An approach to drug-induced liver injuries

Drug-induced liver injury (DILI) is a term increasingly being used by most clinicians and is synonymous with drug-induced hepatotoxicity. A succinct definition of a DILI is ‘a liver injury induced by a drug or herbal medicine resulting in liver test abnormalities or liver dysfunction with a reasonable exclusion of other potential aetiologies’.1 DILIs are a recognised and clinically significant cause of acute, acute-on-chronic and, less commonly, chronic liver disease. The vast majority are idiosyncratic reactions in contrast to the less common dose-dependent predictable injury to drugs, such as paracetamol in overdose. Drugs remain a significant, if not the leading, cause of acute liver failure in the developed world and a prominent aetiological factor in the developing world. As the true frequency of DILIs in users of most drugs is not known and several epidemiological studies have had major methodological limitations, the true incidence of DILI remains mostly unknown.1 Nonetheless, DILI is seemingly relatively uncommon, ranging between 1 in 10 000 and 1 in 100 000 drug exposures.2 Exceedingly few prospective population-based studies have been undertaken to establish the true incidence of DILIs. One such study in France generated an incidence of 13.9 per 100 000, while acute liver injury has been reported to occur in 2 10% of patients hospitalised for jaundice; hence the actual population incidence may be higher than is generally appreciated.3,4 An Achilles heel that often underpins the difficulty in clearly establishing the true incidence of DILIs is demonstrating the causal relationship between a given drug exposure and DILI.5