Comparison of Prothrombin Time and Aspartate Aminotransferase in Predicting Hepatotoxicity After Acetaminophen Overdose

Abstract

Despite decades of experience with acetaminophen (APAP) overdoses, it remains unclear whether elevated hepatic transaminases or coagulopathy develop first. Furthermore, comparison of the predictive value of these two variables in determining hepatic toxicity following APAP overdoses has been poorly elucidated. The primary objective of this study is to determine the test characteristics of the aspartate aminotransferase (AST) and the prothrombin time (PT) in patients with APAP toxicity. A retrospective chart review of APAP overdoses treated with IV N-acetylcysteine at a tertiary care referral center was performed. Of the 304 subjects included in the study, 246 with an initial AST less than 1000 were analyzed to determine predictors of hepatic injury, defined as an AST exceeding 1000 IU/L. The initial AST >50 was 79.5 % sensitive and 82.6 % specific for predicting hepatic injury. The corresponding negative and positive predictive values were 95.5 and 46.3 %, respectively. In contrast, an initial abnormal PT had a sensitivity of 82.1 % and a specificity of 63.6 %. The negative and positive predictive values for initial PT were 94.9 and 30.2 %, respectively. Although the two tests performed similarly for predicting a composite endpoint of death or liver transplant, neither was a useful predictor. Initial AST performed better than the initial PT for predicting hepatic injury in this series of patients with APAP overdose.

Fifteen-minute consultation: The child with an incidental finding of elevated aminotransferases

“…That is, there is poor correlation between extent of elevation of aminotransferases and liver biopsy abnormalities 3. In paracetamol overdose4 or ischaemic hepatitis, for instance, a massive rise in AST and ALT can be encountered but they are not useful in predicting outcome. On the other hand, in advanced liver disease, normal levels of AST and ALT may be encountered indicating ‘burnt out’ status implying that the there is minimal viable liver tissue left.…”

Biomarkers of drug-induced liver injury

“…Decades after the introduction of alkaline phosphatase and aminotransferases (ALT, AST) as the first biomarkers of liver injury, interest in identification of novel DILI biomarkers has been growing (McGill, 2016). Although current clinical laboratory tests are helpful for detection of liver injury or dysfunction in many cases, they are not useful for diagnosis of etiology or for prognosis (Antoine et al, 2013;Senior, 2014;Levine et al, 2016;Dear et al, 2018). The US National Institutes of Health and US Food and Drug Administration Biomarker Working Group has defined a biomarker as a "characteristic that is measured as an indicator of normal biological processes, pathogenic processes, or responses to an exposure or intervention" (US FDA, 2016).…”

Acute acetaminophene-induced hepatotoxicity and nephrotoxicity; therapeutic effect of dexmedetomidine

“…Acetaminophen (APAP: N-acetyl-p-aminophenol, paracetamol) is an analgesic antipyretic medication that is commonly used globally (1,2,3). Therapeutic doses are safe, however toxic metabolites occurring during overdose cause severe organ toxicity (4).…”