Plasma procalcitonin may be an early predictor of liver injury in acetaminophen poisoning: A prospective cohort study

Abstract

Background and aims: Acetaminophen is a common cause of poisoning and liver injury worldwide; however, patient stratification is suboptimal. We aimed to assess the contribution of admission plasma procalcitonin concentration (PCT) to better identify acetaminophen-poisoned patients likely to develop liver injury.

Methods: We conducted a prospective observational cohort study including all acetaminophen-poisoned patients requiring N-acetylcysteine admitted in a toxicological intensive care unit between 2012 and 2017. Multivariate analysis was performed using a Cox regression model to investigate factors associated with liver injury, defined as an increase in alanine aminotransferase (ALT) >100 IU/L.

Results: One hundred seventeen patients (age, 32 years (21-53), median [25th-75th percentiles]) were included after self-ingesting 16 g (9-30) acetaminophen and received N-acetylcysteine infusion administered within a median 6 h-delay (4-12) from exposure. Co-ingestions were reported in 77% of patients. Rumack-Matthew nomogram was non-interpretable in 47% cases. Liver injury occurred in 38 patients (32%) with a median peak ALT of 2020 IU/L (577-4248). In liver injury patients, admission PCT was significantly increased in comparison to patients without liver injury (21.5 ng/ml (3.2-44.9) versus 0.1 ng/ml (0-0.4), respectively, p < 0.01). The increase in PCT preceded the increase in ALT by 33 h (10-74). In a multivariate analysis, PCT > 1 ng/ml was significantly associated with liver injury (hazard ratio, 7.2 [95% confidence interval, 2.3-22.6; p < 0.001]). PCT (area under the receiver-operating characteristics curve, 0.91 [95%CI: 0.84-0.97]) predicted liver injury with sensitivity, specificity, negative, and positive predictive values of 0.92, 0.84, 0.96, and 0.73, respectively.

Conclusion: PCT on admission is associated with liver injury in acetaminophen poisoning. PCT might be used as a predictive tool of liver injury to improve clinical decision-making.

Keywords: PCT; acetaminophen; acute liver injury; biomarker; drug-induced liver injury; hepatotoxicity; paracetamol; poisoning; predictive tool; procalcitonin.

FIGURE 1

Plasma PCT concentrations on admission according to the onset of liver injury in 117 acetaminophen‐poisoned patients. log, logarithmic; ng/ml, nanograms per milliliters; PCT, procalcitonin

FIGURE 2

Value of plasma PCT concentration on admission in the diagnosis of liver injury in the acetaminophen‐poisoned patient (receiver‐operating characteristics curve). AUC, area under the ROC curve; CI, confidence interval; NPV, negative predictive value; PCT, procalcitonin; PPV, positive predictive value Legend table [Table: see text]

FIGURE 3

Probability of acetaminophen‐induced liver injury according to admission PCT concentration (Kaplan–Meier curves, p < 0.001). PCT, procalcitonin

FIGURE 4

Time course of plasma PCT and ALT concentrations in an acetaminophen‐poisoned patient. This 90‐year‐old woman was admitted 16 h post‐ingestion of an unknown dose of paracetamol. On admission, she presented with high acetaminophen plasma levels 136 mg/ml, high procalcitonin levels 27 ng/ml, and normal liver tests. ALT, alanine aminotransferase; PCT, procalcitonin