Relationship between pyrazinamide plasma concentration and liver injury in patients with tuberculosis

Abstract

Objective To analyze the relationship between pyrazinamide plasma concentration and liver injury in patients with tuberculosis and explore the early prediction method of drug-induced liver injury (DILI) in initial treatment in patients with tuberculosis. Methods Data of tuberculosis patients (all the patients were initially treated, no other complications, and underlying disease) receiving 2HREZ/4HR treatment regimen [isoniazid, rifampicin, ethambutol, and pyrazinamide were given at the first 2 months of treatment, isoniazid and rifampicin were given at the later 4 months of treatment] in Nanjing Chest Hospital, Medical School of Southeast University from January to December 2016 were collected. According to the pyrazinamide concentration in serum on the 6th day of treatment, patients were divided into 3 groups, the 40 mg/L group. The incidences of DILI in the 3 groups were compared. Results A total of 45 patients in accordance with the criteria were collected, including 33 males and 17 females with age from 18 to 50 years and an average age of (34±10) years. Among them, 36 patients had pulmonary tuberculous, 9 patients had tuberculous pleurisy, and 5 patients had tuberculosis meningitis. The pyrazinamide concentrations in serum were 16-51 mg/L and the average concentration was (35±9) mg/L. There were 4 patients in the 40 mg/L group. Of the 45 patients, 11 patients developed DILI and the incidence was 24.4%. The pyrazinamide plasma concentrations in the 11 patients with DILI were 26 mg/L to 51 mg/L, 4 patients′ concentrations were 40 mg/L and 7 patients′ concentrations were >40 mg/L. The incidences of DILI in the 40 mg/L groups were 0/4, 14.2 %( 4/28), and 53.85% (7/13), respectively. The difference between the 20-40 mg/L and the >40 mg/L groups was statistically significant (χ2=7.708, P=0.008). Conclusions The DILI incidence in initial treatment of tuberculosis patients increased with increase of pyrazinamide plasma concentration. Early therapeutic drug monitoring for pyrazinamide could predict the occurrence of DILI and was beneficial for reducing or avoiding the effect of DILL for tuberculosis treatment. Key words: Pyrazinamide; Drug-induced liver injury; Tuberculosis