title: Acetaminophen Adducts Detected in Serum of Pediatric Patients With Acute Liver Failure.
abstract: OBJECTIVE
  Previous studies in patients with acute liver failure identified acetaminophen (APAP) protein adducts in the serum of 12% and 19% of children and adults, respectively, with acute liver failure of indeterminate etiology. This article details the testing of APAP adducts in a subset (n = 393) of patients with varied diagnoses in the Pediatric Acute Liver Failure Study Group (PALFSG).
  
  
  METHODS
  Serum samples were available from 393 participants included in the PALFSG registry. Adduct measurement was performed using validated methods. Participants were grouped by diagnostic category as known APAP overdose, known other diagnosis, and indeterminate etiology. Demographic and clinical characteristics and participant outcomes were compared by adduct status (positive or negative) within each group.
  
  
  RESULTS
  APAP adduct testing was positive in 86% of participants with known APAP overdose, 6% with other known diagnoses, and 11% with an indeterminate cause of liver failure. Adduct-positive participants were noted to have marked elevation of serum alanine aminotransferase and aspartate aminotransferase coupled with total serum bilirubin that was significantly lower than adduct-negative patients. In the indeterminate group, adduct-positive patients had different outcomes than adduct-negative patients (P = 0.03); spontaneous survival was 16 of 21 (76%) in adduct-positive patients versus 75 of 169 (44%) in adduct-negative patients. Prognosis did not vary by adduct status in patients with known diagnoses.
  
  
  CONCLUSIONS
  Furthermore, study is needed to understand the relation of APAP exposure, as determined by the presence of APAP adducts, to the clinical phenotype and outcomes of children with acute liver failure.
authors: *Department of Pediatrics, Northwestern Feinberg School of Medicine, Division of Gastroenterology, Hepatology and Nutrition, Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, IL †Department of Pediatrics, University of Arkansas for Medical Sciences, Arkansas Children's Hospital Research Institute, Little Rock ‡Department of Epidemiology, University of Pittsburgh Graduate School of Public Health §Department of Pediatrics, University of Pittsburgh School of Medicine, Division of Gastroenterology, Hepatology and Nutrition, Children's Hospital of Pittsburgh of UPMC, Pittsburgh.
authors: Estella M
authors: EM
authors: Alonso
authors: Laura P
authors: LP
authors: James
authors: Song
authors: S
authors: Zhang
authors: Robert H
authors: RH
authors: Squires
mesh_terms: D000082:Acetaminophen / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood*; D000293:Adolescent; D000410:Alanine Transaminase / Q000097:blood; D001219:Aspartate Aminotransferases / Q000097:blood; D016227:Benzoquinones / Q000097:blood; D056486:Chemical and Drug Induced Liver Injury / Q000097:blood*; D002648:Child; D002675:Child, Preschool; D002851:Chromatography, High Pressure Liquid; D062787:Drug Overdose / Q000097:blood* / Q000150:complications; D005260:Female; D006801:Humans; D007097:Imines / Q000097:blood; D007223:Infant; D008099:Liver / Q000473:pathology*; D017114:Liver Failure, Acute / Q000097:blood* / Q000209:etiology; D008297:Male; D011379:Prognosis; D011506:Proteins / Q000378:metabolism
chemical_list: D016227:Benzoquinones; D007097:Imines; D011506:Proteins; D000082:Acetaminophen; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; C028473:N-acetyl-4-benzoquinoneimine