RESUMEN
OBJECTIVES: We report, for the first time, the distribution of four no-function NAT2 single nucleotide polymorphisms and inferred NAT2 acetylator phenotypes in three indigenous groups (Munduruku, Paiter-Suruí, and Yanomami), living in reservation areas in the Brazilian Amazon. METHODS: Two hundred and seventy-six participants from three indigenous groups (92 for each group) were included and genotyped for four NAT2 polymorphisms (rs1801279, rs1801280, rs1799930, and rs1799931) by the TaqMan system. Minor Allele Frequency (MAF) was determined and NAT2 acetylator phenotypes were inferred. RESULTS: NAT2 rs1801279G>A was absent in all cohorts; rs1799930G>A was absent in Yanomami and rare (MAF 0.016) in Munduruku and Paiter-Suruí; MAF of rs1801280T>C ranged five-fold (0.092-0.433), and MAF of rs1799931G>A varied between 0.179 and 0.283, among the three groups. The distribution of NAT2 phenotypes differed significantly across cohorts; the prevalence of the slow acetylator phenotype ranged from 16.3% in Yanomami to 33.3% in Munduruku to 48.9% in Paiter-Suruí. This three-fold range of variation is of major clinical relevance because the NAT2 slow phenotype is associated with higher risk of hepatotoxicity with antituberculosis chemotherapy and high incidence rates of tuberculosis and burden of latent infection among Munduruku, Paiter-Surui, and Yanomami peoples. According to the frequency of the NAT2 slow acetylator phenotype, the estimated number of individuals needed to be genotyped to prevent one additional event of hepatotoxicity range from 31 (Munduruku) to 39 (Paiter-Surui) and to 67 (Yanomami). CONCLUSION: The rs1801279 polymorphism was not found in any of the cohorts, while the MAF of the other polymorphisms showed significant variation between the cohorts. The difference in the prevalence of the NAT2 slow acetylator phenotype, which is linked to isoniazid-induced hepatotoxicity, was observed in the different study cohorts.
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Arilamina N-Acetiltransferasa , Frecuencia de los Genes , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Acetilación , Antituberculosos/efectos adversos , Arilamina N-Acetiltransferasa/genética , Brasil , Genotipo , Indígenas Sudamericanos/genética , Pueblos Indígenas/genética , Isoniazida/efectos adversos , Fenotipo , Polimorfismo de Nucleótido SimpleRESUMEN
In Peru, 29 292 people were diagnosed with tuberculosis in 2022. Although tuberculosis treatments are effective, 3.4%-13% are associated with significant adverse drug reactions, with drug-induced liver injury (DILI) considered the most predominant. Among the first-line antituberculosis drugs, isoniazid is the main drug responsible for the appearance of DILI. In liver, isoniazid (INH) is metabolized by N-acetyltransferase-2 (NAT2) and cytochrome P450 2E1 (CYP2E1). Limited information exists on genetic risk factors associated with the presence of DILI to antituberculosis drugs in Latin America, and even less is known about these factors in the native and mestizo Peruvian population. The aim of this study was to determine the prevalence of NAT2 and CYP2E1 genotypes in native and mestizo population. An analytical cross-sectional analysis was performed using genetic data from mestizo population in Lima and native participants from south of Peru. NAT2 metabolizer was determined as fast, intermediate and slow, and CYP2E1 genotypes were classified as c1/c1, c1/c2 and c2/c2, from molecular tests and bioinformatic analyses. Of the 472 participants, 36 and 6 NAT2 haplotypes were identified in the mestizo and native population, respectively. In mestizo population, the most frequent NAT2*5B and NAT2*7B haplotypes were associated with DILI risk; while in natives, NAT2*5G and NAT2*13A haplotypes were associated with decreased risk of DILI. For CYP2E1, c1/c1 and c1/c2 genotypes are the most frequent in natives and mestizos, respectively. The linkage disequilibrium of NAT2 single nucleotide polymorphisms (SNPs) was estimated, detecting a block between all SNPs natives. In addition, a block between rs1801280 and rs1799929 for NAT2 was detected in mestizos. Despite the limitations of a secondary study, it was possible to report associations between NAT2 and CYP2E alleles with Peruvian native and mestizo by prevalence ratios. The results of this study will help the development of new therapeutic strategies for a Tuberculosis efficient control between populations.
