title: Female gender as a susceptibility factor for drug-induced liver injury.
abstract: Adverse drug reactions (ADRs) can involve all tissues and organs, but liver injuries are considered among the most serious. A number of prospective, multicenter studies have confirmed a higher risk of ADRs in general among female subjects compared to a male cohort. Although drug-induced liver injury (DILI) is infrequently encountered, the preponderance of evidence suggests that women appear to be more susceptible than men to fulminate hepatic/acute liver failure especially in response to some anti-infective drugs and to autoimmune-like hepatitis following exposure to certain other therapeutic drugs. A number of hypotheses have been proposed to explain this sex difference in susceptibility to DILI. Collectively, these hypotheses suggest three basic sex-dependent mechanisms that include differences in various aspects of drug pharmacokinetics (PK) or pharmacodynamics following the administration of certain drugs; specific hormonal effects or interactions with immunomodulating agents or signaling molecules; and differences in the adverse response of the immune system to some drugs, reactive drug metabolites, or drug-protein adducts. At the preclinical drug safety stage, there is a need for more research on hormonal effects on drug PK and for additional research on gender differences in aberrant immune responses that may lead to idiosyncratic DILI in some female patients. Because the detection of rare but serious hepatic ADRs requires the exposure of very large patient populations, pharmacovigilance networks will continue to play a key role in the postmarketing surveillance for their detection and reporting.
authors.affiliation: Toxadvisor Toxicology Consulting, USA.
authors.forename: David E
authors.initials: DE
authors.lastname: Amacher
mesh_terms: D056486:Chemical and Drug Induced Liver Injury; D064420:Drug-Related Side Effects and Adverse Reactions; D005260:Female; D006801:Humans; D008099:Liver / Q000187:drug effects; D008297:Male; D012307:Risk Factors; D012737:Sex Factors
keywords: Drug-induced liver injury; adverse drug response; female gender