[Hepatotoxicity of tyrosine kinase inhibitors: Mechanisms involved and practical implications]

Abstract

Tyrosine kinase inhibitors (TKIs) are used for the targeted treatment of solid cancers. TKIs produce a variable incidence of liver adverse events (5-25%) which can progress to severe liver injury in a minority of patients if treatment is maintained despite ongoing injury. This risk requires careful patient management to maintain treatment benefit without harm. This review highlights the various mechanisms of idiosyncratic hepatotoxicity, the formation of reactive metabolites and how this leads to toxicity. These critical events depend of the drug-specific characteristics of each TKI and the patient risk factors, especially genetic characterization. With improved understanding of the mechanisms leading to hepatotoxicity, several strategies have been adopted to prevent or treat this side effect. Recommendations on liver function liver test monitoring have been proposed according to each TKI.

Keywords: Hepatotoxicity; Inhibiteurs des tyrosines kinases; Monitoring recommendations; Métabolites réactifs; Reactive metabolites; Recommandations de surveillance; Tyrosine kinase inhibitors; hépatotoxicité.