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Antituberculosos , Arilamina N-Acetiltransferasa , Enfermedad Hepática Inducida por Sustancias y Drogas , Citocromo P-450 CYP2E1 , Isoniazida , Tuberculosis , Adolescente , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto Joven , Antituberculosos/uso terapéutico , Antituberculosos/efectos adversos , Arilamina N-Acetiltransferasa/genética , Biomarcadores , Enfermedad Hepática Inducida por Sustancias y Drogas/genética , Estudios Transversales , Citocromo P-450 CYP2E1/genética , Genotipo , Indígenas Sudamericanos/etnología , Indígenas Sudamericanos/genética , Isoniazida/efectos adversos , Isoniazida/uso terapéutico , Perú , Farmacogenética , Tuberculosis/genética , Tuberculosis/tratamiento farmacológico , Grupos RacialesRESUMEN
BACKGROUND: The treatment strategy for latent tuberculosis infection is to reduce the number of tuberculosis cases and consequently reduce the transmission of pathogenic bacteria. This study aimed to determine the safety, effectiveness, and adherence of isoniazid use for latent tuberculosis infection treatment. METHODS: To identify studies on isoniazid use for latent tuberculosis infection, five electronic databases were searched. The methods and results are presented in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. RESULTS: Most studies (53) used isoniazid for 9 months. The prevalence of use and adherence to treatment varied considerably (18% to 100%), and were evaluated by participant completion of isoniazid treatment for latent tuberculosis infection. The adverse events most frequently reported were hepatotoxicity, gastric intolerance, and neuropathy; the rates of occurrence ranged from < 1% to 48%. In the studies that evaluated the effectiveness of isoniazid for latent tuberculosis infection, the rate varied from 0 to 19.7% for patients who did not have active tuberculosis after the follow-up period. CONCLUSIONS: The importance of maintaining follow up for patients using isoniazid should be emphasized due to the risk of developing adverse events. Despite the treatment challenges, the rates of patients who used isoniazid and developed active tuberculosis during the follow-up period were low. We believe that isoniazid continues to contribute to tuberculosis control worldwide, and better care strategies are required.
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Antituberculosos , Isoniazida , Tuberculosis Latente , Isoniazida/efectos adversos , Isoniazida/uso terapéutico , Humanos , Tuberculosis Latente/tratamiento farmacológico , Antituberculosos/efectos adversos , Antituberculosos/uso terapéutico , Antituberculosos/administración & dosificación , Resultado del Tratamiento , Cumplimiento de la MedicaciónRESUMEN
Isoniazid, a central compound in the treatment of active or latent tuberculosis, is associated with various adverse reactions, including hepatitis and polyneuropathy. The latter is due to functional pyridoxine depletion and can be avoided by appropriate doses and supplementation with pyridoxine. We present the case of a patient with several previous treatment abandonments for active pulmonary tuberculosis who evolved with late postprandial vomiting due to gastroparesis documented by nuclear medicine gastric emptying tests after a new treatment onset. Gastroparesis improved with discontinuation of isoniazid and levosulpiride, reappeared with re-exposure, and improved with definitive withdrawal of isoniazid. Morbidity associated with vomiting led to prolonged hospitalization and treatment failure without the emergence of antituberculosis drug resistance. The association of gastroparesis with isoniazid was considered definitive when applying at least two causality protocols. Gastroparesis associated with isoniazid should be added to the list of adverse effects associated with this drug, even in patients receiving pyridoxine supplementation. Its recognition is initially clinical, can be confirmed with nuclear medicine studies, and affects the eradication of Mycobacterium tuberculosis.
