Hepatotoxicity of rifampin-pyrazinamide and isoniazid preventive therapy and tuberculosis treatment.

Background: Severe liver injury has been attributed to preventive treatment of latent tuberculosis infection with a 2-month course of rifampin-pyrazinamide.
Methods: A retrospective cohort study in The Netherlands compared the hepatotoxicity of preventive treatment with rifampin-pyrazinamide with that of preventive treatment with isoniazid, and also with that of treatment for active tuberculosis containing at least isoniazid, rifampin, and pyrazinamide.
Results: Preventive treatment with rifampin-pyrazinamide caused severe hepatotoxicity more often than did preventive treatment with isoniazid (odds ratio [OR], 2.61; 95% confidence interval [CI], 1.26-5.39; P=.012), especially in patients <25 years old. It also caused severe hepatotoxicity more often than triple- or quadruple-drug tuberculosis treatment (OR, 2.61; 95% CI, 1.21-5.59; P=.016), especially if the pyrazinamide dose was > or =30 mg/kg. Preventive treatment with rifampin-pyrazinamide was more hepatotoxic even when the advised pyrazinamide dose of up to 20 mg/kg for preventive treatment was compared with the pyrazinamide dose of 30 mg/kg for tuberculosis treatment.
Conclusions: Preventive treatment with rifampin-pyrazinamide causes severe hepatotoxicity more often than does preventive treatment with isoniazid or curative treatment for tuberculosis.