Drug-induced liver injury: is it somehow foreseeable?
The classic view on the pathogenesis of drug-induced liver injury is that the so-called parent compounds are made hepatotoxic by metabolism (formation of neo-substances that react abnormally), mainly by cytochromes P-450 (CYP), with further pathways, such as mitochondrial dysfunction and apoptosis, also playing a role. Risk factors for drug-induced liver injury include concomitant hepatic diseases, age and genetic polymorphisms of CYP. However, some susceptibility can today be predicted before drug administration, working on the common substrate, by phenotyping and genotyping studies and by taking in consideration patients' health status. Physicians should always think of this adverse effect in the absence of other clear hepatic disease. Ethical and legal problems towards operators in the health care system are always matters to consider.
Tarantino
Giovanni
G
Di Minno
Matteo Nicola Dario
MN
Capone
Domenico
D
D000367:Age Factors; D000818:Animals; D002118:Calcium / Q000378:metabolism; D056486:Chemical and Drug Induced Liver Injury / Q000453:epidemiology / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000378:metabolism; D019587:Dietary Supplements; D004198:Disease Susceptibility; D004347:Drug Interactions; D064420:Drug-Related Side Effects and Adverse Reactions; D005838:Genotype; D006801:Humans; D006969:Hypersensitivity, Immediate; D015227:Lipid Peroxidation; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008107:Liver Diseases / Q000453:epidemiology / Q000235:genetics / Q000473:pathology; D009752:Nutritional Status; D018384:Oxidative Stress; D010641:Phenotype; D012737:Sex Factors
D003577:Cytochrome P-450 Enzyme System; D002118:Calcium