Drug-Induced Liver Injury-Pharmacological Spectrum Among Children

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2025 Mar 13

PMID 40076629

Authors

Bianca Raluca Maris

Alina Grama

Tudor Lucian Pop

Affiliations

Soon will be listed here.

Abstract

Drug-induced liver injury (DILI) is one of the main causes of acute liver failure in children. Its incidence is probably underestimated, as specific diagnostic tools are currently lacking. Over 1000 known drugs cause DILI, and the list is expanding. The aim of this review is to describe DILI pathogenesis and emphasize the drugs accountable for child DILI in order to aid its recognition. Intrinsic DILI is well described in terms of mechanism, incriminated drugs, and toxic dose. Conversely, idiosyncratic DILI (iDILI) is unpredictable, occurring as a result of a particular response to drug administration, and its occurrence cannot be foreseen in clinical studies. Half of pediatric iDILI cases are linked to antibiotics, mostly amoxicillin-clavulanate, in the immune-allergic group, while autoimmune DILI is the hallmark of minocycline and nitrofurantoin. Secondly, antiepileptics are responsible for 20% of pediatric iDILI cases, children being more prone to iDILI caused by these agents than adults. A similar tendency was observed in anti-tuberculosis drugs, higher incidences being reported in children below three years old. Current data show growing cases of iDILI related to antineoplastic agents, atomoxetine, and albendazole, so that it is advisable for clinicians to maintain a high index of suspicion regarding iDILI.

References

Uetrecht J, Naisbitt D . Idiosyncratic adverse drug reactions: current concepts. Pharmacol Rev. 2013; 65(2):779-808. PMC: 3639727. DOI: 10.1124/pr.113.007450. View

Stine J, Lewis J . Current and future directions in the treatment and prevention of drug-induced liver injury: a systematic review. Expert Rev Gastroenterol Hepatol. 2015; 10(4):517-36. PMC: 5074808. DOI: 10.1586/17474124.2016.1127756. View

Bessone F, Hernandez N, Tagle M, Arrese M, Parana R, Mendez-Sanchez N . Drug-induced liver injury: A management position paper from the Latin American Association for Study of the liver. Ann Hepatol. 2021; 24:100321. DOI: 10.1016/j.aohep.2021.100321. View

Stojanovski S, Casavant M, Mousa H, Baker P, Nahata M . Atomoxetine-induced hepatitis in a child. Clin Toxicol (Phila). 2007; 45(1):51-5. DOI: 10.1080/15563650600795644. View

Bilenko N, Tessler H, Okbe R, Press J, Gorodischer R . Determinants of antipyretic misuse in children up to 5 years of age: a cross-sectional study. Clin Ther. 2006; 28(5):783-93. DOI: 10.1016/j.clinthera.2006.05.010. View

Wolraich M, Hagan Jr J, Allan C, Chan E, Davison D, Earls M . Clinical Practice Guideline for the Diagnosis, Evaluation, and Treatment of Attention-Deficit/Hyperactivity Disorder in Children and Adolescents. Pediatrics. 2019; 144(4). PMC: 7067282. DOI: 10.1542/peds.2019-2528. View

Bjornsson E, Medina-Caliz I, Andrade R, Lucena M . Setting up criteria for drug-induced autoimmune-like hepatitis through a systematic analysis of published reports. Hepatol Commun. 2022; 6(8):1895-1909. PMC: 9315110. DOI: 10.1002/hep4.1959. View

Thangaraju P, Varthya S, Guruthalingam M, Venkatesan S . Cephalosporin's induced hepatic enzyme derangement - An educational report. J Family Med Prim Care. 2020; 9(4):2143-2145. PMC: 7346957. DOI: 10.4103/jfmpc.jfmpc_1133_19. View

Ramadori G, Cameron S . Effects of systemic chemotherapy on the liver. Ann Hepatol. 2010; 9(2):133-43. View

10.

Andrade R, Chalasani N, Bjornsson E, Suzuki A, Kullak-Ublick G, Watkins P . Drug-induced liver injury. Nat Rev Dis Primers. 2019; 5(1):58. DOI: 10.1038/s41572-019-0105-0. View

11.

Hauk L . Acne Vulgaris: Treatment Guidelines from the AAD. Am Fam Physician. 2017; 95(11):740-741. View

12.

Niu H, Atallah E, Alvarez-Alvarez I, Medina-Caliz I, Aithal G, Arikan C . Therapeutic Management of Idiosyncratic Drug-Induced Liver Injury and Acetaminophen Hepatotoxicity in the Paediatric Population: A Systematic Review. Drug Saf. 2022; 45(11):1329-1348. PMC: 9560995. DOI: 10.1007/s40264-022-01224-w. View

13.

Clemens V, Regen F, Le Bret N, Heuser I, Hellmann-Regen J . Anti-inflammatory effects of minocycline are mediated by retinoid signaling. BMC Neurosci. 2018; 19(1):58. PMC: 6151010. DOI: 10.1186/s12868-018-0460-x. View

14.

Kim H, Yang H, Kim S, Park J . Ibuprofen associated acute vanishing bile duct syndrome and toxic epidermal necrolysis in an infant. Yonsei Med J. 2014; 55(3):834-7. PMC: 3990079. DOI: 10.3349/ymj.2014.55.3.834. View

15.

Delungahawatta T, Pokharel A, Paz R, Haas C . Topical Diclofenac-Induced Hepatotoxicity. J Community Hosp Intern Med Perspect. 2023; 13(3):108-112. PMC: 10593164. DOI: 10.55729/2000-9666.1190. View

16.

Qin F, Sang G, Zou X, Cheng D . Drug-Induced Liver Injury during Consolidation Therapy in Childhood Acute Lymphoblastic Leukemia as Assessed for Causality Using the Updated RUCAM. Can J Gastroenterol Hepatol. 2022; 2022:5914593. PMC: 8970867. DOI: 10.1155/2022/5914593. View

17.

Mak A, Uetrecht J . Immune mechanisms of idiosyncratic drug-induced liver injury. J Clin Transl Res. 2019; 3(1):145-156. PMC: 6410666. View

18.

Kataria A, Stolow E, Hubbard H . Pantoprazole-induced acute hepatocellular and cholestatic hepatitis. Postgrad Med J. 2020; 98(1155):11-12. DOI: 10.1136/postgradmedj-2020-138838. View

19.

Ferrajolo C, Capuano A, Verhamme K, Schuemie M, Rossi F, Stricker B . Drug-induced hepatic injury in children: a case/non-case study of suspected adverse drug reactions in VigiBase. Br J Clin Pharmacol. 2010; 70(5):721-8. PMC: 2997312. DOI: 10.1111/j.1365-2125.2010.03754.x. View

20.

Laman M, Tavul L, Karl S, Kotty B, Kerry Z, Kumai S . Mass drug administration of ivermectin, diethylcarbamazine, plus albendazole compared with diethylcarbamazine plus albendazole for reduction of lymphatic filariasis endemicity in Papua New Guinea: a cluster-randomised trial. Lancet Infect Dis. 2022; 22(8):1200-1209. PMC: 9300473. DOI: 10.1016/S1473-3099(22)00026-3. View