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
• paracetamol
• tylenol
• acetylcysteine
• liver injury
• overdose
• poisoning
• risk
• systematic review
• meta-analysis

Acknowledgements

Chun En Yau, Haoyang Chen, Bryant Po-Yuen Lim, Mingwei Ng, R. Ponampalam, Daniel Yan Zheng Lim, Yip Han Chin and Andrew Fu Wah Ho contributed to (1) the conception and design of this project; (2) acquisition, analysis, and interpretation of data; (3) drafting and revising the manuscript. All authors gave their final approval of the version to be published and agree to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Disclosure statement

No potential conflict of interest was reported by the author(s).