Combined therapy for latent tuberculosis with a short course of rifampicin and pyrazinamide is associated with higher risk of hepatotoxicity than isoniazid monotherapy, according to researchers in the United States.

In order to compare the tolerability of treatment with a combination of rifampicin with pyrazinamide and isoniazid as monotherapy, a prospective multicenter open-label study was carried out, which included 589 HIV-negative patients with latent tuberculosis (SCRIPT study). The first group (282 patients) received isoniazid at a dose of 300 mg per day for 6 months, and the second group (307 patients) received rifampicin 600 mg per day in combination with pyrazinamide at a dose of 20 mg / kg per day for 2 months. In all patients, the level of hepatic enzymes and bilirubin in blood serum was assessed at the time of their inclusion in the study, 1 month after the start of treatment and, in addition, in patients taking isoniazid , in addition to 4 months of treatment. Hepatotoxicity was assessed by the level of ALT in the blood serum: degree I - indicators ALT 51-125, II - 126-250, III - 251-500 and degree IV - more than 500 units / liter.

The results of the study showed that out of 207 patients who received rifampicin with pyrazinamide and were under long-term follow-up, 54 people (26%) showed signs of toxic liver damage. At the same time, of the 204 patients on isoniazid, hepatotoxicity was only recorded in 32 (16%). It should be noted that grade III and IV hepatotoxicity developed more often in patients receiving a combination of rifampicin and pyrazinamide than in the isoniazid group (7.7% and 1%, respectively; odds ratio - OR = 8.46; 95% confidence interval - CI = 1.94-76.5).

It should be noted that treatment with rifampicin and pyrazinamide had to be discontinued more often due to the development of hepatotoxicity than treatment with isoniazid (OS = 5.19; 95% CI = 1.11-49.1).

The researchers point out that the results make it possible to recommend mandatory monitoring of the level of liver enzymes during anti-tuberculosis treatment in order to rapidly detect hepatotoxicity and prevent the development of severe liver damage. The results of the study allow us to conclude that combination therapy with rifampicin and pyrazinamide is associated with a significantly higher risk of hepatotoxicity than isoniazid monotherapy and, therefore, should be used with caution.