Cheli Stefania, Torre Alessandro, Schiuma Marco, Montrasio Cristina, Civati Aurora, Galimberti Miriam, Battini Vera, Mariani Ilaria, Mosini Giulia, Carnovale Carla, Radice Sonia, Clementi Emilio, Gori Andrea, Antinori Spinello
ICPS, Pharmacovigilance & Clinical Research, Department of Biomedical and Clinical Sciences, ASST Fatebenefratelli Sacco, University Hospital Luigi Sacco, Università Degli Studi di Milano, Milan, Italy.
III Infectious Disease Unit, ASST Fatebenefratelli Sacco, Luigi Sacco Hospital, Milan, Italy.
Clin Infect Dis. 2025 Aug 1;81(1):145-152. doi: 10.1093/cid/ciae583.
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.
A nested case-control study was conducted in patients at the tuberculosis clinic of Luigi Sacco Hospital in Milan.
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].
NAT2 genotype-guided dosing may help optimize antituberculosis drug treatment and prevent treatment failure.
ClinicalTrials.gov NCT06539455.
在标准治疗下，结核病患者药物性肝损伤（DILI）的发生率为2%至28%。众多研究已确定抗结核药物性肝损伤的危险因素；然而，尚无研究在多民族现实环境中开展。本研究的主要目的是确定在多民族队列中可作为药物性肝损伤最佳预测指标的危险因素。
在米兰路易吉·萨科医院结核病门诊患者中开展了一项巢式病例对照研究。
该研究纳入了102例患者（平均年龄[标准差]，45.6[15.6]岁）。对于每例发生肝毒性的患者，匹配2例在性别、年龄、体重指数、结核病/结核感染诊断及索引日期方面与之相同的对照。我们发现N - 乙酰转移酶2基因（NAT2）慢乙酰化状态是药物性肝损伤的最佳独立预测指标（比值比，5.97[95%置信区间，1.38 - 25.76]；P = 0.02）。
NAT2基因型指导下的给药可能有助于优化抗结核药物治疗并预防治疗失败。
ClinicalTrials.gov NCT06539455。
