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. 2018 Aug;104(2):326-334.
doi: 10.1002/cpt.924. Epub 2017 Nov 23.

Antituberculosis Drug-Induced Adverse Events in the Liver, Kidneys, and Blood: Clinical Profiles and Pharmacogenetic Predictors

Xuejiao Hu  1 , Mei Zhang  1 , Hao Bai  1 , Lijuan Wu  1 , Yanqing Chen  2 , Liu Ding  1 , Zhenzhen Zhao  1 , Wu Peng  1 , Tangyuheng Liu  1 , Jiajia Song  1 , Yinyu Li  3 , Xiaojun Lu  1 , Xuerong Chen  4 , Yanhong Zhou  1 , Binwu Ying  1
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Antituberculosis Drug-Induced Adverse Events in the Liver, Kidneys, and Blood: Clinical Profiles and Pharmacogenetic Predictors

Xuejiao Hu et al. Clin Pharmacol Ther. 2018 Aug.

Abstract

Antituberculosis drug-induced adverse drug reactions (ATD-ADRs) are increasing globally, and it is key to identify candidate ATD-ADRs loci for clinical management. We prospectively enrolled 1,235 highly suspicious tuberculosis (TB) inpatients to investigate the profiles and genetic risk factors of ATD-ADRs in the liver, kidneys, and blood. Overall, 644 subjects were eligible and genotyped for seven polymorphisms in drug-metabolizing enzymes and transporter genes. Clinical follow-up and blood analysis were performed regularly. We found that a notable rate of ATD-ADRs (incidence: 16.5%, drug intervention rate: 10.4%), mainly involving hepatotoxicity (10.6%) and leukopenia (3.3%) in western China. CYP2D6 rs1135840 and NUDT15 rs116855232 increased the risks of hepatotoxicity and leukopenia with an odds ratio of 2.52 and 4.97, respectively. Both variants showed excellent negative predictive values (93.7% and 98.1%, respectively) but moderate sensitivities (72.7% and 52.4%, respectively). These data provide new insight into ATD-ADRs in the Chinese population and may offer future leads for diagnosis and treatment.

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Figure 1
Figure 1
Flow chart of the study population. PTB, pulmonary tuberculosis; EPTB, extrapulmonary tuberculosis; anti‐TB, antituberculosis.
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