{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,12]],"date-time":"2026-06-12T15:34:52Z","timestamp":1781278492948,"version":"3.54.1"},"reference-count":46,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2025,11,6]],"date-time":"2025-11-06T00:00:00Z","timestamp":1762387200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Turkish Society of Pediatric Gastroenterology, Hepatology, and Nutrition"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diagnostics"],"abstract":"<jats:p>Background\/Objectives: Metabolic dysfunction-associated steatotic liver disease (MASLD) is becoming more common among adolescents, but non-invasive biomarkers for early detection are still limited. Liver-expressed antimicrobial peptide-2 (LEAP-2), a ghrelin receptor antagonist, has been connected to obesity and liver fat buildup in adults, but pediatric data are limited. This study investigates the hypothesis that higher levels of LEAP-2 are associated with hepatic steatosis and the role of LEAP-2 serum levels in the earlier and easier diagnosis of MASLD in children. Methods: In this cross-sectional study, 51 adolescents aged 12\u201318 were divided into three groups: one with MASLD and obesity (MASLD-Ob) (confirmed hepatosteatosis by imaging studies such as magnetic resonance or ultrasound, along with at least one cardiometabolic criterion and a body mass index (BMI) &gt; 2 SD) (n = 19), another with obesity without any liver pathology or MASLD (BMI &gt; 2 SD) (n = 14), and healthy controls (n = 18). The controlled attenuation parameter (CAP) was measured using FibroScan\u00ae Mini + 430 (Echosens SA, Cr\u00e9teil, France), and serum ghrelin and LEAP-2 levels were determined via ELISA. Correlations between LEAP-2, ghrelin, CAP, BMI z-score, and metabolic parameters were analyzed. Results: LEAP-2 and ghrelin levels among the three groups were similar (p = 0.148, p = 0.515). A positive correlation was observed between LEAP-2 levels and CAP values in the obese group (both the MASLD-Ob and obesity groups) (r = 0.379, p = 0.030). When a cutoff of 240 dB\/m was used, the median LEAP-2 level in cases above this value was 2.20 ng\/mL, compared to 1.37 ng\/mL in cases below it (p = 0.021), which was significantly different. When analyzing the obese group (both the MASLD-Ob and obese groups) a statistically significant correlation was found between serum LEAP-2 levels and CAP, AST, GGT, and total bilirubin values (r = 0.379, p = 0.030; r = 0.369, p = 0.035; r = 0.369, p = 0.035; r = 0.357, p = 0.049, respectively). Conclusions: Interventional imaging methods and biomarkers for diagnosing and monitoring hepatosteatosis have become well-established in the literature. However, since these tests are not available at all centers and can be costly, there is an increasing search for other easily accessible diagnostic and follow-up parameters. LEAP-2 could be a promising non-invasive biomarker for pediatric MASLD, especially when used alongside CAP measurements. The application of this biomarker in pediatric MASLD provides valuable data to help identify and monitor the condition in adolescents. We believe our study offers strong evidence to support further research and the development of drug treatments for MASLD that aim to reduce plasma LEAP-2.<\/jats:p>","DOI":"10.3390\/diagnostics15212816","type":"journal-article","created":{"date-parts":[[2025,11,6]],"date-time":"2025-11-06T17:51:43Z","timestamp":1762451503000},"page":"2816","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Serum LEAP-2 as a Potential Biomarker for Hepatic Steatosis in Adolescents with Obesity and MASLD: A Cross-Sectional Study"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5129-0923","authenticated-orcid":false,"given":"Sevim","family":"\u00c7akar","sequence":"first","affiliation":[{"name":"Division of Pediatric Gastroenterology, Department of Pediatrics, Faculty of Medicine, Dokuz Eyl\u00fcl University, Izmir 35340, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nur","family":"Arslan","sequence":"additional","affiliation":[{"name":"Division of Pediatric Metabolism and Nutrition, Department of Pediatrics, Dokuz Eyl\u00fcl University, Izmir 35340, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mehmet","family":"Ate\u015f","sequence":"additional","affiliation":[{"name":"Vocational School of Health Services, Dokuz Eyl\u00fcl University, Izmir 35340, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0879-9091","authenticated-orcid":false,"given":"Oya","family":"Say\u0131n","sequence":"additional","affiliation":[{"name":"Vocational School of Health Services, Dokuz Eyl\u00fcl University, Izmir 