RESUMO
INTRODUCCION: En Argentina se reportan alrededor de 11.000 casos nuevos de tuberculosis (TB) por año. El tratamiento con drogas anti-TB produce daño hepático en una gran proporción de los pacientes, y la isoniacida (INH) es la principal inductora de hepatotoxicidad. Algunos polimorfismos de las enzimas NAT-2 y CYP2E1, involucradas en el metabolismo de INH, estarían directamente asociados con el desarrollo de hepatotoxicidad.OBJETIVO: Analizar la distribución de las variantes alélicas *4, *5, *6, *7 y *14 de NAT-2 y c1/c2 de CYP2E1 en población sana argentina y en pacientes con TB que concurren a hospitales públicos de la ciudad de Buenos Aires y estudiar su asociación con el desarrollo de la hepatotoxicidad.METODOS: Se estudiaron 152 pacientes con TB tratados con drogas anti-TB. La distribución de frecuencias alélicas y genotípicas fue determinada por PCR-RFLP, y los resultados fueron comparados entre pacientes con TB con o sin desarrollo de hepatotoxicidad, usando un análisis de regresión logística binaria.RESULTADOS: El estado acetilador lento resultó la única variable independiente en la predicción de hepatotoxicidad relacionada con las drogas anti-TB (p = 0,019; OR = 2,971).CONCLUSIONES: El presente estudio demuestra que, dada la alta prevalencia del estado acetilador lento en la población argentina y su asociación al riesgo de desarrollar hepatotoxicidad, junto con el aumento en los casos de TB y los costos que conllevan las internaciones por daño hepático asociado a drogas anti-TB, el análisis del estado acetilador previo al tratamiento anti-TB podría ser clave.
INTRODUCTION: In Argentina, about 11.000 new cases of tuberculosis (TB) are reported per year. Treatment with anti-TB drugs produces liver damage in a large proportion of patients, being isoniazid (INH) the main responsible for hepatotoxicity. Some polymorphisms of the enzymes NAT-2 and CYP2E1, which are involved in the metabolism of INH, might be directly associated with the development of hepatotoxicity.OBJECTIVE: To analyze the distribution of NAT-2 variants *4, *5, *6, *7 and *14, and CYP2E1 alleles c1 and c2 in a healthy population from Argentina and in patients with TB who attend public hospitals in Buenos Aires city, and to stude their association with the development of hepatotoxicity.METHODS: The study included 152 patients with TB treated with anti-TB drugs. The allelic and genotypic frequency distribution was determined by PCR-RFLP, and the results were compared between TB patients with or without development of hepatotoxicity using a binary logistic refression analysis.RESULTS: The slow acetylator status was the only independent variable in the prediction of hepatotoxicity associated with anti-TB drugs (p = 0.019; OR = 2.971).CONCLUSIONS: This study shows that, given the high prevalence of slow acetylator status in Argentine population and its association with the risk of hepatotoxicity, together with the increase in TB cases and the hospitalization costs due to liver damage associated with anti-TB drugas, the analysis of acetylator status before anti-TB treatment could be fundamental.
