{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T06:00:00Z","timestamp":1790316000660,"version":"4.1.0"},"reference-count":33,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T00:00:00Z","timestamp":1790294400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pediatr."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Low alanine aminotransferase (ALT) has been associated with unfavorable inflammatory and nutritional phenotypes, but its relationship with infliximab (IFX) response in pediatric Crohn's disease (CD) is uncertain.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We retrospectively studied 116 children with CD who received IFX induction at weeks 0, 2, and 6 and underwent response assessment at approximately week 14. Low ALT was defined as &amp;lt;10 U\/L using a rounded, data-informed working threshold. Primary non-response (PNR) required concurrent clinical non-response, biochemical activity, and objective endoscopic or cross-sectional imaging evidence and was independently adjudicated by two pediatric gastroenterologists blinded to baseline ALT. Firth logistic regression assessed the association between low ALT and PNR after adjustment for baseline SES-CD, IFX dose, and concomitant immunomodulator use.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Fifty-eight children (50.0%) had low ALT and 21 (18.1%) had PNR. PNR occurred more often with low ALT (27.6% vs. 8.6%;\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20090.008). Low ALT remained associated with PNR after adjustment (OR, 4.03; 95% CI, 1.48\u201312.65;\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20090.006), and each 5-U\/L decrease in ALT was associated with higher odds of PNR (OR, 1.50; 95% CI, 1.04\u20132.59;\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20090.022). Discrimination was limited (AUC, 0.677; bootstrap 95% CI, 0.547\u20130.802).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Low baseline ALT was associated with PNR to IFX in pediatric CD. This exploratory association and the 10-U\/L working threshold require external validation and should not guide treatment decisions in isolation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fped.2026.1948999","type":"journal-article","created":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T05:33:21Z","timestamp":1790314401000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Low baseline alanine aminotransferase is associated with primary non-response to infliximab induction in pediatric Crohn's disease: a retrospective cohort study"],"prefix":"10.3389","volume":"14","author":[{"given":"Yuhang","family":"Wang","sequence":"first","affiliation":[{"name":"Gastroenterology, Hepatology and Nutrition Center, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheng","family":"Guo","sequence":"additional","affiliation":[{"name":"Gastroenterology, Hepatology and Nutrition Center, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Wu","sequence":"additional","affiliation":[{"name":"Gastroenterology, Hepatology and Nutrition Center, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,25]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"ii31","DOI":"10.1093\/ecco-jcc\/jjae087","article-title":"Considerations in paediatric and adolescent inflammatory bowel disease","volume":"18","author":"Vuijk","year":"2024","journal-title":"J Crohns Colitis"},{"key":"B2","doi-asserted-by":"publisher","first-page":"1106","DOI":"10.1053\/j.gastro.2008.06.079","article-title":"Natural history of pediatric Crohn's Disease: a population-based cohort study","volume":"135","author":"Vernier\u2013Massouille","year":"2008","journal-title":"Gastroenterology"},{"key":"B3","doi-asserted-by":"publisher","first-page":"449","DOI":"10.1097\/MPG.0b013e3182841263","article-title":"Psychosocial issues in pediatric inflammatory bowel disease: report of the north American society for pediatric gastroenterology, hepatology, and nutrition","volume":"56","author":"Mackner","year":"2013","journal-title":"J Pediatr Gastroenterol Nutr"},{"key":"B4","doi-asserted-by":"publisher","first-page":"458","DOI":"10.3390\/biomedicines8110458","article-title":"Growth and puberty in children with inflammatory bowel diseases","volume":"8","author":"Amaro","year":"2020","journal-title":"Biomedicines"},{"key":"B5","doi-asserted-by":"publisher","first-page":"863","DOI":"10.1053\/j.gastro.2006.12.003","article-title":"Induction and maintenance infliximab therapy for the treatment of moderate-to-severe Crohn's Disease in