Liver injury induced by paracetamol and challenges associated with intentional and unintentional use

Drug induced liver injury (DILI) is a common cause of acute liver injury. Paracetamol, also known as acetaminophen, is a widely used anti-pyretic that has long been established to cause liver toxicity once above therapeutic levels. Hepatotoxicity from paracetamol overdose, whether intentional or non-intentional, is the most common cause of DILI in the United States and remains a global issue. Given the increased prevalence of combination medications in the form of pain relievers and antihistamines, paracetamol can be difficult to identify and remains a significant cause of acute hepatotoxicity, as evidenced by its contribution to over half of all acute liver failure cases in the United States. This is especially concerning given that, when co-ingested with other medications, the rise in serum paracetamol levels may be delayed past the 4-hour post-ingestion mark that is currently used to determine patients that require medical therapy. This review serves to describe the clinical and pathophysiologic features of hepatotoxicity secondary to paracetamol and provide an update on current available knowledge and treatment options.