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

中文翻译：

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NAT2 慢乙酰化剂表型是抗结核药物致肝毒性的重要危险因素：一项多种族嵌套病例对照研究的结果


背景 在标准疗法下，结核病患者药物性肝损伤 （DILI） 的发生率为 2% 至 28%。许多研究已经确定了抗结核 DILI 的危险因素;然而，没有一个是在多种族的真实环境中进行的。当前研究的主要结果是确定可用作多种族队列中 DILI 最佳预测因子的风险因素。方法 在米兰 Luigi Sacco 医院结核病诊所的患者中进行巢式病例对照研究。结果 该研究包括 102 例患者 （平均年龄 [SD]，45.6 [15.6] 岁）。对于每例肝毒性患者，2 个对照在性别、年龄、体重指数、结核病/结核病感染诊断和指数日期方面匹配。我们发现 N-乙酰转移酶 2 基因 （NAT2） 慢乙酰化物状态是 DILI 的最佳独立预测因子 （比值比，5.97 [95% 置信区间，1.38-25.76];P = .02]。结论 NAT2 基因型指导剂量可能有助于优化抗结核药物治疗，预防治疗失败。临床试验注册 ClinicalTrials.gov NCT06539455