Larson AM et al. (2005) Acetaminophen-induced acute liver failure: results of a United States multicenter, prospective study. Hepatology 42: 1364–1372

Paracetamol (acetaminophen) is the most commonly used analgesic in the US. Overdose is a well-recognized risk factor for acute liver failure (ALF); this prospective, multicenter, study aimed to test the hypothesis that patients with ALF caused by unintentional overdose would differ, clinically and demographically, from those who had overdosed intentionally.

Of 662 ALF cases treated at 22 US transplant centers, 42% were attributable to paracetamol overdose; this varied from 28% in 1998 to 51% in 2003. Most patients were female and white. Clinical history indicated that 44% (n = 122) of patients with paracetamol-related ALF experienced definitely intentional and 48% (n = 131) definitely unintentional overdose. Those who had overdosed unintentionally presented to hospital later, were more likely to have used multiple preparations containing paracetamol simultaneously, and had more severe hepatic encephalopathy on presentation. Chronic pain was considered a potential risk factor for unintentional overdose.

As patients in this study had evidence of hepatic encephalopathy and, by definition, had altered cognition, the clinical histories obtained might not have been entirely accurate. The authors comment, however, that their sample is biased towards those with severe disease being considered for transplant, and the real incidence of paracetamol-related ALF might be higher. They suggest that legislative changes restricting paracetamol distribution might be necessary to halt the ever-increasing rate of paracetamol-related ALF. This study highlights the worrying contribution of unintentional overdose to ALF as well as the importance of education for both primary-care physicians and susceptible groups.