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.
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.
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Authors: Michael R Narkewicz; Simon Horslen; Regina M Hardison; Benjamin L Shneider; Norberto Rodriguez-Baez; Estella M Alonso; Vicky L Ng; Mike A Leonis; Kathleen M Loomes; David A Rudnick; Philip Rosenthal; Rene Romero; Girish C Subbarao; Ruosha Li; Steven H Belle; Robert H Squires Journal: Clin Gastroenterol Hepatol Date: 2018-04-30 Impact factor: 11.382