insulin resistance. Endokrynol Pol. 2022; 73(6): 959–967.
  31. Zhang P, Ge Z, Wang H, et al. Prolactin improves hepatic steatosis via CD36 pathway. J Hepatol. 2018; 68(6): 1247–1255.
  32. Luque GM, Lopez-Vicchi F, Ornstein AM, et al. Chronic hyperprolactinemia evoked by disruption of lactotrope dopamine D2 receptors impacts on liver and adipocyte genes related to glucose and insulin balance. Am J Physiol Endocrinol Metab. 2016; 311(6): E974–E988.
  33. Takaki Y, Mizuochi T, Nishioka J, et al. Nonalcoholic fatty liver disease with prolactin-secreting pituitary adenoma in an adolescent: A case report. Medicine (Baltimore). 2018; 97(42): e12879.
  34. Zhu C, Ma H, Huang D, et al. J-Shaped Relationship Between Serum Prolactin and Metabolic-Associated Fatty Liver Disease in Female Patients With Type 2 Diabetes. Front Endocrinol (Lausanne). 2022; 13: 815995.
  35. Zhang Y, Liu H. Cross-sectional association between prolactin levels and non-alcoholic fatty liver disease in patients with type 2 diabetes mellitus: a retrospective analysis of patients from a single hospital in China. BMJ Open. 2022; 12(10): e062252.
  36. Szmygin H, Szydełko J, Matyjaszek-Matuszek B. Copeptin as a novel biomarker of cardiometabolic syndrome. Endokrynol Pol. 2021; 72(5): 566–571.
  37. Barchetta I, Enhörning S, Cimini FA, et al. Elevated plasma copeptin levels identify the presence and severity of non-alcoholic fatty liver disease in obesity. BMC Med. 2019; 17(1): 85.
  38. Gomaa R. Copeptin: a novel marker for diagnosis and prognosisof various diseases associated with diabetes. BOHR Int J Gen Int Med. 2022; 1(1): 46–50.
  39. Nashaat E, Riad G, Ghait R, et al. Elevated Plasma Copeptin Levels Identify the Presence and Severity of Nonalcoholic Fatty Liver Disease in Obesity. QJM: Int J Med. 2023; 116(Suppl_1).
  40. Majumdar S, Thakur MB, Ran A. Comparative Evaluation of Serum Copeptin in Obesity with Non Alcoholic Fatty Liver Disease. J Assoc Physicians India. 2023; 71(1): 1.
  41. Rofe AM, Williamson DH. Metabolic effects of vasopressin infusion in the starved rat. Reversal of ketonaemia. Biochem J. 1983; 212(1): 231–239.
  42. Xue B, Moustaid‐Moussa N, Wilkison W, et al. The agouti gene product inhibits lipolysis in human adipocytes via a Ca2+‐dependent mechanism. FASEB J. 1998; 12(13): 1391–1396.
  43. Hiroyama M, Aoyagi T, Fujiwara Y, et al. Hypermetabolism of fat in V1a vasopressin receptor knockout mice. Mol Endocrinol. 2007; 21(1): 247–258.
  44. Bambini F, Gatta E, D'Alessio R, et al. Thyroid disease and autoimmunity in obese patients: a narrative review. Endokrynol Pol. 2023; 74(6).
  45. Bikeyeva V, Abdullah A, Radivojevic A, et al. Nonalcoholic Fatty Liver Disease and Hypothyroidism: What You Need to Know. Cureus. 2022; 14(8): e28052.
  46. Bano A, Chaker L, Plompen EPC, et al. Thyroid Function and the Risk of Nonalcoholic Fatty Liver Disease: The Rotterdam Study. J Clin Endocrinol Metab. 2016; 101(8): 3204–3211.
  47. He W, An X, Li L, et al. Relationship between Hypothyroidism and Non-Alcoholic Fatty Liver Disease: A Systematic Review and Meta-analysis. Front Endocrinol (Lausanne). 2017; 8: 335.
  48. Mantovani A, Nascimbeni F, Lonardo A, et al. Association Between Primary Hypothyroidism and Nonalcoholic Fatty Liver Disease: A Systematic Review and Meta-Analysis. Thyroid. 2018; 28(10): 1270–1284.
  49. Lonardo A, Ballestri S, Mantovani A, et al. Pathogenesis of hypothyroidism-induced NAFLD: Evidence for a distinct disease entity? Dig Liver Dis. 2019; 51(4): 462–470.
  50. Mandato C, D'Acunzo I, Vajro P. Thyroid dysfunction and its role as a risk factor for non-alcoholic fatty liver disease: What's new. Dig Liver Dis. 2018; 50(11): 1163–1165.
  51. Piantanida E, Ippolito S, Gallo D, et al. The interplay between thyroid and liver: implications for clinical practice. J Endocrinol Invest. 2020; 43(7): 885–899.
  52. Xu C, Xu L, Yu C, et al. Association between thyroid function and nonalcoholic fatty liver disease in euthyroid elderly Chinese. Clin Endocrinol (Oxf). 2011; 75(2): 240–246.
