<i>NAT2</i> Slow Acetylator Phenotype as a Significant Risk Factor for Hepatotoxicity Caused by Antituberculosis Drugs: Results From a Multiethnic Nested Case-Control Study

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.