7. Adverse effects of LTBI treatment

The lengthy duration of treatment reduces patient compliance, while the potential occurrence of serious adverse events such as hepatitis, further discourages patients' and providers' acceptance of this therapy [50–52].

INH has the major disadvantage of potential serious adverse events. Of particular concern is hepatotoxicity, as this is difficult to detect, and can be fatal. Surveillance studies have confirmed that hepatotoxicity is quite common in patients taking INH and can be severe resulting in up to 1 per cent mortality in older patients [53].The relative risk for developing hepatotoxicity associated with isoniazid compared with placebo were 3.45 (95% CI, 1.49–7.99) for 12 weeks of treatment, 4.59 (95% CI, 2.03–10.39) for 24 weeks of treatment, and 6.21 (95% CI, 2.79–13.79) for 52 weeks of treatment in the IUAT trial [34].

In another randomized trial, rates of grade 3 and 4 adverse events were significantly lower with 4RIF than 9INH [54]. Grade 3–4 hepatotoxicity occurred in 4% of patients taking 9INH compared to less than 1% in those taking 4RIF [54].

Comparison of drug toxicity of INH and Rifampicin has been studied in many trials. Rates of hepatotoxicity among patients receiving isoniazid were 5.2, 3.7, 34 and 11.4% compared to rates among patients treated with rifampicin (0.0, 0.7 and 4.4%, respectively) [55, 56].

In PREVENT TB study, rates of grade 3 and 4 hepatotoxicity were 4.9 and 1.0% in the rifapentine plus isoniazid arm and 5.5 and 1.1% in the isoniazid-only arm, respectively [57]. The RR for grade 3 or 4 hepatotoxicity was 0.90 (95% CI, 0.75–1.08). Mortality from hepatotoxicity was reported to be 1.0% among patients on isoniazid and 0.8% on those on isoniazid plus rifapentine (RR, 0.83 [95% CI, 0.51–1.35]) [57]. Therefore, unless the index TB case has INHresistant TB or an abbreviated regimen is required in a special situation, there is no reason not to use INH for LTBI chemoprophylaxis.
