Background: In Spain, 30% of cases of acute liver failure remaining undetermined. Paracetamol is the main drug causing acute liver failure in children of some countries like the United States, UK, and other European countries. The key factors to assess in paracetamol toxicity, the ingested dose and the time from the poisoning, are difficult to assess in children were accidental acute poisoning or medication errors are not rare. Metabolomics technology may be able to identify specific biomarkers of toxicity and adverse events in early stages. The identification of paracetamol toxicity biomarkers could have important clinical implications for patients who can not apply the Rumack-Matthew nomogram and could be useful in the evaluation of children with acute liver failure of unknown etiology, and to predict liver damage before the elevation of transaminases.
Methods and design: This is an observational prospective study of case control. The protocol was approved by the Clinical Research Ethics Committee of the La Paz University Hospital. It will recruit patients who will be attending in the emergency paediatric at La Paz University Hospital, at Niño Jesus University Hospital, and at Gregorio Marañón University hospital with suspected acute or chronic intake of paracetamol. Likewise, two cohorts of control will be recruited. It is expected to recruit at least 36 cases and 144 controls, matched for age and clinical characteristics. Peripheral blood, plasma, serum and urine samples will be collected, paracetamol serum concentrations, hepatic and renal function, coagulation and metabolomic analysis.
Discussion: It is important to determine the clinical factors and biomarkers that predict the development of hepatotoxicity in paediatric population following acute and chronic intake of paracetamol and develop a predictive model to assess the risk of hepatotoxicity in both types of intoxication by paracetamol suited to paediatric patients for use in clinical practice.
Protocol code: GEIPA-2012-01
AEMPS classification: EPA-OD
Study Reference Number of European Network of Centers for Pharmacoepidemiology and Pharmacovigilance: ENCePP: ENCePP/SDPP/3276