  53. Sinha RA, Bruinstroop E, Singh BK, et al. Nonalcoholic Fatty Liver Disease and Hypercholesterolemia: Roles of Thyroid Hormones, Metabolites, and Agonists. Thyroid. 2019; 29(9): 1173–1191.
  54. Chen Yi, Wang N, Chen Y, et al. The association of non-alcoholic fatty liver disease with thyroid peroxidase and thyroglobulin antibody: A new insight from SPECT-China study. Autoimmunity. 2018; 51(5): 238–244.
  55. Wang C, Niu Q, Lv H, et al. Elevated TPOAb is a Strong Predictor of Autoimmune Development in Patients of Type 2 Diabetes Mellitus and Non-Alcoholic Fatty Liver Disease: A Case-Control Study. Diabetes Metab Syndr Obes. 2020; 13: 4369–4378.
  56. Kim HJ, Park SJ, Park HK, et al. Association of thyroid autoimmunity with nonalcoholic fatty liver disease in euthyroid middle-aged subjects: A population-based study. J Gastroenterol Hepatol. 2022; 37(8): 1617–1623.
  57. Zhang X, Li R, Chen Y, et al. The Role of Thyroid Hormones and Autoantibodies in Metabolic Dysfunction Associated Fatty Liver Disease: TgAb May Be a Potential Protective Factor. Front Endocrinol (Lausanne). 2020; 11: 598836.
  58. Wang SH, Chen XY, Wang XP. Jidong Restless Legs Syndrome Cohort Study: Objectives, Design, and Baseline Screening. Front Neurol. 2021; 12: 682448.
  59. Xiao R, Ni C, Cai Y, et al. Prevalence and impact of non-alcoholic fatty liver disease in patients with papillary thyroid carcinoma. Endocrine. 2023; 80(3): 619–629.
  60. Liu S, Liu Y, Wan Bo, et al. Association between Vitamin D Status and Non-Alcoholic Fatty Liver Disease: A Population-Based Study. J Nutr Sci Vitaminol (Tokyo). 2019; 65(4): 303–308.
  61. Sindhughosa DA, Wibawa ID, Mariadi IK, et al. Additional treatment of vitamin D for improvement of insulin resistance in non-alcoholic fatty liver disease patients: a systematic review and meta-analysis. Sci Rep. 2022; 12(1): 7716.
  62. Kim Y, Chang Y, Ryu S, et al. Resolution of, and Risk of Incident Non-alcoholic Fatty Liver Disease With Changes in Serum 25-hydroxy Vitamin D Status. J Clin Endocrinol Metab. 2022; 107(8): e3437–e3447.
  63. Dal K, Uzman M, Ata N, et al. The effect of vitamin D status on non-alcoholic fatty liver disease: a population-based observational study. Endokrynol Pol. 2023; 74(1): 63–66.
  64. Abramovitch S, Dahan-Bachar L, Sharvit E, et al. Vitamin D inhibits proliferation and profibrotic marker expression in hepatic stellate cells and decreases thioacetamide-induced liver fibrosis in rats. Gut. 2011; 60(12): 1728–1737.
  65. Beilfuss A, Sowa JP, Sydor S, et al. Vitamin D counteracts fibrogenic TGF-β signalling in human hepatic stellate cells both receptor-dependently and independently. Gut. 2015; 64(5): 791–799.
  66. Farhangi MA, Mesgari-Abbasi M, Hajiluian G, et al. Adipose Tissue Inflammation and Oxidative Stress: the Ameliorative Effects of Vitamin D. Inflammation. 2017; 40(5): 1688–1697.
  67. Abramovitch S, Sharvit E, Weisman Y, et al. Vitamin D inhibits development of liver fibrosis in an animal model but cannot ameliorate established cirrhosis. Am J Physiol Gastrointest Liver Physiol. 2015; 308(2): G112–G120.
  68. Roth CL, Elfers CT, Figlewicz DP, et al. Vitamin D deficiency in obese rats exacerbates nonalcoholic fatty liver disease and increases hepatic resistin and Toll-like receptor activation. Hepatology. 2012; 55(4): 1103–1111.
  69. Sarkar S. Molecular Crosstalk Between Vitamin D and Non-alcoholic Fatty Liver Disease. Explor Res Hypothesis Med. 2023; 9(1): 60–75.
  70. Maestro B, Molero S, Bajo S, et al. Transcriptional activation of the human insulin receptor gene by 1,25-dihydroxyvitamin D(3). Cell Biochem Funct. 2002; 20(3): 227–232.
  71. Shepherd PR, Withers DJ, Siddle K. Phosphoinositide 3-kinase: the key switch mechanism in insulin signalling. Biochem J. 1998; 333 ( Pt 3)(Pt 3): 471–490.
  72. Copps KD, White MF. Regulation of insulin sensitivity by serine/threonine phosphorylation of insulin receptor substrate proteins IRS1 and IRS2. Diabetologia. 2012; 55(10): 2565–2582.
