{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T21:18:27Z","timestamp":1792444707327,"version":"4.5.0"},"reference-count":124,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2024,9,14]],"date-time":"2024-09-14T00:00:00Z","timestamp":1726272000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>In the past thirty years, childhood obesity rates have risen significantly worldwide, affecting over 340 million children in affluent nations. This surge is intricately tied to metabolic disorders, notably insulin resistance, type 2 diabetes mellitus (T2DM), and the continually evolving spectrum of metabolic-associated (dysfunction) steatotic liver disease (MASLD). This review underscores the alarming escalation of childhood obesity and delves comprehensively into the evolving and dynamic changes of nomenclature surrounding diverse conditions of hepatic steatosis, from the initial recognition of non-alcoholic fatty liver disease (NAFLD) to the progressive evolution into MASLD. Moreover, it emphasizes the crucial role of pediatric endocrinologists in thoroughly and accurately investigating MASLD onset in children with T2DM, where each condition influences and exacerbates the progression of the other. This review critically highlights the inadequacies of current screening strategies and diagnosis, stressing the need for a paradigm shift. A proposed solution involves the integration of hepatic magnetic resonance imaging assessment into the diagnostic arsenal for children showing insufficient glycemic control and weight loss post-T2DM diagnosis, thereby complementing conventional liver enzyme testing. This holistic approach aims to significantly enhance diagnostic precision, fostering improved outcomes in this vulnerable high-risk pediatric population.<\/jats:p>","DOI":"10.3390\/ijms25189924","type":"journal-article","created":{"date-parts":[[2024,9,18]],"date-time":"2024-09-18T01:52:31Z","timestamp":1726624351000},"page":"9924","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Converging Pathways between Metabolic Dysfunction\u2013Associated Steatotic Liver Disease (MASLD) and Diabetes in Children"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1899-8337","authenticated-orcid":false,"given":"Maria Felicia","family":"Faienza","sequence":"first","affiliation":[{"name":"Pediatric Unit, Department of Precision and Regenerative Medicine and Ionian Area (DiMePre-J), Medical School, University of Bari \u201cAldo Moro\u201d, 70124 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilaria","family":"Farella","sequence":"additional","affiliation":[{"name":"Clinica Medica \u201cA. Murri\u201d, Department of Precision and Regenerative Medicine and Ionian Area (DiMePre-J), Medical School, University of Bari \u201cAldo Moro\u201d, 70124 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamad","family":"Khalil","sequence":"additional","affiliation":[{"name":"Clinica Medica \u201cA. Murri\u201d, Department of Precision and Regenerative Medicine and Ionian Area (DiMePre-J), Medical School, University of Bari \u201cAldo Moro\u201d, 70124 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5359-1471","authenticated-orcid":false,"given":"Piero","family":"Portincasa","sequence":"additional","affiliation":[{"name":"Clinica Medica \u201cA. Murri\u201d, Department of Precision and Regenerative Medicine and Ionian Area (DiMePre-J), Medical School, University of Bari \u201cAldo Moro\u201d, 70124 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,9,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1016\/S2213-8587(22)00047-X","article-title":"Obesity in children and adolescents: Epidemiology, causes, assessment, and management","volume":"10","author":"Jebeile","year":"2022","journal-title":"Lancet Diabetes Endocrinol."},{"key":"ref_2","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_3","doi-asserted-by":"crossref","unstructured":"Di Bonito, P., Di Sessa, A., Licenziati, M.R., Corica, D., Wasniewska, M., Umano, G.R., Morandi, A., Maffeis, C., Faienza, M.F., and Mozzillo, E. (2023). Is Metabolic Syndrome Useful for Identifying Youths with Obesity at Risk for NAFLD?. Children, 10.","DOI":"10.3390\/children10020233"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1897","DOI":"10.1007\/s11739-023-03355-z","article-title":"Metabolic dysfunction-associated gallstone disease: Expecting more from critical care manifestations","volume":"18","author":"Portincasa","year":"2023","journal-title":"Intern. Emerg. