antituberculosis drug-induced hepatotoxicity in iranian tuberculosis patients: role of isoniazid metabolic polymorphism

the aim of this study was to determine the association of n-acetyltransferase-2 polymorphisms and anti-tuberculosis drug-induced hepatotoxicity in iranian pulmonary tuberculosis patients. acetylating phenotypes was studied in 50 iranian pulmonary tuberculosis patients using metabolic ratio of plasma acetyl-isoniazid to isoniazid. the association between hepatotoxicity and the n-acetyltransferase-2 phenotype was evaluated by using the chi-square (x2) test. the metabolic ratio had a bimodal distribution with an antimode value of 1.0. based on the metabolic ratio of the mentioned patients, 20 (40%) were slow acetylators and 30 (60%) were fast ones. hepatotoxicity was manifested in 9 of 20 slow acetylators (45%) and only in 5 of 30 rapid acetylators (16.7%). there was a significant difference in the frequency of hepatotoxicity between the slow and fast acetylators (x2 = 4.778, and p = 0.03). sex and age were not found to be risk factors for hepatotoxicity. our findings show that slow acetylation profile is significantly associated with a higher risk of developing hepatotoxicity due to the anti-tb drugs in iranian pulmonary tuberculosis patients.