Risk factor for hepatotoxicity in epileptic children with long-term AEDs treatment: A comprehensive analysis

Background and objectives. The use of antiepileptic drugs (AEDs) is often required for extended periods in pediatric patients. However, there is a risk of hepatotoxicity associated with AED use. This study aimed to identify the risk factors that contribute to liver injury in pediatric patients with epilepsy who are treated with AEDs. Materials and methods. This case-control study was conducted at the Pediatric Neurology outpatient clinic of Dr. Soetomo General Hospital in Surabaya, Indonesia, from May to July 2023. Demographic characteristics, epilepsy types, and medications were recorded for 66 children aged 1–18 years who had received AEDs, either as monotherapy or polytherapy, along with liver function tests. Epileptic children with hepatotoxicity were designated as the case group, while those without hepatotoxicity comprised the control group. Collected data were presented descriptively and analyzed using logistic regression, with statistical significance set at p < 0.05 for the two-tailed test. Results. Hepatotoxicity occurred in 31 out of 66 (46.9%) patients. Bivariate analysis revealed that treatment duration (p = 0.014) and phenytoin use (p = 0.002) significantly affected the occurrence of hepatotoxicity in epileptic children. Logistic regression analysis showed that AED treatment durations of >5 years but less than 10 years (OR = 14.00; 95% CI 1.385– 141.48; p = 0.025), phenytoin use (OR = 9.654; 95% CI 2.785–33.465; p < 0.001), and phenobarbital use (OR = 6.573; 95% CI 1.579–27.360; p = 0.01) were significantly correlated with hepatotoxicity. Meanwhile, age, nutritional status, epilepsy type and syndrome, and the incidence of intractable epilepsy were not significant risk factors for the occurrence of hepatotoxicity in children. Conclusions. The duration of AED treatment and the type of AED used are significant risk factors for hepatotoxicity in pediatric epilepsy. Regular monitoring of hepatic enzyme levels is strongly recommended during prolonged AED therapy to mitigate the risk of liver injury.