  73. Wahsh E, Abu-Elsaad N, El-Karef A, et al. The vitamin D receptor agonist, calcipotriol, modulates fibrogenic pathways mitigating liver fibrosis in-vivo: An experimental study. Eur J Pharmacol. 2016; 789: 362–369.
  74. Patel YA, Henao R, Moylan CA, et al. Vitamin D is Not Associated With Severity in NAFLD: Results of a Paired Clinical and Gene Expression Profile Analysis. Am J Gastroenterol. 2016; 111(11): 1591–1598.
  75. Dabbaghmanesh MH, Danafar F, Eshraghian A, et al. Vitamin D supplementation for the treatment of non-alcoholic fatty liver disease: A randomized double blind placebo controlled trial. Diabetes Metab Syndr. 2018; 12(4): 513–517.
  76. Wang N, Chen C, Zhao Li, et al. Vitamin D and Nonalcoholic Fatty Liver Disease: Bi-directional Mendelian Randomization Analysis. EBioMedicine. 2018; 28: 187–193.
  77. Barry EL, Rees JR, Peacock JL, et al. Genetic variants in CYP2R1, CYP24A1, and VDR modify the efficacy of vitamin D3 supplementation for increasing serum 25-hydroxyvitamin D levels in a randomized controlled trial. J Clin Endocrinol Metab. 2014; 99(10): E2133–E2137.
  78. Zhang M, Zhao LJ, Zhou Yu, et al. SNP rs11185644 of RXRA gene is identified for dose-response variability to vitamin D3 supplementation: a randomized clinical trial. Sci Rep. 2017; 7: 40593.
  79. Al-Daghri NM, Mohammed AK, Al-Attas OS, et al. Vitamin D Receptor Gene Polymorphisms Modify Cardiometabolic Response to Vitamin D Supplementation in T2DM Patients. Sci Rep. 2017; 7(1): 8280.
  80. Płudowski P, Kos-Kudła B, Walczak M, et al. Guidelines for Preventing and Treating Vitamin D Deficiency: A 2023 Update in Poland. Nutrients. 2023; 15(3).
  81. Patel R, Williams-Dautovich J, Cummins CL. Minireview: new molecular mediators of glucocorticoid receptor activity in metabolic tissues. Mol Endocrinol. 2014; 28(7): 999–1011.
  82. Papanastasiou L, Fountoulakis S, Vatalas IA. Adrenal disorders and non-alcoholic fatty liver disease. Minerva Endocrinol. 2017; 42(2): 151–163.
  83. Zhou J, Zhang M, Bai X, et al. Demographic Characteristics, Etiology, and Comorbidities of Patients with Cushing's Syndrome: A 10-Year Retrospective Study at a Large General Hospital in China. Int J Endocrinol. 2019; 2019: 7159696.
  84. Remon P, Gutierrez A, Moreno E, et al. MAFLD prevalence in a cohort of patients with Cushing's disease. Endocrine Abstracts. 2023.
  85. Chen K, Chen L, Dai J, et al. MAFLD in Patients with Cushing's Disease Is Negatively Associated with Low Free Thyroxine Levels Rather than with Cortisol or TSH Levels. Int J Endocrinol. 2023; 2023: 6637396.
  86. Targher G, Bertolini L, Padovani R, et al. Associations between liver histology and cortisol secretion in subjects with nonalcoholic fatty liver disease. Clin Endocrinol (Oxf). 2006; 64(3): 337–341.
  87. Zoppini G, Targher G, Venturi C, et al. Relationship of nonalcoholic hepatic steatosis to overnight low-dose dexamethasone suppression test in obese individuals. Clin Endocrinol (Oxf). 2004; 61(6): 711–715.
  88. Masuzaki H, Paterson J, Shinyama H, et al. A transgenic model of visceral obesity and the metabolic syndrome. Science. 2001; 294(5549): 2166–2170.
  89. Morton NM, Holmes MC, Fiévet C, et al. Improved lipid and lipoprotein profile, hepatic insulin sensitivity, and glucose tolerance in 11beta-hydroxysteroid dehydrogenase type 1 null mice. J Biol Chem. 2001; 276(44): 41293–41300.
  90. Morgan SA, McCabe EL, Gathercole LL, et al. 11β-HSD1 is the major regulator of the tissue-specific effects of circulating glucocorticoid excess. Proc Natl Acad Sci U S A. 2014; 111(24): E2482–E2491.
  91. Stefan N, Ramsauer M, Jordan P, et al. Inhibition of 11β-HSD1 with RO5093151 for non-alcoholic fatty liver disease: a multicentre, randomised, double-blind, placebo-controlled trial. Lancet Diabetes Endocrinol. 2014; 2(5): 406–416.
  92. Dowman JK, Hopkins LJ, Reynolds GM, et al. Loss of 5α-reductase type 1 accelerates the development of hepatic steatosis but protects against hepatocellular carcinoma in male mice. Endocrinology. 2013; 154(12): 4536–4547.
