{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T00:21:13Z","timestamp":1792801273242,"version":"4.5.0"},"reference-count":40,"publisher":"Elsevier BV","issue":"5","license":[{"start":{"date-parts":[[2011,5,1]],"date-time":"2011-05-01T00:00:00Z","timestamp":1304208000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Journal of Pediatrics"],"published-print":{"date-parts":[[2011,5]]},"DOI":"10.1016\/j.jpeds.2010.10.033","type":"journal-article","created":{"date-parts":[[2010,12,17]],"date-time":"2010-12-17T09:15:46Z","timestamp":1292577346000},"page":"802-807","source":"Crossref","is-referenced-by-count":38,"title":["Valproic Acid-Associated Acute Liver Failure in Children: Case Report and Analysis of Liver Transplantation Outcomes in the United States"],"prefix":"10.1016","volume":"158","author":[{"given":"Ayse L.","family":"Mindikoglu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dale","family":"King","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurence S.","family":"Magder","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John A.","family":"Ozolek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George V.","family":"Mazariegos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin L.","family":"Shneider","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.jpeds.2010.10.033_bib1","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1212\/WNL.46.2.465","article-title":"Valproic acid hepatic fatalities. III. US experience since 1986","volume":"46","author":"Bryant","year":"1996","journal-title":"Neurology"},{"issue":"Suppl. 2","key":"10.1016\/j.jpeds.2010.10.033_bib2","doi-asserted-by":"crossref","first-page":"S23","DOI":"10.1111\/j.1528-1157.1987.tb05768.x","article-title":"Hepatic considerations in the use of antiepileptic drugs","volume":"28","author":"Dreifuss","year":"1987","journal-title":"Epilepsia"},{"key":"10.1016\/j.jpeds.2010.10.033_bib3","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1212\/WNL.37.3.379","article-title":"Valproic acid hepatic fatalities: a retrospective review","volume":"37","author":"Dreifuss","year":"1987","journal-title":"Neurology"},{"key":"10.1016\/j.jpeds.2010.10.033_bib4","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1002\/lt.21692","article-title":"Outcome of liver transplantation for drug-induced acute liver failure in the United States: analysis of the United Network for Organ Sharing database","volume":"15","author":"Mindikoglu","year":"2009","journal-title":"Liver Transpl"},{"key":"10.1016\/j.jpeds.2010.10.033_bib5","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/0163-7258(95)00012-6","article-title":"Inhibition of mitochondrial beta-oxidation as a mechanism of hepatotoxicity","volume":"67","author":"Fromenty","year":"1995","journal-title":"Pharmacol Ther"},{"key":"10.1016\/j.jpeds.2010.10.033_bib6","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1034\/j.1600-0676.2000.020004346.x","article-title":"Mitochondrial diseases represent a risk factor for valproate-induced fulminant liver failure","volume":"20","author":"Krahenbuhl","year":"2000","journal-title":"Liver"},{"key":"10.1016\/j.jpeds.2010.10.033_bib7","doi-asserted-by":"crossref","first-page":"2435","DOI":"10.1016\/0006-2952(92)90324-C","article-title":"In vitro effects of valproate and valproate metabolites on mitochondrial oxidations. Relevance of CoA sequestration to the observed inhibitions","volume":"43","author":"Ponchaut","year":"1992","journal-title":"Biochem Pharmacol"},{"key":"10.1016\/j.jpeds.2010.10.033_bib8","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1016\/0006-2952(93)90404-K","article-title":"Valproate and mitochondria","volume":"46","author":"Ponchaut","year":"1993","journal-title":"Biochem Pharmacol"},{"key":"10.1016\/j.jpeds.2010.10.033_bib9","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1097\/MOP.0b013e328306ebb6","article-title":"Disorders of mitochondrial function","volume":"20","author":"Debray","year":"2008","journal-title":"Curr Opin Pediatr"},{"key":"10.1016\/j.jpeds.2010.10.033_bib10","doi-asserted-by":"crossref","DOI":"10.1007\/s10545-008-0841-x","article-title":"Valproic acid metabolism and its effects on mitochondrial fatty acid oxidation: a review","author":"Silva","year":"2008","journal-title":"J Inherit Metab Dis"},{"key":"10.1016\/j.jpeds.2010.10.033_bib11","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1034\/j.1399-3046.2000.00090.x","article-title":"Inappropriate liver transplantation in a child with Alpers-Huttenlocher syndrome misdiagnosed as valproate-induced acute liver failure","volume":"4","author":"Delarue","year":"2000","journal-title":"Pediatr