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Hepatotoxicity
Drug-induced liver injury (DILI), also described as hepatotoxicity due to medications, is a common and potentially serious cause of acute and chronic liver disease. Many drugs have the capacity to cause hepatotoxicity ( Fig. 169.1 ). In addition, a growing list of over-the-counter medications, supplements, and herbal remedies have been associated with liver injury. Hepatotoxicity may be acute or chronic; occasionally, they can result in severe acute hepatitis or fulminant hepatitis/liver failure requiring emergency liver transplantation, whereas in other cases it may result in chronic liver disease and liver cirrhosis.
Drug-Induced Hepatic Injuries.
Classification
DILI has been classified as idiosyncratic or intrinsic. Idiosyncratic drug reactions are not predictable, can occur with different amounts of exposure, and are highly variable in clinical presentation. Age, gender, and genetic factors may influence drug metabolism and immune response, as may dietary factors such as protein and alcohol intake. Intrinsic hepatotoxicity is generally a feature of agents that are inherently hepatotoxic or that produce toxic metabolites which can lead to liver injury.
Intrinsic Hepatotoxicity
Intrinsic hepatotoxins may cause liver injury through the production of free radicals or toxic metabolites. This type of hepatotoxicity is characteristically dose related and common among exposed persons, although many variables may influence the development of intrinsic hepatotoxicity. The agent may be directly toxic to cell membranes leading to hepatocellular necrosis; occasionally, there may be accompanying steatosis or cholestasis. In some cases, the toxic agent is produced in context of metabolism in the liver. The classic example of an intrinsic hepatotoxin is carbon tetrachloride (CCl 4 ), which is converted to a toxic metabolite that results in lipid peroxidation, thus causing damage to cell membranes ( Fig. 169.2 ).
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