[Hepatic toxicity of antitubercular agents. Role of different drugs. 199 cases]

Presse Med. 1993 Sep 11;22(26):1212-6.
[Article in French]


One hundred and ninety-nine cases of hepatic injury related to antituberculous treatment were analysed in order to assess the role played by each drug and to look for predisposing factors. This is a retrospective study of 169 cases reported in the literature and 30 cases reported to the regional pharmacovigilance centre of Paris Saint-Antoine. The mortality rate was related to the dose of isoniazid: it was 43 percent with a daily dose higher than 300 mg, and 9 percent with a daily dose of 300 mg or less (P < 0.001). Hepatic injury appeared significantly earlier in the case of rifampicin combination: 11 weeks without rifampicin and 2 weeks with rifampicin (P < 0.01). The role of pyrazinamide was difficult to determine because isoniazid and pyrazinamide were always used in combination. The influence of a preexisting liver disease could not be evaluated because of the small number of cases reported (8 cases). Alcoholism did not increase the mortality rate. Our results confirm the dose-dependent toxicity of isoniazid. Because of the short time elapsed before the apparent onset of hepatitis observed with the rifampicin combination, a close supervision of the patients should be exerted during the first weeks of treatment.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Chemical and Drug Induced Liver Injury / etiology*
  • Chemical and Drug Induced Liver Injury / mortality
  • Child
  • Child, Preschool
  • Dose-Response Relationship, Drug
  • Drug Therapy, Combination
  • Ethambutol / therapeutic use
  • Ethambutol / toxicity*
  • Female
  • Humans
  • Infant
  • Isoniazid / therapeutic use
  • Isoniazid / toxicity*
  • Male
  • Middle Aged
  • Pyrazinamide / therapeutic use
  • Pyrazinamide / toxicity*
  • Retrospective Studies
  • Rifampin / therapeutic use
  • Rifampin / toxicity*
  • Streptomycin / therapeutic use
  • Streptomycin / toxicity*
  • Tuberculosis / drug therapy


  • Pyrazinamide
  • Ethambutol
  • Isoniazid
  • Rifampin
  • Streptomycin