{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,8]],"date-time":"2026-04-08T05:25:52Z","timestamp":1775625952268,"version":"3.50.1"},"reference-count":117,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2024,2,15]],"date-time":"2024-02-15T00:00:00Z","timestamp":1707955200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"European Union-NextGenerationEU","award":["PE00000003"],"award-info":[{"award-number":["PE00000003"]}]},{"name":"European Union-NextGenerationEU","award":["D93C22000890001"],"award-info":[{"award-number":["D93C22000890001"]}]},{"name":"European Union-NextGenerationEU","award":["101128946\u2014PODiaCar\u2014EU4H-2022-PJ-3"],"award-info":[{"award-number":["101128946\u2014PODiaCar\u2014EU4H-2022-PJ-3"]}]},{"name":"Italian Ministry of University and Research","award":["PE00000003"],"award-info":[{"award-number":["PE00000003"]}]},{"name":"Italian Ministry of University and Research","award":["D93C22000890001"],"award-info":[{"award-number":["D93C22000890001"]}]},{"name":"Italian Ministry of University and Research","award":["101128946\u2014PODiaCar\u2014EU4H-2022-PJ-3"],"award-info":[{"award-number":["101128946\u2014PODiaCar\u2014EU4H-2022-PJ-3"]}]},{"name":"ON Foods-Research and innovation network on food and nutrition Sustainability, Safety and Security-Working ON Foods","award":["PE00000003"],"award-info":[{"award-number":["PE00000003"]}]},{"name":"ON Foods-Research and innovation network on food and nutrition Sustainability, Safety and Security-Working ON Foods","award":["D93C22000890001"],"award-info":[{"award-number":["D93C22000890001"]}]},{"name":"ON Foods-Research and innovation network on food and nutrition Sustainability, Safety and Security-Working ON Foods","award":["101128946\u2014PODiaCar\u2014EU4H-2022-PJ-3"],"award-info":[{"award-number":["101128946\u2014PODiaCar\u2014EU4H-2022-PJ-3"]}]},{"name":"European Union","award":["PE00000003"],"award-info":[{"award-number":["PE00000003"]}]},{"name":"European Union","award":["D93C22000890001"],"award-info":[{"award-number":["D93C22000890001"]}]},{"name":"European Union","award":["101128946\u2014PODiaCar\u2014EU4H-2022-PJ-3"],"award-info":[{"award-number":["101128946\u2014PODiaCar\u2014EU4H-2022-PJ-3"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Children"],"abstract":"<jats:p>Metabolic dysfunction\u2013associated fatty liver disease (MAFLD) is a multisystem disorder characterized by the presence of fatty liver degeneration associated with excess adiposity or prediabetes\/type 2 diabetes or metabolic dysregulation. An intricate relationship between the liver and thyroid has been reported in both health and disease. Simultaneously, there is a strong correlation between obesity and both MAFLD and thyroid dysfunction. In this narrative review, we highlighted the relationship between MAFLD and thyroid function in children and adolescents with obesity in order to explore how thyroid hormones (THs) act as predisposing factors in the onset, progression, and sustainability of MAFLD. THs are integral to the intricate balance of metabolic activities, ensuring energy homeostasis, and are indispensable for growth and development. Regarding liver homeostasis, THs have been suggested to interact with liver lipid homeostasis through a series of processes, including stimulating the entry of free fatty acids into the liver for esterification into triglycerides and increasing mitochondrial \u03b2-oxidation of fatty acids to impact hepatic lipid accumulation. The literature supports a correlation between MAFLD and obesity, THs and obesity, and MAFLD and THs; however, results in the pediatric population are very limited. Even though the underlying pathogenic mechanism involved in the relationship between MAFLD and thyroid function remains not fully elucidated, the role of THs as predisposing factors of MAFLD could be postulated. A potential vicious circle among these three conditions cannot be excluded. Identifying novel elements that may contribute to MAFLD could offer a practical approach to assessing children at risk of developing the condition.<\/jats:p>","DOI":"10.3390\/children11020244","type":"journal-article","created":{"date-parts":[[2024,2,15]],"date-time":"2024-02-15T05:55:59Z","timestamp":1707976559000},"page":"244","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Metabolic Dysfunction\u2013Associated Fatty Liver Disease (MAFLD) and Thyroid Function in Childhood Obesity: A Vicious Circle?"