Flutamide-induced acute hepatitis: investigation on the role of immunoallergic mechanisms

Flittamide is a nonsteroidal antiandrogen drug used in the treatment of prostatic cancer. Hepatotoxic reactions due to fliitamide have been reported with an incidence ranging from 1% to 5%. These reactions are usually reversible upon withdrawal of the drug but can occasionally be life-threatening. The mechanism offlutamide-associated hepatotoxicity is not well established. We report a case of a 69-year-old man with prostatic carcinoma in whoinflutamide induced an acute hepatitis which resolved completely soon after drug withdrawal. In this patient, we have studied the possible involvement of an immunological mechanism in causing fliitamide hepatitis by investigating the presence of circulating antibodies directed against reactive metabolites of fliitamide bound to liver proteins with enzyme-linked immunosorbent assay technique. Although, in the present case, we have failed to detect IgG reacting with rat liver microsomes incubated in vitro with fliitamide, this does not completely rule out the possibility of an immunological involvement in fliitamide hepatotoxicity. The possibility of severe fliitamide-related injury, independently of the underlying pathogenic mechanism, strongly suggests the need for careful monitoring of liver enzymes in patients taking this drug.