  93. Livingstone DEW, Barat P, Di Rollo EM, et al. 5α-Reductase type 1 deficiency or inhibition predisposes to insulin resistance, hepatic steatosis, and liver fibrosis in rodents. Diabetes. 2015; 64(2): 447–458.
  94. Ahmed A, Rabbitt E, Brady T, et al. A switch in hepatic cortisol metabolism across the spectrum of non alcoholic fatty liver disease. PLoS One. 2012; 7(2): e29531.
  95. Bataller R, Sancho-Bru P, Ginès P, et al. Activated human hepatic stellate cells express the renin-angiotensin system and synthesize angiotensin II. Gastroenterology. 2003; 125(1): 117–125.
  96. Li Y, Zhang Y, Chen T, et al. Role of aldosterone in the activation of primary mice hepatic stellate cell and liver fibrosis via NLRP3 inflammasome. J Gastroenterol Hepatol. 2020; 35(6): 1069–1077.
  97. Hu J, Cai X, Zhu Q, et al. Relationship Between Plasma Aldosterone Concentrations and Non-Alcoholic Fatty Liver Disease Diagnosis in Patients with Hypertension: A Retrospective Cohort Study. Diabetes Metab Syndr Obes. 2023; 16: 1625–1636.
  98. Wada T, Ohshima S, Fujisawa E, et al. Aldosterone inhibits insulin-induced glucose uptake by degradation of insulin receptor substrate (IRS) 1 and IRS2 via a reactive oxygen species-mediated pathway in 3T3-L1 adipocytes. Endocrinology. 2009; 150(4): 1662–1669.
  99. Yamashita R, Kikuchi T, Mori Y, et al. Aldosterone stimulates gene expression of hepatic gluconeogenic enzymes through the glucocorticoid receptor in a manner independent of the protein kinase B cascade. Endocr J. 2004; 51(2): 243–251.
  100. Kumar A, Blackshear C, Subauste JS, et al. Fatty Liver Disease, Women, and Aldosterone: Finding a Link in the Jackson Heart Study. J Endocr Soc. 2017; 1(5): 460–469.
  101. Chen Yi, Chen X, Chen Q, et al. Non-Alcoholic Fatty Liver Disease and Hypokalemia in Primary Aldosteronism Among Chinese Population. Front Endocrinol (Lausanne). 2021; 12: 565714.
  102. Fallo F, Dalla Pozza A, Tecchio M, et al. Nonalcoholic fatty liver disease in primary aldosteronism: a pilot study. Am J Hypertens. 2010; 23(1): 2–5.
  103. Yokohama S, Yoneda M, Haneda M, et al. Therapeutic efficacy of an angiotensin II receptor antagonist in patients with nonalcoholic steatohepatitis. Hepatology. 2004; 40(5): 1222–1225.
  104. Georgescu EF, Ionescu R, Niculescu M, et al. Angiotensin-receptor blockers as therapy for mild-to-moderate hypertension-associated non-alcoholic steatohepatitis. World J Gastroenterol. 2009; 15(8): 942–954.
  105. Goh GB, Pagadala MR, Dasarathy J, et al. Renin-angiotensin system and fibrosis in non-alcoholic fatty liver disease. Liver Int. 2015; 35(3): 979–985.
  106. Pizarro M, Solís N, Quintero P, et al. Beneficial effects of mineralocorticoid receptor blockade in experimental non-alcoholic steatohepatitis. Liver Int. 2015; 35(9): 2129–2138.
  107. Perakakis N, Bornstein SR, Birkenfeld AL, et al. FIDELIO-DKD and FIGARO-DKD investigators. Efficacy of finerenone in patients with type 2 diabetes, chronic kidney disease and altered markers of liver steatosis and fibrosis: A FIDELITY subgroup analysis. Diabetes Obes Metab. 2024; 26(1): 191–200.
  108. Hirata T, Tomita K, Kawai T, et al. Effect of Telmisartan or Losartan for Treatment of Nonalcoholic Fatty Liver Disease: Fatty Liver Protection Trial by Telmisartan or Losartan Study (FANTASY). Int J Endocrinol. 2013; 2013: 587140.
  109. Kurtz TW. Treating the metabolic syndrome: telmisartan as a peroxisome proliferator-activated receptor-gamma activator. Acta Diabetol. 2005; 42 Suppl 1: S9–16.
  110. Polyzos SA, Kountouras J, Zafeiriadou E, et al. Effect of spironolactone and vitamin E on serum metabolic parameters and insulin resistance in patients with nonalcoholic fatty liver disease. J Renin Angiotensin Aldosterone Syst. 2011; 12(4): 498–503.
  111. Tchernof A, Labrie F. Dehydroepiandrosterone, obesity and cardiovascular disease risk: a review of human studies. Eur J Endocrinol. 2004; 151(1): 1–14.
  112. Celebi F, Yilmaz I, Aksoy H, et al. Dehydroepiandrosterone prevents oxidative injury in obstructive jaundice in rats. J Int Med Res. 2004; 32(4): 400–405.
