polymorphism and clinical factors that increase antituberculosis drug-induced hepatotoxicity.

Hepatotoxicity is a known adverse effect of antituberculosis drugs. The gene polymorphism has been associated with an increased risk of antituberculosis drug-induced hepatotoxicity (ATDIH). This study investigates the association of polymorphism and clinical risk factors that may contribute to the development of ATDIH. The authors sequenced the region of 33 tuberculosis patients who developed ATDIH and 100 tuberculosis patients who did not develop ATDIH during tuberculosis treatment. haplotypes were inferred and NAT2 acetylator status was predicted from the combination of the inferred haplotypes. Multiple logistic regression was performed to identify possible factors that are associated with ATDIH. The TT genotype of and the AA genotype of were found to be substantially linked with the risk of ATDIH, with odds ratios of 3.09 (95% CI: 1.37-6.95) and 3.07 (95% CI: 1.23-7.69), respectively. NAT2 slow acetylators are 3.39-times more likely to develop ATDIH. Factors that were associated with ATDIH include underlying diabetes mellitus (adjusted odds ratio [AOR]: 2.96; 95% CI: 1.05-8.37), pre-treatment serum bilirubin (AOR: 1.09; 95% CI: 1.02-1.16) and NAT2 slow acetylator (AOR: 3.77; 95% CI: 1.51-9.44). Underlying diabetes mellitus, having a higher baseline bilirubin and being a slow acetylator are identified as the risk factors associated with ATDIH among patients in Malaysia.