{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T18:08:43Z","timestamp":1774375723776,"version":"3.50.1"},"reference-count":22,"publisher":"Bentham Science Publishers Ltd.","issue":"2","content-domain":{"domain":["eurekaselect.com"],"crossmark-restriction":true},"short-container-title":["CRR"],"published-print":{"date-parts":[[2021,5]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>Juvenile idiopathic arthritis (JIA) could be disabling if left untreated.\nMethotrexate (MTX) is well known as a cornerstone in management. However, its adverse effects\nmay limit treatment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective:<\/jats:title>\n                    <jats:p>The objective of this study was to evaluate the frequency of hepatotoxicity based on liver\nchemistry in JIA children receiving MTX.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>An observational case-control study of children with JIA who attend the Pediatric Rheumatology\nUnit, Cairo University Pediatric Hospital, Egypt, from January 2018 to December 2018\nwas carried out. Data were retrieved for 80 children; 50 (62.5%) were prescribed MTX. Their demographic,\nclinical characteristics, mean dose, duration of MTX therapy and other medications\nwere described. Hepatotoxicity was defined as at least one value above the normal laboratory range\nof either ALT or AST during the study period.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>Fourteen patients developed hepatotoxicity, giving an incidence of 28%. Children receiving\nMTX had higher alanine aminotransferase (ALT) interquartile range (IQR) (26 [21-359] vs.\n23[20-32]; p =0.003), higher aspartate aminotransferase (AST) interquartile range (IQR) (31\n[22-267] vs. 28[2-35] IU\/L; p &lt;0.001), and lower alkaline phosphatase (ALP) mean (\u00b1SD)\n(98\u00b135.5 vs. 256 \u00b1 39.5 IU\/L; p &lt;0.001). However, there were no significant differences in age,\nsex, weight, type of JIA, and duration of MTX treatment (p&lt; 0.05).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion:<\/jats:title>\n                    <jats:p>Hepatotoxicity due to MTX, based on liver chemistry, is common among children\nwith JIA.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.2174\/1573397116666201211123142","type":"journal-article","created":{"date-parts":[[2020,12,14]],"date-time":"2020-12-14T03:06:53Z","timestamp":1607915213000},"page":"242-246","update-policy":"https:\/\/doi.org\/10.2174\/bsp_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Methotrexate Hepatotoxicity in Children with Juvenile Idiopathic Arthritis: A Single-Center Study"],"prefix":"10.2174","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9297-4990","authenticated-orcid":true,"given":"Noha Adel","family":"Yassin","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Cairo University, Cairo,Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mai","family":"Haroon","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Cairo University, Cairo,Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Azza","family":"Elhamshary","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Cairo University, Cairo,Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"965","reference":[{"key":"ref=1","doi-asserted-by":"publisher","first-page":"216","DOI":"10.1186\/ar2619","volume":"11","author":"Hayward K.","year":"2009","unstructured":"Hayward K.; Wallace C.A.; Recent developments in anti-rheumatic drugs in pediatrics: treatment of juvenile idiopathic arthritis. 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Ann Rheum Dis 2009,68(7),1105-1112","journal-title":"Ann Rheum Dis"},{"key":"ref=4","first-page":"S95","volume":"28","author":"Albrecht K.","year":"2010","unstructured":"Albrecht K.; M&#xFC;ller-Ladner U.; Side effects and management of side effects of methotrexate in rheumatoid arthritis. Clin Exp Rheumatol 2010,28(5)(Suppl. 61),S95-S101","journal-title":"Clin Exp Rheumatol"},{"key":"ref=5","doi-asserted-by":"publisher","first-page":"1092","DOI":"10.4254\/wjh.v9.i26.1092","volume":"9","author":"Conway R.","year":"2017","unstructured":"Conway R.; Carey J.J.; Risk of liver disease in methotrexate treated patients. World J Hepatol 2017,9(26),1092-1100","journal-title":"World J Hepatol"},{"key":"ref=6","year":"2020","unstructured":"British society for Rheumatology. 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J Rheumatol 2017,44(2),230-240","journal-title":"J Rheumatol"},{"key":"ref=15","doi-asserted-by":"publisher","first-page":"297","DOI":"10.1007\/s10875-012-9760-6","volume":"33","author":"Gheita T.A.","year":"2013","unstructured":"Gheita T.A.; El-Gazzar I.I.; El Shazly R.I.; El-Din A.M.; Abdel-Rasheed E.; Bassyouni R.H.; Elevated serum resistin in juvenile idiopathic arthritis: relation to categories and disease activity. J Clin Immunol 2013,33(1),297-301","journal-title":"J Clin Immunol"},{"key":"ref=16","doi-asserted-by":"publisher","unstructured":"Beath SV. The liver in systemic illness.Diseases of the liver and biliary system in children. (4th ed.). John Wiley and Sons Ltd 2017; pp. 369-88.","DOI":"10.1002\/9781119046936.ch22"},{"key":"ref=17","unstructured":"Garnero P, Delmas DP. Investigation of bone: biochemical markers. Bone turnover in rheumatology. (3rd ed.). London, UK: Harcourt Health Sciences Ltd. 2003; pp. 995-1001."},{"key":"ref=18","doi-asserted-by":"publisher","first-page":"217","DOI":"10.1016\/j.ejr.2011.08.001","volume":"3","author":"Alkady E.A.","year":"2011","unstructured":"Alkady E.A.; Rashad S.M.; Khedr T.M.; Mosad E.; Abdel-Wahab N.; Early predictors of increased bone resorption in juvenile idiopathic arthritis: OPG\/RANKL ratio, as a key regulator of bone metabolism. Egypt Rheumatol 2011,3,217-223","journal-title":"Egypt Rheumatol"},{"key":"ref=19","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1007\/BF03347283","volume":"21","author":"Falcini F.","year":"1998","unstructured":"Falcini F.; Ermini M.; Bagnoli F.; Bone turnover is reduced in children with juvenile rheumatoid arthritis. J Endocrinol Invest 1998,21(1),31-36","journal-title":"J Endocrinol Invest"},{"key":"ref=20","doi-asserted-by":"publisher","first-page":"441","DOI":"10.1097\/00008480-199808000-00020","volume":"10","author":"de Ridder C.M.","year":"1998","unstructured":"de Ridder C.M.; Delemarre-van de Waal H.A.; Waal H.A.; Clinical utility of markers of bone turnover in children and adolescents. Curr Opin Pediatr 1998,10(4),441-448","journal-title":"Curr Opin Pediatr"},{"key":"ref=21","first-page":"102","volume":"4","author":"Dehestani V.","year":"2015","unstructured":"Dehestani V.; Shariati-Sarabi Z.; Mohiti S.; Akhlaghi S.; Liver Toxicity in Rheumatoid Arthritis Patients Treated with Methotrexate. 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