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2137-5974","authenticated-orcid":false,"given":"Valeria","family":"Calcaterra","sequence":"first","affiliation":[{"name":"Pediatric and Adolescent Unit, Department of Internal Medicine, University of Pavia, 27100 Pavia, Italy"},{"name":"Pediatric Department, Buzzi Children\u2019s Hospital, 20154 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8123-7522","authenticated-orcid":false,"given":"Irene","family":"Degrassi","sequence":"additional","affiliation":[{"name":"Pediatric Department, Buzzi Children\u2019s Hospital, 20154 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-8113-5829","authenticated-orcid":false,"given":"Silvia","family":"Taranto","sequence":"additional","affiliation":[{"name":"Pediatric Department, Buzzi Children\u2019s Hospital, 20154 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cecilia","family":"Porro","sequence":"additional","affiliation":[{"name":"Pediatric Department, Buzzi Children\u2019s Hospital, 20154 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alice","family":"Bianchi","sequence":"additional","affiliation":[{"name":"Pediatric Department, Buzzi Children\u2019s Hospital, 20154 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sara","family":"L\u2019assainato","sequence":"additional","affiliation":[{"name":"Pediatric Department, Buzzi Children\u2019s Hospital, 20154 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giustino Simone","family":"Silvestro","sequence":"additional","affiliation":[{"name":"Pediatric Department, Buzzi Children\u2019s Hospital, 20154 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antonia","family":"Quatrale","sequence":"additional","affiliation":[{"name":"Pediatric Department, Buzzi Children\u2019s Hospital, 20154 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2795-9874","authenticated-orcid":false,"given":"Gianvincenzo","family":"Zuccotti","sequence":"additional","affiliation":[{"name":"Pediatric Department, Buzzi Children\u2019s Hospital, 20154 Milan, Italy"},{"name":"Department of Biomedical and Clinical Science \u201cL. Sacco\u201d, University of Milan, 20157 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,2,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1388","DOI":"10.1542\/peds.2006-1212","article-title":"Prevalence of fatty liver in children and adolescents","volume":"118","author":"Schwimmer","year":"2006","journal-title":"Pediatrics"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1798","DOI":"10.1053\/j.gastro.2016.03.009","article-title":"Comparison of the Phenotype and Approach to Pediatric versus Adult Patients with Nonalcoholic Fatty Liver Disease","volume":"150","author":"Nobili","year":"2016","journal-title":"Gastroenterology"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1055\/s-0038-1627456","article-title":"Nonalcoholic Fatty Liver Disease in Children","volume":"38","author":"Mann","year":"2018","journal-title":"Semin. Liver Dis."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1999","DOI":"10.1053\/j.gastro.2019.11.312","article-title":"MAFLD: A Consensus-Driven Proposed Nomenclature for Metabolic Associated Fatty Liver Disease","volume":"158","author":"Eslam","year":"2020","journal-title":"Gastroenterology"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"864","DOI":"10.1016\/S2468-1253(21)00183-7","article-title":"Defining paediatric metabolic (dysfunction)-associated fatty liver disease: An international expert consensus statement","volume":"6","author":"Eslam","year":"2021","journal-title":"Lancet Gastroenterol. Hepatol."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Flisiak-Jackiewicz, M., Bobrus-Chociej, A., Wasilewska, N., and Lebensztejn, D.M. (2021). From Nonalcoholic Fatty Liver Disease (NAFLD) to Metabolic Dysfunction-Associated Fatty Liver Disease (MAFLD)\u2014New Terminology in Pediatric Patients as a Step in Good Scientific Direction?. J. Clin. Med., 10.","DOI":"10.20944\/preprints202101.0516.v1"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Wasniewska, M., Pepe, G., Aversa, T., Bellone, S., de Sanctis, L., Di Bonito, P., Faienza, M.F., Improda, N., Licenziati, M.R., and Maffeis, C. (2023). Skeptical Look at the Clinical Implication of Metabolic Syndrome in Childhood Obesity. Children, 10.","DOI":"10.3390\/children10040735"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1111\/j.1399-5448.2007.00271.x","article-title":"The metabolic syndrome in children and adolescents? An IDF consensus report","volume":"8","author":"Zimmet","year":"2007","journal-title":"Pediatr. Diabetes"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Anderson, E.L., Howe, L.D., Jones, H.E., Higgins, J.P.T., Lawlor, D.A., and Fraser, A. (2015). The Prevalence of Non-Alcoholic Fatty Liver Disease in Children and Adolescents: A Systematic Review and Meta-Analysis. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0140908"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2580","DOI":"10.1016\/j.mayocp.2020.10.020","article-title":"The Heightened Risk of Fatty Liver Disorders in the Time of COVID-19","volume":"95","author":"Stanfield","year":"2020","journal-title":"Mayo Clin. Proc."},{"key":"ref_11","unstructured":"Childhood Obesity Facts|Overweight & Obesity|CDC (2021, June 10). Consultato: 5 Gennaio 2024, Available online: https:\/\/www.cdc.gov\/obesity\/data\/childhood.html."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"496","DOI":"10.1016\/j.jpeds.2012.08.043","article-title":"Increasing Prevalence of Nonalcoholic Fatty Liver Disease Among United States Adolescents, 1988\u20131994 to 2007\u20132010","volume":"162","author":"Welsh","year":"2013","journal-title":"J. Pediatr."