Clinical manifestations and management of drug-induced liver diseases

Drug-induced hepatic injury is of major concern to clinicians, pharmaceutical manufacturers, and regulators. Classic predisposing risk factors to drug-induced liver disease include age, race, and sex. Additional factors of interest are the relationship between the dose of the drug and the extent of metabolism of an individual agent. Recent studies have focused on the role of immune response in determining the onset of drug-induced liver injury. The role of genetics with allelic differences in genes associated with the metabolism and transport of drugs and the susceptibility to liver injury is receiving considerable attention. Important genetic influences on genes in the HLA family are known to affect the likelihood of adverse hepatic reactions with several agents. Awareness of the risks of individual agents remains the most important factor in diagnosis, and withdrawal of the offending agent is the cornerstone of therapy. Recently, considerable attention has been directed toward drugs (e.g., minocycline and nitrofurantoin) that unmask or cause autoimmune hepatitis.