  113. Iwasaki T, Mukasa K, Yoneda M, et al. Marked attenuation of production of collagen type I from cardiac fibroblasts by dehydroepiandrosterone. Am J Physiol Endocrinol Metab. 2005; 288(6): E1222–E1228.
  114. Hildebrand F, Pape HC, Hoevel P, et al. The importance of systemic cytokines in the pathogenesis of polymicrobial sepsis and dehydroepiandrosterone treatment in a rodent model. Shock. 2003; 20(4): 338–346.
  115. Yoneda M, Wada K, Katayama K, et al. A novel therapy for acute hepatitis utilizing dehydroepiandrosterone in the murine model of hepatitis. Biochem Pharmacol. 2004; 68(11): 2283–2289.
  116. Apostolova G, Schweizer RAS, Balazs Z, et al. Dehydroepiandrosterone inhibits the amplification of glucocorticoid action in adipose tissue. Am J Physiol Endocrinol Metab. 2005; 288(5): E957–E964.
  117. Tagawa N, Minamitani E, Yamaguchi Y, et al. Alternative mechanism for anti-obesity effect of dehydroepiandrosterone: possible contribution of 11β-hydroxysteroid dehydrogenase type 1 inhibition in rodent adipose tissue. Steroids. 2011; 76(14): 1546–1553.
  118. Jakubowicz D, Beer N, Rengifo R. Effect of dehydroepiandrosterone on cyclic-guanosine monophosphate in men of advancing age. Ann N Y Acad Sci. 1995; 774: 312–315.
  119. Charlton M, Angulo P, Chalasani N, et al. Low circulating levels of dehydroepiandrosterone in histologically advanced nonalcoholic fatty liver disease. Hepatology. 2008; 47(2): 484–492.
  120. Sumida Y, Yonei Y, Kanemasa K, et al. Lower circulating levels of dehydroepiandrosterone, independent of insulin resistance, is an important determinant of severity of non-alcoholic steatohepatitis in Japanese patients. Hepatol Res. 2010; 40(9): 901–910.
  121. Koehler E, Swain J, Sanderson S, et al. Growth hormone, dehydroepiandrosterone and adiponectin levels in non-alcoholic steatohepatitis: an endocrine signature for advanced fibrosis in obese patients. Liver Int. 2012; 32(2): 279–286.
  122. Tokushige K, Hashimoto E, Kodama K, et al. Serum metabolomic profile and potential biomarkers for severity of fibrosis in nonalcoholic fatty liver disease. J Gastroenterol. 2013; 48(12): 1392–1400.
  123. Völzke H, Aumann N, Krebs A, et al. Hepatic steatosis is associated with low serum testosterone and high serum DHEAS levels in men. Int J Androl. 2010; 33(1): 45–53.
  124. Koga M, Saito H, Mukai M, et al. Serum dehydroepiandrosterone sulphate levels in patients with non-alcoholic fatty liver disease. Intern Med. 2011; 50(16): 1657–1661.
  125. Wang WB, She F, Xie LF, et al. Evaluation of Basal Serum Adrenocorticotropic Hormone and Cortisol Levels and Their Relationship with Nonalcoholic Fatty Liver Disease in Male Patients with Idiopathic Hypogonadotropic Hypogonadism. Chin Med J (Engl). 2016; 129(10): 1147–1153.
  126. Zhang X, Mou Y, Aribas E, et al. Associations of Sex Steroids and Sex Hormone-Binding Globulin with Non-Alcoholic Fatty Liver Disease: A Population-Based Study and Meta-Analysis. Genes (Basel). 2022; 13(6).
  127. Licht CMM, Vreeburg SA, van Reedt Dortland AKB, et al. Increased sympathetic and decreased parasympathetic activity rather than changes in hypothalamic-pituitary-adrenal axis activity is associated with metabolic abnormalities. J Clin Endocrinol Metab. 2010; 95(5): 2458–2466.
  128. Ghosh PM, Shu ZJ, Zhu B, et al. Role of β-adrenergic receptors in regulation of hepatic fat accumulation during aging. J Endocrinol. 2012; 213(3): 251–261.
  129. Shi Y, Shu ZJ, Xue X, et al. β2-Adrenergic receptor ablation modulates hepatic lipid accumulation and glucose tolerance in aging mice. Exp Gerontol. 2016; 78: 32–38.
  130. Bruinstroop E, Fliers E, Kalsbeek A. Restoring the autonomic balance to reduce liver steatosis. J Physiol. 2019; 597(18): 4683–4684.
  131. Shi Y, Pizzini J, Wang H, et al. -Adrenergic receptor agonist induced hepatic steatosis in mice: modeling nonalcoholic fatty liver disease in hyperadrenergic states. Am J Physiol Endocrinol Metab. 2021; 321(1): E90–E9E104.
  132. Lelou E, Corlu A, Nesseler N, et al. The Role of Catecholamines in Pathophysiological Liver Processes. Cells. 2022; 11(6).
  133. Sigala B, McKee C, Soeda J, et al. Sympathetic nervous system catecholamines and neuropeptide Y neurotransmitters are upregulated in human NAFLD and modulate the fibrogenic function of hepatic stellate cells. PLoS One. 2013; 8(9): e72928.