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Antituberculosos , Gastroparesia , Isoniazida , Humanos , Isoniazida/efectos adversos , Isoniazida/uso terapéutico , Antituberculosos/efectos adversos , Antituberculosos/uso terapéutico , Gastroparesia/tratamiento farmacológico , Tuberculosis Pulmonar/tratamiento farmacológico , Masculino , Femenino , AdultoRESUMEN
INTRODUCTION: Approximately 5%-10% of individuals with untreated latent tuberculosis infection (LTBI) will progress to active tuberculosis (TB). Children are at a higher risk for progression to TB disease than adults. Isoniazid prophylaxis treatment period is long and can cause liver damage. Alternatives to isoniazid, such as rifamycin containing regimens, should be considered for prophylaxis. Previous systematic reviews, with different study designs and data combining results on children and adults, have evaluated the comparative efficacy and harms of LTBI treatment regimens. We aim to determine the effectiveness and safety of all the different regimens available for the treatment of LTBI for children and adolescents less than 18 years of age, contacts of drug-susceptible TB, without HIV infection. METHODS AND ANALYSIS: MEDLINE, Embase and Cochrane Central Register of Controlled Trials will be systematically searched for randomised controlled trials without any language or publication date restriction. Screening and extraction will be performed in duplicate. Risk of bias will be performed in duplicate with Cochrane Risk of Bias tool V.2. Pairwise meta-analysis of direct comparisons and network meta-analyses (NMAs) will be performed. Heterogeneity will be assessed using I2 and Cochrane thresholds. Direct and indirect estimates in an NMA will be combined if justifiable. Subgroups analyses will be performed in different mean age and study year groups. Sensitivity analysis based on the risk of bias will be conducted. Publication bias will be investigated using funnel plots and Egger's regression test. Grading of Recommendations Assessment, Development and Evaluation (GRADE) criteria will assess certainty of the evidence for the direct comparisons. GRADE approach for NMA will assess the quality of the evidence from the indirect and NMA. ETHICS AND DISSEMINATION: Ethical approval is not required as no primary data are collected. This systematic review will be disseminated in a peer-reviewed journal. PROSPERO REGISTRATION NUMBER: CRD42021271512.
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Infecciones por VIH , Tuberculosis Latente , Tuberculosis , Adolescente , Niño , Infecciones por VIH/tratamiento farmacológico , Humanos , Isoniazida/efectos adversos , Tuberculosis Latente/tratamiento farmacológico , Metaanálisis en Red , Revisiones Sistemáticas como Asunto , Tuberculosis/tratamiento farmacológicoRESUMEN
OBJECTIVE: To determine the prevalence of Latent Tuberculosis in patients with hematological neoplasms at the Instituto Nacional de Cancerología in Mexico City using the Tuberculin skin test (TST). METHODS: This retrospective study included all patients with a recent diagnosis of hematological neoplasms who were admitted for treatment from 2017 to 2018 and who were screened for latent tuberculosis with the TST. The prevalence of latent tuberculosis in this group, tolerance and therapeutic adherence in treated patients are described. RESULTS: The files of 446 patients with hematological malignancy who had a TST were reviewed. The prevalence of latent tuberculosis was 31.2% (n = 139). Ninety-three patients received isoniazid, 15.1% had some adverse reactions, but only 4 (4.3%) had to discontinue treatment. Two patients with latent tuberculosis under treatment with Isoniazid reactivated tuberculosis infection. CONCLUSIONS: The prevalence in our study was within the range of other similar Mexican populations. Isoniazid treatment had an adequate tolerance and adherence. Longer follow-up could offer more information on the risk of reactivation in both groups.
