title: A descriptive analysis of aspartate and alanine aminotransferase rise and fall following acetaminophen overdose.
abstract: BACKGROUND
  Risk prediction following acetaminophen (paracetamol, APAP) overdose is based on serum APAP, aspartate aminotransferase (AST), and alanine aminotransferase (ALT) levels. One recently proposed risk stratification tool, the APAPxAT multiplication product, uses either AST or ALT, whichever is higher, yet their interrelation is not well known following APAP-induced hepatic injury.
  
  
  OBJECTIVE
  To describe the kinetics of AST and ALT release into and disappearance from the circulation following APAP overdose.
  
  
  METHODS
  An observational case series of adult patients with peak AST or ALT > 100 IU/L attributable to APAP toxicity. Cases were identified by electronic search of hospital laboratory database and by discharge diagnosis corroborated by structured explicit medical record review.
  
  
  RESULTS
  Of 68 cases identified (mean age (SD): 39 (18) years, 63% female, and 21% ethanol co-ingested), 28 (41%) developed hepatotoxicity (peak AST or ALT > 1000 IU/L), 28 (41%) coagulopathy (international normalized ratio or INR > 2), and 21 (31%) both. Three patients (4%) were transferred for liver transplantation and ultimately six (8.8%) died. Serum AST and ALT activity rose in a closely aligned 1:1 AST:ALT ratio, but fell at distinctly different rates: AST activity fell with a half-life (interquartile range [IQR]) of 15.1 (12.2, 19.4) hours, and ALT 39.6 (32.9, 47.6) hours. Using an aminotransferase falling to below 50% of peak as the basis for discontinuing acetylcysteine would have resulted in antidotal treatment being stopped 24 (IQR: 9.6, 40) hours earlier (and in no cases later) using AST rather than ALT. Only six patients had an AST:ALT ratio greater than 2:1 at the time of acetylcysteine administration; of these six, four died and one survivor developed coagulopathy.
  
  
  CONCLUSIONS
  AST and ALT release into the circulation appears tightly linked and numerically similar, except in the sickest patients. Once the aminotransferases peak, AST returns to baseline more quickly.
  
  
  CONCLUSIONS
  Either AST or ALT can be used for early risk stratification tools when only one is known. Any criterion for N-AC discontinuation should be based on the decline of AST rather than ALT, with a potential benefit measured in days.
authors: a Departments of Emergency Medicine and of Biomedical & Molecular Sciences , Queen's University , Kingston, Ontario , Canada.
authors: R Mason
authors: RM
authors: Curtis
authors: a Departments of Emergency Medicine and of Biomedical & Molecular Sciences , Queen's University , Kingston, Ontario , Canada.
authors: Marco L A
authors: ML
authors: Sivilotti
mesh_terms: D000082:Acetaminophen / Q000506:poisoning*; D000111:Acetylcysteine / Q000627:therapeutic use; D000328:Adult; D000368:Aged; D000410:Alanine Transaminase / Q000097:blood*; D018712:Analgesics, Non-Narcotic / Q000506:poisoning*; D000931:Antidotes / Q000627:therapeutic use; D001219:Aspartate Aminotransferases / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D056486:Chemical and Drug Induced Liver Injury / Q000097:blood / Q000175:diagnosis* / Q000209:etiology / Q000401:mortality / Q000628:therapy; D004796:Clinical Enzyme Tests; D003661:Decision Support Techniques; D062787:Drug Overdose; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D011237:Predictive Value of Tests; D012189:Retrospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D018712:Analgesics, Non-Narcotic; D000931:Antidotes; D015415:Biomarkers; D000082:Acetaminophen; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D000111:Acetylcysteine
keywords: Liver; N-acetylcysteine; Paracetamol; alanine aminotransferase; aspartate aminotransferase