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"851","DOI":"10.5114\/aoms.2016.58928","article-title":"Obesity and inflammation: The linking mechanism and the complications","volume":"13","author":"Ellulu","year":"2017","journal-title":"Arch. Med. Sci"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1126\/science.7678183","article-title":"Adipose expression of tumor necrosis factor-alpha: Direct role in obesity-linked insulin resistance","volume":"259","author":"Hotamisligil","year":"1993","journal-title":"Science"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"E1143","DOI":"10.1073\/pnas.1200498109","article-title":"Activation of invariant natural killer T cells by lipid excess promotes tissue inflammation, insulin resistance, and hepatic steatosis in obese mice","volume":"109","author":"Wu","year":"2012","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"5133","DOI":"10.1073\/pnas.1215840110","article-title":"B cells promote inflammation in obesity and type 2 diabetes through regulation of T-cell function and an inflammatory cytokine profile","volume":"110","author":"DeFuria","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1016\/j.immuni.2017.01.008","article-title":"Adipose Type One Innate Lymphoid Cells Regulate Macrophage Homeostasis through Targeted Cytotoxicity","volume":"46","author":"Boulenouar","year":"2017","journal-title":"Immunity"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1549","DOI":"10.1161\/CIRCRESAHA.119.315896","article-title":"Metabolic Inflammation and Insulin Resistance in Obesity","volume":"126","author":"Wu","year":"2020","journal-title":"Circ. Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"6613827","DOI":"10.1155\/2021\/6613827","article-title":"NAFLD, Insulin Resistance, and Diabetes Mellitus Type 2","volume":"2021","author":"Marusic","year":"2021","journal-title":"Can. J. Gastroenterol. Hepatol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"434","DOI":"10.1016\/S0025-6196(24)00530-5","article-title":"Nonalcoholic steatohepatitis: Mayo Clinic experiences with a hitherto unnamed disease","volume":"55","author":"Ludwig","year":"1980","journal-title":"Mayo Clin. Proc."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1404","DOI":"10.1002\/hep.32774","article-title":"Geographical similarity and differences in the burden and genetic predisposition of NAFLD","volume":"77","author":"Yip","year":"2023","journal-title":"Hepatology"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1797","DOI":"10.1097\/HEP.0000000000000323","article-title":"AASLD Practice Guidance on the clinical assessment and management of nonalcoholic fatty liver disease","volume":"77","author":"Rinella","year":"2023","journal-title":"Hepatology"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1204","DOI":"10.1002\/hep.32228","article-title":"Global burden of NAFLD and chronic liver disease among adolescents and young adults","volume":"75","author":"Paik","year":"2022","journal-title":"Hepatology"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"993","DOI":"10.1007\/s11739-023-03203-0","article-title":"NAFLD, MAFLD, and beyond: One or several acronyms for better comprehension and patient care","volume":"18","author":"Portincasa","year":"2023","journal-title":"Intern. Emerg. Med."},{"key":"ref_17","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_18","doi-asserted-by":"crossref","first-page":"388","DOI":"10.1016\/S2468-1253(22)00062-0","article-title":"Global multi-stakeholder endorsement of the MAFLD definition","volume":"7","author":"Bugianesi","year":"2022","journal-title":"Lancet Gastroenterol. Hepatol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1966","DOI":"10.1097\/HEP.0000000000000520","article-title":"A multisociety Delphi consensus statement on new fatty liver disease nomenclature","volume":"78","author":"Rinella","year":"2023","journal-title":"Hepatology"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/j.ejim.2024.04.013","article-title":"Metabolic dysfunction-associated steatotic liver disease: Evolution of the final terminology","volume":"124","author":"Portincasa","year":"2024","journal-title":"Eur. J. Intern. Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"e51","DOI":"10.1016\/j.jhep.2023.07.017","article-title":"Confirmatory biomarker diagnostic studies are not needed when transitioning from NAFLD to MASLD","volume":"80","author":"Ratziu","year":"2024","journal-title":"J. Hepatol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"e54","DOI":"10.1016\/j.jhep.2023.07.021","article-title":"Can we use old NAFLD data under the new MASLD definition?","volume":"80","author":"Song","year":"2024","journal-title":"J. Hepatol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1393","DOI":"10.1097\/HEP.0000000000000664","article-title":"Prevalence, distribution, and hepatic fibrosis burden of the different subtypes of steatotic liver disease in primary care settings","volume":"79","author":"Lee","year":"2024","journal-title":"Hepatology"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"100485","DOI":"10.1016\/j.jlr.2023.100485","article-title":"From NAFLD to MASLD: Updated naming and diagnosis criteria for fatty liver disease","volume":"65","author":"Rinella","year":"2024","journal-title":"J. Lipid Res."