Effects of Valproate, Carbamazepine, and Levetiracetam Monotherapy on Liver Enzyme Levels in Children with Epilepsy: A Retrospective Observational Study

Abstract

Antiseizure medications (ASMs) are widely used in childhood epilepsy, and some are associated with alterations in liver enzyme levels, making biochemical monitoring an important component of follow-up. The aim of this study was to evaluate and compare the effects of valproate, carbamazepine, and levetiracetam monotherapy on aspartate aminotransferase (AST/GOT), alanine aminotransferase (ALT/GPT), and gamma-glutamyl transferase (GGT) in children with epilepsy. This retrospective observational study was conducted at the outpatient clinic of Tripoli University Hospital, Libya, from January 2023 to March 2026. It included 120 children aged 1 to 14 years at diagnosis (76 females, 44 males) with normal baseline GOT, GPT, and GGT, treated with valproate (n=45), carbamazepine (n=40), or levetiracetam (n=35) monotherapy and followed for 6 to 24 months. Enzyme results were classified as normal or elevated according to age- and sex-specific reference ranges. Groups were compared using the chi-square or Fisher's exact test. Liver enzyme abnormalities were found in 15 of 45 children (33.3%) on valproate, 19 of 40 (47.5%) on carbamazepine, and 4 of 35 (11.4%) on levetiracetam. GOT elevation was the most frequent abnormality with valproate (8 children), while GOT and GGT elevations were equally frequent with carbamazepine (6 children each). No GGT elevation occurred with levetiracetam, and the four affected children had mild GOT (2) or GPT (2) elevations. The difference in the overall frequency of abnormalities between groups was statistically significant (chi-square, p=0.003). Mild liver enzyme elevations occurred in all three groups, least often with levetiracetam, which had no GGT elevations. Because of the retrospective design and limited sample size, these findings should be confirmed in larger prospective studies that account for dose, duration, and clinical liver injury.