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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...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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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. |
format | Online Article Text |
id | pubmed-9144180 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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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