Unravelling Sex Differences in Drug‐Induced Liver Injury

Abstract

Liver toxicity accounts for 40% of failed drugs in clinical studies and approximately 21% of drugs that are removed from the market. It is suspected that drug-induced liver injury (DILI) is more common in females, thus impacting women's health to a higher degree. However, it is unclear how common this potential sex-based sensitivity may be and the mechanisms underlying the differences. High-content and high-throughput molecular technologies such as DNA microarrays have contributed significantly to the understanding of health and disease at the molecular level. In 2001, DNA microarray studies began to emerge to investigate sex-associated liver gene expression profiles under physiological and pathological conditions. This review is an analysis of clinical reports published to date to determine the weight of evidence in support of sex-biased sensitivity to DILI. Sex differences related to disease susceptibility/progression and adverse drug events are discussed at the molecular level with emphasis on genomic data in an attempt to place the evidence in a biological context. Keywords: DILI; sex difference; genomics; drug-induced liver injury