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Neoplasias Hematológicas/epidemiología , Tuberculosis Latente/epidemiología , Adulto , Antituberculosos/efectos adversos , Antituberculosos/uso terapéutico , Instituciones Oncológicas , Femenino , Neoplasias Hematológicas/microbiología , Humanos , Isoniazida/efectos adversos , Isoniazida/uso terapéutico , Tuberculosis Latente/diagnóstico , Tuberculosis Latente/tratamiento farmacológico , Masculino , México/epidemiología , Persona de Mediana Edad , Mycobacterium tuberculosis/efectos de los fármacos , Prevalencia , Estudios Retrospectivos , Prueba de Tuberculina , Tuberculosis/epidemiología , Tuberculosis/etiologíaRESUMEN
INTRODUÇÃO: Os testes de sonda em linha (LPA) são ensaios qualitativos que utilizam membranas de nitrocelulose com sondas de regiões parciais de genes de resistência. O GenoType MTBDRplus® , a partir de amostras de escarro positivo ou de culturas positivas, identifica o complexo M. tuberculosis e as principais mutações que conferem resistência à rifampicina e isoniazida a partir de sondas das regiões parciais de resistência de determinados genes. O GenoType MTBDRsl® possibilita a identificação de resistência também aos medicamentos injetáveis e de segunda linha, por meio de sondas de genes de resistência conhecidos. A população alvo desse abarca indivíduos com comorbidades ou não, de ambos os sexos, todas as idades, provenientes de qualquer país independentemente da incidência e prevalência regionais da doença, com suspeita de tuberculose pulmonar ou extrapulmonar ou indivíduos diagnosticados com tuberculose, independentemente da baciloscopia, tratados previamente ou não, e suspeita de resistência a drogas de primeira ou segunda linha utilizadas no tratamento das formas resistentes da doença. EQUIPAMENTO: Testes comerciais de sondas em linha para detecção do complexo Mycobacterium tuberculosis (MTB), de mutações nas regiões determinan
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Humanos , Rifampin/efectos adversos , Fluoroquinolonas/efectos adversos , Técnicas de Genotipaje/métodos , Aminoglicósidos/efectos adversos , Isoniazida/efectos adversos , Infecciones por Mycobacterium/diagnóstico , Mycobacterium tuberculosis/aislamiento & purificación , Sistema Único de Salud , Brasil , Análisis Costo-BeneficioAsunto(s)
Humanos , Rifampin/efectos adversos , Tuberculosis/diagnóstico , Stents/provisión & distribución , Fluoroquinolonas/efectos adversos , Aminoglicósidos/efectos adversos , Isoniazida/efectos adversos , Mycobacterium tuberculosis/aislamiento & purificación , Sistema Único de Salud , Brasil , Análisis Costo-BeneficioRESUMEN
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.
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Terapia Antirretroviral Altamente Activa , Antituberculosos/efectos adversos , Arilamina N-Acetiltransferasa/genética , Enfermedad Hepática Inducida por Sustancias y Drogas/genética , Infecciones por VIH/tratamiento farmacológico , Isoniazida/efectos adversos , Tuberculosis/tratamiento farmacológico , Adulto , Anciano , Antituberculosos/uso terapéutico , Brasil , Enfermedad Hepática Inducida por Sustancias y Drogas/etiología , Quimioterapia Combinada , Etambutol/uso terapéutico , Femenino , Infecciones por VIH/complicaciones , Humanos , Masculino , Persona de Mediana Edad , Variantes Farmacogenómicas , Polimorfismo Genético , Polimorfismo de Nucleótido Simple , Estudios Prospectivos , Pirazinamida/uso terapéutico , Rifampin/uso terapéutico , Tuberculosis/complicaciones , Adulto JovenRESUMEN
T lymphocytes, cytokines, and macrophages play important roles in the clearance of Mycobacterium tuberculosis (Mtb) by the immune system. This study aimed to investigate the effects of isoniazid on the functions of both innate and adaptive immune cells. Healthy rats were randomly divided into experimental and control groups. Each group was randomly divided into three subgroups and named according to the duration of drug feeding, 1, 3, and 3 months followed by drug withdrawal for 1 month. The experimental groups were fed with isoniazid (12 mg/mL) and the control groups with normal saline. The percentage of CD4+ and CD8+T lymphocytes, level of interleukin (IL)-12 and interferon (IFN)-γ, and function of macrophages were determined at these three time points. Isoniazid significantly increased the percentage of CD4+T lymphocytes and the CD4+/CD8+T lymphocyte cell ratio (P < 0.05). It transiently (<1 month) enhanced the functions of rat macrophages significantly (P < 0.05). In summary, isoniazid could increase the percentage of CD4+T lymphocytes, CD4+/CD8+T lymphocyte cell ratio, and enhance macrophage function in healthy rats
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Animales , Masculino , Ratas , Linfocitos T/inmunología , Citocinas/inmunología , Isoniazida/efectos adversos , Macrófagos/inmunología , Preparaciones Farmacéuticas/análisis , Sistema Inmunológico , Mycobacterium tuberculosis/aislamiento & purificaciónAsunto(s)
Humanos , Masculino , Femenino , Niño , Adulto , Pirazinamida/uso terapéutico , Rifampin/uso terapéutico , Tuberculosis Latente/tratamiento farmacológico , Isoniazida/uso terapéutico , Antituberculosos/uso terapéutico , Pirazinamida/efectos adversos , Rifampin/efectos adversos , Literatura de Revisión como Asunto , Metaanálisis como Asunto , Combinación de Medicamentos , Enfermedad Hepática Inducida por Sustancias y Drogas/etiología , Metaanálisis en Red , Isoniazida/efectos adversos , Antituberculosos/efectos adversosRESUMEN
TITLE: Tuberculomas optoquiasmaticos como reaccion paradojica al tratamiento de tuberculosis meningea.
