CONTEXT: Paracetamol (acetaminophen or APAP) is the most common pharmaceutical exposure in the US. Elevations in aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels indicate hepatic toxicity. AST and ALT levels rise in similar proportions but later decline at different rates, with AST falling more rapidly than ALT. OBJECTIVE: To determine whether the AST/ALT ratio can indicate that a patient has passed the time of peak AST concentration. METHODS: We retrospectively identified cases of patients hospitalized for acute APAP poisoning by querying the pharmacy database of all patients treated with acetylcysteine (NAC) from January 1, 2001 to March 19, 2013. We included all patients with severe APAP poisoning, defined as AST or ALT greater than 1000 IU/L. Patients who were given NAC for other indications, those without APAP poisoning, and those receiving liver transplantation were excluded. We then recorded paired AST and ALT concentrations from each patient's hospital course. We classified each pair as clearly post-peak or not, and calculated the AST/ALT ratio for each pair of values. We compared different thresholds of AST/ALT ratio in increments of 0.1 to find the optimal value that reliably indicated resolving transaminases. RESULTS: We identified 1820 patients who received NAC during the study period. Of these, 333 received NAC for suspected poisoning by APAP. After excluding patients without severe APAP poisoning, other diagnoses explaining transaminase elevations, and patients who underwent liver transplantation, we had 37 evaluable patients with 343 evaluable pairs of AST and ALT concentrations. An AST/ALT ratio less than or equal to 0.4 was 99% sensitive for identifying patients with resolving transaminases. CONCLUSION: An AST/ALT ratio less than or equal to 0.4 following severe hepatoxicity from paracetamol poisoning appears to be highly predictive of recovery in patients treated with NAC. This has potential to be an indicator of safe discontinuation of NAC treatment.
CONTEXT: Paracetamol (acetaminophen or APAP) is the most common pharmaceutical exposure in the US. Elevations in aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels indicate hepatic toxicity. AST and ALT levels rise in similar proportions but later decline at different rates, with AST falling more rapidly than ALT. OBJECTIVE: To determine whether the AST/ALT ratio can indicate that a patient has passed the time of peak AST concentration. METHODS: We retrospectively identified cases of patients hospitalized for acute APAP poisoning by querying the pharmacy database of all patients treated with acetylcysteine (NAC) from January 1, 2001 to March 19, 2013. We included all patients with severe APAP poisoning, defined as AST or ALT greater than 1000 IU/L. Patients who were given NAC for other indications, those without APAP poisoning, and those receiving liver transplantation were excluded. We then recorded paired AST and ALT concentrations from each patient's hospital course. We classified each pair as clearly post-peak or not, and calculated the AST/ALT ratio for each pair of values. We compared different thresholds of AST/ALT ratio in increments of 0.1 to find the optimal value that reliably indicated resolving transaminases. RESULTS: We identified 1820 patients who received NAC during the study period. Of these, 333 received NAC for suspected poisoning by APAP. After excluding patients without severe APAP poisoning, other diagnoses explaining transaminase elevations, and patients who underwent liver transplantation, we had 37 evaluable patients with 343 evaluable pairs of AST and ALT concentrations. An AST/ALT ratio less than or equal to 0.4 was 99% sensitive for identifying patients with resolving transaminases. CONCLUSION: An AST/ALT ratio less than or equal to 0.4 following severe hepatoxicity from paracetamolpoisoning appears to be highly predictive of recovery in patients treated with NAC. This has potential to be an indicator of safe discontinuation of NAC treatment.