Hepatotoxicity associated with isoniazid preventive therapy: a 7-year survey from a public health tuberculosis clinic

JAMA. 1999 Mar 17;281(11):1014-8. doi: 10.1001/jama.281.11.1014.


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.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antitubercular Agents / adverse effects*
  • Chemical and Drug Induced Liver Injury / epidemiology
  • Chemical and Drug Induced Liver Injury / etiology*
  • Child
  • Female
  • Humans
  • Isoniazid / adverse effects*
  • Logistic Models
  • Male
  • Middle Aged
  • Prospective Studies
  • Tuberculosis / drug therapy
  • Tuberculosis / prevention & control*


  • Antitubercular Agents
  • Isoniazid