Context: Isoniazid preventive therapy for latent tuberculosis (TB) infection has been debated because of the risk of hepatotoxicity. The frequency of hepatotoxicity was 0.5% to 2.0% in early studies but may have changed with new criteria for diagnosis and patient selection.
Objective: To determine the rate of isoniazid hepatotoxicity in patients managed according to current guidelines and practice standards.
Design: Prospective cohort study.
Setting: A public health clinic operated by the TB control program of a city-county public health agency.
Patients: A total of 11141 consecutive patients who started a regimen of isoniazid preventive therapy for latent TB infection from January 1989 through December 1995.
Main outcome measures: The rate of developing symptoms and signs of hepatotoxicity among all persons starting isoniazid preventive therapy, among all those completing therapy, and by age, sex, and race.
Results: Eleven patients (0.10% of those starting, and 0.15% of those completing treatment) had hepatotoxic reactions to isoniazid during preventive treatment. The rate of hepatotoxicity in persons receiving preventive therapy increased with increasing age (chi2 for linear trend = 5.22, P=.02) and there were trends toward increased rates in women (odds ratio [OR], 3.30; 95% confidence interval [CI], 0.87-12.45; chi2 = 3.28; P=.07) and in whites (OR, 2.60; 95% CI, 0.75-8.95; chi2 = 3.08; P=.08).
Conclusions: The rate of isoniazid hepatotoxicity during clinically monitored preventive therapy was lower than has been reported previously. Clinicians should have greater confidence in the safety of isoniazid preventive therapy.