35340, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"O\u011fuzhan","family":"Akyaz","sequence":"additional","affiliation":[{"name":"Division of Pediatric Gastroenterology, Department of Pediatrics, Faculty of Medicine, Dokuz Eyl\u00fcl University, Izmir 35340, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tu\u011f\u00e7e","family":"Tatar Ar\u0131k","sequence":"additional","affiliation":[{"name":"Division of Pediatric Gastroenterology, Department of Pediatrics, Faculty of Medicine, Dokuz Eyl\u00fcl University, Izmir 35340, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rabia","family":"Ilg\u0131n","sequence":"additional","affiliation":[{"name":"Department of Physiology, School of Medicine, Dokuz Eyl\u00fcl University, Izmir 35340, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nilay","family":"Dan\u0131\u015f","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Faculty of Medicine, Dokuz Eyl\u00fcl University, Izmir 35340, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"100164","DOI":"10.1016\/j.obpill.2025.100164","article-title":"Metabolic dysfunction-associated steatotic liver disease (MASLD) in children with obesity: An Obesity Medicine Association (OMA) and expert joint perspective 2025","volume":"14","author":"Panganiban","year":"2025","journal-title":"Obes. Pillars"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e2022060640","DOI":"10.1542\/peds.2022-060640","article-title":"Clinical practice guideline for the evaluation and treatment of children and adolescents with obesity","volume":"151","author":"Hampl","year":"2023","journal-title":"Pediatrics"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1352","DOI":"10.1097\/HEP.0000000000001368","article-title":"AASLD practice statement on the evaluation and management of metabolic dysfunction-associated steatotic liver disease in children","volume":"82","author":"Xanthakos","year":"2025","journal-title":"Hepatology"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"101133","DOI":"10.1016\/j.aohep.2023.101133","article-title":"A multisociety Delphi consensus statement on new fatty liver disease nomenclature","volume":"29","author":"Rinella","year":"2024","journal-title":"Ann. Hepatol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1136\/gutjnl-2024-332398","article-title":"Interplay between gut microbiome, host genetic and epigenetic modifications in MASLD and MASLD-related hepatocellular carcinoma","volume":"74","author":"Ha","year":"2024","journal-title":"Gut"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1007\/s11154-019-09528-6","article-title":"Ghrelin and liver disease","volume":"21","year":"2020","journal-title":"Rev. Endocr. Metab. Disord."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"833","DOI":"10.1007\/s13105-022-00933-1","article-title":"Molecular and cellular mechanisms underlying the hepatoprotective role of ghrelin against NAFLD progression","volume":"79","author":"Tuero","year":"2023","journal-title":"J. Physiol. Biochem."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1016\/j.molmet.2015.03.005","article-title":"Ghrelin","volume":"4","author":"Nogueiras","year":"2015","journal-title":"Mol. Metab."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"101128","DOI":"10.1016\/j.molmet.2020.101128","article-title":"A LEAP2 conclusion? Targeting the ghrelin system to treat obesity and diabetes","volume":"46","author":"Gupta","year":"2021","journal-title":"Mol. Metab."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"843","DOI":"10.1016\/j.tem.2017.10.001","article-title":"Ghrelin as a survival hormone","volume":"28","author":"Mani","year":"2017","journal-title":"Trends Endocrinol. Metab."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2439","DOI":"10.2147\/DMSO.S536270","article-title":"Serum LEAP2 levels across the spectrum of metabolic dysfunction-associated fatty liver disease: A potential noninvasive biomarker for severity stratification","volume":"18","author":"Huang","year":"2025","journal-title":"Diabetes Metab. Syndr. Obes."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"101950","DOI":"10.1016\/j.molmet.2024.101950","article-title":"A long-acting LEAP2 analog reduces hepatic steatosis and inflammation and causes marked weight loss in mice","volume":"84","author":"Shankar","year":"2024","journal-title":"Mol. Metab."