NAT2 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 NCT06539455This retrospective study offers valuable insights into the tolerability and safety of standard antituberculosis therapy in a multiethnic real-world setting. The findings underscore the importance of assessing a patient's acetylation status before initiating antituberculosis therapy.