Drug-induced liver injury: past, present and future.
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.
Daly
Ann K
AK
Institute of Cellular Medicine, Newcastle University Medical School, Newcastle upon Tyne, UK. a.k.daly@ncl.ac.uk
D000483:Alleles; D019980:Amoxicillin-Potassium Clavulanate Combination / Q000009:adverse effects; D001191:Arylamine N-Acetyltransferase; D056486:Chemical and Drug Induced Liver Injury / Q000235:genetics*; D064420:Drug-Related Side Effects and Adverse Reactions; D005544:Forecasting; D055106:Genome-Wide Association Study; D005838:Genotype; D005982:Glutathione Transferase / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007538:Isoniazid / Q000009:adverse effects; D012307:Risk Factors
D019980:Amoxicillin-Potassium Clavulanate Combination; D001191:Arylamine N-Acetyltransferase; D005982:Glutathione Transferase; D007538:Isoniazid; C478900:NAT2 protein, human; C413545:glutathione S-transferase T1