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1604371","DOI":"10.3389\/ijph.2021.1604371","article-title":"Estimating Global Prevalence of Metabolic Dysfunction-Associated Fatty Liver Disease in Overweight or Obese Children and Adolescents: Systematic Review and Meta-Analysis","volume":"66","author":"Liu","year":"2021","journal-title":"Int. J. Public Health"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1186\/s12967-020-02399-5","article-title":"Eating habits and lifestyle changes during COVID-19 lockdown: An Italian survey","volume":"18","author":"Gualtieri","year":"2020","journal-title":"J. Transl. Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1218","DOI":"10.1016\/j.jhep.2012.12.003","article-title":"A 360-degree overview of paediatric NAFLD: Recent insights","volume":"58","author":"Nobili","year":"2013","journal-title":"J. Hepatol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1008","DOI":"10.1002\/oby.22813","article-title":"COVID-19\u2013Related School Closings and Risk of Weight Gain Among Children","volume":"28","author":"Rundle","year":"2020","journal-title":"Obesity"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1038\/s41575-019-0169-z","article-title":"NAFLD in children: New genes, new diagnostic modalities and new drugs","volume":"16","author":"Nobili","year":"2019","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1376","DOI":"10.1002\/hep.30035","article-title":"Metabolic Features of Nonalcoholic Fatty Liver (NAFL) in Obese Adolescents: Findings From a Multiethnic Cohort","volume":"68","author":"Caprio","year":"2018","journal-title":"Hepatology"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1038","DOI":"10.1016\/j.metabol.2015.12.012","article-title":"The multiple-hit pathogenesis of non-alcoholic fatty liver disease (NAFLD)","volume":"65","author":"Buzzetti","year":"2016","journal-title":"Metabolism"},{"key":"ref_20","first-page":"180","article-title":"A narrative review of factors associated with the development and progression if non-alcoholic fatty liver disease","volume":"1","author":"Vreugdenhil","year":"2019","journal-title":"GastroHep"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"392","DOI":"10.1007\/s12263-014-0392-8","article-title":"Influence of dietary pattern, physical activity, and I148M PNPLA3 on steatosis severity in at-risk adolescents","volume":"9","author":"Nobili","year":"2014","journal-title":"Genes Nutr."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"881","DOI":"10.1038\/nature05488","article-title":"Abdominal obesity and metabolic syndrome","volume":"444","author":"Lemieux","year":"2006","journal-title":"Nature"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1055\/s-0035-1562945","article-title":"Fatty Acid and Glucose Sensors in Hepatic Lipid Metabolism: Implications in NAFLD","volume":"35","author":"Allison","year":"2015","journal-title":"Semin. Liver Dis."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Santoro, N., Savoye, M., Kim, G., Marotto, K., Shaw, M.M., Pierpont, B., and Caprio, S. (2012). Hepatic fat accumulation is modulated by the interaction between the rs738409 variant in the PNPLA3 gene and the dietary Omega6\/Omega3 PUFA intake. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0037827"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Daniel, P.V., and Mondal, P. (2020). Causative and Sanative dynamicity of ChREBP in Hepato-Metabolic disorders. Eur. J. Cell Biol., 99.","DOI":"10.1016\/j.ejcb.2020.151128"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2525","DOI":"10.1002\/hep.26299","article-title":"Dietary fructose in nonalcoholic fatty liver disease","volume":"57","author":"Vos","year":"2013","journal-title":"Hepatology"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"743","DOI":"10.1053\/j.gastro.2017.05.043","article-title":"Effects of Dietary Fructose Restriction on Liver Fat, De Novo Lipogenesis, and Insulin Kinetics in Children With Obesity","volume":"153","author":"Schwarz","year":"2017","journal-title":"Gastroenterology"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"4059","DOI":"10.1172\/JCI94585","article-title":"Divergent effects of glucose and fructose on hepatic lipogenesis and insulin signaling","volume":"127","author":"Softic","year":"2017","journal-title":"J. Clin. Investig."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1031","DOI":"10.1016\/j.jhep.2016.12.025","article-title":"Serum uric acid concentrations and fructose consumption are independently associated with NASH in children and adolescents","volume":"66","author":"Mosca","year":"2017","journal-title":"J. Hepatol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1001\/jama.2018.20579","article-title":"Effect of a Low Free Sugar Diet vs Usual Diet on Nonalcoholic Fatty Liver Disease in Adolescent Boys","volume":"321","author":"Schwimmer","year":"2019","journal-title":"JAMA"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"700","DOI":"10.1097\/MPG.0b013e318252a13f","article-title":"Diagnosis of nonalcoholic fatty liver disease in children and adolescents","volume":"54","author":"Vajro","year":"2012","journal-title":"J. Pediatr. Gastroenterol. Nutr."