Hepatotoxicity during TB treatment in people with HIV/AIDS related to NAT2 polymorphisms in Pernambuco, Northeast Brazil
Introduction and objective: Hepatotoxicity during tuberculosis (TB) treatment is frequent and may be related to the Arylamine N-Acetyltransferase (NAT2) acetylator profile, in which allele frequencies differ according to the population. The aim of this study was to investigate functional polymorphis...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2020-03-01
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| Series: | Annals of Hepatology |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S1665268119322598 |
| _version_ | 1818741463459037184 |
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| author | Carolline Araujo-Mariz Maria de Fátima P. Militão de Albuquerque Edmundo P. Lopes Ricardo A.A. Ximenes Heloísa R. Lacerda Demócrito B. Miranda-Filho Brena B. Lustosa-Martins André Filipe P. Pastor Bartolomeu Acioli-Santos |
| author_facet | Carolline Araujo-Mariz Maria de Fátima P. Militão de Albuquerque Edmundo P. Lopes Ricardo A.A. Ximenes Heloísa R. Lacerda Demócrito B. Miranda-Filho Brena B. Lustosa-Martins André Filipe P. Pastor Bartolomeu Acioli-Santos |
| author_sort | Carolline Araujo-Mariz |
| collection | DOAJ |
| description | Introduction and objective: Hepatotoxicity during tuberculosis (TB) treatment is frequent and may be related to the Arylamine N-Acetyltransferase (NAT2) acetylator profile, in which allele frequencies differ according to the population. The aim of this study was to investigate functional polymorphisms in NAT2 associated with the development of hepatotoxicity after initiating treatment for TB in people living with HIV/AIDS (PLWHA) in Pernambuco, Northeast Brazil. Material and methods: This was a prospective cohort study that investigated seven single nucleotide polymorphisms located in the NAT2 coding region in 173 PLWHA undergoing TB treatment. Hepatotoxicity was defined as elevated aminotransferase levels and identified as being three times higher than it was before initiating TB treatment, with associated symptoms of hepatitis. A further 80 healthy subjects, without HIV infection or TB were used as a control group. All individuals were genotyped by direct sequencing. Results: The NAT2*13A and NAT2*6B variant alleles were significantly associated with the development of hepatotoxicity during TB treatment in PLWHA (p < 0.05). Individual comparisons between the wild type and each variant genotype revealed that PLWHA with signatures NAT2*13A/NAT2*13A (OR 4.4; CI95% 1.1–18.8; p 0.037) and NAT2*13A/NAT2*6B (OR 4.4; CI95% 1.5–12.7; p 0.005) significantly increased the risk of hepatotoxicity. Conclusion: This study suggests that NAT2*13A and NAT2*6B variant alleles are risk factors for developing hepatotoxicity, and PLWHA with genotypes NAT2*13A/NAT2*13A and NAT2*13A/NAT2*6B should be targeted for specific care to reduce the risk of hepatotoxicity during treatment for tuberculosis. |
| first_indexed | 2024-12-18T01:57:01Z |
| format | Article |
| id | doaj.art-8490cbb076b44e429b04695510e9753a |
| institution | Directory Open Access Journal |
| issn | 1665-2681 |
| language | English |
| last_indexed | 2024-12-18T01:57:01Z |
| publishDate | 2020-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Annals of Hepatology |
| spelling | doaj.art-8490cbb076b44e429b04695510e9753a2022-12-21T21:24:54ZengElsevierAnnals of Hepatology1665-26812020-03-01192153160Hepatotoxicity during TB treatment in people with HIV/AIDS related to NAT2 polymorphisms in Pernambuco, Northeast BrazilCarolline Araujo-Mariz0Maria de Fátima P. Militão de Albuquerque1Edmundo P. Lopes2Ricardo A.A. Ximenes3Heloísa R. Lacerda4Demócrito B. Miranda-Filho5Brena B. Lustosa-Martins6André Filipe P. Pastor7Bartolomeu Acioli-Santos8Departamento de Medicina Tropical, Universidade Federal de Pernambuco, Recife, PE, Brazil; Corresponding author at: Rua de Casa Forte, 65/201, Casa Forte, CEP: 52061-460 Recife, PE, Brazil.Departamento de Saúde Coletiva, Centro de Pesquisas