title: Valproic acid-associated acute liver failure in children: case report and analysis of liver transplantation outcomes in the United States.
abstract: OBJECTIVE
  To determine whether valproic acid (VPA)-associated acute liver failure (ALF; VPA-ALF) explains the poor outcomes after liver transplantation (LT) in children.
  
  
  METHODS
  Organ Procurement and Transplantation Network data of pediatric patients who underwent LT for VPA-ALF and ALF caused by other drugs (non-VPA-drug-induced acute liver failure [DIALF]) were analyzed. Pre- and post-transplant variables and post-LT survival were compared between VPA-ALF and non-VPA-DIALF.
  
  
  RESULTS
  Seventeen children were transplanted for VPA-ALF. Of the 17 children, 82% died within 1 year of LT. Pre- and post-transplant parameters of VPA versus non-VPA-DIALF were comparable with two exceptions. The median alanine aminotransferase level at transplant was remarkably lower in VPA-ALF compared with non-VPA-DIALF (45 versus 1179 IU/L, P = .004). One-year survival probability was worse in VPA-ALF than non-VPA-DIALF (20% versus 69%, P < .0001). Median post-LT survival time for VPA-ALF was 2.8 months.
  
  
  CONCLUSIONS
  Children who underwent LT for VPA-ALF had a significantly lower survival probability than children with non-VPA-DIALF. Current data suggest that VPA-ALF in children represents an "unmasking" of mitochondrial disease. VPA-ALF should be a contraindication for LT, even in the absence of a documented mitochondrial disease.
authors.affiliation: Department of Medicine, Division of Gastroenterology and Hepatology, University of Maryland School of Medicine, Baltimore, MD, USA. amindiko@medicine.umaryland.edu
authors.forename: Ayse L
authors.initials: AL
authors.lastname: Mindikoglu
authors.forename: Dale
authors.initials: D
authors.lastname: King
authors.forename: Laurence S
authors.initials: LS
authors.lastname: Magder
authors.forename: John A
authors.initials: JA
authors.lastname: Ozolek
authors.forename: George V
authors.initials: GV
authors.lastname: Mazariegos
authors.forename: Benjamin L
authors.initials: BL
authors.lastname: Shneider
mesh_terms: D000293:Adolescent; D000927:Anticonvulsants / Q000506:poisoning / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D004827:Epilepsy / Q000188:drug therapy; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007223:Infant; D017114:Liver Failure, Acute / Q000139:chemically induced* / Q000601:surgery; D016031:Liver Transplantation; D008297:Male; D014481:United States; D014635:Valproic Acid / Q000506:poisoning* / Q000627:therapeutic use
chemical_list: D000927:Anticonvulsants; D014635:Valproic Acid