title: Drug-induced liver injury: mechanisms, types and biomarkers.
abstract: Drug-induced liver injury is a ubiquitous issue in clinical settings and pharmaceutical industry. Hepatotoxicity elicited by drugs may be intrinsic or idiosyncratic, both which are driven by different molecular mechanisms. Recently, a unifying mechanistic model of drug-induced liver injury has been introduced. According to this model, drug-induced hepatotoxicity relies on 3 consecutive steps, namely an initial cellular insult that leads to the occurrence of mitochondrial permeability transition, which in turn ultimately burgeons into the onset of cell death. Clinically, drug-induced liver injury can be manifested in a number of acute and chronic conditions, including hepatitis, cholestasis, steatosis and fibrosis. These pathologies can be diagnosed and monitored by addressing well-established physical, clinical chemistry and histopathological biomarkers. In the last few years, several novel read-outs of drug-induced liver injury have been proposed, involving genetic, epigenetic, transcriptomic, proteomic and metabolomic parameters. These new concepts and recent developments in the field of drug-induced liver injury are revised in the current paper.
authors.affiliation: Department of Toxicology, Center for Pharmaceutical Research, Vrije Universiteit Brussel, Laarbeeklaan 103, B-1090 Brussels, Belgium. mvinken@vub.ac.be
authors.forename: M
authors.initials: M
authors.lastname: Vinken
authors.forename: M
authors.initials: M
authors.lastname: Maes
authors.forename: T
authors.initials: T
authors.lastname: Vanhaecke
authors.forename: V
authors.initials: V
authors.lastname: Rogiers
mesh_terms: D000410:Alanine Transaminase / Q000032:analysis; D000469:Alkaline Phosphatase / Q000032:analysis; D001219:Aspartate Aminotransferases / Q000032:analysis; D015415:Biomarkers / Q000032:analysis; D056486:Chemical and Drug Induced Liver Injury; D002779:Cholestasis / Q000139:chemically induced; D064420:Drug-Related Side Effects and Adverse Reactions; D005234:Fatty Liver / Q000209:etiology; D006801:Humans; D008099:Liver / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008103:Liver Cirrhosis; D055432:Metabolomics; D008930:Mitochondria, Liver / Q000187:drug effects / Q000378:metabolism; D040901:Proteomics; D012307:Risk Factors
chemical_list: D015415:Biomarkers; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D000469:Alkaline Phosphatase