Drug-induced liver injury: mechanisms, types and biomarkers

• Published in: Current medicinal chemistry Vol. 20; no. 24; p. 3011
• Main Authors: Vinken, M, Maes, M, Vanhaecke, T, Rogiers, V
• Format: Journal Article
• Language: English
• Published: United Arab Emirates 01-08-2013
• Subjects: Alanine Transaminase - analysis; Alkaline Phosphatase - analysis; Aspartate Aminotransferases - analysis; Biomarkers - analysis; Chemical and Drug Induced Liver Injury; Cholestasis - chemically induced; Drug-Related Side Effects and Adverse Reactions; Fatty Liver - etiology; Humans; Liver - drug effects; Liver - immunology; Liver - metabolism; Liver - pathology; Liver Cirrhosis; Metabolomics; Mitochondria, Liver - drug effects; Mitochondria, Liver - metabolism; Proteomics; Risk Factors
• ISSN: 1875-533X
• DOI: 10.2174/0929867311320240006

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.