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A 7-Year Survey From a Public Health Tuberculosis Clinic

Charles M. Nolan, MD; Stefan V. Goldberg, MD; Susan E. Buskin, PhD

JAMA. 1999;281:1014-1018.

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 11,141 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 (² 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; ²=3.28; P=.07) and in whites (OR, 2.60; 95% CI, 0.75-8.95; ²=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.

Author Affiliations: Seattle-King County Department of Public Health (Drs Nolan, Goldberg, and Buskin), and the Departments of Medicine (Drs Goldberg and Nolan) and Epidemiology (Dr Buskin), University of Washington, Seattle.

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