{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T03:57:05Z","timestamp":1790913425084,"version":"4.1.0"},"reference-count":38,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,2,18]],"date-time":"2025-02-18T00:00:00Z","timestamp":1739836800000},"content-version":"vor","delay-in-days":48,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,1,1]],"date-time":"2025-01-01T00:00:00Z","timestamp":1735689600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["JP23mk0121274"],"award-info":[{"award-number":["JP23mk0121274"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pediatrics International"],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Drug\u2010induced liver injury (DILI) is a common adverse drug event with limited pediatric data in the literature. This study aimed to use pediatric electronic medical records to assess hepatocellular DILI in pediatric patients who were prescribed liver\u2010injury\u2010inducing drugs.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The Pediatric Medical Information Collection System (P\u2010MICS) is a centralized database integrating electronic medical records from over 40 medical pediatric centers. Pediatric patients in the P\u2010MICS with serum alanine aminotransferase (ALT) levels five or more times the upper limit of normal and who were below 15\u2009years of age were selected. Those with liver diseases unrelated to drug\u2010induced causes were excluded. We identified drugs prescribed 2 to 90\u2009days before the first elevated ALT reading. High\u2010risk liver\u2010injury\u2010causing drugs were determined based on the LiverTox score. We analyzed post\u2010event ALT and total bilirubin levels (TB) and DILI management.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Of the 817 patients with suspected DILI, 251 were prescribed four drugs identified as high\u2010risk drugs for hepatocellular DILI: methotrexate (\n                      <jats:italic>n<\/jats:italic>\n                      =\u2009129), aspirin (\n                      <jats:italic>n<\/jats:italic>\n                      =\u200982), vancomycin (\n                      <jats:italic>n<\/jats:italic>\n                      =\u200958), and cyclophosphamide (\n                      <jats:italic>n<\/jats:italic>\n                      =\u200951). The median ALT level at the first event was 245\u2009U\/L. Approximately 35% of methotrexate users and cyclophosphamide users experienced recurrent ALT elevation. Some methotrexate users also showed TB elevation. Discontinuation of high\u2010risk drugs resulted in fewer relapses and TB elevations than pharmacotherapy.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The P\u2010MICS effectively identifies pediatric patients with potential liver injury and tracks liver function in those prescribed liver\u2010injury\u2010causing drugs. This study underscores liver injury risks in pediatric anticancer drug users, highlighting the utility of the P\u2010MICS in monitoring off\u2010label drug safety in children.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/ped.15847","type":"journal-article","created":{"date-parts":[[2025,2,18]],"date-time":"2025-02-18T23:42:11Z","timestamp":1739922131000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Liver function trends in children with suspected drug\u2010induced hepatocellular injury: A survey using an electronic medical records database"],"prefix":"10.1111","volume":"67","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0324-6084","authenticated-orcid":false,"given":"Masayoshi","family":"Nakakuni","sequence":"first","affiliation":[{"name":"Center for Clinical Research and Development National Center for Child Health and Development  Tokyo Japan"},{"name":"Social Pharmacy and Regulatory Science Showa Pharmaceutical University  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kosuke","family":"Nakano","sequence":"additional","affiliation":[{"name":"Center for Clinical Research and Development National Center for Child Health and Development  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayano","family":"Inui","sequence":"additional","affiliation":[{"name":"Department Pediatric Hepatology and Gastroenterology Saiseikai Yokohamashi Tobu Hospital  Kanagawa Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shinji","family":"Kobayashi","sequence":"additional","affiliation":[{"name":"Nature Insight Co., Ltd.  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naoko","family":"Deguchi","sequence":"additional","affiliation":[{"name":"Center for Clinical Research and Development National Center for Child Health and Development  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seiji","family":"Mitsui","sequence":"additional","affiliation":[{"name":"Center for Clinical Research and Development National Center for Child Health and Development  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takeshi","family":"Kuriyama","sequence":"additional","affiliation":[{"name":"Center for Clinical Research and Development National Center for Child Health and Development  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seiko","family":"Miyazaki","sequence":"additional","affiliation":[{"name":"Center for Clinical Research and Development National Center for Child Health and Development  Tokyo Japan"},{"name":"Social Pharmacy and Regulatory Science Showa Pharmaceutical University  Tokyo Japan"},{"name":"Pharmacoepidemiology, Faculty of Pharmaceutical Sciences Teikyo Heisei University  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,2,18]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00204-020-02885-1"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.5009\/gnl15114"},{"key":"e_1_2_9_4_1","unstructured":"US Department of Health and Human Services Food and Drug Administration Center for Drug Evaluation and Research Center for Biologics Evaluation and Research.Guidance for Industry Drug\u2010Induced Liver Injury: Premarketing Clinical Evaluation.2009. [cited 2024 Jan 15]. Available from:https:\/\/www.fda.gov\/regulatory\u2010information\/search\u2010fda\u2010guidance\u2010documents\/drug\u2010induced\u2010liver\u2010injury\u2010premarketing\u2010clinical\u2010evaluation"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2008.09.011"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.20800"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.32327"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.hepres.2005.05.007"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/hepr.13288"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1177\/1091581817721675"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1097\/MPG.0000000000002383"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1097\/MPG.0b013e31821d6cfd"},{"key":"e_1_2_9_13_1","unstructured":"Pharmaceutical and Medical Devices Agency.PMDA Alert for Proper Use of Drugs. Toward Promotion of Pediatric Clinical Development (Development and Safety Measures) Using a Medical Information Database (Part 1) (in Japanese). [cited 2024 May 11]. Available from:https:\/\/www.pmda.go.jp\/files\/000233817.pdf#page=3"},{"key":"e_1_2_9_14_1","unstructured":"National Center for Child Health and Development [homepage on the Internet].Pediatric Medical Information Collection System. [cited 2023 Aug 18]. Available from:https:\/\/pharma\u2010net.ncchd.go.jp\/en\/"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/1751-2980.12684"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.14218\/JCTH.2013.D002X"},{"key":"e_1_2_9_17_1","unstructured":"The Council for International Organizations of Medical Sciences (CIOMS) Working Group.Drug\u2010induced liver injury (DILI): Current status and future directions for drug development and the post\u2010market setting.2020. [cited 2023 Aug 18]. Available from:https:\/\/cioms.ch\/publications\/product\/drug\u2010induced\u2010liver\u2010injury\/"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/clpt.2011.58"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12072-021-10144-3"},{"key":"e_1_2_9_20_1","first-page":"1117","article-title":"Reference intervals of clinical tests in children determined by a latent reference value extraction method","volume":"112","author":"Tanaka T","year":"2008","journal-title":"J Jpn Pediatr Soc"},{"key":"e_1_2_9_21_1","unstructured":"National Institute of Diabetes and Digestive and Kidney Diseases [homepage on the Internet].LiverTox: Clinical and Research Information on Drug\u2010Induced Liver Injury. [cited 2023 Aug 18]. 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