Transplant"},{"key":"10.1016\/j.jpeds.2010.10.033_bib12","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1034\/j.1399-3046.2000.00115.x","article-title":"Fatal deterioration of neurological disease after orthotopic liver transplantation for valproic acid-induced liver damage","volume":"4","author":"Kayihan","year":"2000","journal-title":"Pediatr Transplant"},{"key":"10.1016\/j.jpeds.2010.10.033_bib13","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1136\/adc.2007.122911","article-title":"Reversible valproate hepatotoxicity due to mutations in mitochondrial DNA polymerase gamma (POLG1)","volume":"93","author":"McFarland","year":"2008","journal-title":"Arch Dis Child"},{"key":"10.1016\/j.jpeds.2010.10.033_bib14","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1017\/S0317167100030353","article-title":"The high incidence of valproate hepatotoxicity in infants may relate to familial metabolic defects","volume":"17","author":"Appleton","year":"1990","journal-title":"Can J Neurol Sci"},{"key":"10.1016\/j.jpeds.2010.10.033_bib15","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1001\/archneurpsyc.1931.02230030027002","article-title":"Diffuse progressive degeneration of gray matter of cerebrum","volume":"25","author":"Alpers","year":"1931","journal-title":"Arch Neurol Psychiatr"},{"key":"10.1016\/j.jpeds.2010.10.033_bib16","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1001\/archneur.1976.00500030042009","article-title":"Infantile diffuse cerebral degeneration with hepatic cirrhosis","volume":"33","author":"Huttenlocher","year":"1976","journal-title":"Arch Neurol"},{"key":"10.1016\/j.jpeds.2010.10.033_bib17","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1097\/00007890-200103150-00009","article-title":"Orthotopic liver transplantation for mitochondrial respiratory chain disorders: a study of 5 children","volume":"71","author":"Dubern","year":"2001","journal-title":"Transplantation"},{"key":"10.1016\/j.jpeds.2010.10.033_bib18","doi-asserted-by":"crossref","first-page":"478","DOI":"10.1097\/00005176-199804000-00024","article-title":"Generalised mitochondrial cytopathy is an absolute contraindication to orthotopic liver transplant in childhood","volume":"26","author":"Thomson","year":"1998","journal-title":"J Pediatr Gastroenterol Nutr"},{"key":"10.1016\/j.jpeds.2010.10.033_bib19","doi-asserted-by":"crossref","first-page":"1555","DOI":"10.1002\/hep.21710","article-title":"Mitochondrial hepatopathies: advances in genetics and pathogenesis","volume":"45","author":"Lee","year":"2007","journal-title":"Hepatology"},{"issue":"Suppl. 2","key":"10.1016\/j.jpeds.2010.10.033_bib20","doi-asserted-by":"crossref","first-page":"S81","DOI":"10.1007\/PL00014328","article-title":"Liver transplantation in mitochondrial respiratory chain disorders","volume":"158","author":"Sokal","year":"1999","journal-title":"Eur J Pediatr"},{"key":"10.1016\/j.jpeds.2010.10.033_bib21","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1097\/00005176-200402000-00022","article-title":"Hepatocerebral mitochondrial DNA depletion syndrome: clinical and morphologic features of a nuclear gene mutation","volume":"38","author":"Rabinowitz","year":"2004","journal-title":"J Pediatr Gastroenterol Nutr"},{"key":"10.1016\/j.jpeds.2010.10.033_bib22","unstructured":"SAS Institute. SAS , V9.2. Cary, NC. Available at http:\/\/www.sas.com\/."},{"key":"10.1016\/j.jpeds.2010.10.033_bib23","unstructured":"Minitab 15 Statistical Software (2007). (Computer software]. State College PM. Available at: www.minitab.com."},{"key":"10.1016\/j.jpeds.2010.10.033_bib24","doi-asserted-by":"crossref","first-page":"1018","DOI":"10.1002\/lt.20204","article-title":"Liver transplantation for acute liver failure from drug induced liver injury in the United States","volume":"10","author":"Russo","year":"2004","journal-title":"Liver Transpl"},{"key":"10.1016\/j.jpeds.2010.10.033_bib25","doi-asserted-by":"crossref","first-page":"1608","DOI":"10.1212\/WNL.47.6.1608","article-title":"Valproate toxicity","volume":"47","author":"Parra","year":"1996","journal-title":"Neurology"},{"key":"10.1016\/j.jpeds.2010.10.033_bib26","doi-asserted-by":"crossref","first-page":"1005","DOI":"10.1111\/j.1528-1157.1994.tb02546.x","article-title":"Severe hepatotoxicity during valproate therapy: an update and report of eight new fatalities","volume":"35","author":"Konig","year":"1994","journal-title":"Epilepsia"},{"key":"10.1016\/j.jpeds.2010.10.033_bib27","doi-asserted-by":"crossref","first-page":"630","DOI":"10.1345\/aph.19242","article-title":"The role of carnitine supplementation during valproic acid therapy","volume":"34","author":"Raskind","year":"2000","journal-title":"Ann