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BMC Pediatrics
Published in: BMC Pediatrics 1/2023

Open Access 01-12-2023 | Acetylcysteine | Research

Liver injury in children: signal analysis of suspected drugs based on the food and drug administration adverse event reporting system

Authors: Yan Liu, Hailong Li, Liang Huang, Chaomin Wan, Huiqing Wang, Xuefeng Jiao, Linan Zeng, Zhijun Jia, Guo Cheng, Lei Zhang, Wei Zhang, Lingli Zhang

Published in: BMC Pediatrics | Issue 1/2023

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Abstract

Background

Evidence of drug-induced liver injury is abundant in adults but is lacking in children. Our aim was to identify suspected drug signals associated with pediatric liver injury.

Methods

Hepatic adverse events (HAEs) among children reported in the Food and Drug Administration Adverse Event Reporting System were analyzed. A descriptive analysis was performed to summarize pediatric HAEs, and a disproportionality analysis was conducted by evaluating reporting odds ratios (RORs) and proportional reporting ratios to detect suspected drugs.

Results

Here, 14,143 pediatric cases were reported, specifically 49.6% in males, 45.1% in females, and 5.2% unknown. Most patients (68.8%) were 6–18 years old. Hospitalization ranked first among definite outcomes (7,207 cases, 37.2%). In total, 264 disproportionate drug signals were identified. The top 10 drugs by the number of reports were paracetamol (1,365; ROR, 3.6; 95% confidence interval (CI), 3.4–3.8), methotrexate (878; ROR, 2.5; 95% CI, 2.3–2.7), vincristine (649; ROR, 3.0; 95% CI, 2.8–3.3), valproic acid (511; ROR, 3.2; 95% CI, 2.9–3.6), cyclophosphamide (490; ROR, 2.4; 95% CI, 2.2–2.6), tacrolimus (427; ROR, 2.4; 95% CI, 2.2–2.7), prednisone (416; ROR, 2.1; 95% CI, 1.9–2.3), prednisolone (401; ROR, 2.3; 95% CI, 2.1–2.5), etoposide (378; ROR, 2.3; 95% CI, 2.1–2.6), and cytarabine (344; ROR, 2.8; 95% CI, 2.5–3.2). After excluding validated hepatotoxic drugs, six were newly detected, specifically acetylcysteine, thiopental, temazepam, nefopam, primaquine, and pyrimethamine.

Conclusions

The hepatotoxic risk associated with 264 signals needs to be noted in practice. The causality of hepatotoxicity and mechanism among new signals should be verified with preclinical and clinical studies.
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Metadata
Title
Liver injury in children: signal analysis of suspected drugs based on the food and drug administration adverse event reporting system
Authors
Yan Liu
Hailong Li
Liang Huang
Chaomin Wan
Huiqing Wang
Xuefeng Jiao
Linan Zeng
Zhijun Jia
Guo Cheng
Lei Zhang
Wei Zhang
Lingli Zhang
Publication date
01-12-2023
Publisher
BioMed Central
Published in
BMC Pediatrics / Issue 1/2023
Electronic ISSN: 1471-2431
DOI
https://doi.org/10.1186/s12887-023-04097-9

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