Correlation between Level of Serum Transaminases and Duration of Antiepileptic Drugs in Epilepsy Children in Sanglah Hospital

I Gusti Ngurah Made Suwarba; Anak Agung Ratna Purnama Santhi; Dewi Sutriani Mahalini

doi:10.3889/oamjms.2022.7736

Authors

I Gusti Ngurah Made Suwarba Department of Child Health
Anak Agung Ratna Purnama Santhi Department of Child Health, Medical Faculty, Udayana University, Denpasar, Bali, Indonesia
Dewi Sutriani Mahalini Department of Child Health, Medical Faculty, Udayana University, Denpasar, Bali, Indonesia

DOI:

https://doi.org/10.3889/oamjms.2022.7736

Keywords:

Serum transaminases, Antiepileptic, Duration, Children, Epilepsy

Abstract

BACKGROUND: Some antiepileptic drugs (AEDs), particularly sodium valproate, phenytoin, phenobarbital, and carbamazepine induce and increase production of hepatic enzymes. The adverse metabolic effects of AEDs treatments have become main concern, however data about evaluation of serum transaminases and duration of AEDs in Indonesia still limited.

AIM: The aim of the study was to investigate correlation of AEDs and serum transaminases in children with epilepsy.

METHODS: This cross-sectional research was conducted in pediatric neurology outpatient clinic in Sanglah Hospital. The target was children with epilepsy who had taken AEDs for at least 6 months. Data were collected from January 2020 to the number of samples were achieved. The exclusion criteria were concomitant liver disease, taking drugs which induce elevated serum transaminase or alcohol abuse. Data including age, gender, nutritional status, type, and duration of AEDs were obtained from medical record. Correlation was analyzed by Pearson’s or Spearman’s correlation, p < 0.05 was considered significant.

RESULTS: Total 148 epileptic children enrolled in this study. Aspartate transaminase (AST) and alanine aminotransferase (ALT) level were highest in the group receiving combination therapy (34.37 ± 24.9 U/L and 35.96 ± 23.3 U/L). There was a significant negative correlation between duration of carbamazepine and AST (r = –0.723, p = 0.0001) and ALT (r = –0.457, p = 0.009), as well as duration of valproic acid with AST and ALT (r = –0.689 and –0.677, p = 0.0001). Duration of phenobarbital administration was positively correlated with AST and ALT (r = 0.546 and 0.425, p = 0.0001). Combination therapy also had positive correlation with AST and ALT (r = 0.815 and 0.781, p = 0.0001, respectively).

CONCLUSION: Duration administration of carbamazepine and valproic acid had negative correlation with AST and ALT; however, phenobarbital and combination therapy were positively correlated with AST and ALT.

Downloads

Download data is not yet available.

Metrics

Metrics Loading ...

Plum Analytics Artifact Widget Block

References

Aaberg KM, Gunnes N, Bakken IJ, Soraas CL, Berntsen A, Magnus P, et al. Incidence and prevalence of childhood epilepsy: A nationwide cohort study. Pediatrics. 2017;139(5):e20163908. https://doi.org/10.1542/peds.2016-3908 PMid:28557750 DOI: https://doi.org/10.1542/peds.2016-3908

Farghaly WM, Elhamed MA, Hassan EM, Soliman WT, Yhia MA, Hamdy NA. Prevalence of Childhood and Adolescence Epilepsy in Upper Egypt (dessert areas). Egyptian J Neurol Psychiatry Neurosurg. 2018;54(1):34. https://doi.org/10.1186/s41983-018-0032-0 PMid:30532513 DOI: https://doi.org/10.1186/s41983-018-0032-0

Andrianti PT, Gunawan PI, Hoesin F. Pediatric epilepsy profile and the success of treatment at dr. soetomo hospital year 2013. Sari Pediatri. 2016;18(1):34-9. DOI: https://doi.org/10.14238/sp18.1.2016.34-39

Suwarba IGNM. Incidence and clinical characteristics of epilepsy in children. Sari Pediatri. 2011;13(2):123-8.

Rosati A, De Masi S, Guerrini R. Antiepileptic drug treatment in children with epilepsy. CNS Drugs. 2015;29(10):847-63. https://doi.org/10.1007/s40263-015-0281-8 PMid:26400189 DOI: https://doi.org/10.1007/s40263-015-0281-8

Verrotti A, Lapadre G, Di Donato G, Di Francesco L, Zagaroli L, Matricardi S, et al. Pharmacokinetic considerations for antiepileptic drugs in children. Expert Opin Drug Metab Toxicol. 2019;15(3):199-211. https://doi.org/10.1080/17425255.2019.1575361 PMid:30689454 DOI: https://doi.org/10.1080/17425255.2019.1575361

Bengleil MS, Sherif FM. Pattern of anti-epileptic drug use in Libyan children and their effects on serum transaminase activities. J Pharmacol Pharm Res. 2018;1(1):1-4.

