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Isoniazid Hepatotoxicity Revisited
Monitoring AST levels might be appropriate in people older than 35.
In the past, isoniazid (INH) was not prescribed routinely to asymptomatic, low-risk people who were older than 35 and had positive tuberculin tests (i.e., latent tuberculosis), because of concern about age-related hepatotoxicity. However, recent guidelines from CDC and the American Thoracic Society state that tuberculin testing should focus on people at risk for exposure or reactivation and that "a decision to test is a decision to treat," regardless of age. Thus, updated estimates of age-specific INH hepatotoxicity are of interest.
In this study from the Memphis public health department, researchers reviewed hepatotoxicity data from 3377 people with latent tuberculosis (72% black) who were started on INH between 1996 and 2003. Serum aspartate aminotransferase (AST) levels were measured at baseline and at months 1, 3, and 6; patients with mildly elevated baseline AST levels were permitted to receive INH.
Nineteen patients (0.6%) experienced hepatotoxicity (AST levels >5 times the upper limit of normal). The only predictors of hepatotoxicity were age and elevated AST levels at baseline. The age-specific incidence of hepatotoxicity per 1000 patients was 4.4 for those aged 25 to 34, 8.5 for those aged 35 to 49, and 20.8 for those aged 50 or older. Baseline AST levels higher than 40 U/L were associated with a fivefold increased risk for hepatotoxicity.
Comment: Because of nonadherence to therapy, these results might underestimate the rate of INH hepatotoxicity: Only 41% of patients completed 3 months of therapy, and 22% completed 6 months. Current guidelines do not recommend AST monitoring for INH toxicity on the basis of age alone, but these authors imply that such monitoring might be appropriate for people older than 35.
— Allan S. Brett, MD
Published in Journal Watch General Medicine August 12, 2005
Citation(s):
Fountain FF et al. Isoniazid hepatotoxicity associated with treatment of latent tuberculosis infection: A 7-year evaluation from a public health tuberculosis clinic. Chest 2005 Jul; 128:116-23.
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