Characteristics of Idiosyncratic Drug‐induced Liver Injury in Children

Molleston, Jean P.; Fontana, Robert J.; López, Mariana; Kleiner, David E.; J, Gu; Chalasani, Naga

doi:10.1097/mpg.0b013e31821d6cfd

Cited by 92 publications

(49 citation statements)

References 38 publications

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“…Thus, our results can only be compared with adult data, descriptive studies from drug/induced liver injury registries [11] and results from signal detection analyses [1, 10]. …”

Section: Discussionmentioning

confidence: 99%

Antibiotic-Induced Liver Injury in Paediatric Outpatients: A Case-Control Study in Primary Care Databases

Ferrajolo¹,

Verhamme²,

Trifirò

et al. 2016

Drug Saf

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IntroductionAntibiotics are the most commonly prescribed drug class in children. Real-world data mining on the paediatric population showed potential associations between antibiotic use and acute liver injury.ObjectiveWe assessed risk estimates of liver injury associated with antibiotic use in children and adolescent outpatients.MethodsA large, multi-database, population-based, case-control study was performed in people <18 years of age from two European countries (Italy and The Netherlands) during the period 2000–2008. All potential cases of liver injury were automatically extracted from three databases and then manually validated based on Council for International Organizations of Medical Sciences (CIOMS) criteria and by exclusion of all competing causes for liver injury. Up to 100 control participants were sampled for each case and were matched on index date of the event, age, sex and database. Based on prescription data, antibiotic exposure was categorized as current, recent or past use by calculating the time period between the end of prescription and the index date. Multivariate conditional logistic regression analyses were applied to calculate odds ratios (ORs) as a measure of the association (with 95% confidence interval [CI]).ResultsWe identified 938 cases of liver injury and matched to 93,665 controls. Current use of overall antibiotics is associated with a threefold increased risk of liver injury compared with past use (adjusted OR [ORadj] 3.22, 95% CI 2.57–4.03). With regard to individual antibiotics, the risk is significantly increased for current use of each antibiotic (p < 0.005), except for azithromycin. Risk estimates vary from the lowest ORadj of 1.86 (95% CI 1.08–3.21) for amoxicillin to the highest ORadj of 24.16 (95% CI 11.78–49.54) for cotrimoxazole (i.e. sulphamethoxazole/trimethoprim) and 26.70 (95% CI 12.09–58.96) for ceftriaxone. Sensitivity analyses confirm the associations for ceftriaxone, cotrimoxazole, and clarithromycin.ConclusionAntibiotic-induced liver injury in children is heterogeneous across the use of individual antibiotics. When prescribing ceftriaxone, cotrimoxazole and clarithromycin in children, paediatricians should definitely be aware of their potential risk of liver injury, even if for short periods.Electronic supplementary materialThe online version of this article (doi:10.1007/s40264-016-0493-y) contains supplementary material, which is available to authorized users.

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“…Thus, our results can only be compared with adult data, descriptive studies from drug/induced liver injury registries [11] and results from signal detection analyses [1, 10]. …”

Section: Discussionmentioning

confidence: 99%

Antibiotic-Induced Liver Injury in Paediatric Outpatients: A Case-Control Study in Primary Care Databases

Ferrajolo¹,

Verhamme²,

Trifirò

et al. 2016

Drug Saf

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“…Drug-induced liver injury (DILI) is an increasingly recognized cause of clinically significant acute and chronic liver disease in both children and adults (90,91). DILI is a leading cause of acute liver failure (ALF) in western countries and the most common reason for removal of approved medications from the marketplace (92, 93).…”

Section: Direct Acting Antivirals In the Pipelinementioning

confidence: 99%

Drug-drug interactions with oral anti-HCV agents and idiosyncratic hepatotoxicity in the liver transplant setting

Tischer

Fontana

2014

Journal of Hepatology

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Preliminary studies of boceprevir and telaprevir based antiviral therapy in liver transplant (LT) recipients with hepatitis C have demonstrated dramatic increases in tacrolimus, cyclosporine, and the mTOR inhibitor exposure. In addition to empiric dose reductions, daily monitoring of immunosuppressant blood levels is required when initiating as well as discontinuing the protease inhibitors to maximize patient safety. Although improved suppression of HCV replication is anticipated, 20 to 40% of treated subjects have required early treatment discontinuation due to various adverse events including anemia (100%), infection (30%), nephrotoxicity (20%) and rejection (5 to 10%). Simeprevir and faldepravir are 2nd generation protease inhibitors which may have improved efficacy and tolerability profiles but potential drug interactions with other OATP1B1 substrates and unconjugated hyperbilirubinemia are expected. In contrast, sofosbuvir and daclatasvir based therapies are not expected to lead to clinically significant drug-drug interactions in LT recipients but confirmatory studies are needed. Liver transplant recipients may also be at increased risk of developing drug induced liver injury (DILI). Establishing a diagnosis of DILI in the transplant setting is very difficult with the variable latency, laboratory features and histopathological manifestations of hepatotoxicity associated with a given drug, the need to exclude competing causes of allograft injury, and the lack of an objective and verifiable confirmatory test. Nonetheless, a heightened awareness of the possibility of DILI is warranted in light of the large number of medications used in LT recipients and the potential adverse impact that DILI may have on patient outcomes.

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“…Idiosyncratic hepatotoxic effects are those drugs that exhibit toxicity that is not predictable or dose-dependent [13]. Common examples of such drugs include isoniazid, propylthiouracil, and halothane [5].…”

Section: Pediatric Acute Liver Failure (Palf)mentioning

confidence: 99%

Etiology for Liver Diseases in Pediatric Population

Karakkattu¹,

Pr²

2016

Asian J Pharm Clin Res

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Objective: The liver diseases affect both the pediatric and adult populations. In the adult population, the stereotype diagnosis in the Indian population is targeted toward males due to excessive alcoholic consumption. Nevertheless, the liver diseases can also affect both the female and pediatric populations. Pediatric liver diseases include cirrhosis, fatty liver diseases, and hepatic failure. The liver diseases are commonly caused by biliary atresia and genetic metabolic diseases. In children, the signs and symptoms of liver diseases are dependent on the principal reason of the liver disease. This review article is to cover all the etiologies that have been identified to cause liver diseases with a special focus on pediatric acute liver failure.Methods: An extensive PubMed search was conducted and articles that were published after 2007 were included in this article. Results:The pediatric population etiology of liver diseases can be broadly categorized into infections, immunologic, metabolic, toxin or drug related, indeterminate, and diseases resulting in liver cirrhosis. Complications of pediatric liver diseases include malnutrition, infection, gastroesophageal varices, and hepatic encephalopathy. Conclusion:Overall, the etiology for liver diseases in the pediatric population is many. Early identification of these factors can improve the quality of life of the pediatric patient. With the correct diagnostic parameters and treatment certain conditions can be completely cured. As for those whose effective treatment is still lacking it is essential to continue the ongoing research until the missing pieces have been identified.

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Characteristics of Idiosyncratic Drug‐induced Liver Injury in Children

Cited by 92 publications

References 38 publications

Antibiotic-Induced Liver Injury in Paediatric Outpatients: A Case-Control Study in Primary Care Databases

Antibiotic-Induced Liver Injury in Paediatric Outpatients: A Case-Control Study in Primary Care Databases

Drug-drug interactions with oral anti-HCV agents and idiosyncratic hepatotoxicity in the liver transplant setting

Etiology for Liver Diseases in Pediatric Population

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