Assuntos
Antituberculosos , Arilamina N-Acetiltransferase , Doença Hepática Induzida por Substâncias e Drogas , Isoniazida , Tuberculose , Argentina , Saúde PúblicaRESUMO
INTRODUCCION: En Argentina se reportan alrededor de 11.000 casos nuevos de tuberculosis (TB) por año. El tratamiento con drogas anti-TB produce daño hepático en una gran proporción de los pacientes, y la isoniacida (INH) es la principal inductora de hepatotoxicidad. Algunos polimorfismos de las enzimas NAT-2 y CYP2E1, involucradas en el metabolismo de INH, estarían directamente asociados con el desarrollo de hepatotoxicidad.OBJETIVO: Analizar la distribución de las variantes alélicas *4, *5, *6, *7 y *14 de NAT-2 y c1/c2 de CYP2E1 en población sana argentina y en pacientes con TB que concurren a hospitales públicos de la ciudad de Buenos Aires y estudiar su asociación con el desarrollo de la hepatotoxicidad.METODOS: Se estudiaron 152 pacientes con TB tratados con drogas anti-TB. La distribución de frecuencias alélicas y genotípicas fue determinada por PCR-RFLP, y los resultados fueron comparados entre pacientes con TB con o sin desarrollo de hepatotoxicidad, usando un análisis de regresión logística binaria.RESULTADOS: El estado acetilador lento resultó la única variable independiente en la predicción de hepatotoxicidad relacionada con las drogas anti-TB (p = 0,019; OR = 2,971).CONCLUSIONES: El presente estudio demuestra que, dada la alta prevalencia del estado acetilador lento en la población argentina y su asociación al riesgo de desarrollar hepatotoxicidad, junto con el aumento en los casos de TB y los costos que conllevan las internaciones por daño hepático asociado a drogas anti-TB, el análisis del estado acetilador previo al tratamiento anti-TB podría ser clave.
INTRODUCTION: In Argentina, about 11.000 new cases of tuberculosis (TB) are reported per year. Treatment with anti-TB drugs produces liver damage in a large proportion of patients, being isoniazid (INH) the main responsible for hepatotoxicity. Some polymorphisms of the enzymes NAT-2 and CYP2E1, which are involved in the metabolism of INH, might be directly associated with the development of hepatotoxicity.OBJECTIVE: To analyze the distribution of NAT-2 variants *4, *5, *6, *7 and *14, and CYP2E1 alleles c1 and c2 in a healthy population from Argentina and in patients with TB who attend public hospitals in Buenos Aires city, and to stude their association with the development of hepatotoxicity.METHODS: The study included 152 patients with TB treated with anti-TB drugs. The allelic and genotypic frequency distribution was determined by PCR-RFLP, and the results were compared between TB patients with or without development of hepatotoxicity using a binary logistic refression analysis.RESULTS: The slow acetylator status was the only independent variable in the prediction of hepatotoxicity associated with anti-TB drugs (p = 0.019; OR = 2.971).CONCLUSIONS: This study shows that, given the high prevalence of slow acetylator status in Argentine population and its association with the risk of hepatotoxicity, together with the increase in TB cases and the hospitalization costs due to liver damage associated with anti-TB drugas, the analysis of acetylator status before anti-TB treatment could be fundamental.
Assuntos
Tuberculose , Antituberculosos , Citocromo P-450 CYP2E1 , Arilamina N-Acetiltransferase , Isoniazida , Doença Hepática Induzida por Substâncias e Drogas , Saúde Pública , ArgentinaRESUMO
Antiphospholipid antibodies (aPL) have been associated with different diseases. They are defined as a large family of immunoglobulins (Ig) of either alloantibodies or autoantibodies. The autoimmune antibodies are associated with venous and/or arterial thrombosis, thrombocytopenia and recurrent fetal loss in the so-called antiphospholipid syndrome or in systemic lupus erythematosus. These antibodies are directed against proteins or phospholipid-protein complexes. On the contrary, antiphospholipid antibodies (alloantibodies) which are found in infectious diseases sera (syphilis, HIV, and other viral diseases), disappear with illness remission and are directed to phospholipids alone (particularly cardiolipin) and are not associated with thrombosis or recurrent fetal loss. However, the role and type of aPL found during hepatic diseases is still unclear. To investigate the prevalence of autoimmune aPL (IgG and IgM) during different hepatic diseases, we have studied 128 patients with hepatitis C virus, hepatitis B virus and hepatic autoimmune diseases without treatment as well as 40 healthy control subjects. We have used a specific ELISA kit, that uses a mixture of phospholipid instead of cardiolipin alone, and allows a better detection of aPL of the autoimmune type. Our results show that autoimmune aPL are not significantly increased in viral hepatic diseases (2) or autoimmune diseases of the liver (3) when compared to the control group (0).(Au)
