Risk factors for hepatotoxicity associated with rifampin and pyrazinamide for the treatment of latent tuberculosis infection: experience from three public health tuberculosis clinics

Authors: Lee A. M.; Mennone J. Z.; Jones R. C.; Paul W. S.

Source: The International Journal of Tuberculosis and Lung Disease, Volume 6, Number 11, November 2002 , pp. 995-1000(6)

Publisher: International Union Against Tuberculosis and Lung Disease

Abstract:

SETTING: Three municipal tuberculosis (TB) clinics.

OBJECTIVES: Reports of liver injury in patients treated with a 2-month regimen of daily rifampin and pyrazinamide (2RZ) for latent TB infection have raised concern about its safety. We aimed to evaluate the safety and tolerability of 2RZ and identify risk factors for hepatotoxicity.

METHODS: We reviewed charts of adults started on 2RZ between 1999 and 2001. Cases with grade 3 hepatotoxicity (AST or ALT >5.0–20.0 × upper limit of normal) and grade 4 hepatotoxicity (AST or ALT >20.0 × upper limit of normal) were identified.

RESULTS: Of 148 patients prescribed 2RZ, 85 (57.4%) completed therapy. Grade 3 or 4 hepatotoxicity occurred in 14 patients (eight grade 4 cases). In multivariate analysis, hepatotoxicity was associated with female sex (odds ratio [OR] 4.1; 95% confidence interval [CI] 1.2–14.3) and with presumed recent infection (recent tuberculin skin test conversion or contact with a TB case) (OR 14.3; 95%CI 1.8–115), but not with alcohol use, illicit drug use, age, race, or pyrazinamide dose.

CONCLUSIONS: Hepatotoxicity occurred in a high proportion of patients prescribed 2RZ, and was more common among females and those with recent infection. Caution is warranted in using 2RZ in populations where its safety has not been established.

Keywords: tuberculosis; hepatotoxicity; rifampin; pyrazinamide; risk factors

Language: English

Document Type: Regular paper

Affiliations: 1: Chicago Department of Public Health, Chicago, Illinois, USA

Publication date: 2002-11-01

• The International Journal of Tuberculosis and Lung Disease publishes articles on all aspects of lung health, including public health-related issues such as training programmes, cost-benefit analysis, legislation, epidemiology, intervention studies and health systems research. The IJTLD is dedicated to the continuing education of physicians and health personnel and the dissemination of information on tuberculosis and lung health world-wide.

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