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Antituberculosos/efectos adversos , Interacciones Huésped-Patógeno , Quiasma Óptico/patología , Tuberculoma/etiología , Tuberculosis Meníngea/patología , Adulto , Antituberculosos/uso terapéutico , Infarto Encefálico/etiología , Errores Diagnósticos , Progresión de la Enfermedad , Farmacorresistencia Microbiana , Sustitución de Medicamentos , Etambutol/efectos adversos , Etambutol/uso terapéutico , Femenino , Humanos , Isoniazida/efectos adversos , Isoniazida/uso terapéutico , Imagen por Resonancia Magnética , Meningitis Viral/diagnóstico , Moxifloxacino/uso terapéutico , Mycobacterium tuberculosis/efectos de los fármacos , Mycobacterium tuberculosis/aislamiento & purificación , Neuroimagen , Quiasma Óptico/diagnóstico por imagen , Paresia/etiología , Prednisona/uso terapéutico , Pirazinamida/efectos adversos , Pirazinamida/uso terapéutico , Rifampin/efectos adversos , Rifampin/uso terapéutico , Tálamo/irrigación sanguínea , Tuberculoma/patología , Tuberculosis Meníngea/líquido cefalorraquídeo , Tuberculosis Meníngea/complicaciones , Tuberculosis Meníngea/tratamiento farmacológico , Trastornos de la Visión/etiologíaRESUMEN
BACKGROUND: Isoniazid preventive therapy (IPT) reduces mortality among people living with HIV (PLHIV) and is recommended for those without active tuberculosis (TB) symptoms. Heavy alcohol use, however, is contraindicated for liver toxicity concerns. We evaluated the risks and benefits of IPT at antiretroviral therapy (ART) initiation to ART alone for PLHIV who are heavy drinkers in 3 high TB-/HIV-burden countries. METHODS: We developed a Markov simulation model to compare ART alone to ART with either 6 or 36 months of IPT for heavy drinking PLHIV enrolling in care in Brazil, India, and Uganda. Outcomes included nonfatal toxicity, fatal toxicity, life expectancy, TB cases, and TB death. RESULTS: In this simulation, 6 months of IPT + ART (IPT6) extended life expectancy over both ART alone and 36 months of IPT + ART (IPT36) in India and Uganda, but ART alone dominated in Brazil in 51.5% of simulations. Toxicity occurred in 160/1000 persons on IPT6 and 415/1000 persons on IPT36, with fatal toxicity in 8/1000 on IPT6 and 21/1000 on IPT36. Sensitivity analyses favored IPT6 in India and Uganda with high toxicity thresholds. CONCLUSIONS: The benefits of IPT for heavy drinkers outweighed its risks in India and Uganda when given for a 6-month course. The toxicity/efficacy trade-off was less in Brazil where TB incidence is lower. IPT6 resulted in fatal toxicity in 8/1000 people, whereas even higher toxicities of IPT36 negated its benefits in all countries. Data to better characterize IPT toxicity among HIV-infected drinkers are needed to improve guidance.
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Alcoholismo/complicaciones , Antituberculosos/administración & dosificación , Quimioprevención/métodos , Infecciones por VIH/complicaciones , Isoniazida/administración & dosificación , Tuberculosis/prevención & control , Adulto , Antirretrovirales/administración & dosificación , Antituberculosos/efectos adversos , Brasil , Femenino , Infecciones por VIH/tratamiento farmacológico , Humanos , India , Isoniazida/efectos adversos , Fallo Hepático/inducido químicamente , Fallo Hepático/mortalidad , Modelos Estadísticos , Análisis de Supervivencia , Resultado del Tratamiento , Tuberculosis/mortalidad , Uganda , Adulto JovenRESUMEN
Los fármacos anti factor de necrosis tumoral alfa (TNF-α) bloquean una de las citoquinas implicadas en la patogénesis de la Enfermedad Inflamatoria intestinal (EII). Su uso se relaciona con aumento de tuberculosis (TB), por lo que el despistaje previo es obligatorio. En la infección tuberculosa latente (ITBL) se utiliza isoniazida como quimioprofilaxis, fármaco que no se encuentra libre de reacciones adversas. Se presenta y discute el caso de una paciente con reacción adversa en piel secundaria al uso de isoniazida.
