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

Autor:	Cheli S; ICPS, Pharmacovigilance & Clinical Research, Department of Biomedical and Clinical Sciences, ASST Fatebenefratelli Sacco, University Hospital Luigi Sacco, Università Degli Studi di Milano, Milan, Italy., Torre A; III Infectious Disease Unit, ASST Fatebenefratelli Sacco, Luigi Sacco Hospital, Milan, Italy., Schiuma M; II Infectious Disease Unit, ASST Fatebenefratelli Sacco, Luigi Sacco Hospital, Milan, Italy., Montrasio C; Center of Functional Genomics and Rare Diseases, Buzzi Children's Hospital, Milan, Italy., Civati A; Department of Biomedical and Clinical Sciences, Università Degli Studi di Milano, Milan, Italy., Galimberti M; Department of Biomedical and Clinical Sciences, Università Degli Studi di Milano, Milan, Italy., Battini V; ICPS, Pharmacovigilance & Clinical Research, Department of Biomedical and Clinical Sciences, ASST Fatebenefratelli Sacco, University Hospital Luigi Sacco, Università Degli Studi di Milano, Milan, Italy., Mariani I; ICPS, Pharmacovigilance & Clinical Research, Department of Biomedical and Clinical Sciences, ASST Fatebenefratelli Sacco, University Hospital Luigi Sacco, Università Degli Studi di Milano, Milan, Italy., Mosini G; ICPS, Pharmacovigilance & Clinical Research, Department of Biomedical and Clinical Sciences, ASST Fatebenefratelli Sacco, University Hospital Luigi Sacco, Università Degli Studi di Milano, Milan, Italy., Carnovale C; ICPS, Pharmacovigilance & Clinical Research, Department of Biomedical and Clinical Sciences, ASST Fatebenefratelli Sacco, University Hospital Luigi Sacco, Università Degli Studi di Milano, Milan, Italy., Radice S; ICPS, Pharmacovigilance & Clinical Research, Department of Biomedical and Clinical Sciences, ASST Fatebenefratelli Sacco, University Hospital Luigi Sacco, Università Degli Studi di Milano, Milan, Italy., Clementi E; 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.; II Infectious Disease Unit, ASST Fatebenefratelli Sacco, Luigi Sacco Hospital, Milan, Italy.; Center of Functional Genomics and Rare Diseases, Buzzi Children's Hospital, Milan, Italy.; Department of Biomedical and Clinical Sciences, Università Degli Studi di Milano, Milan, Italy.; Scientific Institute, IRCCS E. Medea, Bosisio Parini, LC, Italy., Gori A; II Infectious Disease Unit, ASST Fatebenefratelli Sacco, Luigi Sacco Hospital, Milan, Italy.; Center of Functional Genomics and Rare Diseases, Buzzi Children's Hospital, Milan, Italy.; Department of Biomedical and Clinical Sciences, Università Degli Studi di Milano, Milan, Italy., Antinori S; III Infectious Disease Unit, ASST Fatebenefratelli Sacco, Luigi Sacco Hospital, Milan, Italy.; II Infectious Disease Unit, ASST Fatebenefratelli Sacco, Luigi Sacco Hospital, Milan, Italy.; Center of Functional Genomics and Rare Diseases, Buzzi Children's Hospital, Milan, Italy.; Department of Biomedical and Clinical Sciences, Università Degli Studi di Milano, Milan, Italy.
Jazyk:	angličtina
Zdroj:	Clinical infectious diseases : an official publication of the Infectious Diseases Society of America [Clin Infect Dis] 2024 Dec 27. Date of Electronic Publication: 2024 Dec 27.
DOI:	10.1093/cid/ciae583
Abstrakt:	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. Competing Interests: Potential conflicts of interest. The authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)
Databáze:	MEDLINE
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