Isoniazid-associated hepatitis in 114 patients.
Analysis of the overt hepatic disease that developed in 114 patients while taking isoniazid for chemoprophylaxis of tuberculosis showed it to be mainly hepatocellular. The severity of the hepatic injury was manifested by the 13 fatalities (12.3%) and by the histological demonstration of submassive necrosis in 9 and massive necrosis in 4 patients. The 20 other patients from whom hepatic tissue was available for study included 16 with moderately severe acute hepatocellular injury (4 had a mixed hepatocellular-cholestatic pattern), and 4 with chronic hepatic diseases (1 had cirrhosis). Clinical manifestations of hepatic disease prior to the onset of jaundice included vague digestive complaints in 55% of the group and "viral' disease-like complaints in 35%, some with and some without gastrointestinal symptoms. Jaundice was the presenting complaint in 10% of patients. Fever and rash were reported in very few patients (less than 4%) and eosinophilia of modest degree was noted in approximately 10%. Hepatic injury was recognized during the 1st month of isoniazid administration in 15% and during the 2nd month in an additional 31%. In the remaining 54% of patients, the drug had been administered for periods of 2 to 11 months before hepatic injury was noted. Analyses of variables suggested that hepatic injury which presented after 2 months, especially with bilirubin levels that exceeded 20 mg per 100 ml, was more likely to have a fatal outcome than disease that presented during the first 2 months even with higher bilirubin levels. The case fatality rate was significantly higher in black females than in black males or in whites of either sex. The observations of the present study offer no support for the view that isoniazid-induced hepatic disease results from hypersensitivity to the drug. Other data that support the view that hepatotoxic metabolites of isoniazid may be responsible for the injury are considered.
D000367:Age Factors; D000410:Alanine Transaminase / Q000097:blood; D000469:Alkaline Phosphatase / Q000097:blood; D044466:Asian People; D001219:Aspartate Aminotransferases / Q000097:blood; D001663:Bilirubin / Q000097:blood; D044383:Black People; D056486:Chemical and Drug Induced Liver Injury / Q000097:blood / Q000209:etiology* / Q000473:pathology; D005260:Female; D006400:Hematocrit; D006801:Humans; D007538:Isoniazid / Q000009:adverse effects*; D008099:Liver / Q000473:pathology; D008297:Male; D012737:Sex Factors; D013997:Time Factors; D014376:Tuberculosis / Q000517:prevention & control; D014481:United States; D044465:White People; D001741:Black or African American
D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D000469:Alkaline Phosphatase; D001663:Bilirubin; D007538:Isoniazid