Severe hepatotoxicity due to anti-tuberculosis drugs in Spain

To determine the frequency of severe hepatotoxicity due to anti-tuberculosis (TB) drugs, and predictors of development of acute liver failure or of death.

A retrospective study conducted by members of the Spanish Society of Pneumology from 18 hospitals during 1997-2001. A case of severe hepatotoxicity was defined as any asymptomatic patient with a ten-fold increase in transaminases or three-fold increase in colostasis parameters, or, among patients with hepatitis symptoms, any raised hepatic parameters or development of hepatic failure. Predictive factors were studied using logistic regression, calculating odds ratios (OR) and their 95% confidence intervals (CI).

One hundred and six patients developed severe hepatotoxicity. Of a total of 3510 patients, 90 were treated for active TB (2.56%). Eleven cases (10.3%) presented with acute liver failure, three of whom underwent liver transplant. The global case fatality rate was 4.7% (five cases, three associated with alcohol use or hepatotoxic drugs). The predictors of poor prognosis were total bilirubin > 2 mg/dl (OR 9.4, 95% CI 1.0-85.5) and serum creatinine > 1.5 mg/dl (OR 32.1, 95% CI 2.4-424.6).

Severe hepatotoxicity due to anti-tuberculosis drugs is associated with a high fatality rate. Prevention should be based on informing patients and frequent clinical and laboratory controls.