Aggeu Magalhães/FIOCRUZ, Recife, PE, BrazilDepartamento de Medicina Tropical, Universidade Federal de Pernambuco, Recife, PE, BrazilDepartamento de Medicina Tropical, Universidade Federal de Pernambuco, Recife, PE, BrazilDepartamento de Medicina Tropical, Universidade Federal de Pernambuco, Recife, PE, BrazilFaculdade de Ciências Médicas, Universidade de Pernambuco, Recife, PE, BrazilLaboratório de Virologia, Centro de Pesquisas Aggeu Magalhães/FIOCRUZ, Recife, PE, BrazilInstituto Federal de Educação, Ciência e Tecnologia do Sertão Pernambucano/IFSertão, Floresta, PE, BrazilLaboratório de Virologia, Centro de Pesquisas Aggeu Magalhães/FIOCRUZ, Recife, PE, BrazilIntroduction and objective: Hepatotoxicity during tuberculosis (TB) treatment is frequent and may be related to the Arylamine N-Acetyltransferase (NAT2) acetylator profile, in which allele frequencies differ according to the population. The aim of this study was to investigate functional polymorphisms in NAT2 associated with the development of hepatotoxicity after initiating treatment for TB in people living with HIV/AIDS (PLWHA) in Pernambuco, Northeast Brazil. Material and methods: This was a prospective cohort study that investigated seven single nucleotide polymorphisms located in the NAT2 coding region in 173 PLWHA undergoing TB treatment. Hepatotoxicity was defined as elevated aminotransferase levels and identified as being three times higher than it was before initiating TB treatment, with associated symptoms of hepatitis. A further 80 healthy subjects, without HIV infection or TB were used as a control group. All individuals were genotyped by direct sequencing. Results: The NAT2*13A and NAT2*6B variant alleles were significantly associated with the development of hepatotoxicity during TB treatment in PLWHA (p < 0.05). Individual comparisons between the wild type and each variant genotype revealed that PLWHA with signatures NAT2*13A/NAT2*13A (OR 4.4; CI95% 1.1–18.8; p 0.037) and NAT2*13A/NAT2*6B (OR 4.4; CI95% 1.5–12.7; p 0.005) significantly increased the risk of hepatotoxicity. Conclusion: This study suggests that NAT2*13A and NAT2*6B variant alleles are risk factors for developing hepatotoxicity, and PLWHA with genotypes NAT2*13A/NAT2*13A and NAT2*13A/NAT2*6B should be targeted for specific care to reduce the risk of hepatotoxicity during treatment for tuberculosis.http://www.sciencedirect.com/science/article/pii/S1665268119322598Arylamine N-acetyltransferaseLiver diseaseToxicityAntitubercular drugsCo-infection |
| spellingShingle | Carolline Araujo-Mariz Maria de Fátima P. Militão de Albuquerque Edmundo P. Lopes Ricardo A.A. Ximenes Heloísa R. Lacerda Demócrito B. Miranda-Filho Brena B. Lustosa-Martins André Filipe P. Pastor Bartolomeu Acioli-Santos Hepatotoxicity during TB treatment in people with HIV/AIDS related to NAT2 polymorphisms in Pernambuco, Northeast Brazil Annals of Hepatology Arylamine N-acetyltransferase Liver disease Toxicity Antitubercular drugs Co-infection |
| title | Hepatotoxicity during TB treatment in people with HIV/AIDS related to NAT2 polymorphisms in Pernambuco, Northeast Brazil |
| title_full | Hepatotoxicity during TB treatment in people with HIV/AIDS related to NAT2 polymorphisms in Pernambuco, Northeast Brazil |
| title_fullStr | Hepatotoxicity during TB treatment in people with HIV/AIDS related to NAT2 polymorphisms in Pernambuco, Northeast Brazil |
| title_full_unstemmed | Hepatotoxicity during TB treatment in people with HIV/AIDS related to NAT2 polymorphisms in Pernambuco, Northeast Brazil |
| title_short | Hepatotoxicity during TB treatment in people with HIV/AIDS related to NAT2 polymorphisms in Pernambuco, Northeast Brazil |
| title_sort | hepatotoxicity during tb treatment in people with hiv aids related to nat2 polymorphisms in pernambuco northeast brazil |
| topic | Arylamine N-acetyltransferase Liver disease Toxicity Antitubercular drugs Co-infection |
| url | http://www.sciencedirect.com/science/article/pii/S1665268119322598 |
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