Isoniazid hepatotoxicity associated with treatment of latent tuberculosis infection: a 7-year evaluation from a public health tuberculosis clinic.
OBJECTIVE
To determine the overall incidence of isoniazid (INH) hepatotoxicity in a public health tuberculosis clinic over a 7-year period, and to determine if systematic, limited aspartate aminotransferase (AST) monitoring would be of benefit in detecting INH hepatotoxicity.


METHODS
Evaluation of INH hepatotoxicity in adults aged > or = 25 years from a database maintained from fall 1996 to 2003 in a public health department clinic. Hepatotoxicity was defined as AST levels more than five times the upper limit of normal (ULN).


RESULTS
Among 3,377 patients started on INH therapy, 19 patients had AST levels more than five times the ULN, or a rate of 5.6 per 1,000 patients. Only 1 of 19 patients had prodromal symptoms associated with hepatotoxicity. After 1 month, 3 months, and 6 months of therapy, the numbers of hepatotoxic events per 1,000 patients were 2.75, 7.20, and 4.10. The age-specific numbers of hepatotoxic events per 1,000 patients were 4.40 for those from 25 to 34 years of age, inclusive; 8.54 for those between 35 to 49 years of age, inclusive; and 20.83 for those > or = 50 years old. Age > 49 years (p < 0.02) and baseline AST greater than ULN (p < 0.0003) were risk factors for hepatotoxicity.


CONCLUSIONS
Consistent with earlier trials, INH hepatoxicity is age related. Our results suggest hepatotoxicity is also related to baseline AST greater than ULN. Moderate-to-severe hepatotoxicity frequently occurs without symptoms, suggesting the value of more widespread AST monitoring.
College of Pharmacy, University of Tennessee Health Science Center, 910 Madison Ave, Room 308, Memphis, TN 38163, USA.
Francis F
FF
Fountain
Elizabeth
E
Tolley
Cary R
CR
Chrisman
Timothy H
TH
Self
D000328:Adult; D000995:Antitubercular Agents / Q000009:adverse effects*; D001219:Aspartate Aminotransferases / Q000378:metabolism; D056486:Chemical and Drug Induced Liver Injury / Q000201:enzymology / Q000208:ethnology / Q000209:etiology*; D005260:Female; D006801:Humans; D015994:Incidence; D007538:Isoniazid / Q000009:adverse effects*; D016015:Logistic Models; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D014376:Tuberculosis / Q000188:drug therapy*
D000995:Antitubercular Agents; D001219:Aspartate Aminotransferases; D007538:Isoniazid