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Portincasa, P., Khalil, M., Mahdi, L., Perniola, V., Idone, V., Graziani, A., Baffy, G., and Di Ciaula, A. (2024). Metabolic Dysfunction-Associated Steatotic Liver Disease: From Pathogenesis to Current Therapeutic Options. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25115640"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1264","DOI":"10.1053\/j.gastro.2018.12.036","article-title":"Noninvasive Assessment of Liver Disease in Patients With Nonalcoholic Fatty Liver Disease","volume":"156","author":"Castera","year":"2019","journal-title":"Gastroenterology"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"889","DOI":"10.1007\/s12072-020-10094-2","article-title":"The Asian Pacific Association for the Study of the Liver clinical practice guidelines for the diagnosis and management of metabolic associated fatty liver disease","volume":"14","author":"Eslam","year":"2020","journal-title":"Hepatol. Int."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"345","DOI":"10.5604\/01.3001.0011.7380","article-title":"Non-Alcoholic Fatty Liver Disease in Children and Adolescents: Lifestyle Change\u2014A Systematic Review and Meta-Analysis","volume":"17","author":"Epifanio","year":"2018","journal-title":"Ann. Hepatol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1097\/MPG.0000000000000520","article-title":"Hepatic steatosis is prevalent in stillborns delivered to women with diabetes mellitus","volume":"60","author":"Patel","year":"2015","journal-title":"J. Pediatr. Gastroenterol. Nutr."},{"key":"ref_30","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_31","first-page":"408","article-title":"Fatty liver and its fibrous changes found in simple obesity of children","volume":"3","author":"Kinugasa","year":"1984","journal-title":"J. Pediatr. Gastroenterol. Nutr."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1468","DOI":"10.1038\/ijo.2010.106","article-title":"Obese boys at increased risk for nonalcoholic liver disease: Evaluation of 16,390 overweight or obese children and adolescents","volume":"34","author":"Wiegand","year":"2010","journal-title":"Int. J. Obes."},{"key":"ref_33","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_34","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_35","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1097\/MPG.0000000000003795","article-title":"Prevalence of Elevated ALT in Adolescents in the US 2011\u20132018","volume":"77","author":"Mischel","year":"2023","journal-title":"J. Pediatr. Gastroenterol. Nutr."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Anderson, E.L., Howe, L.D., Jones, H.E., Higgins, J.P., 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_37","doi-asserted-by":"crossref","first-page":"765","DOI":"10.1016\/j.cgh.2013.09.050","article-title":"Evidence and recommendations for imaging liver fat in children, based on systematic review","volume":"12","author":"Awai","year":"2014","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"384","DOI":"10.1016\/j.cgh.2020.06.048","article-title":"Prevalence of Liver Steatosis and Fibrosis Detected by Transient Elastography in Adolescents in the 2017\u20132018 National Health and Nutrition Examination Survey","volume":"19","author":"Ciardullo","year":"2021","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"ref_39","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_40","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1016\/j.jpeds.2018.04.047","article-title":"Pediatric Nonalcoholic Fatty Liver Disease in New York City: An Autopsy Study","volume":"200","author":"Fernandes","year":"2018","journal-title":"J. Pediatr."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"6596","DOI":"10.1038\/ncomms7596","article-title":"Unravelling the hidden ancestry of American admixed populations","volume":"6","author":"Montinaro","year":"2015","journal-title":"Nat. Commun."