Age-related risk of hepatotoxicity in the treatment of latent tuberculosis infection: a systematic review.

OBJECTIVE To determine the age-related risk of hepatotoxicity under currently recommended treatment regimens for latent tuberculosis (TB) infection (LTBI). METHODS A systematic review of the MEDLINE and EMBASE databases (from database inception to 2008) was performed to determine the risk of isoniazid (INH) and/or rifampicin hepatotoxicity in LTBI treatment stratified by patient age. Study selection, study quality assessment and data extraction were performed using piloted proformas. Rate data were meta-analysed to generate summary rates with 95%CI within age-related subgroups using a random effects model. RESULTS Seven relevant studies (18,610 participants, including 115 cases of hepatotoxicity) met the selection criteria. The median rate of hepatotoxicity was 1.8% (range 0.07-11.9). On average, rates were higher among those aged ≥ 35 years (1.7%, 95%CI 1.4-2.2) than those aged <35 years (0.2%, 95%CI 0.1-0.3). CONCLUSION The rates of hepatotoxicity were low. Summary estimates of risks generated in this review can be used for counselling individuals for whom chemoprophylaxis is recommended. The use of INH for the treatment of LTBI is safe in older patients with clinical or biochemical monitoring.