NAT2慢乙酰化表型是抗结核药物引起肝毒性的重要危险因素:来自多种族巢式病例对照研究的结果

IF 8.2 1区 医学 Q1 IMMUNOLOGY Clinical Infectious Diseases Pub Date : 2024-12-27 DOI:10.1093/cid/ciae583
Stefania Cheli, Alessandro Torre, Marco Schiuma, Cristina Montrasio, Aurora Civati, Miriam Galimberti, Vera Battini, Ilaria Mariani, Giulia Mosini, Carla Carnovale, Sonia Radice, Emilio Clementi, Andrea Gori, Spinello Antinori
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引用次数: 0

摘要

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%。许多研究已经确定了抗结核DILI的危险因素;然而,没有一项研究是在多种族的现实环境中进行的。当前研究的主要结果是确定可作为多民族队列中DILI的最佳预测因子的危险因素。方法对米兰Luigi Sacco医院肺结核门诊患者进行巢式病例对照研究。结果纳入102例患者,平均年龄[SD], 45.6[15.6]岁。对于每例肝毒性患者,匹配2例对照,性别、年龄、体重指数、结核/结核感染诊断和指标日期。我们发现n -乙酰转移酶2基因(NAT2)慢乙酰化状态是DILI的最佳独立预测因子(优势比,5.97[95%可信区间,1.38-25.76];P = .02]。结论NAT2基因型指导给药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
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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 NCT06539455
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来源期刊
Clinical Infectious Diseases
Clinical Infectious Diseases 医学-传染病学
CiteScore
25.00
自引率
2.50%
发文量
900
审稿时长
3 months
期刊介绍: Clinical Infectious Diseases (CID) is dedicated to publishing original research, reviews, guidelines, and perspectives with the potential to reshape clinical practice, providing clinicians with valuable insights for patient care. CID comprehensively addresses the clinical presentation, diagnosis, treatment, and prevention of a wide spectrum of infectious diseases. The journal places a high priority on the assessment of current and innovative treatments, microbiology, immunology, and policies, ensuring relevance to patient care in its commitment to advancing the field of infectious diseases.
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