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Yanai, H., Adachi, H., Hakoshima, M., Iida, S., and Katsuyama, H. (2023). Metabolic-Dysfunction-Associated Steatotic Liver Disease-Its Pathophysiology, Association with Atherosclerosis and Cardiovascular Disease, and Treatments. Int. J. Mol. Sci., 24.","DOI":"10.20944\/preprints202309.1062.v1"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Ahmed, B., Sultana, R., and Greene, M.W. (2021). Adipose tissue and insulin resistance in obese. Biomed. Pharmacother., 137.","DOI":"10.1016\/j.biopha.2021.111315"},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Ziolkowska, S., Binienda, A., Jablkowski, M., Szemraj, J., and Czarny, P. (2021). The Interplay between Insulin Resistance, Inflammation, Oxidative Stress, Base Excision Repair and Metabolic Syndrome in Nonalcoholic Fatty Liver Disease. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms222011128"},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Longo, M., Zatterale, F., Naderi, J., Parrillo, L., Formisano, P., Raciti, G.A., Beguinot, F., and Miele, C. (2019). Adipose Tissue Dysfunction as Determinant of Obesity-Associated Metabolic Complications. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20092358"},{"key":"ref_46","first-page":"1","article-title":"Triglyceride Metabolism in the Liver","volume":"8","author":"Cohen","year":"2017","journal-title":"Compr. Physiol."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Gong, J., Tu, W., Liu, J., and Tian, D. (2022). Hepatocytes: A key role in liver inflammation. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.1083780"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"101092","DOI":"10.1016\/j.molmet.2020.101092","article-title":"Dysregulated lipid metabolism links NAFLD to cardiovascular disease","volume":"42","author":"Deprince","year":"2020","journal-title":"Mol. Metab."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Bhat, N., and Mani, A. (2023). Dysregulation of Lipid and Glucose Metabolism in Nonalcoholic Fatty Liver Disease. Nutrients, 15.","DOI":"10.3390\/nu15102323"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"4079","DOI":"10.3748\/wjg.v22.i16.4079","article-title":"Nonalcoholic fatty liver disease as a multi-systemic disease","volume":"22","author":"Fotbolcu","year":"2016","journal-title":"World J. Gastroenterol."},{"key":"ref_51","first-page":"691","article-title":"MASLD: A systemic metabolic disorder with cardiovascular and malignant complications","volume":"73","author":"Targher","year":"2024","journal-title":"Gut"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1871","DOI":"10.1210\/jc.2004-1389","article-title":"Childhood obesity","volume":"90","author":"Speiser","year":"2005","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"700","DOI":"10.1016\/S0022-3476(95)70156-7","article-title":"Idiopathic steatohepatitis in childhood: A multicenter retrospective study","volume":"127","author":"Baldridge","year":"1995","journal-title":"J. Pediatr."},{"key":"ref_54","first-page":"48","article-title":"Nonalcoholic steatohepatitis in children","volume":"30","author":"Rashid","year":"2000","journal-title":"J. Pediatr. Gastroenterol. Nutr."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1097\/MPG.0000000000000670","article-title":"Obesity and gastrointestinal disorders in children","volume":"60","author":"Phatak","year":"2015","journal-title":"J. Pediatr. Gastroenterol. Nutr."},{"key":"ref_56","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":"2014","journal-title":"J. Pediatr."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1097\/MPG.0b013e31826d3c62","article-title":"Childhood obesity for pediatric gastroenterologists","volume":"56","author":"Huang","year":"2013","journal-title":"J. Pediatr. Gastroenterol. Nutr."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1428","DOI":"10.1023\/A:1018850223495","article-title":"Liver involvement in obese children. Ultrasonography and liver enzyme levels at diagnosis and during follow-up in an Italian population","volume":"42","author":"Franzese","year":"1997","journal-title":"Dig. Dis. Sci."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1111\/j.1651-2227.1997.tb08881.x","article-title":"Serum alanine aminotransferase activity in obese children","volume":"86","author":"Tazawa","year":"1997","journal-title":"Acta Paediatr."},{"key":"ref_60","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_61","doi-asserted-by":"crossref","first-page":"1267","DOI":"10.1111\/apt.12518","article-title":"Paediatric gastroenterology evaluation of overweight and obese children referred from primary care for suspected non-alcoholic fatty liver disease","volume":"38","author":"Schwimmer","year":"2013","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1016\/j.cct.2009.09.001","article-title":"Treatment of nonalcoholic fatty liver disease in children: TONIC trial design","volume":"31","author":"Lavine","year":"2010","journal-title":"Contemp. Clin. Trials"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"854","DOI":"10.1373\/clinchem.2011.177741","article-title":"Closing the gaps in pediatric laboratory reference intervals: A CALIPER database of 40 biochemical markers in a healthy and multiethnic population of children","volume":"58","author":"Colantonio","year":"2012","journal-title":"Clin. Chem."