children","volume":"132","author":"Hyams","year":"2007","journal-title":"Gastroenterology"},{"key":"B6","doi-asserted-by":"publisher","first-page":"171","DOI":"10.1093\/ecco-jcc\/jjaa161","article-title":"The medical management of paediatric Crohn's Disease: an ECCO-ESPGHAN guideline update","volume":"15","author":"van Rheenen","year":"2021","journal-title":"J Crohns Colitis"},{"key":"B7","doi-asserted-by":"publisher","first-page":"e135","DOI":"10.1038\/ctg.2015.63","article-title":"Loss of response to anti-TNFs: definition, epidemiology, and management","volume":"7","author":"Roda","year":"2016","journal-title":"Clin Transl Gastroenterol"},{"key":"B8","doi-asserted-by":"publisher","first-page":"1702","DOI":"10.1093\/aje\/kwt209","article-title":"The association of low serum alanine aminotransferase activity with mortality in the US population","volume":"178","author":"Ruhl","year":"2013","journal-title":"Am J Epidemiol"},{"key":"B9","doi-asserted-by":"publisher","first-page":"209","DOI":"10.1007\/s11606-015-3480-6","article-title":"Low ALT levels independently associated with 22-year all-cause mortality among coronary heart disease patients","volume":"31","author":"Peltz-Sinvani","year":"2016","journal-title":"J Gen Intern Med"},{"key":"B10","doi-asserted-by":"publisher","first-page":"925","DOI":"10.1093\/gerona\/glx126","article-title":"Low alanine aminotransferase levels in the elderly population: frailty, disability, sarcopenia, and reduced survival","volume":"73","author":"Vespasiani-Gentilucci","year":"2018","journal-title":"J Gerontol A Biol Sci Med Sci"},{"key":"B11","doi-asserted-by":"publisher","first-page":"133","DOI":"10.1186\/s12890-020-1169-z","article-title":"Baseline low ALT activity is associated with increased long-term mortality after COPD exacerbations","volume":"20","author":"Lasman","year":"2020","journal-title":"BMC Pulm Med"},{"key":"B12","doi-asserted-by":"publisher","first-page":"3185","DOI":"10.3390\/jcm9103185","article-title":"Low ALT levels associated with poor outcomes in 8700 hospitalized heart failure patients","volume":"9","author":"Segev","year":"2020","journal-title":"J Clin Med"},{"key":"B13","doi-asserted-by":"publisher","first-page":"843","DOI":"10.1093\/qjmed\/hcaa219","article-title":"Low ALT values amongst hospitalized patients are associated with increased risk of hypoglycemia and overall mortality: a retrospective, big-data analysis of 51 831 patients","volume":"114","author":"Itelman","year":"2021","journal-title":"QJM"},{"key":"B14","doi-asserted-by":"publisher","first-page":"e33659","DOI":"10.1097\/MD.0000000000033659","article-title":"Low ALT, a marker of sarcopenia and frailty, is associated with shortened survival amongst myelodysplastic syndrome patients: a retrospective study","volume":"102","author":"Uliel","year":"2023","journal-title":"Medicine (Baltimore)"},{"key":"B15","doi-asserted-by":"publisher","first-page":"1869","DOI":"10.3390\/jcm13071869","article-title":"Low ALT is associated with IBD and disease activity: results from a nationwide study","volume":"13","author":"Shafrir","year":"2024","journal-title":"J Clin Med"},{"key":"B16","doi-asserted-by":"publisher","first-page":"143","DOI":"10.1007\/s12519-019-00235-5","article-title":"Clinical significance of low transaminase levels in children with inflammatory bowel disease","volume":"15","author":"Cakir","year":"2019","journal-title":"World J Pediatr"},{"key":"B17","doi-asserted-by":"publisher","first-page":"413","DOI":"10.1093\/ajcn\/82.2.413","article-title":"Body-composition alterations consistent with cachexia in children and young adults with Crohn disease","volume":"82","author":"Burnham","year":"2005","journal-title":"Am J Clin Nutr"},{"key":"B18","doi-asserted-by":"publisher","first-page":"16","DOI":"10.21037\/tp.2018.12.04","article-title":"Growth failure in pediatric onset inflammatory bowel disease: mechanisms, epidemiology, and management","volume":"8","author":"Ishige","year":"2019","journal-title":"Transl Pediatr"},{"key":"B19","doi-asserted-by":"publisher","first-page":"694217","DOI":"10.3389\/fimmu.2021.694217","article-title":"Inflammatory bowel diseases and sarcopenia: the role of inflammation and gut microbiota in the development of muscle failure","volume":"12","author":"Nardone","year":"2021","journal-title":"Front Immunol"},{"key":"B20","doi-asserted-by":"publisher","first-page":"1611","DOI":"10.3390\/nu13051611","article-title":"Dietary management in pediatric patients with Crohn's disease","volume":"13","author":"Scarallo","year":"2021","journal-title":"Nutrients"},{"key":"B21","doi-asserted-by":"publisher","first-page":"1453","DOI":"10.1016\/S0140-6736(07)61602-X","article-title":"The