Genetic risk factors in the development of idiosyncratic drug-induced liver injury

Abstract

ABSTRACT Introduction: Idiosyncratic drug-induced liver injury (DILI) is a challenging condition with widespread implications. The underlying mechanism of DILI is not yet fully elucidated, but genetic predispositions are believed to contribute to DILI susceptibility. The identification of genetic risk factors has been a goal in DILI research for more than two decades. Areas covered: Here we provide an overview of genetic studies in DILI performed to date and outline polymorphisms identified to have a potential role in DILI development. This review covers both earlier candidate gene studies and more recent genome-wide association studies. The clinical applications of these findings are also discussed. Expert opinion: Various polymorphisms have been identified as associated with DILI susceptibility, but all of these have not been confirmed in independent studies or contradictive findings are available. Genome-wide significant associations between distinct HLA risk alleles and DILI due to specific causative agents strengthen the hypothesis that DILI is partially immune-mediated. These HLA alleles generally have low positive predictive value and are therefore not useful in preemptive tests to reduce DILI incidences, but can aid DILI diagnosis and clinical decision-making.