Immune-mediated drug-induced liver injury

Abstract

Drug-induced liver injury (DILI) has previously been classified into immunologic or metabolic idiosyncracy. Metabolic idiosyncrasy implies that a subject developing adverse reaction metabolises the drug in a different way than the most individuals or lacks adequate protective mechanisms to neutralise reactive metabolites formed. An immunologic idiosyncrasy implies that the susceptible individual has an immune system that would more readily recognise the formed neoantigens. Alternatively, immune system through cytokines and chemokines may modulate the degree of hepatic inflammation secondary to toxic injury. However, this classification derived from clinical observations such as latent period, presence or absence of manifestations attributable to hypersensitivity and pattern of response to re-challenge is too simplistic to be accurate. Increasingly, it is evident that the development of idiosyncratic DILI is a multistep process involving both metabolic and immunologic factors.