  134. Adori C, Daraio T, Kuiper R, et al. Disorganization and degeneration of liver sympathetic innervations in nonalcoholic fatty liver disease revealed by 3D imaging. Sci Adv. 2021; 7(30).
  135. Zhang H, Liu Y, Wang Li, et al. Differential effects of estrogen/androgen on the prevention of nonalcoholic fatty liver disease in the male rat. J Lipid Res. 2013; 54(2): 345–357.
  136. Hart-Unger S, Arao Y, Hamilton KJ, et al. Hormone signaling and fatty liver in females: analysis of estrogen receptor α mutant mice. Int J Obes (Lond). 2017; 41(6): 945–954.
  137. Pal SC, Eslam M, Mendez-Sanchez N, et al. Detangling the interrelations between MAFLD, insulin resistance, and key hormones. Hormones (Athens). 2022; 21(4): 573–589.
  138. Gutierrez-Grobe Y, Ponciano-Rodríguez G, Ramos MH, et al. Prevalence of non alcoholic fatty liver disease in premenopausal, posmenopausal and polycystic ovary syndrome women. The role of estrogens. Ann Hepatol. 2010; 9(4): 402–409.
  139. Klair JS, Yang JuD, Abdelmalek MF, et al. Nonalcoholic Steatohepatitis Clinical Research Network. A longer duration of estrogen deficiency increases fibrosis risk among postmenopausal women with nonalcoholic fatty liver disease. Hepatology. 2016; 64(1): 85–91.
  140. Von-Hafe M, Borges-Canha M, Vale C, et al. Nonalcoholic Fatty Liver Disease and Endocrine Axes-A Scoping Review. Metabolites. 2022; 12(4).
  141. Zhu L, Brown WC, Cai Q, et al. Estrogen treatment after ovariectomy protects against fatty liver and may improve pathway-selective insulin resistance. Diabetes. 2013; 62(2): 424–434.
  142. D'Eon TM, Souza SC, Aronovitz M, et al. Estrogen regulation of adiposity and fuel partitioning. Evidence of genomic and non-genomic regulation of lipogenic and oxidative pathways. J Biol Chem. 2005; 280(43): 35983–35991.
  143. Camporez JP, Jornayvaz FR, Lee HY, et al. Cellular mechanism by which estradiol protects female ovariectomized mice from high-fat diet-induced hepatic and muscle insulin resistance. Endocrinology. 2013; 154(3): 1021–1028.
  144. Matsuo K, Gualtieri MR, Cahoon SS, et al. Surgical menopause and increased risk of nonalcoholic fatty liver disease in endometrial cancer. Menopause. 2016; 23(2): 189–196.
  145. Florio AA, Graubard BI, Yang B, et al. Oophorectomy and risk of non-alcoholic fatty liver disease and primary liver cancer in the Clinical Practice Research Datalink. Eur J Epidemiol. 2019; 34(9): 871–878.
  146. Yang JuD, Abdelmalek MF, Guy CD, et al. Nonalcoholic Steatohepatitis Clinical Research Network. Patient Sex, Reproductive Status, and Synthetic Hormone Use Associate With Histologic Severity of Nonalcoholic Steatohepatitis. Clin Gastroenterol Hepatol. 2017; 15(1): 127–131.e2.
  147. Nguyen MC, Stewart RB, Banerji MA, et al. Relationships between tamoxifen use, liver fat and body fat distribution in women with breast cancer. Int J Obes Relat Metab Disord. 2001; 25(2): 296–298.
  148. Yang YJ, Kim KMo, An JiH, et al. Clinical significance of fatty liver disease induced by tamoxifen and toremifene in breast cancer patients. Breast. 2016; 28: 67–72.
  149. Hong N, Yoon HG, Seo DaH, et al. Different patterns in the risk of newly developed fatty liver and lipid changes with tamoxifen versus aromatase inhibitors in postmenopausal women with early breast cancer: A propensity score-matched cohort study. Eur J Cancer. 2017; 82: 103–114.
  150. Yoo JJ, Lim YS, Kim MS, et al. Risk of fatty liver after long-term use of tamoxifen in patients with breast cancer. PLoS One. 2020; 15(7): e0236506.
  151. Bruno S, Maisonneuve P, Castellana P, et al. Incidence and risk factors for non-alcoholic steatohepatitis: prospective study of 5408 women enrolled in Italian tamoxifen chemoprevention trial. BMJ. 2005; 330(7497): 932.
  152. Saphner T, Triest-Robertson S, Li H, et al. The association of nonalcoholic steatohepatitis and tamoxifen in patients with breast cancer. Cancer. 2009; 115(14): 3189–3195.
  153. Jones H, Sprung VS, Pugh CJA, et al. Polycystic ovary syndrome with hyperandrogenism is characterized by an increased risk of hepatic steatosis compared to nonhyperandrogenic PCOS phenotypes and healthy controls, independent of obesity and insulin resistance. J Clin Endocrinol Metab. 2012; 97(10): 3709–3716.
