Characteristics of Idiosyncratic Drug‐induced Liver Injury in Children
- 1 August 2011
- journal article
- research article
- Published by Wiley in Journal of Pediatric Gastroenterology and Nutrition
- Vol. 53 (2), 182-189
- https://doi.org/10.1097/mpg.0b013e31821d6cfd
Abstract
Background: The spectrum and severity of idiosyncratic drug-induced liver injury (DILI) in children are not well established. Patients and Methods: The DILIN (Drug-Induced Liver Injury Network) Prospective Study is a longitudinal multicenter study designed to determine the etiologies, risk factors, and outcomes of suspected DILI. Between September 2004 and September 2009, 30 children ages 2 to 18 years with suspected DILI who met eligibility criteria were enrolled and studied for at least 6 months. Results: Mean age was 14 years; 70% were girls. Antimicrobial (50%) and central nervous system agents (40%) were the most commonly implicated drug classes, with minocycline (4), isoniazid (3), azithromycin (3), atomoxetine (3), and lamotrigine (3) the leading agents. Median time from drug initiation to symptom onset was 32 days. Peak (median) liver chemistries were aspartate aminotransferase 503 U/L, alanine aminotransferase 727 U/L, alkaline phosphatase 331 U/L, and total bilirubin 3.9 mg/dL. Autoantibodies were common (64%). Liver injury pattern was hepatocellular 78%, cholestatic 13%, and mixed 9%. The DILI episode was scored: mild 32%, moderate 44%, severe 20%, and fatal (within 6 months) 4%. Causality assessment was definite 36%, very likely 36%, probable 16%, possible 8%, and unlikely 4%. Seven percent had persistent liver test abnormalities at 6-month follow-up suggesting chronic DILI. Liver biopsies from 12 children most frequently demonstrated chronic hepatitis or bile duct injury. Conclusions: Idiosyncratic DILI in children is most commonly caused by antimicrobial or central nervous system agents and usually presents with a hepatocellular injury pattern. The majority of patients recover, but morbidity and infrequent mortality are seen.Keywords
Funding Information
- National Institute of Diabetes and Digestive and Kidney Diseases (1U01DK065021, 1U01DK065193, 1U01DK065201, 1U01DK065193, 1U01DK065184, 1U01DK065211, 1U01DK065238, 1U01DK065176)
This publication has 37 references indexed in Scilit:
- Standardization of nomenclature and causality assessment in drug-induced liver injury: Summary of a clinical research workshopJournal of Hepatology, 2010
- The Pathology of Drug-Induced Liver InjurySeminars in Liver Disease, 2009
- The Natural History of Drug-Induced Liver InjurySeminars in Liver Disease, 2009
- Causes, Clinical Features, and Outcomes From a Prospective Study of Drug-Induced Liver Injury in the United StatesGastroenterology, 2008
- Severe liver injury after initiating therapy with atomoxetine in two childrenThe Journal of Pediatrics, 2006
- Acute liver failure in children: The first 348 patients in the pediatric acute liver failure study groupThe Journal of Pediatrics, 2006
- Drug-induced liver injury: Summary of a single topic clinical research conferenceJournal of Hepatology, 2006
- Acute Hepatitis Associated with Lamotrigine and Managed with the Molecular Adsorbents Recirculating System (MARS)Epilepsia, 2005
- Immunotoxicology of the liver: adverse reactions to drugsJournal of Hepatology, 1997
- Histological grading and staging of chronic hepatitisJournal of Hepatology, 1995