[Severe hepatotoxicity of tuberculostatic agents. Increase in the incidence].

Hepatotoxicity by antituberculous drugs is well known. Nonetheless, severe liver involvement is infrequent. Several series of fulminant hepatitis by antituberculous drugs have recently been reported with a much greater frequency than previously reported. The present study describes the authors' experience which, similar to other groups, has shown a marked increase with respect to previous experience. During 1994 5 patients with acute severe hepatitis associated to antituberculous drugs were admitted to the authors' unit. The mean age of the patients was 43 years (range: 25-62). Two patients were healthy HBsAg carriers, one undergoing enzymatic inducer treatment and was anti-HIV positive. Another patient presented compensated liver cirrhosis by HCV. The 5 cases received combined isoniazid and rifampicin and four had also received pyrazinamide. Four patients presented hepatic encephalopathy. Of these cases, three could not undergo emergency liver transplantation because of contraindications and died due to complications of acute severe liver failure. Another patient evolved favorably following emergency liver transplantation. The only patient who presented good evolution with conservative treatment and who did not present hepatic encephalopathy had discontinued isoniazid because of the finding of slight hypertransaminasemia during a routine analytical control. Several risk factors have been reported for the appearance of hepatotoxicity by antituberculous drugs. The factor of greatest clinical importance for the development of severe hepatotoxicity is probably continuation of the treatment once hepatic dysfunction has initiated. The important increase in cases of severe toxicity urges the need for strict analytical monitoring following initiation of treatment.