Making the World a Safer Place

Abstract

Drug-induced liver injury (DILI) is an area of increasing interest to me and to multiple stakeholders including academia, industry, regulatory agencies, practitioners, and the general public. In the past 2 years, several approved drugs had restrictions placed on their use (e.g., telithromycin), and others were removed from the marketplace altogether (e.g., nefazodone) due to unpredictable and potentially severe hepatotoxicity. In addition, the development of promising new drugs was halted due to hepatotoxicity (e.g., ximelagatran and lumiracoxib). Although liver injury from an individual drug is rare, with an estimated incidence of only 1 to 100 episodes per 1,000,000 patient-years, the overall incidence of DILI in the general U.S. population may exceed 40,000 cases per year. Establishing a diagnosis of DILI is invariably retrospective and delayed due to the need to exclude other more common causes of liver injury and to follow patients after discontinuation of the suspect drug for clinical improvement (i.e., de-challenge). Furthermore, an increasing proportion of patients are on multiple medications, and each drug may be associated with a variable latency period as well as variable biochemical injury patterns and severity at presentation. Finally, there is no objective laboratory test to confirm a diagnosis of DILI. As a result of these complex circumstances, it is not surprising that research into risk factors and outcomes with DILI has been limited.