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1097\/MPG.0000000000001482","article-title":"NASPGHAN Clinical Practice Guideline for the Diagnosis and Treatment of Nonalcoholic Fatty Liver Disease in Children: Recommendations from the Expert Committee on NAFLD (ECON) and the North American Society of Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN)","volume":"64","author":"Vos","year":"2017","journal-title":"J. Pediatr. Gastroenterol. Nutr."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"598","DOI":"10.1016\/S2468-1253(23)00100-0","article-title":"Diagnosis of fatty liver in children should occur in parallel to investigation for other causes of liver disease","volume":"8","author":"Mann","year":"2023","journal-title":"Lancet Gastroenterol. Hepatol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1869","DOI":"10.2337\/dc10-2234","article-title":"The triglyceride-to-HDL cholesterol ratio: Association with insulin resistance in obese youths of different ethnic backgrounds","volume":"34","author":"Giannini","year":"2011","journal-title":"Diabetes Care"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1002\/hep.29367","article-title":"The diagnosis and management of nonalcoholic fatty liver disease: Practice guidance from the American Association for the Study of Liver Diseases","volume":"67","author":"Chalasani","year":"2018","journal-title":"Hepatology"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1357","DOI":"10.1053\/j.gastro.2009.12.052","article-title":"SAFETY Study: Alanine Aminotransferase Cutoff Values Are Set Too High for Reliable Detection of Pediatric Chronic Liver Disease","volume":"138","author":"Schwimmer","year":"2010","journal-title":"Gastroenterology"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"863","DOI":"10.1007\/s00431-019-03362-3","article-title":"Comparison of diagnostic accuracy of screening tests ALT and ultrasound for pediatric non-alcoholic fatty liver disease","volume":"178","author":"Draijer","year":"2019","journal-title":"Eur. J. Pediatr."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1967","DOI":"10.1053\/j.gastro.2020.01.048","article-title":"Nonalcoholic Fatty Liver Disease in Children: Unique Considerations and Challenges","volume":"158","author":"Goldner","year":"2020","journal-title":"Gastroenterology"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"707","DOI":"10.1016\/j.jpeds.2013.10.071","article-title":"Histological Abnormalities in Children with Nonalcoholic Fatty Liver Disease and Normal or Mildly Elevated Alanine Aminotransferase Levels","volume":"164","author":"Molleston","year":"2013","journal-title":"J. Pediatr."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Ma, X., Liu, S., Zhang, J., Dong, M., Wang, Y., Wang, M., and Xin, Y. (2020). Proportion of NAFLD patients with normal ALT value in overall NAFLD patients: A systematic review and meta-analysis. BMC Gastroenterol., 20.","DOI":"10.1186\/s12876-020-1165-z"},{"key":"ref_41","first-page":"833","article-title":"Non-alcoholic fatty liver disease in obese children evaluated by magnetic resonance imaging","volume":"95","author":"Radetti","year":"2006","journal-title":"Acta Paediatr."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"590","DOI":"10.1097\/MPG.0b013e31822960be","article-title":"Biochemical Parameters and Anthropometry Predict NAFLD in Obese Children","volume":"53","author":"Maffeis","year":"2011","journal-title":"J. Pediatr. Gastroenterol. Nutr."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1887","DOI":"10.1002\/hep.27666","article-title":"Magnetic resonance imaging and liver histology as biomarkers of hepatic steatosis in children with nonalcoholic fatty liver disease","volume":"61","author":"Schwimmer","year":"2015","journal-title":"Hepatology"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1016\/j.prp.2013.04.001","article-title":"Liver steatosis assessment: Correlations among pathology, radiology, clinical data and automated image analysis software","volume":"209","author":"Lee","year":"2013","journal-title":"Pathol. Res. Pract."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"416","DOI":"10.1148\/radiol.14140754","article-title":"Accuracy of MR imaging\u2013estimated proton density fat fraction for classification of dichotomized histologic steatosis grades in nonalcoholic fatty liver disease","volume":"274","author":"Tang","year":"2015","journal-title":"Radiology"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1457","DOI":"10.1016\/j.cgh.2018.05.023","article-title":"Evaluations of Lifestyle, Dietary, and Pharmacologic Treatments for Pediatric Nonalcoholic Fatty Liver Disease: A Systematic Review","volume":"17","author":"Mann","year":"2019","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Mandala, A., Janssen, R.C., Palle, S., Short, K.R., and Friedman, J.E. (2020). Pediatric Non-Alcoholic Fatty Liver Disease: Nutritional Origins and Potential Molecular Mechanisms. Nutrients, 12.","DOI":"10.3390\/nu12103166"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1358","DOI":"10.1016\/j.jpeds.2015.01.056","article-title":"Omega-3 fatty acids therapy in children with nonalcoholic fatty liver disease: A randomized controlled trial","volume":"166","author":"Janczyk","year":"2015","journal-title":"J. Pediatr."