S11: Morphology of drug-induced hepatotoxicity

Abstract

The liver is the major site for drug metabolism. It is not surprising, therefore, that drug toxicity and adverse drug reactions frequently affect the liver. Drug-induced liver disease represents an important problem. More than 1100 drugs have been implicated in causing liver disease at the least on rare occasions. Drug-induced liver injury appears to account for about 10% of hepatitis in adults and more than 40% of cases of hepatitis among patients over 50 years of age. Most forms of drug injury are less common in children compared to adults. Some forms of drug-induced liver disease, however, are more common in children, e.g. valproic and aspirin-induced injury. Up to 25% of cases of fulminat hepatic failure and 20–50% of cases of non-viral chronic hepatitis may be drug induced. Hepatic manifestations of drug-induced liver injury can mimic almost the entire spectrum of liver diseases. The predominant clinical presentations, however, resemble either acute hepatitis (from hepatocellular injury) or cholestatic liver disease. Acute hepatotoxic injuries develop over a relatively short time and show no histopathological features of chronicity. Subacute hepatotoxicity includes damage developing over weeks to months, with fibrosis and possibly cellular regeneration. Chronic hepatotoxic lesions include those with fibrosis or cirrhosis, predominantly vascular lesions and neoplasia. Some drugs can cause clinical liver disease indistinguishable from autoimmune hepatitis. In addition to hepatocellular necrosis, hepatoxicity with some drugs is manifested as acquired phospholipidosis (e.g. amiodarone), steatohepatitis (e.g. amiodarone, tamoxifen), and microvesicular steatosis (e.g. valproate, tetracycline, aspirin).