  154. Kelley CE, Brown AJ, Diehl AM, et al. Review of nonalcoholic fatty liver disease in women with polycystic ovary syndrome. World J Gastroenterol. 2014; 20(39): 14172–14184.
  155. Schiffer L, Kempegowda P, Arlt W, et al. MECHANISMS IN ENDOCRINOLOGY: The sexually dimorphic role of androgens in human metabolic disease. Eur J Endocrinol. 2017; 177(3): R125–R143.
  156. Kumarendran B, O'Reilly MW, Manolopoulos KN, et al. Polycystic ovary syndrome, androgen excess, and the risk of nonalcoholic fatty liver disease in women: A longitudinal study based on a United Kingdom primary care database. PLoS Med. 2018; 15(3): e1002542.
  157. Yao K, Zheng H, Peng H. Association between polycystic ovary syndrome and risk of non-alcoholic fatty liver disease: a meta-analysis. Endokrynol Pol. 2023; 74(5): 520–527.
  158. Lin HY, Yu IC, Wang RS, et al. Increased hepatic steatosis and insulin resistance in mice lacking hepatic androgen receptor. Hepatology. 2008; 47(6): 1924–1935.
  159. Dubois V, Laurent MR, Jardi F, et al. Androgen Deficiency Exacerbates High-Fat Diet-Induced Metabolic Alterations in Male Mice. Endocrinology. 2016; 157(2): 648–665.
  160. Senmaru T, Fukui M, Okada H, et al. Testosterone deficiency induces markedly decreased serum triglycerides, increased small dense LDL, and hepatic steatosis mediated by dysregulation of lipid assembly and secretion in mice fed a high-fat diet. Metabolism. 2013; 62(6): 851–860.
  161. Xia F, Xu X, Zhai H, et al. Castration-induced testosterone deficiency increases fasting glucose associated with hepatic and extra-hepatic insulin resistance in adult male rats. Reprod Biol Endocrinol. 2013; 11: 106.
  162. Schwinge D, Carambia A, Quaas A, et al. Testosterone suppresses hepatic inflammation by the downregulation of IL-17, CXCL-9, and CXCL-10 in a mouse model of experimental acute cholangitis. J Immunol. 2015; 194(6): 2522–2530.
  163. Jia Y, Yee JK, Wang C, et al. Testosterone replacement ameliorates nonalcoholic fatty liver disease in castrated male rats. Endocrinology. 2014; 155(2): 417–428.
  164. Jia Y, Yee JK, Wang C, et al. Testosterone protects high-fat/low-carbohydrate diet-induced nonalcoholic fatty liver disease in castrated male rats mainly via modulating endoplasmic reticulum stress. Am J Physiol Endocrinol Metab. 2018; 314(4): E366–E376.
  165. Barbonetti A, Caterina Vassallo MR, Cotugno M, et al. Low testosterone and non-alcoholic fatty liver disease: Evidence for their independent association in men with chronic spinal cord injury. J Spinal Cord Med. 2016; 39(4): 443–449.
  166. Haider A, Gooren LJG, Padungtod P, et al. Improvement of the metabolic syndrome and of non-alcoholic liver steatosis upon treatment of hypogonadal elderly men with parenteral testosterone undecanoate. Exp Clin Endocrinol Diabetes. 2010; 118(3): 167–171.
  167. Khodamoradi K, Khosravizadeh Z, Seetharam D, et al. The role of leptin and low testosterone in obesity. Int J Impot Res. 2022; 34(7): 704–713.
  168. Mancini M, Pecori Giraldi F, Andreassi A, et al. Obesity Is Strongly Associated With Low Testosterone and Reduced Penis Growth During Development. J Clin Endocrinol Metab. 2021; 106(11): 3151–3159.
  169. Fan C, Wei D, Wang L, et al. The association of serum testosterone with dyslipidemia is mediated by obesity: the Henan Rural Cohort Study. J Endocrinol Invest. 2023; 46(4): 679–686.
  170. Pelusi C. The Effects of the New Therapeutic Treatments for Diabetes Mellitus on the Male Reproductive Axis. Front Endocrinol (Lausanne). 2022; 13: 821113.
  171. Bril F, Ortiz-Lopez C, Lomonaco R, et al. Clinical value of liver ultrasound for the diagnosis of nonalcoholic fatty liver disease in overweight and obese patients. Liver Int. 2015; 35(9): 2139–2146.
  172. Salmi A, di Filippo L, Ferrari C, et al. Ultrasound and FibroScan Controlled Attenuation Parameter in patients with MAFLD: head to head comparison in assessing liver steatosis. Endocrine. 2022; 78(2): 262–269.
  173. Song YS, Fang CH, So BI, et al. Time course of the development of nonalcoholic Fatty liver disease in the Otsuka long-evans Tokushima Fatty rat. Gastroenterol Res Pract. 2013; 2013: 342648.
  174. Laursen TL, Kjær MB, Kristensen L, et al. Clinical Progression of Metabolic-Associated Fatty Liver Disease Is Rare in a Danish Tertiary Liver Center. J Clin Med. 2022; 11(9).
