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Clinical and Genetic Risk Factors for Drug-Induced Liver Injury Associated with Anti-Tuberculosis Treatment—A Study from Patients of Portuguese Health Centers

Drug-induced liver injury (DILI) is an unpredictable and feared side effect of antituberculosis treatment (AT). The present study aimed to identify clinical and genetic variables associated with susceptibility to AT-associated hepatotoxicity in patients with pulmonary tuberculosis treated with a sta...

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Autores principales: Cavaco, Maria João, Alcobia, Celeste, Oliveiros, Bárbara, Mesquita, Luís Alcides, Carvalho, Aurora, Matos, Fernando, Carvalho, José Miguel, Villar, Miguel, Duarte, Raquel, Mendes, João, Ribeiro, Carolina, Cordeiro, Carlos Robalo, Regateiro, Fernando, Silva, Henriqueta Coimbra
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9144180/
https://www.ncbi.nlm.nih.gov/pubmed/35629211
http://dx.doi.org/10.3390/jpm12050790
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author Cavaco, Maria João
Alcobia, Celeste
Oliveiros, Bárbara
Mesquita, Luís Alcides
Carvalho, Aurora
Matos, Fernando
Carvalho, José Miguel
Villar, Miguel
Duarte, Raquel
Mendes, João
Ribeiro, Carolina
Cordeiro, Carlos Robalo
Regateiro, Fernando
Silva, Henriqueta Coimbra
author_facet Cavaco, Maria João
Alcobia, Celeste
Oliveiros, Bárbara
Mesquita, Luís Alcides
Carvalho, Aurora
Matos, Fernando
Carvalho, José Miguel
Villar, Miguel
Duarte, Raquel
Mendes, João
Ribeiro, Carolina
Cordeiro, Carlos Robalo
Regateiro, Fernando
Silva, Henriqueta Coimbra
author_sort Cavaco, Maria João
collection PubMed
description Drug-induced liver injury (DILI) is an unpredictable and feared side effect of antituberculosis treatment (AT). The present study aimed to identify clinical and genetic variables associated with susceptibility to AT-associated hepatotoxicity in patients with pulmonary tuberculosis treated with a standard protocol. Of 233 patients enrolled, 90% prospectively, 103 developed liver injury: 37 with mild and 66 with severe phenotype (DILI). All patients with mild hepatitis had a RUCAM score ≥4 and all patients with DILI had a RUCAM score ≥ 6. Eight clinical variables and variants in six candidate genes were assessed. A logistic multivariate regression analysis identified four risk factors for AT-DILI: age ≥ 55 years (OR:3.67; 95% CI:1.82–7.41; p < 0.001), concomitant medication with other hepatotoxic drugs (OR:2.54; 95% CI:1.23–5.26; p = 0.012), NAT2 slow acetylator status (OR:2.46; 95% CI:1.25–4.84; p = 0.009), and carriers of p.Val444Ala variant for ABCB11 gene (OR:2.06; 95%CI:1.02–4.17; p = 0.044). The statistical model explains 24.9% of the susceptibility to AT-DILI, with an 8.9 times difference between patients in the highest and in the lowest quartiles of risk scores. This study sustains the complex architecture of AT-DILI. Prospective studies should evaluate the benefit of NAT2 and ABCB11 genotyping in AT personalization, particularly in patients over 55 years.
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spelling pubmed-91441802022-05-29 Clinical and Genetic Risk Factors for Drug-Induced Liver Injury Associated with Anti-Tuberculosis Treatment—A Study from Patients of Portuguese Health Centers Cavaco, Maria João Alcobia, Celeste Oliveiros, Bárbara Mesquita, Luís Alcides Carvalho, Aurora Matos, Fernando Carvalho, José Miguel Villar, Miguel Duarte, Raquel Mendes, João Ribeiro, Carolina Cordeiro, Carlos Robalo Regateiro, Fernando Silva, Henriqueta Coimbra J Pers Med Article Drug-induced liver injury (DILI) is an unpredictable and feared side effect of antituberculosis treatment (AT). The present study aimed to identify clinical and genetic variables associated with susceptibility to AT-associated hepatotoxicity in patients with pulmonary tuberculosis treated with a standard protocol. Of 233 patients enrolled, 90% prospectively, 103 developed liver injury: 37 with mild and 66 with severe phenotype (DILI). All patients with mild hepatitis had a RUCAM score ≥4 and all patients with DILI had a RUCAM score ≥ 6. Eight clinical variables and variants in six candidate genes were assessed. A logistic multivariate regression analysis identified four risk factors for AT-DILI: age ≥ 55 years (OR:3.67; 95% CI:1.82–7.41; p < 0.001), concomitant medication with other hepatotoxic drugs (OR:2.54; 95% CI:1.23–5.26; p = 0.012), NAT2 slow acetylator status (OR:2.46; 95% CI:1.25–4.84; p = 0.009), and carriers of p.Val444Ala variant for ABCB11 gene (OR:2.06; 95%CI:1.02–4.17; p = 0.044). The statistical model explains 24.9% of the susceptibility to AT-DILI, with an 8.9 times difference between patients in the highest and in the lowest quartiles of risk scores. This study sustains the complex architecture of AT-DILI. Prospective studies should evaluate the benefit of NAT2 and ABCB11 genotyping in AT personalization, particularly in patients over 55 years. MDPI 2022-05-13 /pmc/articles/PMC9144180/ /pubmed/35629211 http://dx.doi.org/10.3390/jpm12050790 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Cavaco, Maria João
Alcobia, Celeste
Oliveiros, Bárbara
Mesquita, Luís Alcides
Carvalho, Aurora
Matos, Fernando
Carvalho, José Miguel
Villar, Miguel
Duarte, Raquel
Mendes, João
Ribeiro, Carolina
Cordeiro, Carlos Robalo
Regateiro, Fernando
Silva, Henriqueta Coimbra
Clinical and Genetic Risk Factors for Drug-Induced Liver Injury Associated with Anti-Tuberculosis Treatment—A Study from Patients of Portuguese Health Centers
title Clinical and Genetic Risk Factors for Drug-Induced Liver Injury Associated with Anti-Tuberculosis Treatment—A Study from Patients of Portuguese Health Centers
title_full Clinical and Genetic Risk Factors for Drug-Induced Liver Injury Associated with Anti-Tuberculosis Treatment—A Study from Patients of Portuguese Health Centers
title_fullStr Clinical and Genetic Risk Factors for Drug-Induced Liver Injury Associated with Anti-Tuberculosis Treatment—A Study from Patients of Portuguese Health Centers
title_full_unstemmed Clinical and Genetic Risk Factors for Drug-Induced Liver Injury Associated with Anti-Tuberculosis Treatment—A Study from Patients of Portuguese Health Centers
title_short Clinical and Genetic Risk Factors for Drug-Induced Liver Injury Associated with Anti-Tuberculosis Treatment—A Study from Patients of Portuguese Health Centers
title_sort clinical and genetic risk factors for drug-induced liver injury associated with anti-tuberculosis treatment—a study from patients of portuguese health centers
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9144180/
https://www.ncbi.nlm.nih.gov/pubmed/35629211
http://dx.doi.org/10.3390/jpm12050790
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