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1097\/MPG.0b013e31821b4b61","article-title":"Ultrasonographic quantitative estimation of hepatic steatosis in children With NAFLD","volume":"53","author":"Shannon","year":"2011","journal-title":"J. Pediatr. Gastroenterol. Nutr."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1148\/radiol.11111094","article-title":"US cannot be used to predict the presence or severity of hepatic steatosis in severely obese adolescents","volume":"262","author":"Bohte","year":"2012","journal-title":"Radiology"},{"key":"ref_66","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_67","doi-asserted-by":"crossref","first-page":"254","DOI":"10.14309\/ajg.0000000000001054","article-title":"Role of Noninvasive Tests in Clinical Gastroenterology Practices to Identify Patients With Nonalcoholic Steatohepatitis at High Risk of Adverse Outcomes: Expert Panel Recommendations","volume":"116","author":"Younossi","year":"2021","journal-title":"Am. J. Gastroenterol."},{"key":"ref_68","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_69","doi-asserted-by":"crossref","first-page":"700","DOI":"10.1097\/MPG.0b013e318252a13f","article-title":"Diagnosis of nonalcoholic fatty liver disease in children and adolescents: Position paper of the ESPGHAN Hepatology Committee","volume":"54","author":"Vajro","year":"2012","journal-title":"J. Pediatr. Gastroenterol. Nutr."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1016\/j.jhepr.2019.06.005","article-title":"Comparison between non-alcoholic fatty liver disease screening guidelines in children and adolescents","volume":"1","author":"Ezaizi","year":"2019","journal-title":"JHEP Rep."},{"key":"ref_71","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_72","doi-asserted-by":"crossref","first-page":"1319","DOI":"10.1002\/hep.29542","article-title":"New pediatric percentiles of liver enzyme serum levels (alanine aminotransferase, aspartate aminotransferase, gamma-glutamyltransferase): Effects of age, sex, body mass index, and pubertal stage","volume":"68","author":"Bussler","year":"2018","journal-title":"Hepatology"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1016\/j.clinbiochem.2013.11.008","article-title":"Validity of establishing pediatric reference intervals based on hospital patient data: A comparison of the modified Hoffmann approach to CALIPER reference intervals obtained in healthy children","volume":"47","author":"Shaw","year":"2014","journal-title":"Clin. Biochem."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1016\/j.jpeds.2013.10.072","article-title":"Obstructive sleep apnea and hypoxemia are associated with advanced liver histology in pediatric nonalcoholic fatty liver disease","volume":"164","author":"Sundaram","year":"2014","journal-title":"J. Pediatr."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1016\/j.cgh.2017.09.041","article-title":"Racial and Ethnic Disparities in Nonalcoholic Fatty Liver Disease Prevalence, Severity, and Outcomes in the United States: A Systematic Review and Meta-analysis","volume":"16","author":"Rich","year":"2018","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1016\/S1542-3565(04)00014-X","article-title":"Nonalcoholic fatty liver disease in patients with type 2 diabetes","volume":"2","author":"Younossi","year":"2004","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"Riekki, H., Aitokari, L., Kivela, L., Lahti, S., Hiltunen, P., Vuorela, N., Huhtala, H., Lakka, T.A., and Kurppa, K. (2023). Prevalence and associated factors of metabolic-associated fatty liver disease in overweight Finnish children and adolescents. Front. Endocrinol., 14.","DOI":"10.3389\/fendo.2023.1090344"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1038\/ajg.2011.327","article-title":"Large-scale long-term follow-up study of Japanese patients with non-alcoholic Fatty liver disease for the onset of hepatocellular carcinoma","volume":"107","author":"Kawamura","year":"2012","journal-title":"Am. J. Gastroenterol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1823","DOI":"10.1016\/S0140-6736(07)60821-6","article-title":"Acute and chronic complications of type 2 diabetes mellitus in children and adolescents","volume":"369","author":"Zeitler","year":"2007","journal-title":"Lancet"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"1719","DOI":"10.1007\/s40618-022-01809-3","article-title":"Phenotypes of prediabetes and metabolic risk in Caucasian youths with overweight or obesity","volume":"45","author":"Licenziati","year":"2022","journal-title":"J. Endocrinol. Investig."