Please use this identifier to cite or link to this item: https://www.arca.fiocruz.br/handle/icict/37516
Title: Hepatotoxicity during TB treatment in people with HIV/AIDS related to NAT2 polymorphisms in Pernambuco, Northeast Brazil
Authors: Araujo-Mariz, Carolline
Militão de Albuquerque, Maria de Fátima P.
Lopes, Edmundo P.
Ximenes, Ricardo A. A.
Lacerda, Heloísa R.
Miranda-Filho, Demócrito B.
Lustosa-Martins, Brena B.
Pastor, André Filipe P.
Acioli-Santos, Bartolomeu
Affilliation: Universidade Federal de Pernambuco. Departamento de Medicina Tropical. Recife, PE, Brasil.
Fundação Oswaldo Cruz. Instituto Aggeu Magalhães. Departamento de Saúde Coletiva. Recife, PE, Brasil.
Universidade Federal de Pernambuco. Departamento de Medicina Tropical. Recife, PE, Brasil.
Universidade Federal de Pernambuco. Departamento de Medicina Tropical. Recife, PE, Brasil.
Universidade Federal de Pernambuco. Departamento de Medicina Tropical. Recife, PE, Brasil.
Universidade de Pernambuco. Faculdade de Ciências Médicas. Recife, PE, Brasil.
Fundação Oswaldo Cruz. Instituto Aggeu Magalhães. Laboratório de Virologia. Recife, PE, Brasil.
Instituto Federal de Educação, Ciência e Tecnologia do Sertão Pernambucano. Floresta, PE, Brasil.
Fundação Oswaldo Cruz. Instituto Aggeu Magalhães. Laboratório de Virologia. Recife, PE, Brasil.
Abstract: 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.
Keywords: Antitubercular drugs
Arylamine N-acetyltransferase
Co-infection
Liver disease
Toxicity
DeCS: Antituberculosos
Arilamina N-Acetiltransferase
Coinfecção
Hepatopatias
Toxicidade
Issue Date: 2019
Citation: ARAUJO-MARIZ, Caroline et al. Hepatotoxicity during TB treatment in people with HIV/AIDS related to NAT2 polymorphisms in Pernambuco, Northeast Brazil. Annals of Hepatology, p. 1-8, Oct. 2019.
DOI: 10.1016/j.aohep.2019.09.008
ISSN: 1665-2681
Copyright: restricted access
Appears in Collections:PE - IAM - Artigos de Periódicos




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