A PROSPECTIVE CLINICAL-STUDY OF ISONIAZID-RIFAMPICIN-PYRAZINAMIDE-INDUCED LIVER-INJURY IN AN AREA ENDEMIC FOR HEPATITIS-B

In order to evaluate the incidence, predisposing factors and clinical course of antituberculous drug-induced liver injury in hepatitis B sur face antigen (HBsAg)-positive carriers and non-carriers, in an area en demic for hepatitis B, we prospectively followed 240 patients (154 mal e, 86 female; mean age 40 years) who had received daily isoniazid, rif ampicin, ethambutol and pyrazinamide for the treatment of pulmonary tu berculosis. Patients with heavy alcohol consumption, with pretreatment serum alanine aminotransferase (ALT) elevation and who had less than 3 months post-treatment follow-up were excluded from the study. Thirty -one (13%) patients were positive for serum HBsAg before treatment. Si xty-three (26%; 95% CI: 21-32%) patients developed antituberculous dru g-induced liver injury. The incidence of drug-induced liver injury was significantly more frequent in patients > 35 years of age than in pat ients less than or equal to 35 years of age (33 vs 17%; P< 0.05), but was not different between HBsAg carriers and non-carriers (29 vs 26%; P> 0.05). Using step-wise logistic regression analysis, patient age > 35 years was the only independent variable for predicting antitubercul ous drug-induced liver injury, while sex, acetylator phenotype, HBsAg carrier status and severity of tuberculosis were not. The peak serum A LT levels in antituberculous drug-induced liver injury were not signif icantly different between HBsAg carriers and non-carriers. Only one 61 -year-old HBsAg carrier developed severe jaundice after 6 months antit uberculous therapy; he subsequently died of hepatic failure. In conclu sion, the incidence of antituberculous drug-induced liver injury was s ignificantly higher in patients > 35 years of age than in patients les s than or equal to 35 years of age, but was not different between HBsA g carriers and non-carriers. Mortality occurred in an aged HBsAg carri er superimposed with antituberculous drug-induced liver injury.