Drug-Induced Liver Injury: Mechanisms, Types and Biomarkers
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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