title: Characteristics of idiosyncratic drug-induced liver injury in children: results from the DILIN prospective study.
abstract: BACKGROUND
  The spectrum and severity of idiosyncratic drug-induced liver injury (DILI) in children are not well established.
  
  
  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.
authors.affiliation: Indiana University School of Medicine, Indianapolis, IN, USA. jpmolles@iupui.edu
authors.forename: Jean P
authors.initials: JP
authors.lastname: Molleston
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Fontana
authors.forename: M James
authors.initials: MJ
authors.lastname: Lopez
authors.forename: David E
authors.initials: DE
authors.lastname: Kleiner
authors.forename: Jiezhun
authors.initials: J
authors.lastname: Gu
authors.forename: Naga
authors.initials: N
authors.lastname: Chalasani
mesh_terms: D000293:Adolescent; D000890:Anti-Infective Agents / Q000009:adverse effects; D001323:Autoantibodies / Q000032:analysis; D001652:Bile Ducts / Q000187:drug effects / Q000473:pathology; D015984:Causality; D002491:Central Nervous System Agents / Q000009:adverse effects; D056486:Chemical and Drug Induced Liver Injury / Q000453:epidemiology / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology*; D056487:Chemical and Drug Induced Liver Injury, Chronic / Q000453:epidemiology / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D002648:Child; D002675:Child, Preschool; D005260:Female; D006505:Hepatitis / Q000453:epidemiology / Q000209:etiology / Q000473:pathology; D006801:Humans; D008099:Liver / Q000187:drug effects* / Q000473:pathology; D008137:Longitudinal Studies; D008297:Male; D011446:Prospective Studies; D012307:Risk Factors; D012720:Severity of Illness Index; D014481:United States / Q000453:epidemiology
chemical_list: D000890:Anti-Infective Agents; D001323:Autoantibodies; D002491:Central Nervous System Agents