Pharmacother"},{"key":"10.1016\/j.jpeds.2010.10.033_bib28","doi-asserted-by":"crossref","first-page":"332","DOI":"10.1111\/j.1528-1157.1993.tb02419.x","article-title":"Valproate (VPA) metabolites in various clinical conditions of probable VPA-associated hepatotoxicity","volume":"34","author":"Siemes","year":"1993","journal-title":"Epilepsia"},{"key":"10.1016\/j.jpeds.2010.10.033_bib29","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1177\/088307389100600102","article-title":"Carnitine, valproate, and toxicity","volume":"6","author":"Coulter","year":"1991","journal-title":"J Child Neurol"},{"key":"10.1016\/j.jpeds.2010.10.033_bib30","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1097\/MOP.0b013e32805e879a","article-title":"Carnitine as an antidote for acute valproate toxicity in children","volume":"19","author":"Russell","year":"2007","journal-title":"Curr Opin Pediatr"},{"key":"10.1016\/j.jpeds.2010.10.033_bib31","doi-asserted-by":"crossref","first-page":"789","DOI":"10.1081\/CLT-120014645","article-title":"Valproic acid toxicity: overview and management","volume":"40","author":"Sztajnkrycer","year":"2002","journal-title":"J\u00a0Toxicol Clin Toxicol"},{"key":"10.1016\/j.jpeds.2010.10.033_bib32","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1016\/S0041-1345(99)00936-7","article-title":"Orthotopic liver transplantation with poor neurologic outcome in valproate-associated liver failure: a need for critical risk-benefit appraisal in the use of valproate","volume":"32","author":"Thomson","year":"2000","journal-title":"Transplant Proc"},{"issue":"Suppl. 2","key":"10.1016\/j.jpeds.2010.10.033_bib33","doi-asserted-by":"crossref","first-page":"SP237","DOI":"10.2131\/jts.34.SP237","article-title":"Children\u2019s toxicology from bench to bed\u2014liver injury (4): mitochondrial respiratory chain disorder and liver disease in children","volume":"34","author":"Murayama","year":"2009","journal-title":"J Toxicol Sci"},{"key":"10.1016\/j.jpeds.2010.10.033_bib34","doi-asserted-by":"crossref","first-page":"706","DOI":"10.1002\/ana.20079","article-title":"POLG mutations associated with Alpers\u2019 syndrome and mitochondrial DNA depletion","volume":"55","author":"Naviaux","year":"2004","journal-title":"Ann Neurol"},{"key":"10.1016\/j.jpeds.2010.10.033_bib35","doi-asserted-by":"crossref","first-page":"1493","DOI":"10.1212\/01.wnl.0000182814.55361.70","article-title":"POLG mutations in Alpers syndrome","volume":"65","author":"Nguyen","year":"2005","journal-title":"Neurology"},{"key":"10.1016\/j.jpeds.2010.10.033_bib36","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1016\/j.jhep.2005.12.026","article-title":"Molecular diagnosis of Alpers syndrome","volume":"45","author":"Nguyen","year":"2006","journal-title":"J Hepatol"},{"key":"10.1016\/j.jpeds.2010.10.033_bib37","doi-asserted-by":"crossref","first-page":"1674","DOI":"10.1093\/brain\/awl088","article-title":"Phenotypic spectrum associated with mutations of the mitochondrial polymerase gamma gene","volume":"129","author":"Horvath","year":"2006","journal-title":"Brain"},{"key":"10.1016\/j.jpeds.2010.10.033_bib38","doi-asserted-by":"crossref","DOI":"10.1002\/hep.23891","article-title":"POLG determines the risk of sodium valproate induced liver toxicity","author":"Stewart","year":"2010","journal-title":"Hepatology"},{"key":"10.1016\/j.jpeds.2010.10.033_bib39","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1186\/cc3742","article-title":"Science review: carnitine in the treatment of valproic acid-induced toxicity\u2014what is the evidence?","volume":"9","author":"Lheureux","year":"2005","journal-title":"Crit Care"},{"key":"10.1016\/j.jpeds.2010.10.033_bib40","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1080\/15563650902752376","article-title":"Carnitine in the treatment of valproic acid-induced toxicity","volume":"47","author":"Lheureux","year":"2009","journal-title":"Clin Toxicol (Phila)"}],"container-title":["The Journal of Pediatrics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0022347610009248?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0022347610009248?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2018,12,6]],"date-time":"2018-12-06T06:26:12Z","timestamp":1544077572000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0022347610009248"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2011,5]]},"references-count":40,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2011,5]]}},"alternative-id":["S0022347610009248"],"URL":"https:\/\/doi.org\/10.1016\/j.jpeds.2010.10.033","relation":{},"ISSN":["0022-3476"],"issn-type":[{"value":"0022-3476","type":"print"}],"subject":[],"published":{"date-parts":[[2011,5]]}}}