Current Medicinal Chemistry

Atta-ur-Rahman, FRS
Honorary Life Fellow
Kings College
University of Cambridge
Cambridge
UK

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Drug-Induced Liver Injury: Mechanisms, Types and Biomarkers

Author(s): M. Vinken, M. Maes, T. Vanhaecke, V. Rogiers.

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.

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Article Details

VOLUME: 20
ISSUE: 24
Year: 2013
Page: [3011 - 3021]
Pages: 11
DOI: 10.2174/0929867311320240006
Price: $58