Valproic Acid-Associated Acute Liver Failure in Children: Case Report and Analysis of Liver Transplantation Outcomes in the United States

Objective To determine whether valproic acid (VPA)-associated acute liver failure (ALF; VPA-ALF) explains the poor outcomes after liver transplantation (LT) in children. Study design Organ Procurement and Transplantation Network data of pediatric patients who underwent LT for VPA-ALF and ALF caused...

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Bibliographic Details
Published in:The Journal of pediatrics 2011-05, Vol.158 (5), p.802-807
Main Authors: Mindikoglu, Ayse L., MD, MPH, King, Dale, MD, Magder, Laurence S., PhD, MPH, Ozolek, John A., MD, Mazariegos, George V., MD, Shneider, Benjamin L., MD
Format: Article
Language:English
Subjects:
Adolescent
alanine transaminase
Anticonvulsants - poisoning
Anticonvulsants - therapeutic use
case studies
Child
Child, Preschool
children
Epilepsy - drug therapy
Female
Follow-Up Studies
Humans
Infant
liver failure
Liver Failure, Acute - chemically induced
Liver Failure, Acute - surgery
liver transplant
Liver Transplantation
Male
patients
Pediatrics
probability
United States
valproic acid
Valproic Acid - poisoning
Valproic Acid - therapeutic use
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Summary:Objective To determine whether valproic acid (VPA)-associated acute liver failure (ALF; VPA-ALF) explains the poor outcomes after liver transplantation (LT) in children. Study design 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. Conclusion 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.
ISSN:0022-3476
1097-6833
DOI:10.1016/j.jpeds.2010.10.033