Analysis of Immunogenetic Factors in Idiosyncratic Drug‐induced Liver Injury in the Pediatric Population

Ocete-Hita, Esther; Salmerón-Fernández, MaJ.; Urrutia-Maldonado, Emilia; Muñoz-de-Rueda, Paloma; Salmerón-Ruiz, María Angustias; Martinez-Padilla, MaC.; Ruiz-Extremera, Ángeles

doi:10.1097/mpg.0000000000001502

Cited by 14 publications

(11 citation statements)

References 34 publications

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“…They found that the children with the HLA-DQA0102 and HLA-DR*12 markers had more frequently DILI, suggesting their possible use as a genetic risk factor. In contrast, HLA-C0401 and HLA-DQB0603 markers were more likely to be seen in the control patients without evidence of DILI, suggesting a possible hepato-protective effect with these HLA haplotypes (Ocete-Hita et al, 2017).…”

Section: Major Histocompatibility Complexmentioning

confidence: 80%

Drug-Induced Liver Injury: Biomarkers, Requirements, Candidates, and Validation

Meunier

Larrey

2019

Front. Pharmacol.

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The hepatotoxicity of drugs is the main cause of drug withdrawal from the pharmaceutical market and interruption of the development of new molecules. Biomarkers are useful in several situations. In case of suspected drug-induced liver injury (DILI), biomarkers can be used to confirm liver damage, its severity, prognosis, confirm drug causality, or define the type of DILI. In this review, we will first present the currently used biomarkers and candidate biomarkers for the future. The current biomarkers are certainly very helpful including with the assistance of diagnostic method such the Roussel Uclaf Causality Assessment Method, but provide a limited information for the early detection of liver injury, the role of specific drug and the prediction of DILI. Some biomarkers are promising but they are not yet available for routine use. Studies are still needed to confirm their interest, particularly in comparison to Roussel Uclaf Causality Assessment Method.

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Section: Major Histocompatibility Complexmentioning

confidence: 80%

Drug-Induced Liver Injury: Biomarkers, Requirements, Candidates, and Validation

Meunier

Larrey

2019

Front. Pharmacol.

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“…Third, subjective bias existed when the drugs were assessed by RUCAM. Throughout the study, most of the research focused on DILI in patients during hospitalization [18,27];thus, our research on outpatients is de cient.…”

Section: Discussionmentioning

confidence: 99%

Drug-Induced Hepatic Injury in Newborns and Children in Intensive Care Unit: A Retrospective Study of China

Guo

Feng

et al. 2021

Preprint

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Purpose Drug-induced liver injury (DILI) is a common adverse reaction in the clinic; however, there are relatively few reports of DILI in critically ill newborns and children. Making use of the Pediatric Intensive Care database (PIC), this study identifies which drugs are related to DILI in neonates and children in China. Methods Using the PIC, we screened for patients whose liver was suspected of being injured by drugs during hospitalization. The medicine they used was then assessed by the Roussel Uclaf Causality Assessment Method (RUCAM). We also collated drug combinations that may affect CYP enzyme metabolism, which may be one of the mechanisms that lead to DILI. Results A total of 13,449 patients were assessed, of whom 77 newborns and 261 children were finally included. The main type of liver injury in neonates was mixed (83.1%), while children’s hepatic injury types were mostly distributed between hepatocellular (59.4%) and cholestatic (28.4%). In terms of the assessment by the RUCAM, in newborns, the drugs that were most considered to cause or associated with hepatic injury comprised medium and long chain fat emulsion (17%), sodium glycerophosphate (12%) and meropenem (9%); while omeprazole (11%), methylprednisolone sodium succinate (10%) and meropenem (8%) are the primary culprit of DILI in children. Drug combinations that may affect CYP enzyme metabolism frequently seen in neonates are omeprazole + budesonide (16.9%), dexamethasone + midazolam (10.4%) and midazolam + sildenafil (10.4%). In children, the commonly used drug combinations are fentanyl + midazolam (20.7%), ibuprofen + furosemide (18.4%) and diazepam + omeprazole (15.3%). Conclusions The drugs that have been found to have hepatotoxicity (meropenem, medium and long chain fat emulsion, ibuprofen.etc.) are also related to DILI in newborns and children. When giving these drugs to newborns and children, physicians need to be more cautious. Also, pay attention to the effect on CYP 450 enzymes when using multiple drugs at the same time.

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“…The majority of pediatric DILI reports have focused on hospitalized cases of DILI 7,8,30 . Our ADR mechanisms were able to detect potential iDILI in affiliated outpatient settings in addition to hospitalized patients.…”

Section: Discussionmentioning

confidence: 99%

An electronic medical records-based approach to identify idiosyncratic drug-induced liver injury in children

Sandritter

Goldman

Habiger

et al. 2019

Sci Rep

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Drug-induced liver injury (DILI) is the leading cause of liver failure in the United States and the most common cause of drug recall. As opposed to the recognized direct toxicity of super-therapeutic acetaminophen or chemotherapeutic agents in children, limited data exists for pediatric populations on the incidence of idiosyncratic DILI (iDILI) that may develop independently of drug dose or duration of administration. To improve the detection of adverse drug reactions at our hospital, we utilized electronic medical records-based automated trigger tools to alert providers of potential iDILI. Clinical criteria concerning for iDILI were defined as serum ALT > 5x or serum bilirubin > 1.5x upper limit of normal in the setting of medication exposure. Over a two year period, 12 patients were identified as having possible or probable iDILI. Out of the identified patients, three were males, and the mean age was 10.8 years. Implicated agents included eight antibiotics, two anti-epileptics, one anti-psychotic, and one anti-inflammatory medication. Roussel-Uclaf Causality Assessment Methods identified one “possible” case, 11 “probable” cases, and one “highly probable” case of iDILI. Improved awareness and more vigilant programming can generate better data on iDILI and improve our understanding of the condition and its incidence in children.

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Analysis of Immunogenetic Factors in Idiosyncratic Drug‐induced Liver Injury in the Pediatric Population

Abstract: Polymorphisms that are low producers of interleukin-10 occur more frequently in children who have experienced hepatotoxicity.

Cited by 14 publications

References 34 publications

Drug-Induced Liver Injury: Biomarkers, Requirements, Candidates, and Validation

Drug-Induced Liver Injury: Biomarkers, Requirements, Candidates, and Validation

Drug-Induced Hepatic Injury in Newborns and Children in Intensive Care Unit: A Retrospective Study of China

An electronic medical records-based approach to identify idiosyncratic drug-induced liver injury in children

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