strengthening the reporting of observational studies in epidemiology (STROBE) statement: guidelines for reporting observational studies","volume":"370","author":"Von Elm","year":"2007","journal-title":"Lancet"},{"key":"B22","doi-asserted-by":"publisher","first-page":"795","DOI":"10.1097\/MPG.0000000000000239","article-title":"ESPGHAN revised porto criteria for the diagnosis of inflammatory bowel disease in children and adolescents","volume":"58","author":"Levine","year":"2014","journal-title":"J Pediatr Gastroenterol Nutr"},{"key":"B23","doi-asserted-by":"publisher","first-page":"1314","DOI":"10.1002\/ibd.21493","article-title":"Pediatric modification of the Montreal classification for inflammatory bowel disease: the Paris classification","volume":"17","author":"Levine","year":"2011","journal-title":"Inflamm Bowel Dis"},{"key":"B24","doi-asserted-by":"publisher","first-page":"439","DOI":"10.1002\/j.1536-4801.1991.tb10268.x","article-title":"Development and validation of a pediatric Crohn's Disease activity index","volume":"12","author":"Hyams","year":"1991","journal-title":"J Pediatr Gastroenterol Nutr"},{"key":"B25","doi-asserted-by":"publisher","first-page":"505","DOI":"10.1016\/S0016-5107(04)01878-4","article-title":"Development and validation of a new, simplified endoscopic activity score for Crohn's Disease: the SES-CD","volume":"60","author":"Daperno","year":"2004","journal-title":"Gastrointest Endosc"},{"key":"B26","doi-asserted-by":"publisher","first-page":"2409","DOI":"10.1002\/sim.1047","article-title":"A solution to the problem of separation in logistic regression","volume":"21","author":"Heinze","year":"2002","journal-title":"Stat Med"},{"key":"B27","doi-asserted-by":"publisher","first-page":"266","DOI":"10.1002\/jpn3.70075","article-title":"Clinical risk factors for body composition deficits in children with inflammatory bowel disease","volume":"81","author":"Alexander","year":"2025","journal-title":"J Pediatr Gastroenterol Nutr"},{"key":"B28","doi-asserted-by":"publisher","first-page":"723","DOI":"10.1097\/MPG.0000000000001123","article-title":"Infliximab dosing strategies and predicted trough exposure in children with crohn disease","volume":"62","author":"Frymoyer","year":"2016","journal-title":"J Pediatr Gastroenterol Nutr"},{"key":"B29","doi-asserted-by":"publisher","first-page":"429","DOI":"10.1093\/ibd\/izz143","article-title":"Improved population pharmacokinetic model for predicting optimized infliximab exposure in pediatric inflammatory bowel disease","volume":"26","author":"Bauman","year":"2020","journal-title":"Inflamm Bowel Dis"},{"key":"B30","doi-asserted-by":"publisher","first-page":"1100","DOI":"10.1002\/jpn3.70158","article-title":"North American society for pediatric gastroenterology, hepatology, and nutrition position paper on the therapeutic drug monitoring in pediatric inflammatory bowel disease","volume":"81","author":"Felipez","year":"2025","journal-title":"J Pediatr Gastroenterol Nutr"},{"key":"B31","doi-asserted-by":"publisher","first-page":"151","DOI":"10.1007\/s12519-018-0126-x","article-title":"Establishment of age- and gender-specific pediatric reference intervals for liver function tests in healthy han children","volume":"14","author":"Li","year":"2018","journal-title":"World J Pediatr"},{"key":"B32","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1016\/j.crohns.2011.06.013","article-title":"Upper gastrointestinal involvement in paediatric onset Crohn's disease: prevalence and clinical implications","volume":"6","author":"Crocco","year":"2012","journal-title":"J Crohns Colitis"},{"key":"B33","doi-asserted-by":"publisher","first-page":"21","DOI":"10.3345\/cep.2021.00661","article-title":"Upper gastrointestinal tract involvement of Crohn disease: clinical implications in children and adolescents","volume":"65","author":"Kim","year":"2022","journal-title":"Clin Exp Pediatr"}],"container-title":["Frontiers in Pediatrics"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fped.2026.1948999\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T05:33:21Z","timestamp":1790314401000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fped.2026.1948999\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,25]]},"references-count":33,"alternative-id":["10.3389\/fped.2026.1948999"],"URL":"https:\/\/doi.org\/10.3389\/fped.2026.1948999","relation":{},"ISSN":["2296-2360"],"issn-type":[{"value":"2296-2360","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,25]]},"article-number":"1948999"}}