Anti-tumor necrosis factor alfa drugs are responsible for blocking one of the cytoquines implicated on inflammatory bowel disease pathogenesis. Its use has been linked to an increase in tuberculosis cases which is why screening before starting treatment is mandatory. Latent tuberculosis is treated with isoniazid as chemoprophylaxis although its use may provoke adverse effects. A case is presented of a patient with skin adverse reaction due to the use of isoniazid.
Os medicamentos anti factor de necrose tumoral alfa (TNF-α ) bloqueiam uma das citocinas envolvidas na patogénese da doença inflamatória intestinal (DII). A sua utilização está associada com um aumento da tuberculose (TB), de modo que a despistagem anterior dessa doença é necessária. Na TB latente, frequentemente se utiliza a isoniazida é usado como quimioprofilaxia, uma droga que não está livre de reações adversas. Apresentamos e discutimos o caso de uma paciente com reação adversa na pele secundária ao uso da isoniazida.
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Humanos , Femenino , Adulto , Fármacos Gastrointestinales/efectos adversos , Tuberculosis Latente/inducido químicamente , Tuberculosis Latente/tratamiento farmacológico , Infliximab/efectos adversos , Isoniazida/efectos adversos , Antituberculosos/efectos adversos , Enfermedad de Crohn/tratamiento farmacológico , Erupciones por Medicamentos , Edema/inducido químicamente , Exantema/inducido químicamente , Dermatosis Facial/inducido químicamente , Tuberculosis Latente/diagnósticoRESUMEN
Anti-tuberculosis drug-induced hepatotoxicity (ATDH) is a serious adverse reaction to anti-tuberculosis (TB) treatment. Thioredoxin reductase 1 (TXNRD1), encoded by the TXNRD1 gene, is an important enzyme involved in oxidant challenge. TXNRD1 plays a key role in regulating cell growth and transformation, and protects cells against oxidative damage. We investigated the association between TXNRD1 polymorphisms and ATDH susceptibility. In this prospective study, 280 newly diagnosed TB patients were followed-up for 3 months after beginning anti-TB therapy. Tag single-nucleotide polymorphisms (tag-SNPs) of TXNRD1 were selected using Haploview 4.2 based on the HapMap database of the Chinese Han in Beijing (CHB) panel. Genotyping was performed using the MassARRAY platform. Of the 280 patients enrolled in this study, 33 were lost to follow-up, 24 had ATDH, and 223 were free from ATDH. After adjusting for sex, age, smoking status, and body mass index, there were no significant differences in the allele and genotype frequency distributions of TXNRD1 SNPs between the ATDH and non-ATDH groups (all P > 0.05). The haplotype analysis showed that haplotype TCAGCC was associated with an increased risk of ATDH susceptibility [P = 0.024, OR (95%CI) = 6.273 (1.023-38.485)]. Further stratified analyses showed that the haplotype TCAGCC was associated with ATDH susceptibility in female subjects [P = 0.036, OR (95%CI) = 5.711 (0.917-35.560)] and non-smokers [P = 0.029, OR (95%CI) = 6.008 (0.971-37.158)]. Our results suggest that TXNRD1 variants may favor ATDH susceptibility in females and non-smokers. Further studies are required to verify this association.
