Journal
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Volume 17, Issue 10, Pages -Publisher
MDPI
DOI: 10.3390/ijms17101714
Keywords
drug-induced liver injury; hepatotoxicity; liver disease; pharmacogenetics
Funding
- European Union [668353]
- Swedish Research Council
- European Community under the Innovative Medicine Initiative project MIP-DILI [115336]
- Swedish Cancer Foundation
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Responses to drugs and pharmacological treatments differ considerably between individuals. Importantly, only 50%-75% of patients have been shown to react adequately to pharmacological interventions, whereas the others experience either a lack of efficacy or suffer from adverse events. The liver is of central importance in the metabolism of most drugs. Because of this exposed status, hepatotoxicity is amongst the most common adverse drug reactions and hepatic liabilities are the most prevalent reason for the termination of development programs of novel drug candidates. In recent years, more and more factors were unveiled that shape hepatic drug responses and thus underlie the observed inter-individual variability. In this review, we provide a comprehensive overview of different principle mechanisms of drug hepatotoxicity and illustrate how patient-specific factors, such as genetic, physiological and environmental factors, can shape drug responses. Furthermore, we highlight other parameters, such as concomitantly prescribed medications or liver diseases and how they modulate drug toxicity, pharmacokinetics and dynamics. Finally, we discuss recent progress in the field of in vitro toxicity models and evaluate their utility in reflecting patient-specific factors to study inter-individual differences in drug response and toxicity, as this understanding is necessary to pave the way for a patient-adjusted medicine.
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