Drug-induced liver injury: mechanisms, types and biomarkers

Curr Med Chem. 2013;20(24):3011-21. 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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


  • Biomarkers
  • Aspartate Aminotransferases
  • Alanine Transaminase
  • Alkaline Phosphatase