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Antituberculosos/efectos adversos , Enfermedad Hepática Inducida por Sustancias y Drogas/genética , Polimorfismo de Nucleótido Simple , Tiorredoxina Reductasa 1/genética , Tuberculosis Pulmonar/tratamiento farmacológico , Adulto , Factores de Edad , Alelos , Enfermedad Hepática Inducida por Sustancias y Drogas/etiología , Enfermedad Hepática Inducida por Sustancias y Drogas/patología , Etambutol/efectos adversos , Femenino , Expresión Génica , Frecuencia de los Genes , Haplotipos , Humanos , Isoniazida/efectos adversos , Hígado/efectos de los fármacos , Hígado/patología , Pulmón/efectos de los fármacos , Pulmón/microbiología , Masculino , Persona de Mediana Edad , Mycobacterium tuberculosis/efectos de los fármacos , Mycobacterium tuberculosis/crecimiento & desarrollo , Estudios Prospectivos , Pirazinamida/efectos adversos , Rifampin/efectos adversos , Factores de Riesgo , Factores Sexuales , Tuberculosis Pulmonar/microbiologíaRESUMEN
Background The use of biological therapy has been linked with an increased risk of tuberculosis (TB) reactivation. Objective The aim of this study was to present the follow-up results for Isoniazid (INH) chemoprophylaxis in patients with psoriasis receiving different biological therapies. Methods In this prospective observational study, patients with latent tuberculosis infection (LTBI) were given INH chemoprophylaxis between two and nine months prior to the beginning of biological therapy. All patients were followed up monthly for any signs or symptoms of active TB or INH toxicity. Results A total of 101 patients, 44.5% females, with a mean age of 46.9 ± 11.5 years (20-73) were enrolled. LTBI was identified in 100 patients (99%), of whom 81.2% completed nine months of chemoprophylaxis. Three patients (2.9%) developed active TB and 17 patients (16.8%) developed intolerance or toxicity related to INH. Conclusions Chemoprophylaxis with INH seems to be effective and safe for the prevention of most TB reactivations in individuals with LTBI receiving biological therapy, but toxicity must be monitored during follow-up.
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Antituberculosos/efectos adversos , Inmunosupresores/uso terapéutico , Isoniazida/efectos adversos , Tuberculosis Latente/prevención & control , Psoriasis/tratamiento farmacológico , Adulto , Anciano , Colombia , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Prueba de Tuberculina , Factor de Necrosis Tumoral alfa/antagonistas & inhibidoresRESUMEN
Many studies have shown that the pathogenesis of liver injury includes oxidative stress. MicroRNA-122 may be a marker for the early diagnosis of drug-induced liver injury. However, the relationship between microRNA-122 and oxidative stress in anti-tuberculosis drug-induced liver injury remains unknown. We measured changes in tissue microRNA-122 levels and indices of oxidative stress during liver injury in mice after administration of isoniazid, a first-line anti-tuberculosis drug. We quantified microRNA-122 expression and indices of oxidative stress at 7 time points, including 1, 3, and 5 days and 1, 2, 3, and 4 weeks. The tissue microRNA-122 levels and oxidative stress significantly changed at 3 and 5 days, suggesting that isoniazid-induced liver injury reduces oxidative stress and microRNA-122 expression compared to in the control group (P < 0.05). Notably, over the time course of isoniazid-induced liver injury, mitochondrial ribosome protein S11 gene, the target of microRNA-122, began to change at 5 days (P < 0.05). The tissue microRNA-122 profile may affect oxidative stress by regulating mitochondrial ribosome protein S11 gene during isoniazid-induced liver injury, which may contribute to the response mechanisms of microRNA-122 and oxidative stress.
