Multiplying the serum aminotransferase by the acetaminophen concentration to predict toxicity following overdose

The first available predictors of hepatic injury following acetaminophen (APAP) overdose are the serum APAP and aminotransferases [AT, i.e., aspartate (AST) aminotransferase or alanine (ALT) aminotransferase].

We describe the initial value, rate of change, and interrelationship between these biomarkers in patients who develop hepatotoxicity despite treatment following acute overdose. A new parameter, the APAP × AT multiplication product, is proposed for early risk stratification.

We conducted a descriptive study of individuals selected from a multicenter retrospective cohort of patients hospitalized for APAP poisoning. We selected those acute APAP overdose patients who subsequently developed AT  > 1,000 IU/L. Rising serum AT values were compared to simultaneously measured (or estimated) falling serum APAP. The APAP × AT was expressed relative to initiation of acetylcysteine therapy and grouped by time to meeting hepatotoxicity criteria.

In the 94 cases studied, serum APAP concentrations were still appreciable [median 570 (interquartile range (IQR) 314-983) μmol/L] at the time of the first measured AT [211 (77-511) IU/L at 15.3 (12.1-19.2) h post-ingestion], yielding an initial APAP × AT of 99,000 (52,000-240,000) μmol × IU/L(2). Because serum AT rose rapidly (doubling time 9.5 h ) and APAP fell slowly (half-life 4.8 h), the multiplication product remained elevated during the first 12-24 h of antidotal therapy, especially among patients who developed earlier hepatotoxicity (AT > 1,000 IU/L).

The APAP × AT multiplication product, calculated at the time of presentation and after several h of antidotal therapy, holds promise as a new risk predictor following APAP overdose. It requires neither graphical interpretation nor accurate time of ingestion, two limitations to current risk stratification.