title: Mechanisms of drug-induced liver injury.
abstract: OBJECTIVE
  Idiosyncratic drug-induced liver injury (iDILI) is a relatively rare condition, but can have serious consequences for the individual patient, public health, regulatory agencies and the pharmaceutical industry. Despite increased awareness of iDILI, its underlying mechanism is still not fully understood. This review summarizes the current understanding of the molecular mechanism behind iDILI.
  
  
  RESULTS
  Genetic variations in drug metabolizing genes are in line with proposed mechanisms based on acetaminophen hepatotoxicity, whereby reactive metabolites covalently bind to cellular proteins and disturb the redox balance. In addition, immune-mediated effects have been reported for flucloxacillin hepatotoxicity, demonstrating both haptenization and direct binding between the drug and immune receptors.
  
  
  CONCLUSIONS
  Idiosyncratic DILI development is believed to be orchestrated by multiple events, such as reactive metabolite formations, oxidative stress and signalling pathway inductions, with the mitochondria taking centre stage. Evidence also points towards the immune system (innate and adaptive responses) as important components in iDILI. Interindividual differences in one or more of these events, due to genetic variations and environmental factors, are likely to contribute to the idiosyncratic nature of this condition and subsequently distinguish between patient susceptibility and tolerance.
authors.affiliation: Servicio de Farmacología Clínica and UGC de Gastroenterología y Hepatología, Instituto de Investigación Biomédica de Málaga (IBIMA), Hospital Universitario Virgen de la Victoria, Universidad de Málaga, Málaga and Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd) Madrid, Spain.
authors.forename: Camilla
authors.initials: C
authors.lastname: Stephens
authors.forename: Raúl J
authors.initials: RJ
authors.lastname: Andrade
authors.forename: M Isabel
authors.initials: MI
authors.lastname: Lucena
mesh_terms: D000082:Acetaminophen / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology*; D018712:Analgesics, Non-Narcotic / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology*; D056486:Chemical and Drug Induced Liver Injury / Q000235:genetics / Q000276:immunology*; D006801:Humans; D018384:Oxidative Stress / Q000235:genetics / Q000276:immunology*; D010597:Pharmacogenetics / Q000379:methods
chemical_list: D018712:Analgesics, Non-Narcotic; D000082:Acetaminophen