[Drug-induced liver injury]

Abstract

Drugs may cause acute or chronic liver damage depending on their mode of action. Hepatotoxic drugs include anaesthetics, psychotropic and anticonvulsant drugs, antiinflammatory agents, steroids, antimicrobial agents and cardiovascular drugs as well as antineoplastic agents. Hepatotoxic agents, including drugs, fall into two categories: (i) intrinsic and obligatory liver toxins with dose-dependent and predictable adverse effects, and (ii) facultative (idiosyncratic) hepatotoxins with non-predictable and non-dose-dependent liver toxicity affecting only few exposed individuals. Intrinsic hepatotoxins may either injure hepatocytes directly, e.g. by direct physicochemical effects, or indirectly by interfering with specific metabolic processes. In the idiosyncratic type of liver injury immunologic hypersensitivity reactions or toxic metabolites may be involved. Clinical and morphologic consequences of adverse drug reactions are acute or chronic liver diseases, including parenchymal damage (finally leading to necrosis or apoptosis), steatosis, cholestasis, various types of vascular alterations, granuloma formation and also neoplastic transformation. Thus, drugs are important causes of liver diseases and may account for up to 40% of cases of hepatitis and up to 25% of fulminant hepatic failure. Moreover, drug-induced injury also plays a leading role as cause of acute cholestasis.