Hepatotoxicity due to rifampicin, isoniazid and pyrazinamide in patients with tuberculosis: is anti-HCV a risk factor?

BACKGROUND AND RATIONALE: Among the adverse events related to tuberculosis treatment, hepatotoxicity is the most serious, and recognition of risk factors for it is essential to achieve successful therapy. The aim of the study is to evaluate the role of anti-HCV as a risk factor for hepatotoxicity in hospitalized patients under tuberculosis treatment with rifampicin, isoniazid and pyrazinamide (RHZ).

METHODS: Historical cohort study carried out at Hospital Sanatório Partenon, from 1998 to 2006. Patients aged 18 years or older, tested for anti-HCV, who presented normal pre-treatment aminotransferases (AST, ALT) and bilirrubin and who used RHZ during hospitalization were included in the study. Individuals who used anti-tuberculosis drugs six months prior to hospitalization, had clinical evidence of chronic liver disease or showed previous history of hepatotoxicity to RHZ were excluded.

RESULTS: A sample of 534 patients was studied. The incidence of hepatotoxicity was 8.8% (n = 47). After univariate analysis, the following variables were associated to hepatotoxicity: anti-HIV positive, anti-HCV positive, use of antiretroviral therapy and high doses of rifampicin and isoniazid per kg of body weight (p < 0.05). When Cox regression was performed, anti-HIV positive [RR = 2.3 (IC(95% )1.2-4.1); p = 0.008] and high doses of isoniazid per kg of body weight [RR = 1.3 (IC(95%) 1.1-1.7); p = 0.016] remained independently associated to development of hepatotoxicity.

CONCLUSIONS: In conclusion, the anti-HIV positive and high doses of isoniazid were considered independent risk factors for hepatotoxicity due to RHZ esqueme in the present study. Though univariate analysis showed that anti-HCV was associated to the outcome, it was not identified as an independent risk factor for hepatotoxicity related to the use of RHZ when the analysis was controlled to HIV.