Drug-induced liver injury: past, present and future

Pharmacogenomics. 2010 May;11(5):607-11. doi: 10.2217/pgs.10.24.

Abstract

Drug-induced liver injury (DILI) is a rare but potentially serious idiosyncratic reaction. By using candidate gene and genome-wide association studies, replicated associations for DILI susceptibility with HLA genes and genes relevant to drug metabolism have been detected, mainly since 2000. The HLA associations include a strong association between flucloxacillin-induced injury and the class I allele B*5701 and weaker associations for co-amoxiclav and ximelagatran DILI with the class II genotype. These associations suggest an injury mechanism involving an immune response, possibly to a complex of drug or metabolite and protein. For genes relevant to drug metabolism, the best replicated association is between isoniazid DILI and NAT2 slow acetylation. Homozygosity for GSTM1 null and/or GSTT1 null alleles also seems to be a risk factor for DILI, with associations described independently for several drugs. Other not-yet-replicated associations have been described for genes relevant to drug metabolism and oxidative stress and cytokine genes.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Alleles
  • Amoxicillin-Potassium Clavulanate Combination / adverse effects
  • Arylamine N-Acetyltransferase
  • Chemical and Drug Induced Liver Injury / genetics*
  • Drug-Related Side Effects and Adverse Reactions*
  • Forecasting
  • Genome-Wide Association Study
  • Genotype
  • Glutathione Transferase / genetics
  • Glutathione Transferase / metabolism
  • Humans
  • Isoniazid / adverse effects
  • Risk Factors

Substances

  • Amoxicillin-Potassium Clavulanate Combination
  • Arylamine N-Acetyltransferase
  • NAT2 protein, human
  • glutathione S-transferase T1
  • Glutathione Transferase
  • glutathione S-transferase M1
  • Isoniazid