Evaluation of isoniazid-associated hepatitis by immunological tests

In a retrospective study of patients developing hepatitis or persistent serum glutamic oxaloacetic transaminase (SGOT) elevations while receiving isoniazid, it was found that the lymphocyte transformation test (LTT) was positive in nineteen cases (95%) in response to stimulation by isoniazid, isonicotinic acid and conjugates of these compounds with human serum albumin. However, no significant amount of antibody against isoniazid was detected in the sera of these patients by a sensitive radioimmunoassay. By contrast, no positive LTT was seen in normal controls or in patients receiving isoniazid without evidence of liver damage, while in patients with transient SGOT abnormalities, the LTT was positive only at the time of liver dysfunction. There was no correlation between the degree of lymphocyte transformation and the severity of liver damage. However, there were differences in the patterns of response to the four stimulatory preparations used. Thus patients with overt hepatitis most frequently responded to isoniazid, while individuals with only SGOT abnormalities showed stimulation in the LTT more often with a conjugate of isonicotinic acid and human serum albumin. It appears, therefore, that the presence of isoniazid-induced liver damage is associated with the presence of cellular hypersensitivity to the drug. The differences in lymphocyte reactivity in the two groups might indicate a potential means of predicting which individuals are at increased risk of developing overt hepatitis when exhibiting evidence of minor liver dysfunction while receiving isoniazid.