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Lin, C.E., and Chen, C.Y. (2024). Impacts of central administration of the novel peptide, LEAP-2, in different food intake models in conscious rats. Nutrients, 16.","DOI":"10.3390\/nu16121946"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Lugilde, J., Casado, S., Beiroa, D., Cu\u00f1arro, J., Garcia-Lavandeira, M., \u00c1lvarez, C.V., Nogueiras, R., Di\u00e9guez, C., and Tovar, S. (2022). LEAP-2 counteracts ghrelin-induced food intake in a nutrient, growth hormone and age independent manner. Cells, 11.","DOI":"10.3390\/cells11030324"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1530\/EJE-19-0684","article-title":"Plasma levels of ghrelin, des-acyl ghrelin and LEAP2 in children with obesity: Correlation with age and insulin resistance","volume":"182","author":"Fittipaldi","year":"2020","journal-title":"Eur. J. Endocrinol."},{"key":"ref_16","first-page":"564","article-title":"Antagonic effect of ghrelin and LEAP-2 on hepatic stellate cell activation and liver fibrosis in obesity-associated nonalcoholic fatty liver disease","volume":"188","author":"Ezquerro","year":"2023","journal-title":"Eur. J. Endocrinol."},{"key":"ref_17","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_18","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1016\/j.cmet.2017.10.016","article-title":"LEAP2 is an endogenous antagonist of the ghrelin receptor","volume":"27","author":"Ge","year":"2018","journal-title":"Cell Metab."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"5674","DOI":"10.1210\/jc.2003-031094","article-title":"Low ghrelin concentrations in nonalcoholic fatty liver disease are related to insulin resistance","volume":"88","author":"Marchesini","year":"2003","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1091","DOI":"10.1007\/s40618-014-0160-z","article-title":"Evaluation of serum xenin and ghrelin levels and their relationship with nonalcoholic fatty liver disease and insulin resistance in obese adolescents","volume":"37","author":"Arslan","year":"2014","journal-title":"J. Endocrinol. Investig."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Lv, Y., Liang, T., Wang, G., and Li, Z. (2018). Ghrelin, a gastrointestinal hormone, regulates energy balance and lipid metabolism. Biosci. Rep., 38.","DOI":"10.1042\/BSR20181061"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Lu, X., Huang, L., Huang, Z., Feng, D., Clark, R.J., and Chen, C. (2021). LEAP-2: An emerging endogenous ghrelin receptor antagonist in the pathophysiology of obesity. Front. Endocrinol., 12.","DOI":"10.3389\/fendo.2021.717544"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1055\/a-1210-2357","article-title":"Liver expressed antimicrobial peptide 2 is associated with steatosis in mice and humans","volume":"129","author":"Ma","year":"2020","journal-title":"Exp. Clin. Endocrinol. Diabetes"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"100582","DOI":"10.1016\/j.xcrm.2022.100582","article-title":"LEAP2 reduces postprandial glucose excursions and ad libitum food intake in healthy men","volume":"3","author":"Hagemann","year":"2022","journal-title":"Cell Rep. Med."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"937","DOI":"10.1002\/hep.31317","article-title":"Alanine aminotransferase and gamma-glutamyl transpeptidase predict histologic improvement in pediatric nonalcoholic steatohepatitis","volume":"73","author":"Newton","year":"2021","journal-title":"Hepatology"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Liu, Z., Ren, Q., Mu, H., Zeng, Y., An, Z., and He, H. (2024). Preliminary study on the diagnostic value of LEAP-2 and CK18 in biopsy-proven MAFLD. BMC Gastroenterol., 24.","DOI":"10.1186\/s12876-024-03258-z"},{"key":"ref_27","first-page":"817","article-title":"The past and present of serum aminotransferases and the future of liver injury biomarkers","volume":"15","author":"McGill","year":"2016","journal-title":"EXCLI J."},{"key":"ref_28","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","volume":"64","author":"Vos","year":"2017","journal-title":"J. Pediatr. Gastroenterol. Nutr."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1002\/jpn3.12230","article-title":"Fibrosis and steatotic liver disease in US adolescents according to the new nomenclature","volume":"79","author":"Ma","year":"2024","journal-title":"J. Pediatr. Gastroenterol. Nutr."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"865","DOI":"10.1053\/j.gastro.2009.06.005","article-title":"Prediction of non-alcoholic fatty liver disease and liver fat using metabolic and genetic factors","volume":"137","author":"Kotronen","year":"2009","journal-title":"Gastroenterology"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1016\/j.dld.2009.08.002","article-title":"Hepatic steatosis index: A simple screening tool reflecting nonalcoholic fatty liver disease","volume":"42","author":"Lee","year":"2010","journal-title":"Dig. Liver Dis."