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"121","DOI":"10.4274\/jcrpe.1749","article-title":"Long-Term Treatment with n-3 Polyunsaturated Fatty Acids as a Monotherapy in Children with Nonalcoholic Fatty Liver Disease","volume":"7","author":"Boyraz","year":"2015","journal-title":"J. Clin. Res. Pediatr. Endocrinol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1066","DOI":"10.1016\/j.numecd.2012.10.010","article-title":"Docosahexaenoic acid for the treatment of fatty liver: Randomised controlled trial in children","volume":"23","author":"Nobili","year":"2012","journal-title":"Nutr. Metab. Cardiovasc. Dis."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/j.jpeds.2018.03.028","article-title":"Treating Obstructive Sleep Apnea and Chronic Intermittent Hypoxia Improves the Severity of Nonalcoholic Fatty Liver Disease in Children","volume":"198","author":"Sundaram","year":"2018","journal-title":"J. Pediatr."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1038\/s41430-019-0493-y","article-title":"Vitamin D deficiency: Prevalence and association with liver disease severity in pediatric nonalcoholic fatty liver disease","volume":"74","author":"Yodoshi","year":"2019","journal-title":"Eur. J. Clin. Nutr."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.psym.2018.09.001","article-title":"Psychosocial Issues in Pediatric Nonalcoholic Fatty Liver Disease","volume":"60","author":"Karaivazoglou","year":"2018","journal-title":"Psychosomatics"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"693507","DOI":"10.3389\/fmed.2021.693507","article-title":"NAFLD or MAFLD: Which Has Closer Association With All-Cause and Cause-Specific Mortality?\u2014Results From NHANES III","volume":"8","author":"Huang","year":"2021","journal-title":"Front. Med."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"2082","DOI":"10.1111\/liv.14548","article-title":"Comparison of MAFLD and NAFLD diagnostic criteria in real world","volume":"40","author":"Lin","year":"2020","journal-title":"Liver Int."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1290","DOI":"10.1111\/liv.14828","article-title":"Prevalence of NAFLD, MAFLD and associated advanced fibrosis in the contemporary United States population","volume":"41","author":"Ciardullo","year":"2021","journal-title":"Liver Int."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1292","DOI":"10.1002\/hep.24767","article-title":"The TONIC trial: A step forward in treating pediatric nonalcoholic fatty liver disease","volume":"55","author":"Alkhouri","year":"2012","journal-title":"Hepatology"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1136\/postgradmedj-2018-136364","article-title":"Effect of vitamin E in non-alcoholic fatty liver disease: A systematic review and meta-analysis of randomised controlled trials","volume":"95","author":"Amanullah","year":"2019","journal-title":"Postgrad. Med. J."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1016\/j.ecl.2023.02.001","article-title":"Metabolic-Associated Fatty Liver Disease in Childhood and Adolescence","volume":"52","author":"Vespoli","year":"2023","journal-title":"Endocrinol. Metab. Clin. N. Am."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"e31","DOI":"10.1097\/MPG.0000000000003537","article-title":"The Benefit of Probiotics in Pediatric Nonalcoholic Fatty Liver Disease: A Meta-analysis of Randomized Control Trials","volume":"75","author":"Gkiourtzis","year":"2022","journal-title":"J. Pediatr. Gastroenterol. Nutr."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1141","DOI":"10.1053\/j.gastro.2016.08.027","article-title":"In Children With Nonalcoholic Fatty Liver Disease, Cysteamine Bitartrate Delayed Release Improves Liver Enzymes but Does Not Reduce Disease Activity Scores","volume":"151","author":"Schwimmer","year":"2016","journal-title":"Gastroenterology"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"106","DOI":"10.3109\/10408363.2015.1092106","article-title":"Omega-3 fatty acids: Mechanisms of benefit and therapeutic effects in pediatric and adult NAFLD","volume":"53","author":"Nobili","year":"2016","journal-title":"Crit. Rev. Clin. Lab. Sci."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1016\/j.mam.2018.03.001","article-title":"Omega-3 fatty acids and non-alcoholic fatty liver disease: Evidence of efficacy and mechanism of action","volume":"64","author":"Scorletti","year":"2018","journal-title":"Mol. Asp. Med."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1016\/S0140-6736(15)00803-X","article-title":"Liraglutide safety and efficacy in patients with non-alcoholic steatohepatitis (LEAN): A multicentre, double-blind, randomised, placebo-controlled phase 2 study","volume":"387","author":"Armstrong","year":"2016","journal-title":"Lancet"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"e3292","DOI":"10.1002\/dmrr.3292","article-title":"Efficacy of exenatide and insulin glargine on nonalcoholic fatty liver disease in patients with type 2 diabetes","volume":"36","author":"Liu","year":"2020","journal-title":"Diabetes\/Metab. Res. Rev."