Performance of the paracetamol-aminotransferase multiplication product in risk stratification after paracetamol (acetaminophen) poisoning: a systematic review and meta-analysis

Abstract

Background: Risk stratification in paracetamol (acetaminophen) poisoning is crucial because hepatotoxicity is common and can be mitigated with treatment. However, current risk stratification tools have limitations.

Aims: We evaluated the diagnostic performance of the paracetamol concentration × aminotransferase multiplication product, for predicting hepatotoxicity after paracetamol overdose.

Methods: Medline, Cochrane Library and Embase were searched for eligible papers. We used random effects models to obtain pooled estimates of the likelihood ratios and diagnostic odds ratios, from which sensitivity and specificity were computed. We assessed two commonly used cut-off values of paracetamol × aminotransferase, 1500 mg/L × IU/L and 10,000 mg/L × IU/L. Using the confusion matrices of these two cut-offs, area under the summary receiver operator characteristic curve and optimal cut-off values in different clinical scenarios were established.

Results: Six studies comprising 5036 participants were included. In 4051 patients, using the cut-off of 1500 mg/L × IU/L, a diagnostic odds ratio of 31.90 (95%CI: 9.52-106.90), sensitivity of 0.98 (95%CI: 0.94-1.00) and specificity of 0.66 (95%CI: 0.49-0.89) were obtained. In 3983 patients, using the cut-off of 10,000 mg/L × IU/L, a diagnostic odds ratio of 99.34 (95%CI: 12.26-804.87), sensitivity of 0.65 (95%CI: 0.51-0.82) and specificity of 0.97 (95%CI: 0.95-1.00) were obtained. For staggered ingestions, the 1500 mg/L × IU/L cut-off yielded a diagnostic odds ratio of 69.53 (95%CI: 4.03-1199.75), sensitivity of 1.00 (95%CI: 0.87-1.00) and specificity of 0.74 (95%CI: 0.43-1.00). Next, using the 10,000 mg/L × IU/L cut-off in this scenario yielded a diagnostic odds ratio of 254.58 (95%CI: 11.12-5827.60), sensitivity of 0.79 (95%CI: 0.59-1.00) and specificity of 0.98 (95%CI: 0.94-1.00). The overall summary receiver operator characteristic curve was 0.91 (95%CI: 0.75-0.97), and the optimal cut-off value was 3840 mg/L × IU/L. The summary receiver operator characteristic curve in patients with staggered ingestions was 0.96 (95%CI: 0.85-0.99). The summary receiver operator characteristic curve in patients with staggered ingestions and whose paracetamol concentration was below the detectable limit of 10 mg/L at presentation was 0.97 (95%CI: 0.94-0.99).

Conclusion: In this first meta-analysis, paracetamol × aminotransferase demonstrates its use in prognosticating hepatotoxicity in patients with paracetamol poisoning. It complements the Rumack-Matthew nomogram as it has shown promise in addressing two key limitations of the nomogram: it is usable after more than 24 h between overdose and acetylcysteine treatment, and it is applicable in staggered ingestions.

Keywords: Hepatotoxicity; acetaminophen; acetylcysteine; liver injury; meta-analysis; overdose; paracetamol; poisoning; risk; systematic review; tylenol.