A comparative study on the effect of sodium valproate therapy on liver enzyme levels in children with seizure disorder compared to other antiepileptic drugs
DOI:
https://doi.org/10.18203/2349-3291.ijcp20253779Keywords:
Levetiracetam, Liver enzymes, Phenytoin, Sodium valproateAbstract
Background: Sodium valproate is a commonly prescribed antiepileptic drug known for its effectiveness in controlling seizures in pediatric patients but is also associated with concerns over altered liver enzyme levels and rarely hepatotoxicity. Comparisons with other antiepileptic drugs are essential to understand their relative impacts on hepatic function in children with seizure disorder.
Methods: A prospective study was conducted in the department of paediatrics at the Government Cuddalore Medical College Hospital over a one-year period, enrolling children aged 1 to 12 years diagnosed with seizure disorder and on sodium valproate, phenytoin or levetiracetam therapy. Liver function was assessed by measuring serum glutamic oxaloacetic transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT), and alkaline phosphatase (ALP) measured at baseline and after 12 months. Inclusion and exclusion criteria ensured well-defined cohorts, and enzyme levels were measured using standard clinical laboratory techniques. Data was collected via structured proforma and analysed by SPSS version 25 software.
Results: Among the 40 recruited children, those receiving sodium valproate demonstrated significant elevations in SGOT, SGPT, and ALP levels after one year of therapy. In contrast, children receiving levetiracetam showed increased ALP levels only, while no significant changes were observed in the phenytoin group. Statistical analysis confirmed the significance of these findings, underscoring sodium valproate’s stronger association with hepatic enzyme elevation compared to the other drugs.
Conclusions: The study indicates that sodium valproate therapy in children with seizure disorder is associated with significant elevations in liver enzyme levels compared to phenytoin and levetiracetam. Regular liver function monitoring, particularly before and at six-month intervals during sodium valproate therapy, is recommended to detect early signs of hepatotoxicity.
Metrics
References
Kliegman RM, Stanton BF, St. Geme JW, Schor NF, Behrman RE. eds. Seizures in Childhood. In: Nelson Textbook of pediatrics. 22nd ed, Vol. 2. Elsevier; 2024.
Divya P, Kumar RS, Lakshmi V, Kalpana S. Effect of antiepileptic drugs on serum lipid profile among children with epilepsy at a tertiary care hospital, Chennai, India. J Clin Diagn Res. 2022;16(9). DOI: https://doi.org/10.7860/JCDR/2022/56275.16973
Hadzagic-Catibusic F, Hasanbegovic E, Melunovic M, Zubcevic S, Uzicanin S. Effects of carbamazepine and valproate on serum aspartate aminotransferase, alanine aminotransferase and gamma- glutamyltransferase in children. Med Arch. 2017;71(4):239-42. DOI: https://doi.org/10.5455/medarh.2017.71.239-242
Wang L, Li H, Zeng G, Shi L, Zhu M, Luo J, et al. Correlation of GSTP1 rs1695 and CAT rs769217 with elevated AST induced by valproate sodium in Chinese children with epilepsy. Pak J Pharm Sci. 2021;34(5):1759-66.
Sridharan K, Daylami AA, Ajjawi R, Ajooz HAMA. Drug-induced liver injury in critically ill children taking antiepileptic drugs: a retrospective study. Curr Ther Res Clin Exp. 2020;92:100580. DOI: https://doi.org/10.1016/j.curtheres.2020.100580
Vafaee-Shahi M, Soheilipour F, Mohagheghi P, Riahi A, Borghei NS, Taleb, A. Effect of sodium valproate on weight, body mass index, uric acid, vitamin D3, blood insulin, and serum lipid profile in children. Open Neurol J. 2022;16:e2202070. DOI: https://doi.org/10.2174/1874205X-v16-e2202070
Adedapo ADA, Demaki WE, Lagunju I. Non-dose-dependent changes in liver enzyme levels of children with epilepsy on treatment with sodium valproate. Dose Resp. 2020;18(2):1559325820918445. DOI: https://doi.org/10.1177/1559325820918445
Mahgoub A, Abdoun M, Azam S, Babiker R. Effect of carbamazepine and sodium valproate on liver enzymes of epileptic children. Dr. Sulaiman Al Habib Med J. 2020;2(3):123-7. DOI: https://doi.org/10.2991/dsahmj.k.210719.002
Huang YT, Huang YM, Kung FL, Lin CJ, Jao T, Ho YF. Physiologically based mechanistic insight into differential risk of valproate hepatotoxicity between children and adults: A focus on ontogeny impact. CPT Pharmacomet Syst Pharmacol. 2023;12(12):1960-71. DOI: https://doi.org/10.1002/psp4.13045
Amini-Shirazi N, Ghahremani MH, Ahmadkhaniha R, Mandegary A, Dadgar A, Abdollahi M, et al. Influence of CYP2C9 polymorphism on metabolism of valproate and its hepatotoxin metabolite in Iranian patients. Toxicol Mech Methods. 2010;20(8):452-7. DOI: https://doi.org/10.3109/15376516.2010.497977
Meseguer ES, Elizalde MU, Borobia AM, Ramírez E. Valproic acid-induced liver injury: a case-control study from a prospective pharmacovigilance program in a tertiary hospital. J Clin Med. 2021;10(6):1153. DOI: https://doi.org/10.3390/jcm10061153
Shi Q, Yang X, Greenhaw JJ, Salminen AT, Russotti GM, Salminen WF. Drug-induced liver injury in children: clinical observations, animal models, and regulatory status. Int J Toxicol. 2017;36(5):365-79. DOI: https://doi.org/10.1177/1091581817721675
Dehury S, Patro P, Sahu L, Nayak L, Mallik AK. Evaluation of metabolic parameters on use of newer antiepileptics conventional antiepileptics in patients of generalised tonic-clonic seizure: an observational study. Cureus. 2023;15(2):e35181. DOI: https://doi.org/10.7759/cureus.35181
Pathak SM, Ziechmann R, Menzer J, Hoeft A, Villanueva P. Discontinuation of levetiracetam and valproic acid due to adverse effects in early post-traumatic seizure prophylaxis. Cureus. 2023;15(10):e47742. DOI: https://doi.org/10.7759/cureus.47742
Downloads
Published
How to Cite
Issue
Section
