Background: Under standard therapies, the incidence of drug-induced liver injury (DILI) in patients with tuberculosis ranges from 2% to 28%. Numerous studies have identified the risk factors for antituberculosis DILI; however, none have been conducted in a multiethnic real-world setting. The primary outcome of the current study was to identify the risk factors that could be used as the best predictors of DILI in a multiethnic cohort.
Methods: A nested case-control study was conducted in patients at the tuberculosis clinic of Luigi Sacco Hospital in Milan.
Results: The study included 102 patients (mean age [SD], 45.6 [15.6] years). For each patient with hepatotoxicity, 2 controls were matched for sex, age, body mass index, tuberculosis/tuberculosis infection diagnosis, and index date. We found that N-acetyltransferase 2 gene (NAT2) slow acetylator status was the best independent predictor of DILI (odds ratio, 5.97 [95% confidence interval, 1.38-25.76]; P = .02].
Conclusions: NAT2 genotype-guided dosing may help optimize antituberculosis drug treatment and prevent treatment failure.
Clinical trials registration: ClinicalTrials.gov NCT06539455.
Keywords: NAT2 genotype; antituberculosis drugs; hepatotoxicity; slow acetylator; tuberculosis.
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