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1111\/j.1399-5448.2011.00846.x","article-title":"Metformin monotherapy in youth with recent onset type 2 diabetes: Experience from the prerandomization run-in phase of the TODAY study","volume":"13","author":"Laffel","year":"2012","journal-title":"Pediatr. Diabetes"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"872","DOI":"10.1111\/pedi.13409","article-title":"ISPAD Clinical Practice Consensus Guidelines 2022: Type 2 diabetes in children and adolescents","volume":"23","author":"Shah","year":"2022","journal-title":"Pediatr. Diabetes"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"802","DOI":"10.1016\/j.jhep.2019.06.023","article-title":"Prevalence of prediabetes and diabetes in children and adolescents with biopsy-proven non-alcoholic fatty liver disease","volume":"71","author":"Nobili","year":"2019","journal-title":"J. Hepatol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"e161971","DOI":"10.1001\/jamapediatrics.2016.1971","article-title":"Prevalence of Prediabetes and Type 2 Diabetes in Children With Nonalcoholic Fatty Liver Disease","volume":"170","author":"Newton","year":"2016","journal-title":"JAMA Pediatr."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"e34","DOI":"10.1210\/clinem\/dgaa753","article-title":"Adolescent Nonalcoholic Fatty Liver Disease and Type 2 Diabetes in Young Adulthood","volume":"106","author":"Bardugo","year":"2021","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"1335","DOI":"10.1097\/HEP.0000000000000004","article-title":"The global epidemiology of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH): A systematic review","volume":"77","author":"Younossi","year":"2023","journal-title":"Hepatology"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"1817","DOI":"10.2337\/dc10-0284","article-title":"Central role of fatty liver in the pathogenesis of insulin resistance in obese adolescents","volume":"33","author":"Cali","year":"2010","journal-title":"Diabetes Care"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"1896","DOI":"10.1002\/hep.22858","article-title":"Glucose dysregulation and hepatic steatosis in obese adolescents: Is there a link?","volume":"49","author":"Cali","year":"2009","journal-title":"Hepatology"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"2138","DOI":"10.1136\/gutjnl-2023-330110","article-title":"Global prevalence of non-alcoholic fatty liver disease in type 2 diabetes mellitus: An updated systematic review and meta-analysis","volume":"72","author":"Ang","year":"2023","journal-title":"Gut"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"793","DOI":"10.1016\/j.jhep.2019.06.021","article-title":"The global epidemiology of NAFLD and NASH in patients with type 2 diabetes: A systematic review and meta-analysis","volume":"71","author":"Younossi","year":"2019","journal-title":"J. Hepatol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"1731","DOI":"10.1053\/j.gastro.2020.07.034","article-title":"Progression of Fatty Liver Disease in Children Receiving Standard of Care Lifestyle Advice","volume":"159","author":"Xanthakos","year":"2020","journal-title":"Gastroenterology"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/j.jhep.2013.02.007","article-title":"The liver diseases of lipodystrophy: The long-term effect of leptin treatment","volume":"59","author":"Lungu","year":"2013","journal-title":"J. Hepatol."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"556","DOI":"10.1136\/postgradmedj-2018-135967","article-title":"Pharmacological interventions for non-alcoholic fatty liver disease: A systematic review and network meta-analysis","volume":"94","author":"Sridharan","year":"2018","journal-title":"Postgrad. Med. J."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1016\/j.diabet.2019.12.007","article-title":"Efficacy and safety of anti-hyperglycaemic drugs in patients with non-alcoholic fatty liver disease with or without diabetes: An updated systematic review of randomized controlled trials","volume":"46","author":"Mantovani","year":"2020","journal-title":"Diabetes Metab."