PREDISPOSING FACTORS IN HEPATITIS INDUCED BY ISONIAZID-RIFAMPIN TREATMENT OF TUBERCULOSIS

Abstract

Patients (75) who developed mild hepatic reactions (serum transaminase concentrations of 45-149 units) and 50 patients who showed more serious liver damage (serum transaminase values > 150 units/l) were compared with 261 consecutive patients who had no liver reactions during treatment with rifampin and isoniazid. Generally, liver toxicity occurred in 18% of patients receiving combined anti-tuberculous drug therapy. Small increases in transaminase occurred in 14% of the patients; large increases occurred in 4%. Elderly women comprised a risk group. Among patients exhibiting a more serious hepatic lesion (transaminase values > 150 units/l), alcoholics, mostly men, formed another risk group, together with other patients with a history of previous liver or biliary disease. Of 261 patients who did not develop a liver reaction, 57% were slow isoniazid acetylators. In this study, the groups with small and large increases in transaminase were clearly separated; in the former group there was no preponderance of phenotype, whereas in the latter group, slow acetylators clearly dominated among early (1st 4, wk of treatment) hepatic reactions (P < 0.01). Studies of single-drug regimens of isoniazid showed that slow rapid acetylation had no causal influence on isoniazid-induced hepatitis. Because the metabolism of rifampin is independent of the acetylation process, rifampin and isoniazid in combination seem to cause a toxic hepatitis that differs from the hepatitis induced by either drug separately.