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.
Keywords: Biomarkers, drugs, hepatotoxicity, mechanisms, hepatitis, cholestasis, steatosis, fibrosis.
Current Medicinal Chemistry
Title:Drug-Induced Liver Injury: Mechanisms, Types and Biomarkers
Volume: 20 Issue: 24
Author(s): M. Vinken, M. Maes, T. Vanhaecke and V. Rogiers
Affiliation:
Keywords: Biomarkers, drugs, hepatotoxicity, mechanisms, hepatitis, cholestasis, steatosis, fibrosis.
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.
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Cite this article as:
Vinken M., Maes M., Vanhaecke T. and Rogiers V., Drug-Induced Liver Injury: Mechanisms, Types and Biomarkers, Current Medicinal Chemistry 2013; 20 (24) . https://dx.doi.org/10.2174/0929867311320240006
DOI https://dx.doi.org/10.2174/0929867311320240006 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
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