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"1168","DOI":"10.1016\/j.clinthera.2008.06.012","article-title":"Metformin use in children with nonalcoholic fatty liver disease: An open-label, 24-month, observational pilot study","volume":"30","author":"Nobili","year":"2008","journal-title":"Clin. Ther."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1002\/hep.22336","article-title":"Lifestyle intervention and antioxidant therapy in children with nonalcoholic fatty liver disease: A randomized, controlled trial","volume":"48","author":"Nobili","year":"2008","journal-title":"Hepatology"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/j.metabol.2016.12.006","article-title":"Effects of lifestyle interventions on clinical characteristics of patients with non-alcoholic fatty liver disease: A meta-analysis","volume":"68","author":"Katsagoni","year":"2017","journal-title":"Metab. Clin. Exp."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1016\/j.jnutbio.2018.03.025","article-title":"Non-alcoholic fatty liver disease severity and metabolic complications in obese children: Impact of omega-3 fatty acids","volume":"58","author":"Spahis","year":"2018","journal-title":"J. Nutr. Biochem."},{"key":"ref_99","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":"2013","journal-title":"Nutr. Metab. Cardiovasc. Dis."},{"key":"ref_100","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_101","doi-asserted-by":"crossref","unstructured":"Della Corte, C., Carpino, G., De Vito, R., De Stefanis, C., Alisi, A., Cianfarani, S., Overi, D., Mosca, A., Stronati, L., and Cucchiara, S. (2016). Docosahexanoic Acid Plus Vitamin D Treatment Improves Features of NAFLD in Children with Serum Vitamin D Deficiency: Results from a Single Centre Trial. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0168216"},{"key":"ref_102","doi-asserted-by":"crossref","unstructured":"Xue, J., Liang, S., Ma, J., and Xiao, Y. (2022). Effect of growth hormone therapy on liver enzyme and other cardiometabolic risk factors in boys with obesity and nonalcoholic fatty liver disease. BMC Endocr. Disord., 22.","DOI":"10.1186\/s12902-022-00967-y"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"1154","DOI":"10.1016\/j.dld.2020.09.021","article-title":"Antioxidant activity of Hydroxytyrosol and Vitamin E reduces systemic inflammation in children with paediatric NAFLD","volume":"53","author":"Mosca","year":"2021","journal-title":"Dig. Liver Dis."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1007\/s00431-021-04243-4","article-title":"Vitamin D and nonalcoholic fatty liver disease in children: A randomized controlled clinical trial","volume":"181","author":"Abdelhai","year":"2022","journal-title":"Eur. J. Pediatr."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1002\/hep.32403","article-title":"Randomized placebo-controlled trial of losartan for pediatric NAFLD","volume":"76","author":"Vos","year":"2022","journal-title":"Hepatology"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"897","DOI":"10.1515\/jpem-2020-0642","article-title":"Effect of l-carnitine supplementation on children and adolescents with nonalcoholic fatty liver disease (NAFLD): A randomized, triple-blind, placebo-controlled clinical trial","volume":"34","author":"Saneian","year":"2021","journal-title":"J. Pediatr. Endocrinol. Metab."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1097\/MPG.0000000000003796","article-title":"An Open Label, Randomized, Multicenter Study of Elafibranor in Children with Nonalcoholic Steatohepatitis","volume":"77","author":"Goyal","year":"2023","journal-title":"J. Pediatr. Gastroenterol. Nutr."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"3496","DOI":"10.1007\/s12011-023-03954-z","article-title":"Effects of Zinc Supplementation on Inflammatory Status and Nonalcoholic Steatohepatitis in Overweight or Obese Children: A Randomized Clinical Trial","volume":"202","author":"Ostadmohammadi","year":"2024","journal-title":"Biol. Trace Elem. Res."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"1173","DOI":"10.1007\/s00431-023-05369-3","article-title":"The effect of orlistat in the treatment of non-alcoholic fatty liver in adolescents with overweight and obese","volume":"183","author":"Zahmatkesh","year":"2024","journal-title":"Eur. J. Pediatr."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1038\/482027a","article-title":"Public health: The toxic truth about sugar","volume":"482","author":"Lustig","year":"2012","journal-title":"Nature"},{"key":"ref_111","first-page":"1","article-title":"The role of nutrition in non-alcoholic fatty liver disease treatment in obese children","volume":"29","author":"Guimber","year":"2022","journal-title":"Arch. Pediatr."