Idiosyncratic Drug-Induced Liver Injury: Mechanisms and Susceptibility Factors

摘要: Idiosyncratic (host-dependent) and therefore unpredictable drug-induced liver injury (DILI) is rare but nevertheless has become a major clinical problem. This mainly due to the large number of drugs causing DILI consumer populations worldwide, also consequence an increased awareness inherent hepatotoxic potential many drugs. single cause for withdrawal successfully launched or discontinuation in development. chapter summarizes currently known mechanisms determinants susceptibility risk modulators patients. Certain (or their metabolites) immunoallergic reactions whose are poorly understood. In other cases nonimmune-mediated DILI, reactive intermediates electrophilic oxidative stress involved. Importantly, direct mitochondrial through distinct increasingly recognized hazard. However, it much less well understood why majority patients do not develop what underlying put small subset at risk. Genetic polymorphisms drug-metabolizing enzymes, HLA (human leukocyte antigen) haplotypes, detoxifying enzymes involved cannot fully explain low incidence. More recent paradigms based on multifactorial pathogenesis include inflammatory conditions genetic acquired abnormalities function that may increase both penetrance expressivity intrinsic toxicity drug.