DELETERIOUS INFLUENCE OF PYRAZINAMIDE ON THE OUTCOME OF PATIENTS WITHFULMINANT OR SUBFULMINANT LIVER-FAILURE DURING ANTITUBERCULOUS TREATMENT INCLUDING ISONIAZID

Isoniazid and pyrazinamide are well-known hepatotoxic drugs, often use d in combination. The aim of this study was to assess the prognostic i nfluence of pyrazinamide on the outcome of fulminant or subfulminant l iver failure caused by antituberculous therapy. Eighteen patients with fulminant or subfulminant liver failure due to antituberculous therap y were studied. Nine patients received isoniazid and rifampicin withou t pyrazinamide (group 1), and nine patients received isoniazid and rif ampicin together with pyrazinamide (group 2). The severity of fulminan t and subfulminant liver failure, as judged by the prevalence of coma and the lowest level of factor V, was similar in the two groups. Spont aneous survival was greater in group 1 (eight of nine) than in group 2 (two of nine) (P < .02). The authors conclude that pyrazinamide co-ad ministration was associated with an increased mortality in patients wi th fulminant or subfulminant hepatitis occurring during antituberculou s therapy, In these patients, pyrazinamide administration and an inter val of more than 15 days between the onset of antituberculous treatmen t and jauudice, combined with grade III encephalopathy and factor V be low 20%, predicted death without liver transplantation.