ACETAMINOPHEN-INDUCED ACUTE LIVER FAILURE: PATHOPHYSIOLOGY, DIAGNOSIS, AND CLINICAL MANAGEMENT

Abstract

Introduction: Paracetamol, known as acetaminophen, is a non-steroidal anti-inflammatory drug (NSAID) that inhibits cyclooxygenase-3 (COX-3). Its antipyretic and analgesic actions, combined with low cost and safety, make it widely used, even without a medical prescription. However, due to hepatic metabolism and its high hepatotoxic potential at elevated doses or in the presence of hepatic comorbidities, paracetamol is the leading cause of drug-induced acute liver injury worldwide. This study aims to discuss the pathophysiology, diagnosis, and clinical management of paracetamol-induced acute liver failure. Methodology: A search was conducted in the electronic databases PubMed, Scielo, and LILACS using the descriptors "Acetaminophen," "Overdose," "Treatment," and "Acetylcysteine." Fifteen relevant articles were selected after applying inclusion and exclusion criteria. Results and Discussion: Paracetamol is metabolized in the liver, producing inactive metabolites excreted in the urine. However, a small fraction is metabolized to N-acetyl-p-benzoquinone imine (NAPQI), a highly hepatotoxic compound that causes cell necrosis by covalently binding to hepatic proteins. NAPQI is neutralized by glutathione (GSH), forming an inert compound excreted in the urine. Symptoms of paracetamol intoxication range from mild (nausea, vomiting, abdominal discomfort) to severe (jaundice, hepatic encephalopathy, coagulopathy) and occur in four phases. Rapid identification of the condition, assessment of the ingested dose, and time since ingestion are crucial. Conclusion: Effective management requires rapid identification, accurate assessment of the ingested dose, monitoring of hepatic markers, and early administration of NAC. Timely interventions are essential to prevent fatal complications and ensure patient recovery.