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1113","DOI":"10.1056\/NEJMoa2028395","article-title":"A Placebo-Controlled Trial of Subcutaneous Semaglutide in Nonalcoholic Steatohepatitis","volume":"384","author":"Newsome","year":"2021","journal-title":"N. Engl. J. Med."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1038\/s42255-020-0209-6","article-title":"Resolution of NASH and hepatic fibrosis by the GLP-1R and GCGR dual-agonist cotadutide via modulating mitochondrial function and lipogenesis","volume":"2","author":"Boland","year":"2020","journal-title":"Nat. Metab."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1352","DOI":"10.2337\/dc19-1892","article-title":"Effects of Novel Dual GIP and GLP-1 Receptor Agonist Tirzepatide on Biomarkers of Nonalcoholic Steatohepatitis in Patients With Type 2 Diabetes","volume":"43","author":"Hartman","year":"2020","journal-title":"Diabetes Care"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1186\/s40814-018-0306-4","article-title":"A randomized, controlled, crossover pilot study of losartan for pediatric nonalcoholic fatty liver disease","volume":"4","author":"Vos","year":"2018","journal-title":"Pilot Feasibility Stud."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1147","DOI":"10.1053\/j.gastro.2016.01.038","article-title":"Elafibranor, an Agonist of the Peroxisome Proliferator\u2212Activated Receptor\u2212\u03b1 and \u2212\u03b4, Induces Resolution of Nonalcoholic Steatohepatitis Without Fibrosis Worsening","volume":"150","author":"Ratziu","year":"2016","journal-title":"Gastroenterology"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"D1","DOI":"10.1530\/EJE-16-0906","article-title":"Should bariatric surgery be performed in adolescents?","volume":"176","author":"Beamish","year":"2017","journal-title":"Eur. J. Endocrinol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1097\/MPG.0000000000000715","article-title":"Indications and limitations of bariatric intervention in severely obese children and adolescents with and without nonalcoholic steatohepatitis","volume":"60","author":"Nobili","year":"2015","journal-title":"J. Pediatr. Gastroenterol. Nutr."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"3614","DOI":"10.1210\/jc.2010-1245","article-title":"Thyroid and Obesity: An Intriguing Relationship","volume":"95","author":"Biondi","year":"2010","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1159\/000197872","article-title":"Prevalence of Thyroid Dysfunction in Obese Children and Adolescents before and after Weight Reduction and Its Relation to Other Metabolic Parameters","volume":"71","author":"Shalitin","year":"2009","journal-title":"Horm. Res. Paediatr."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"3088","DOI":"10.1210\/jc.2006-0095","article-title":"Hyperthyrotropinemia in Obese Children Is Reversible after Weight Loss and Is Not Related to Lipids","volume":"91","author":"Reinehr","year":"2006","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1111\/cob.12184","article-title":"How does obesity affect the endocrine system? A narrative review","volume":"7","author":"Poddar","year":"2017","journal-title":"Clin. Obes."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1089\/thy.2006.16.73","article-title":"Thyroid Function in Humans with Morbid Obesity","volume":"16","author":"Michalaki","year":"2006","journal-title":"Thyroid"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1210\/jcem-51-1-106","article-title":"Solubilized Nuclear Thyroid Hormone Receptors in Circulating Human Mononuclear Cells","volume":"51","author":"Burman","year":"1980","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_79","first-page":"54","article-title":"Thyroid dysfunction in obese and overweight children","volume":"68","author":"Kucharska","year":"2017","journal-title":"Endokrynol. Polska"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1530\/eje.1.01850","article-title":"l-Tri-iodothyronine is a major determinant of resting energy expenditure in underweight patients with anorexia nervosa and during weight gain","volume":"152","author":"Onur","year":"2005","journal-title":"Eur. J. Endocrinol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1159\/000063431","article-title":"Thyroid Function and Obesity in Children and Adolescents","volume":"54","author":"Stichel","year":"2000","journal-title":"Horm. Res. Paediatr."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1177\/2042018815571892","article-title":"Thyroid hormonal status among children with obesity","volume":"6","author":"Ghergherehchi","year":"2015","journal-title":"Ther. Adv. Endocrinol. Metab."