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Bedogni, G., Bellentani, S., Miglioli, L., Masutti, F., Passalacqua, M., Castiglione, A., and Tiribelli, C. (2006). The fatty liver index: A simple and accurate predictor of hepatic steatosis in the general population. BMC Gastroenterol., 6.","DOI":"10.1186\/1471-230X-6-33"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1471","DOI":"10.2337\/diacare.22.9.1471","article-title":"Age-related increase in visceral adipose tissue and body fat and the metabolic risk profile of premenopausal women","volume":"22","author":"Pascot","year":"1999","journal-title":"Diabetes Care"},{"key":"ref_34","first-page":"303","article-title":"The neo-epitope specific PRO-C3 ELISA measures true formation of type III collagen associated with liver and muscle parameters","volume":"5","author":"Nielsen","year":"2013","journal-title":"Am. J. Transl. Res."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1867","DOI":"10.1016\/j.cgh.2018.11.004","article-title":"Validation of serum test for advanced liver fibrosis in patients with nonalcoholic steatohepatitis","volume":"17","author":"Loomba","year":"2019","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"500","DOI":"10.1097\/MPG.0b013e3181e376be","article-title":"Serum levels of CK18 M30 and leptin are useful predictors of steatohepatitis and fibrosis in paediatric NAFLD","volume":"51","author":"Fitzpatrick","year":"2010","journal-title":"J. Pediatr. Gastroenterol. Nutr."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"462","DOI":"10.1038\/ajg.2015.29","article-title":"Plasma cathepsin D levels: A novel tool to predict pediatric hepatic inflammation","volume":"110","author":"Walenbergh","year":"2015","journal-title":"Am. J. Gastroenterol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1781","DOI":"10.1038\/s41390-021-01666-5","article-title":"Angiopoietin-2 levels correlate with disease activity in children with nonalcoholic fatty liver disease","volume":"91","author":"Manco","year":"2022","journal-title":"Pediatr. Res."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1002\/hep4.1068","article-title":"Association between cytokines and liver histology in children with nonalcoholic fatty liver disease","volume":"1","author":"Perito","year":"2017","journal-title":"Hepatol. Commun."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"510","DOI":"10.1007\/s13679-024-00574-z","article-title":"Non-invasive scores and serum biomarkers for fatty liver in the era of metabolic dysfunction-associated steatotic liver disease (MASLD): A comprehensive review from NAFLD to MAFLD and MASLD","volume":"13","author":"Abdelhameed","year":"2024","journal-title":"Curr. Obes. Rep."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Piazzolla, V.A., and Mangia, A. (2020). Noninvasive diagnosis of NAFLD and NASH. Cells, 9.","DOI":"10.3390\/cells9041005"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1016\/j.jpeds.2016.03.021","article-title":"Comparison of controlled attenuation parameter and liver biopsy to assess hepatic steatosis in pediatric patients","volume":"173","author":"Desai","year":"2016","journal-title":"J. Pediatr."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1588","DOI":"10.1007\/s00330-020-07245-2","article-title":"Accuracy of controlled attenuation parameter compared with ultrasound for detecting hepatic steatosis in children with severe obesity","volume":"31","author":"Runge","year":"2021","journal-title":"Eur. Radiol."},{"key":"ref_44","first-page":"e160","article-title":"Usefulness of transient elastography for non-invasive diagnosis of liver fibrosis in pediatric non-alcoholic steatohepatitis","volume":"34","author":"Ko","year":"2019","journal-title":"J. Korean Med. Sci."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"101755","DOI":"10.1016\/j.clinre.2021.101755","article-title":"Non-invasive assessment of fibrosis and steatosis in pediatric non-alcoholic fatty liver disease","volume":"46","author":"Chen","year":"2022","journal-title":"Clin. Res. Hepatol. Gastroenterol."},{"key":"ref_46","unstructured":"(2025). ESPGHAN 57th Annual Meeting Abstracts. JPGN Rep., 6, S1\u2013S1656."}],"container-title":["Diagnostics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-4418\/15\/21\/2816\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,6]],"date-time":"2025-11-06T18:02:36Z","timestamp":1762452156000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-4418\/15\/21\/2816"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,6]]},"references-count":46,"journal-issue":{"issue":"21","published-online":{"date-parts":[[2025,11]]}},"alternative-id":["diagnostics15212816"],"URL":"https:\/\/doi.org\/10.3390\/diagnostics15212816","relation":{},"ISSN":["2075-4418"],"issn-type":[{"value":"2075-4418","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,6]]}}}