  175. Ekstedt M, Franzén LE, Mathiesen UL, et al. Long-term follow-up of patients with NAFLD and elevated liver enzymes. Hepatology. 2006; 44(4): 865–873.
  176. Rafiq N, Bai C, Fang Y, et al. Long-term follow-up of patients with nonalcoholic fatty liver. Clin Gastroenterol Hepatol. 2009; 7(2): 234–238.
  177. Le P, Payne JY, Zhang Lu, et al. Disease State Transition Probabilities Across the Spectrum of NAFLD: A Systematic Review and Meta-Analysis of Paired Biopsy or Imaging Studies. Clin Gastroenterol Hepatol. 2023; 21(5): 1154–1168.
  178. Wai CT, Greenson JK, Fontana RJ, et al. A simple noninvasive index can predict both significant fibrosis and cirrhosis in patients with chronic hepatitis C. Hepatology. 2003; 38(2): 518–526.
  179. Harrison SA, Oliver D, Arnold HL, et al. Development and validation of a simple NAFLD clinical scoring system for identifying patients without advanced disease. Gut. 2008; 57(10): 1441–1447.
  180. Sterling RK, Lissen E, Clumeck N, et al. APRICOT Clinical Investigators. Development of a simple noninvasive index to predict significant fibrosis in patients with HIV/HCV coinfection. Hepatology. 2006; 43(6): 1317–1325.
  181. Sterling RK, Lissen E, Clumeck N, et al. APRICOT Clinical Investigators. Development of a simple noninvasive index to predict significant fibrosis in patients with HIV/HCV coinfection. Hepatology. 2006; 43(6): 1317–1325.
  182. Angulo P, Hui JM, Marchesini G, et al. The NAFLD fibrosis score: a noninvasive system that identifies liver fibrosis in patients with NAFLD. Hepatology. 2007; 45(4): 846–854.
  183. Rosenberg WMC, Voelker M, Thiel R, et al. European Liver Fibrosis Group. Serum markers detect the presence of liver fibrosis: a cohort study. Gastroenterology. 2004; 127(6): 1704–1713.
  184. Calès P, Lainé F, Boursier J, et al. Comparison of blood tests for liver fibrosis specific or not to NAFLD. J Hepatol. 2009; 50(1): 165–173.
  185. Stefanska A, Bergmann K, Suwała S, et al. Performance Evaluation of a Novel Non-Invasive Test for the Detection of Advanced Liver Fibrosis in Metabolic Dysfunction-Associated Fatty Liver Disease. Metabolites. 2024; 14(1).
  186. 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(5): 1797–1835.
  187. Ryan MC, Itsiopoulos C, Thodis T, et al. The Mediterranean diet improves hepatic steatosis and insulin sensitivity in individuals with non-alcoholic fatty liver disease. J Hepatol. 2013; 59(1): 138–143.
  188. Trovato FM, Catalano D, Martines GF, et al. Mediterranean diet and non-alcoholic fatty liver disease: the need of extended and comprehensive interventions. Clin Nutr. 2015; 34(1): 86–88.
  189. Misciagna G, Del Pilar Díaz M, Caramia DV, et al. Effect of a Low Glycemic Index Mediterranean Diet on Non-Alcoholic Fatty Liver Disease. A Randomized Controlled Clinici Trial. J Nutr Health Aging. 2017; 21(4): 404–412.
  190. Kouvari M, Boutari C, Chrysohoou C, et al. ATTICA study Investigators. Mediterranean diet is inversely associated with steatosis and fibrosis and decreases ten-year diabetes and cardiovascular risk in NAFLD subjects: Results from the ATTICA prospective cohort study. Clin Nutr. 2021; 40(5): 3314–3324.
  191. Eslam M, Sarin SK, Wong VWS, 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; 14(6): 889–919.
  192. Ma J, Hennein R, Liu C, et al. Improved Diet Quality Associates With Reduction in Liver Fat, Particularly in Individuals With High Genetic Risk Scores for Nonalcoholic Fatty Liver Disease. Gastroenterology. 2018; 155(1): 107–117.
  193. Vilar-Gomez E, Pirola CJ, Sookoian S, et al. Impact of the Association Between PNPLA3 Genetic Variation and Dietary Intake on the Risk of Significant Fibrosis in Patients With NAFLD. Am J Gastroenterol. 2021; 116(5): 994–1006.
  194. Johnson NA, Sachinwalla T, Walton DW, et al. Aerobic exercise training reduces hepatic and visceral lipids in obese individuals without weight loss. Hepatology. 2009; 50(4): 1105–1112.
  195. St George A, Bauman A, Johnston A, et al. Independent effects of physical activity in patients with nonalcoholic fatty liver disease. Hepatology. 2009; 50(1): 68–76.
  196. Sung KC, Ryu S, Lee JY, et al. Effect of exercise on the development of new fatty liver and the resolution of existing fatty liver. J Hepatol. 2016; 65(4): 791–797.