The role of chronic hepatitis in isoniazid hepatotoxicity during treatment for latent tuberculosis infection

Abstract

Background: To examine chronic viral hepatitis (CVH) as a risk factor for hepatotoxicity during isoniazid (INH) treatment for latent tuberculosis infection (LTBI).

Methods: A search of MEDLINE (1966-May 2008) was conducted using the terms 'tuberculosis', 'antitubercular', 'therapeutics', 'treatment', 'prevention', 'prophylaxis', 'hepatitis', 'toxic hepatitis', 'hepatotoxic', 'liver' and 'injury'. Peer-reviewed, English-language articles describing the relationship between a history of CVH and occurrence of hepatotoxicity during LTBI treatment were selected. We limited CVH diagnoses to reports with positive serological test or biopsy for hepatitis B or C. Risk ratios and 95% confidence intervals were abstracted or derived.

Results: We reviewed 486 abstracts, and 11 studies met the selection criteria. Populations included in the studies were the general population (n = 6) and transplant recipients (n = 5). The variability in study designs and case finding practices precluded performing a quantitative meta-analysis. Two studies of former or current drug users reported a consistent, positive association between chronic hepatitis C infection and INH hepatotoxicity. Other risk ratios did not significantly or consistently show any association between CVH in patients treated for LTBI and the development of INH hepatotoxicity.

Conclusion: Owing to the limited number of published papers, CVH was not established as a risk factor for INH hepatotoxicity during LTBI treatment. Controlled studies are needed to define the safety and tolerability of LTBI treatment in those with CVH and to provide an evidence base for recommendations for LTBI treatment in persons with CVH.