Vidaurre J, Gedela S, Yarosz S. Antiepileptic drugs and liver disease. Pediatr Neurol. 2017;77:23-36. https://doi.org/10.1016/j.pediatrneurol.2017.09.013 PMid:29097018 DOI: https://doi.org/10.1016/j.pediatrneurol.2017.09.013

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. PMid:28974841

Adepapo AD, Demaki WE, Lagunju I. Non-dose-dependent changes in serum transaminase levels of children with epilepsy on treatment with sodium valproate. Dose Response. 2020;18(2):1559325820918445. https://doi.org/10.1177/1559325820918445 PMid:32362796 DOI: https://doi.org/10.1177/1559325820918445

O’Hare JA, Duggan B, O’Driscoll D, Callaghan N. Biochemical evidence for osteomalacia with carbamazepine therapy. Acta Neurol Scand. 1980;62(5):282-6. https://doi.org/10.1111/j.1600-0404.1980.tb03037.x PMid:7468150 DOI: https://doi.org/10.1111/j.1600-0404.1980.tb03037.x

Bjornsson E. Hepatotoxicity associated with antiepileptic drugs. Acta Neurol Scand. 2008;118(5):281-90. https://doi.org/10.1111/j.1600-0404.2008.01009.x PMid:18341684 DOI: https://doi.org/10.1111/j.1600-0404.2008.01009.x

Hussein RR, Soliman RH, Ali AM, Tawfeik MH, Abdelrahim ME. Effect of antiepileptic drugs on serum transaminase. Beni Suef Univ J Basic Appl Sci. 2013;2(1):14-9.

Huang YL, Hong HS, Wang ZW, Kuo TT. Fatal sodium valproateinduced hypersensitivity syndrome with lichenoid dermatitis and fulminant hepatitis. J Am Acad Dermatol. 2003;49(2):316-9. https://doi.org/10.1067/s0190-9622(03)00748-5 PMid:12894087 DOI: https://doi.org/10.1067/S0190-9622(03)00748-5

Star K, Edwards IR, Choonara I. Valproic acid and fatalities in children: A review of individual case safety reports in VigiBase. PLoS One. 2014;9(10):e108970. https://doi.org/10.1371/journal.pone.0108970 PMid:25302991 DOI: https://doi.org/10.1371/journal.pone.0108970

Sridharan K, Daylami AA, Ajjawi R, Ajooz HA. Drug-induced liver injury in critically ill children taking antiepileptic drugs: A retrospective study. Curr Ther Res Clin Exp. 2020;92:100580. https://doi.org/10.1016/j.curtheres.2020.100580 PMid:32280391 DOI: https://doi.org/10.1016/j.curtheres.2020.100580

George M, Joseph L, Jose PC. A review article on assessing the effect of antiepileptics and statins on serum transaminase in epileptic patients. Pharm J. 2016;5(3):11-4.

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. https://doi.org/10.3390/jcm10061153 PMid:33801850 DOI: https://doi.org/10.3390/jcm10061153

Gopaul S, Farrell K, Abbott F. Effects of age and polytherapy, risk factors of valproic acid (VPA) hepatotoxicity, on the excretion of thiol conjugates of (E)2,4-diene VPA in people with epilepsy taking VPA. Epilepsia. 2003;44(3):322-8. https://doi.org/10.1046/j.1528-1157.2003.07202.x PMid:12614387 DOI: https://doi.org/10.1046/j.1528-1157.2003.07202.x

Sonmez FM, Demir E, Orem A, Yildirmis S, Orhan F, et al. Effect of antiepileptic drugs on plasma lipids, lipoprotein (A), and liver enzymes. J Child Neurol. 2006;21(1):70-4. PMid:16551457

Craig S. Phenytoin poisoning. Neurocrit Care. 2005;3(2):161-70. https://doi.org/10.1385/NCC:3:2:161 PMid:16174888 DOI: https://doi.org/10.1385/NCC:3:2:161

Meythaler JM, Hazlewood J, DeVivo MJ, Rosner M. Elevated liver enzymes after non-traumatic intracranial hemorrhages. Arch Phys Med Rehabil. 1998;79(7):766-71. https://doi.org/10.1016/s0003-9993(98)90354-9 PMid:9685089 DOI: https://doi.org/10.1016/S0003-9993(98)90354-9

Perucca E. Clinically relevant drug interactions with antiepileptic drugs. Br J Clin Pharmacol. 2006;61(3):246-55. https://doi.org/10.1111/j.1365-2125.2005.02529.x PMid:16487217 DOI: https://doi.org/10.1111/j.1365-2125.2005.02529.x

Foster GR, Goldin RD, Freeth CJ, Nieman E, Oliveira DB. Liver damage in long-term anticonvulsant therapy: A serological and histological study Q. J Med. 1991;79:315-22.

Rao BS. Comparative effect of single and poly therapy on serum transaminase in epileptic patients under long-term treatment. J NIMHANS. 1995;13:141-6.

Hussein A, Abdulgalil A, Omer F, Eltoum H, Hamad A, El-Adil O, et al. Correlation between serum level of antiepileptic drugs and their side effects. Oman Med J. 2010;25(1):17-21. https://doi.org/10.5001/omj.2010.5 PMid:22125692 DOI: https://doi.org/10.5001/omj.2010.5

Buzzetti E, Parikh PM, Gerussi A, Tsochatzis E. Gender differences in liver disease and the drug-dose gender gap. Pharmacol Res. 2017;120:97-108. https://doi.org/10.1016/j.phrs.2017.03.014 PMid:28336373 DOI: https://doi.org/10.1016/j.phrs.2017.03.014

Pirmohamed M, Leeder SJ. Anticonvulsant agents. In: Kaplowitz N, DeLeve LD, editors. Drug-induced Liver Disease. 3rd ed. Amsterdam: Elsevier; 2013. p. 423-42.

Walia KS, Khan EA, Ko DH, Raza SS, Khan YN. Side effects of antiepileptics a review. Pain Pract. 2004;4(3):194-203. https://doi.org/10.1111/j.1533-2500.2004.04304.x PMid:17173601 DOI: https://doi.org/10.1111/j.1533-2500.2004.04304.x