Mechanisms of drug-induced liver injury

Liver toxicity remains the first cause of drug withdrawal from th pharmaceutical market. Drugs shown to be toxic have been withdrawn and replaced by new compounds, some of which appear to be hepatotoxic. The late detection of hepatotoxicity (in average 1 to 2 years after starting the marketing) may be explained by a low rate of toxicity for most drugs (1/10,000 to 1/100,000), whereas the number of patients included in therapeutic trials for obtaining a marketing authorization usually averages 1,000 to 3,000. The overall number of drugs susceptible to be toxic to the liver is estimated to exceed 1,000. The spectrum of liver damages caused by drugs is very broad and involves various mechanisms. The mechanisms have been mainly investigated for acute hepatitis which represents the major form of drug-induced liver injury.