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Enfermedad Hepática Inducida por Sustancias y Drogas/genética , MicroARNs/genética , Estrés Oxidativo/genética , Animales , Enfermedad Hepática Inducida por Sustancias y Drogas/metabolismo , Enfermedad Hepática Inducida por Sustancias y Drogas/patología , Modelos Animales de Enfermedad , Femenino , Expresión Génica , Isoniazida/efectos adversos , Pruebas de Función Hepática , Masculino , Metalotioneína/metabolismo , Ratones , Oxidación-Reducción , Factores de TiempoRESUMEN
SETTING: Nine months of daily isoniazid (9H) and 3 months of once-weekly rifapentine plus isoniazid (3HP) are recommended treatments for latent tuberculous infection (LTBI). The risk profile for 3HP and the contribution of hepatitis C virus (HCV) infection to hepatotoxicity are unclear. OBJECTIVES: To evaluate the hepatotoxicity risk associated with 3HP compared to 9H, and factors associated with hepatotoxicity. DESIGN: Hepatotoxicity was defined as aspartate aminotransferase (AST) >3 times the upper limit of normal (ULN) with symptoms (nausea, vomiting, jaundice, or fatigue), or AST >5 x ULN. We analyzed risk factors among adults who took at least 1 dose of their assigned treatment. A nested case-control study assessed the role of HCV. RESULTS: Of 6862 participants, 77 (1.1%) developed hepatotoxicity; 52 (0.8%) were symptomatic; 1.8% (61/3317) were on 9H and 0.4% (15/3545) were on 3HP (P < 0.0001). Risk factors for hepatotoxicity were age, female sex, white race, non-Hispanic ethnicity, decreased body mass index, elevated baseline AST, and 9H. In the case-control study, HCV infection was associated with hepatotoxicity when controlling for other factors. CONCLUSION: The risk of hepatotoxicity during LTBI treatment with 3HP was lower than the risk with 9H. HCV and elevated baseline AST were risk factors for hepatotoxicity. For persons with these risk factors, 3HP may be preferred.
Asunto(s)
Antituberculosos/administración & dosificación , Enfermedad Hepática Inducida por Sustancias y Drogas , Isoniazida/administración & dosificación , Tuberculosis Latente/tratamiento farmacológico , Rifampin/análogos & derivados , Adulto , Antituberculosos/efectos adversos , Aspartato Aminotransferasas/sangre , Brasil , Canadá , Estudios de Casos y Controles , Esquema de Medicación , Quimioterapia Combinada , Femenino , Hepatitis C/complicaciones , Humanos , Isoniazida/efectos adversos , Tuberculosis Latente/complicaciones , Masculino , Persona de Mediana Edad , Análisis Multivariante , Rifampin/administración & dosificación , Rifampin/efectos adversos , Factores de Riesgo , España , Estados UnidosRESUMEN
This is a substudy of the Agence Nationale de Recherches sur le Sida et les Hépatites Virales (ANRS) Comparison of Nevirapine and Efavirenz for the Treatment of HIV-TB Co-infected Patients (ANRS 12146-CARINEMO) trial, which assessed the pharmacokinetics of rifampin or isoniazid with or without the coadministration of nonnucleoside reverse transcriptase inhibitor-based HIV antiretroviral therapy in HIV-tuberculosis-coinfected patients in Mozambique. Thirty-eight patients on antituberculosis therapy based on rifampin and isoniazid participated in the substudy (57.9% males; median age, 33 years; median weight, 51.9 kg; median CD4(+) T cell count, 104 cells/µl; median HIV-1 RNA load, 5.5 log copies/ml). The daily doses of rifampin and isoniazid were 10 and 5 mg/kg of body weight, respectively. Twenty-one patients received 200 mg of nevirapine twice a day (b.i.d.), and 17 patients received 600 mg of efavirenz once a day (q.d.) in combination with lamivudine and stavudine from day 1 until the end of the study. Blood samples were collected at regular time-dosing intervals after morning administration of a fixed-dose combination of rifampin and isoniazid. When rifampin was administered alone, the median maximum concentration of drug in serum (Cmax) and the area under the concentration-time curve (AUC) at steady state were 6.59 mg/liter (range, 2.70 to 14.07 mg/liter) and 27.69 mg · h/liter (range, 11.41 to 109.75 mg · h/liter), respectively. Concentrations remained unchanged when rifampin was coadministered with nevirapine or efavirenz. When isoniazid was administered alone, the median isoniazid Cmax and AUC at steady state were 5.08 mg/liter (range, 1.26 to 11.51 mg/liter) and 20.92 mg · h/liter (range, 7.73 to 56.95 mg · h/liter), respectively. Concentrations remained unchanged when isoniazid was coadministered with nevirapine; however, a 29% decrease in the isoniazid AUC was observed when isoniazid was combined with efavirenz. The pharmacokinetic parameters of rifampin and isoniazid when coadministered with nevirapine or efavirenz were not altered to a clinically significant extent in these severely immunosuppressed HIV-infected patients. Patients experienced favorable clinical outcomes. (This study has been registered at ClinicalTrials.gov under registration no. NCT00495326.).