Liver injury in children: signal analysis of suspected drugs based on the food and drug administration adverse event reporting system
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...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2023-09-01
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| Series: | BMC Pediatrics |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12887-023-04097-9 |
| _version_ | 1797451480205099008 |
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| author | Yan Liu Hailong Li Liang Huang Chaomin Wan Huiqing Wang Xuefeng Jiao Linan Zeng Zhijun Jia Guo Cheng Lei Zhang Wei Zhang Lingli Zhang |
| author_facet | Yan Liu Hailong Li Liang Huang Chaomin Wan Huiqing Wang Xuefeng Jiao Linan Zeng Zhijun Jia Guo Cheng Lei Zhang Wei Zhang Lingli Zhang |
| author_sort | Yan Liu |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-09T14:55:15Z |
| format | Article |
| id | doaj.art-72bd4be3ff204320a9c05a021d2fad86 |
| institution | Directory Open Access Journal |
| issn | 1471-2431 |
| language | English |
| last_indexed | 2024-03-09T14:55:15Z |
| publishDate | 2023-09-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Pediatrics |
| spelling | doaj.art-72bd4be3ff204320a9c05a021d2fad862023-11-26T14:15:31ZengBMCBMC Pediatrics1471-24312023-09-012311910.1186/s12887-023-04097-9Liver injury in children: signal analysis of suspected drugs based on the food and drug administration adverse event reporting systemYan Liu0Hailong Li1Liang Huang2Chaomin Wan3Huiqing Wang4Xuefeng Jiao5Linan Zeng6Zhijun Jia7Guo Cheng8Lei Zhang9Wei Zhang10Lingli Zhang11Department of Pharmacy, West China Second University Hospital, Sichuan UniversityDepartment of Pharmacy, West China Second University Hospital, Sichuan UniversityDepartment of Pharmacy, West China Second University Hospital, Sichuan UniversityKey Laboratory of Birth Defects and Related Diseases of Women and Children, Sichuan University, Ministry of EducationKey Laboratory of Birth Defects and Related Diseases of Women and Children, Sichuan University, Ministry of EducationDepartment of Pharmacy, West China Second University Hospital, Sichuan UniversityDepartment of Pharmacy, West China Second University Hospital, Sichuan UniversityDepartment of Pharmacy, West China Second University Hospital, Sichuan UniversityKey Laboratory of Birth Defects and Related Diseases of Women and Children, Sichuan University, Ministry of EducationCollege of Computer Science, Sichuan UniversityWest China Biomedical Big Data Center, West China Hospital, Sichuan UniversityDepartment of Pharmacy, West China Second University Hospital, Sichuan UniversityAbstract 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.https://doi.org/10.1186/s12887-023-04097-9Liver injuryChildrenSignal analysisPharmacovigilance |
| spellingShingle | Yan Liu Hailong Li Liang Huang Chaomin Wan Huiqing Wang Xuefeng Jiao Linan Zeng Zhijun Jia Guo Cheng Lei Zhang Wei Zhang Lingli Zhang Liver injury in children: signal analysis of suspected drugs based on the food and drug administration adverse event reporting system BMC Pediatrics Liver injury Children Signal analysis Pharmacovigilance |
| title | Liver injury in children: signal analysis of suspected drugs based on the food and drug administration adverse event reporting system |
| title_full | Liver injury in children: signal analysis of suspected drugs based on the food and drug administration adverse event reporting system |
| title_fullStr | Liver injury in children: signal analysis of suspected drugs based on the food and drug administration adverse event reporting system |
| title_full_unstemmed | Liver injury in children: signal analysis of suspected drugs based on the food and drug administration adverse event reporting system |
| title_short | Liver injury in children: signal analysis of suspected drugs based on the food and drug administration adverse event reporting system |
| title_sort | liver injury in children signal analysis of suspected drugs based on the food and drug administration adverse event reporting system |
| topic | Liver injury Children Signal analysis Pharmacovigilance |
| url | https://doi.org/10.1186/s12887-023-04097-9 |
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