Genetic predisposition to drug-induced hepatotoxicity

Drug-induced hepatitis is uncommon and generally unpredictable, Hepatotoxicity may be related to the drug itself, or to chemically reactive metabolites which can bind covalently to hepatic macromolecules and may lead to either idiosyncratic, toxic hepatitis or to immunoallergic hepatitis. There is now evidence indicating that genetic variations in systems of biotransformation or detoxication may modulate either the toxic or sensitizing effects of some drugs, Thus, the genetic deficiency in a particular hepatic cytochrome P 450 isozyme (CYP 2D6) is involved in perhexiline liver injury, The deficiency in CYP 2C19 might also contribute to Atrium hepatotoxicity. Slow acetylation related to N-acetyltransferase 2 deficiency contributes to sulfonamide hepatitis, The genetic deficiency in glutathione synthetase may increase the susceptibility to several drugs including acetaminophen, A constitutional deficiency in another cell defense mechanism, still not characterized, seems to increase significantly the risk of hepatotoxicity with halothane, phenytoin, carbamazepine, phenobarbital, sulfamides and amineptine.