Predicting acute acetaminophen hepatotoxicity with acetaminophen-aminotransferase multiplication product and the Psi parameter.
BACKGROUND
Prediction of potential hepatotoxicity is important for individualizing therapy with N-acetylcysteine (NAC) in patients with acute acetaminophen overdose. Acetaminophen-aminotransferase multiplication product (APAP × AT) and the Psi Parameter (Psi) have been reported to be the predictors of acetaminophen hepatotoxicity.


OBJECTIVE
To determine the validity of APAP × AT and Psi in predicting hepatotoxicity secondary to acute acetaminophen overdose.


METHODS
We retrospectively reviewed acute acetaminophen overdose cases who were treated with NAC at Siriraj Hospital, Thailand during January 2004-June 2012. The patients' ages were 12 years or more. Initial acetaminophen concentration (mg/L) and aminotransferase (IU/L) were multiplied to obtain APAP × AT. Psi were derived from initial acetaminophen concentrations (mg/L) and lag time (hours) to NAC therapy. The cut-off values for APAP × AT and Psi were 1500 mg∙IU/L(2) and 5 mM∙h, respectively. Hepatotoxicity (defined as aspartate or alanine aminotransferase (ALT) greater than 1000 IU/L) was the outcome of interest.


RESULTS
A total of 255 patients were included, 32 of whom developed hepatotoxicity. APAP × AT had sensitivity, specificity, and negative likelihood ratio of 90.6%, 62.8%, and 0.2, respectively. The sensitivity of Psi, specificity, and negative likelihood ratio were 96.9%, 91.5%, and 0.0, respectively. The areas under the curve of the receiver operating characteristic (ROC) curve for APAP × AT and Psi were 0.82 and 0.96, respectively, with a statistically significant difference between the two methods (p = 0.002). APAP × AT showed higher specificity (92.5%) in patients who presented 8-24 h after the overdose.


CONCLUSIONS
Psi and APAP × AT are valid clinical tools in predicting hepatotoxicity secondary to acute acetaminophen overdose in adults. APAP × AT is useful in predicting a low likelihood of hepatotoxicity after standard NAC therapy among late-presenting patients.
Faculty of Medicine Siriraj Hospital, Mahidol University , Bangkok , Thailand.
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Chomchai
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Chomchai
D000082:Acetaminophen / Q000008:administration & dosage / Q000506:poisoning*; D000111:Acetylcysteine / Q000008:administration & dosage / Q000627:therapeutic use*; D000328:Adult; D000410:Alanine Transaminase / Q000097:blood*; D000931:Antidotes / Q000008:administration & dosage / Q000627:therapeutic use; D001219:Aspartate Aminotransferases / Q000097:blood*; D056486:Chemical and Drug Induced Liver Injury / Q000188:drug therapy / Q000209:etiology*; D062787:Drug Overdose; D005260:Female; D006801:Humans; D016013:Likelihood Functions; D008297:Male; D012372:ROC Curve; D012189:Retrospective Studies; D012680:Sensitivity and Specificity; D013785:Thailand; D013997:Time Factors; D055815:Young Adult
D000931:Antidotes; D000082:Acetaminophen; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D000111:Acetylcysteine
Half-life; Hepatitis; N-acetylcysteine; Paracetamol; Psi