Isoniazid-rifampin fulminant hepatitis. A possible consequence of the enhancement of isoniazid hepatotoxicity by enzyme induction.
The authors report 6 cases of fulminant hepatitis in patients treated with isoniazid and rifampin. In 4 of these patients, the treatment had been started within 3 days after a general anesthesia. The course of the disease was remarkably similar in all 6 patients: (1) the time interval from the beginning of the isoniazid-rifampin administration to the onset of jaundice was 6 to 10 days; (2) disorders of consciousness appeared less than 3 days after the onset of jaundice; (3) serum transaminases were 26 to 80 times the upper limit of normal; (4) the main liver lesion was centrilobular necrosis; (5) hypersensitivity manifestations were absent; (6) all 6 patients recovered. Fulminant hepatitis might be attributable to a hepatotoxic metabolite of isoniazid, the production of which would be attributable to a hepatotoxic metabolite of isoniazid, the production of which would be increased as a consequence of the enzyme-inducing effect of rifampin and, possibly, other drugs administered for general anesthesia.
D000293:Adolescent; D000328:Adult; D000368:Aged; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology* / Q000473:pathology; D004790:Enzyme Induction; D005260:Female; D006801:Humans; D007538:Isoniazid / Q000009:adverse effects*; D008099:Liver / Q000187:drug effects*; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology; D012293:Rifampin / Q000009:adverse effects*
D007538:Isoniazid; D012293:Rifampin