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"8","DOI":"10.4274\/jcrpe.3319","article-title":"Subclinical Hypothyroidism in Danish Lean and Obese Children and Adolescents","volume":"9","author":"Dahl","year":"2017","journal-title":"J. Clin. Res. Pediatr. Endocrinol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"e1221","DOI":"10.1210\/clinem\/dgaa900","article-title":"Relationship of TSH Levels with Cardiometabolic Risk Factors in US Youth and Reference Percentiles for Thyroid Function","volume":"106","author":"Chen","year":"2020","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"296","DOI":"10.15557\/JoU.2018.0043","article-title":"Serum TSH level in obese children and its correlations with atherogenic lipid indicators and carotid intima media thickness","volume":"18","author":"Majcher","year":"2018","journal-title":"J. Ultrason."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"141","DOI":"10.6065\/apem.2018.23.3.141","article-title":"Thyroid function in obese Korean children and adolescents: Korea National Health and Nutrition Examination Survey 2013\u20132015","volume":"23","author":"An","year":"2018","journal-title":"Ann. Pediatr. Endocrinol. Metab."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1159\/000129678","article-title":"Thyroid hormones and their relation to weight status","volume":"70","author":"Reinehr","year":"2008","journal-title":"Horm. Res. Paediatr."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"4659","DOI":"10.1210\/jc.2005-0920","article-title":"High Circulating Thyrotropin Levels in Obese Women Are Reduced after Body Weight Loss Induced by Caloric Restriction","volume":"90","author":"Kok","year":"2005","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_89","first-page":"40","article-title":"Thyroid Function and Obesity","volume":"4","author":"Longhi","year":"2012","journal-title":"J. Clin. Res. Pediatr. Endocrinol."},{"key":"ref_90","first-page":"432","article-title":"Changes of systemic microinflammation after weight loss and regain\u2014A five-year follow up study","volume":"63","author":"Chudek","year":"2012","journal-title":"Endokrynol. Pol."},{"key":"ref_91","first-page":"499","article-title":"Changes in inflammatory biomarkers after successful lifestyle intervention in obese children","volume":"62","author":"Syrenicz","year":"2011","journal-title":"Endokrynol. Pol."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"G1","DOI":"10.1530\/EJE-19-0893","article-title":"European Society of Endocrinology Clinical Practice Guideline: Endocrine work-up in obesity","volume":"182","author":"Pasquali","year":"2020","journal-title":"Eur. J. Endocrinol."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"3663","DOI":"10.1210\/jc.2009-0899","article-title":"Thyroid Hormone Therapy for Obesity and Nonthyroidal Illnesses: A Systematic Review","volume":"94","author":"Kaptein","year":"2009","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_94","doi-asserted-by":"crossref","unstructured":"Walczak, K., and Sieminska, L. (2021). Obesity and Thyroid Axis. Int. J. Environ. Res. Public Health, 18.","DOI":"10.3390\/ijerph18189434"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"R13","DOI":"10.1530\/EJE-20-0051","article-title":"Management of Endocrine Disease Subclinical hypothyroidism in children","volume":"183","author":"Salerno","year":"2020","journal-title":"Eur. J. Endocrinol."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"1205331","DOI":"10.3389\/fnut.2023.1205331","article-title":"Thyroid dysfunction in children and adolescents affected by undernourished and overnourished eating disorders","volume":"10","author":"Calcaterra","year":"2023","journal-title":"Front. Nutr."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"462","DOI":"10.1016\/j.dld.2018.12.014","article-title":"Pathogenesis of hypothyroidism-induced NAFLD: Evidence for a distinct disease entity?","volume":"51","author":"Lonardo","year":"2019","journal-title":"Dig. Liver Dis."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"1153","DOI":"10.1016\/j.dld.2018.08.012","article-title":"Association of non-alcoholic fatty liver disease with thyroid function: A systematic review and meta-analysis","volume":"50","author":"Guo","year":"2018","journal-title":"Dig. Liver Dis."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"E9172","DOI":"10.1073\/pnas.1707797114","article-title":"Pathogenesis of hypothyroidism-induced NAFLD is driven by intra- and extrahepatic mechanisms","volume":"114","author":"Ferrandino","year":"2017","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_100","first-page":"e28052","article-title":"Nonalcoholic Fatty Liver Disease and Hypothyroidism: What You Need to Know","volume":"14","author":"Bikeyeva","year":"2022","journal-title":"Cureus"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1111\/j.1365-2265.2007.03068.x","article-title":"Association between serum TSH, free T4 and serum liver enzyme activities in a large cohort of unselected outpatients","volume":"68","author":"Targher","year":"2008","journal-title":"Clin. Endocrinol."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"8102","DOI":"10.3748\/wjg.v20.i25.8102","article-title":"Non-alcoholic fatty liver disease and thyroid dysfunction: A systematic review","volume":"20","author":"Eshraghian","year":"2014","journal-title":"World J. Gastroenterol."