Latest advances in predicting DILI in human subjects: focus on biomarkers.

INTRODUCTION: The quest for a biomarker that would reliably identify patients at risk of developing acute drug-induced liver injury (DILI) to a specific agent or class of agents before it occurs, has been underway for years. Historical host factors for DILI, such as older age and female gender, are not considered sufficient to truly predict an individual's inherent risk of DILI. In vitro and animal-based biomarker discoveries, in many instances, have not been considered accurate enough for drug development in human subjects nor for use in clinical practice. AREAS COVERED: In order to assess the current state of biomarkers to predict idiosyncratic human DILI, the authors utilized the PubMed literature search tool to identify research reports dealing with clinical DILI biomarkers covering the period of 2010 through to June 2012. Studies involving pharmacogenetic, proteomic and toxicogenomic analyses are preferentially reviewed. EXPERT OPINION: Although acute DILI has been linked to specific genetic associations (e.g., flucloxacillin and HLA-B*5701; and certain polymorphisms seen with anti-TB agent DILI), such predictors have been able to identify only some patients at risk for only a limited number of drugs. Proteomic-based biomarkers from stored sera in the US DILI Network, such as apolipoprotein E, have been identified as potential candidates, but require further study. As it currently stands, the quest for a widely applicable, validated DILI biomarker remains an ongoing clinical challenge.