},{"key":"ref_112","doi-asserted-by":"crossref","unstructured":"Pixner, T., Stummer, N., Schneider, A.M., Lukas, A., Gramlinger, K., Julian, V., Thivel, D., Morwald, K., Maruszczak, K., and Mangge, H. (2022). The Role of Macronutrients in the Pathogenesis, Prevention and Treatment of Non-Alcoholic Fatty Liver Disease (NAFLD) in the Paediatric Population-A Review. Life, 12.","DOI":"10.3390\/life12060839"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1007\/978-3-031-58572-2_7","article-title":"Nutritional Interventions, Probiotics, Synbiotics and Fecal Microbiota Transplantation in Steatotic Liver Disease: Pediatric Fatty Liver and Probiotics","volume":"1449","author":"Nicastro","year":"2024","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1097\/MPG.0b013e3181d70468","article-title":"Liver fat change in obese children after a 1-year nutrition-behavior intervention","volume":"51","author":"Pozzato","year":"2010","journal-title":"J. Pediatr. Gastroenterol. Nutr."},{"key":"ref_115","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: A Randomized Clinical Trial","volume":"321","author":"Schwimmer","year":"2019","journal-title":"JAMA"},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"e12872","DOI":"10.1111\/ijpo.12872","article-title":"The effects of Mediterranean diet on hepatic steatosis, oxidative stress, and inflammation in adolescents with non-alcoholic fatty liver disease: A randomized controlled trial","volume":"17","author":"Yurtdas","year":"2022","journal-title":"Pediatr. Obes."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1111\/pedi.12949","article-title":"Prevalence of responders for hepatic fat, adiposity and liver enzyme levels in response to a lifestyle intervention in children with overweight\/obesity: EFIGRO randomized controlled trial","volume":"21","author":"Medrano","year":"2020","journal-title":"Pediatr. Diabetes"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1089\/chi.2013.0022","article-title":"A low-glycemic-load versus low-fat diet in the treatment of fatty liver in obese children","volume":"9","author":"Salsberg","year":"2013","journal-title":"Child Obes."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"e150996","DOI":"10.1172\/JCI150996","article-title":"Dietary sugar restriction reduces hepatic de novo lipogenesis in adolescent boys with fatty liver disease","volume":"131","author":"Cohen","year":"2021","journal-title":"J. Clin. Investig."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"857","DOI":"10.1002\/jimd.12155","article-title":"Higher dietary protein intake preserves lean body mass, lowers liver lipid deposition, and maintains metabolic control in participants with long-chain fatty acid oxidation disorders","volume":"42","author":"Gillingham","year":"2019","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"e12630","DOI":"10.1111\/ijpo.12630","article-title":"Effects of a carbohydrate-restricted diet on hepatic lipid content in adolescents with non-alcoholic fatty liver disease: A pilot, randomized trial","volume":"15","author":"Goss","year":"2020","journal-title":"Pediatr. Obes."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"109827","DOI":"10.1016\/j.diabres.2022.109827","article-title":"Prevalence of non-alcoholic fatty liver disease (NAFLD) and its association with surrogate markers of insulin resistance in patients with type 1 diabetes","volume":"186","author":"Westerink","year":"2022","journal-title":"Diabetes Res. Clin. Pract."},{"key":"ref_123","doi-asserted-by":"crossref","unstructured":"Clark, M., Kroger, C.J., and Tisch, R.M. (2017). Type 1 Diabetes: A Chronic Anti-Self-Inflammatory Response. Front. Immunol., 8.","DOI":"10.3389\/fimmu.2017.01898"},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"528","DOI":"10.1016\/j.eprac.2022.03.010","article-title":"American Association of Clinical Endocrinology Clinical Practice Guideline for the Diagnosis and Management of Nonalcoholic Fatty Liver Disease in Primary Care and Endocrinology Clinical Settings: Co-Sponsored by the American Association for the Study of Liver Diseases (AASLD)","volume":"28","author":"Cusi","year":"2022","journal-title":"Endocr. Pract."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/18\/9924\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T15:56:11Z","timestamp":1760111771000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/18\/9924"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,9,14]]},"references-count":124,"journal-issue":{"issue":"18","published-online":{"date-parts":[[2024,9]]}},"alternative-id":["ijms25189924"],"URL":"https:\/\/doi.org\/10.3390\/ijms25189924","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,9,14]]}}}