Valproic Acid and the Liver Injury in Patients with Epilepsy: An Update

• Published in: Current pharmaceutical design Vol. 25; no. 3; p. 343
• Main Authors: Guo, Hong-Li, Jing, Xia, Sun, Jie-Yu, Hu, Ya-Hui, Xu, Ze-Jun, Ni, Ming-Ming, Chen, Feng, Lu, Xiao-Peng, Qiu, Jin-Chun, Wang, Tengfei
• Format: Journal Article
• Language: English
• Published: United Arab Emirates 01.01.2019
• Subjects: Anticonvulsants - adverse effects; Anticonvulsants - therapeutic use; Antioxidants - therapeutic use; Carnitine - therapeutic use; Chemical and Drug Induced Liver Injury; Epilepsy; Humans; Liver - drug effects; Liver - pathology; Valproic Acid - adverse effects; Valproic Acid - therapeutic use; genetic variants; liver injury; management; glucuronic acid conjugation; β-oxidation; antiepileptic treatment; Valproic acid; oxidative stress
• DOI: 10.2174/1381612825666190329145428

Valproic acid (VPA) as a widely used primary medication in the treatment of epilepsy is associated with reversible or irreversible hepatotoxicity. Long-term VPA therapy is also related to increased risk for the development of non-alcoholic fatty liver disease (NAFLD). In this review, metabolic elimination pathways of VPA in the liver and underlying mechanisms of VPA-induced hepatotoxicity are discussed. We searched in PubMed for manuscripts published in English, combining terms such as "Valproic acid", "hepatotoxicity", "liver injury", and "mechanisms". The data of screened papers were analyzed and summarized. The formation of VPA reactive metabolites, inhibition of fatty acid β-oxidation, excessive oxidative stress and genetic variants of some enzymes, such as CPS1, POLG, GSTs, SOD2, UGTs and CYPs genes, have been reported to be associated with VPA hepatotoxicity. Furthermore, carnitine supplementation and antioxidants administration proved to be positive treatment strategies for VPA-induced hepatotoxicity. Therapeutic drug monitoring (TDM) and routine liver biochemistry monitoring during VPA-therapy, as well as genotype screening for certain patients before VPA administration, could improve the safety profile of this antiepileptic drug.