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1038\/nrendo.2018.10","article-title":"Direct effects of thyroid hormones on hepatic lipid metabolism","volume":"14","author":"Sinha","year":"2018","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1111\/ijpo.12110","article-title":"Thyroid dysfunction and hepatic steatosis in overweight children and adolescents","volume":"12","author":"Kaltenbach","year":"2017","journal-title":"Pediatr. Obes."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"1358","DOI":"10.1016\/j.jhep.2014.06.037","article-title":"Thyrotropin increases hepatic triglyceride content through upregulation of SREBP-1c activity","volume":"61","author":"Yan","year":"2014","journal-title":"J. Hepatol."},{"key":"ref_106","doi-asserted-by":"crossref","unstructured":"Vidal-Cevallos, P., Gall, S.M.-B., Uribe, M., and Ch\u00e1vez-Tapia, N.C. (2023). Understanding the Relationship between Nonalcoholic Fatty Liver Disease and Thyroid Disease. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms241914605"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"1163","DOI":"10.1016\/j.dld.2018.08.026","article-title":"Thyroid dysfunction and its role as a risk factor for non-alcoholic fatty liver disease: What\u2019s new","volume":"50","author":"Mandato","year":"2018","journal-title":"Dig. Liver Dis."},{"key":"ref_108","doi-asserted-by":"crossref","unstructured":"Chen, C.-L., and Lin, Y.-C. (2022). Autophagy Dysregulation in Metabolic Associated Fatty Liver Disease: A New Therapeutic Target. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms231710055"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"e434","DOI":"10.1210\/clinem\/dgad016","article-title":"Impact of Thyroid Function on the Prevalence and Mortality of Metabolic Dysfunction-Associated Fatty Liver Disease","volume":"108","author":"Chen","year":"2023","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1016\/j.dld.2022.11.020","article-title":"The association between thyroid hormones and MAFLD is mediated by obesity and metabolic disorders and varies among MAFLD subtypes","volume":"55","author":"Fan","year":"2022","journal-title":"Dig. Liver Dis."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"2153","DOI":"10.2147\/DMSO.S420872","article-title":"Association Between Sensitivity to Thyroid Hormones and Metabolic Dysfunction-Associated Fatty Liver Disease in Euthyroid Subjects: A Cross-Sectional Study","volume":"16","author":"Liu","year":"2023","journal-title":"Diabetes Metab. Syndr. Obes. Targets Ther."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"1553","DOI":"10.3906\/sag-2007-109","article-title":"Investigation of the effect of hyperthyroidism on endoplasmic reticulum stress and tran-sient receptor potential canonical 1 channel in the kidney","volume":"51","author":"Aykanat","year":"2021","journal-title":"Turk. J. Med. Sci."},{"key":"ref_113","doi-asserted-by":"crossref","unstructured":"Sinha, R.A., and Yen, P.M. (2016). Thyroid hormone-mediated autophagy and mitochondrial turnover in NAFLD. Cell Biosci., 6.","DOI":"10.1186\/s13578-016-0113-7"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"500","DOI":"10.1016\/j.tem.2021.04.008","article-title":"Links between metabolic syndrome and metabolic dysfunction-associated fatty liver disease","volume":"32","author":"Lim","year":"2021","journal-title":"Trends Endocrinol. Metab."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1055\/s-0042-119211","article-title":"Tumor Necrosis Factor-\u03b1 is Inversely Related to Free Thyroxine in Euthyroid Subjects Without Diabetes","volume":"49","author":"Dullaart","year":"2016","journal-title":"Horm. Metab. Res."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"237","DOI":"10.4103\/1735-5362.258490","article-title":"Effects of thyroxine on adhesion molecules and proinflammatory cytokines secretion on human umbilical vein endothelial cells","volume":"14","author":"Milani","year":"2019","journal-title":"Res. Pharm. Sci."},{"key":"ref_117","doi-asserted-by":"crossref","unstructured":"Caddeo, A., Kowalik, M.A., Serra, M., Runfola, M., Bacci, A., Rapposelli, S., Columbano, A., and Perra, A. (2021). TG68, a Novel Thyroid Hormone Receptor-\u03b2 Agonist for the Treatment of NAFLD. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms222313105"}],"container-title":["Children"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2227-9067\/11\/2\/244\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:00:06Z","timestamp":1760104806000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2227-9067\/11\/2\/244"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,2,15]]},"references-count":117,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2024,2]]}},"alternative-id":["children11020244"],"URL":"https:\/\/doi.org\/10.3390\/children11020244","relation":{},"ISSN":["2227-9067"],"issn-type":[{"value":"2227-9067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,2,15]]}}}