Daño hepático inducido por drogas

Abstract

Drug induced liver disease is responsible of about 5% of hospital admissions for jaundice in USA, and 10% of acute hepatitis in France and North Europe, In addition, 20 to 50% of the cases of fulminant hepatic failure in USA are due to drugs. Traditionally drug induced liver disease has been divided in two groups: 1. Non predictable toxicity (idiosyncratic reaction). 2. Predictable toxicity (Intrinsic toxicity). From the clinical point of view, most of the patients present jaundice associated with elevation of aminotransferases and alkaline phosphatase. However, some patients presents acute liver failure and death. The duration of illness permit another classification in two groups: acute, frequently characterized by microvesicular steatosis; a picture similar to acute viral hepatitis or biliary obstruction (cholestatic jaundice) with elevated alkaline phosphatase and pruritus. Chronic, manifested by different presentations such as acute hepatitis, chronic hepatitis (autoimmune), sclerosing cholangitis, phospholipidosis and non cirrhotic or cirrhotic portal hypertension. Histologically drug toxicity can induce the following morphologic changes: a) Pure cholestasis more frequently seen with estrogens, b) Viral hepatitis like, c) Fulminant hepatic failure more commonly seen with halothane, acetaminophen, phenytoin and methyldopa shows multilobular necrosis frequently associated with hypersensitivity features (fever, pruritus, eosinophilia). d) Cirrhosis.

Drug toxicity induced by prolonged exposure to the specific agent (chronic toxicity) more frequently presents with the following features: a) Steatosis: valproic acid, b) Cholestasis: chlorpromazine. c) Chronic active hepatitis, d) Phospholipidosis, antiarrhytmics. e) Portal hypertension: methyldopa, oxifenisatin, chlorpromazine, methotrexate.

Other unusual manifestations of drug toxicity are: Vascular: Budd Chiari syndrome: contraceptives. Venooclusive disease, pirralidizine alkaloids, bush tea, azathioprine. Peliosis hepatica: anabolics, contraceptives. Hypersensitivity: granulomatous hepatitis. Hepatic tumors: anabolic steroids, contraceptives, vinyl chloride.

Liver toxicity in general occurs more frequently as a result of metabolic transformation of the original compound. These biochemical changes results in products with intrinsic toxicity or induced haptens and hypersensitivity. The most common enzymes responsible of these changes are: cytochrome P 450 and epoxide hydrolase. Examples of drugs that suffer these changes and lead to liver toxicity are: halothane, isoniazid, acetaminophen,phenytoin. Alcohol induction of these enzymes can potentiate liver toxicity