Serological prevalence of hepatitis B virus (HBV) in Mardan district, Khyber Pakhtunkhwa, Pakistan / Prevalência sorológica do vírus da hepatite B (HBV) no distrito de Mardan, Khyber Pakhtunkhwa, Paquistão

Hepatitis B virus infection is perilous among the five types of Hepatitis, as it remains clinically asymptomatic. The present study draws up-to-date prevalence of Hepatitis B virus (HBV) in the general population of Mardan, Khyber Pakhtunkhwa Pakistan. The blood samples from 4803 individuals including 2399 male and 2404 females were investigated. All the suspected samples were analyzed for hepatitis B surface antigen using Immuno-chromatographic test (ICT), Enzyme-linked immunosorbent assay (ELISA), and followed by Reverse transcription-polymerase chain reaction (RT-PCR). Results showed that 312 (13.00%) out of 2399 individuals contained antibodies in their blood against HBV, while among the different age groups, the highest incidences of HBV antibodies were found in the age of 21-30 groups (10.73%). Furthermore, the ICT positive samples were screened by nested polymerase chain reaction to detect the existence of active HBV-DNA. It was observed that 169 (7.04%) out of (2399) male of the total population (4803) tested was positive. On the other hand, the female 463 (19.25%) possessed antibodies in their blood against HBV. Accumulatively, our results showed a higher percentage of HBV prevalence in males than females in the age group 21-30 years. The total HCV infected in Mardan general population was recorded at 5.7% comprising both male and female.

A infecção pelo vírus da hepatite B é perigosa entre os cinco tipos de hepatite, pois permanece clinicamente assintomática. O presente estudo traça a prevalência atualizada do vírus da hepatite B (HBV) na população geral de Mardan, Khyber Pakhtunkhwa, no Paquistão. Amostras de sangue de 4.803 indivíduos, incluindo 2.399 homens e 2.404 mulheres, foram investigadas. Todas as amostras suspeitas foram analisadas para o antígeno de superfície da hepatite B usando teste imunocromatográfico (ICT), enzyme-linked immunosorbent assay (ELISA), seguido por transcrição reversa-reação em cadeia da polimerase (RT-PCR). Os resultados mostraram que 312 (13,00%) de 2.399 indivíduos continham anticorpos no sangue contra o VHB, enquanto, entre as diferentes faixas etárias, as maiores incidências de anticorpos VHB foram encontradas nos grupos de 21 a 30 anos (10,73%). Além disso, amostras positivas para ICT foram rastreadas por reação em cadeia da polimerase aninhada para detectar a existência de HBV-DNA ativo. Observou-se que 169 (7,04%) de 2.399 homens do total da população (4803) testados foram positivos. Por outro lado, 463 mulheres (19,25%) possuíam anticorpos no sangue contra VHB. Acumulativamente, nossos resultados mostraram uma porcentagem maior de prevalência de HBV em homens do que em mulheres na faixa etária de 21 a 30 anos. O total de HCV infectados na população geral de Mardan foi registrado em 5,7%, incluindo homens e mulheres.

Serological prevalence of hepatitis B virus (HBV) in Mardan district, Khyber Pakhtunkhwa, Pakistan / Prevalência sorológica do vírus da hepatite B (HBV) no distrito de Mardan, Khyber Pakhtunkhwa, Paquistão

Hepatitis B virus infection is perilous among the five types of Hepatitis, as it remains clinically asymptomatic. The present study draws up-to-date prevalence of Hepatitis B virus (HBV) in the general population of Mardan, Khyber Pakhtunkhwa Pakistan. The blood samples from 4803 individuals including 2399 male and 2404 females were investigated. All the suspected samples were analyzed for hepatitis B surface antigen using Immuno-chromatographic test (ICT), Enzyme-linked immunosorbent assay (ELISA), and followed by Reverse transcription-polymerase chain reaction (RT-PCR). Results showed that 312 (13.00%) out of 2399 individuals contained antibodies in their blood against HBV, while among the different age groups, the highest incidences of HBV antibodies were found in the age of 21-30 groups (10.73%). Furthermore, the ICT positive samples were screened by nested polymerase chain reaction to detect the existence of active HBV-DNA. It was observed that 169 (7.04%) out of (2399) male of the total population (4803) tested was positive. On the other hand, the female 463 (19.25%) possessed antibodies in their blood against HBV. Accumulatively, our results showed a higher percentage of HBV prevalence in males than females in the age group 21-30 years. The total HCV infected in Mardan general population was recorded at 5.7% comprising both male and female.

A infecção pelo vírus da hepatite B é perigosa entre os cinco tipos de hepatite, pois permanece clinicamente assintomática. O presente estudo traça a prevalência atualizada do vírus da hepatite B (HBV) na população geral de Mardan, Khyber Pakhtunkhwa, no Paquistão. Amostras de sangue de 4.803 indivíduos, incluindo 2.399 homens e 2.404 mulheres, foram investigadas. Todas as amostras suspeitas foram analisadas para o antígeno de superfície da hepatite B usando teste imunocromatográfico (ICT), enzyme-linked immunosorbent assay (ELISA), seguido por transcrição reversa-reação em cadeia da polimerase (RT-PCR). Os resultados mostraram que 312 (13,00%) de 2.399 indivíduos continham anticorpos no sangue contra o VHB, enquanto, entre as diferentes faixas etárias, as maiores incidências de anticorpos VHB foram encontradas nos grupos de 21 a 30 anos (10,73%). Além disso, amostras positivas para ICT foram rastreadas por reação em cadeia da polimerase aninhada para detectar a existência de HBV-DNA ativo. Observou-se que 169 (7,04%) de 2.399 homens do total da população (4803) testados foram positivos. Por outro lado, 463 mulheres (19,25%) possuíam anticorpos no sangue contra VHB. Acumulativamente, nossos resultados mostraram uma porcentagem maior de prevalência de HBV em homens do que em mulheres na faixa etária de 21 a 30 anos. O total de HCV infectados na população geral de Mardan foi registrado em 5,7%, incluindo homens e mulheres.

Serological prevalence of hepatitis B virus (HBV) in Mardan district, Khyber Pakhtunkhwa, Pakistan

Abstract Hepatitis B virus infection is perilous among the five types of Hepatitis, as it remains clinically asymptomatic. The present study draws up-to-date prevalence of Hepatitis B virus (HBV) in the general population of Mardan, Khyber Pakhtunkhwa Pakistan. The blood samples from 4803 individuals including 2399 male and 2404 females were investigated. All the suspected samples were analyzed for hepatitis B surface antigen using Immuno-chromatographic test (ICT), Enzyme-linked immunosorbent assay (ELISA), and followed by Reverse transcription-polymerase chain reaction (RT-PCR). Results showed that 312 (13.00%) out of 2399 individuals contained antibodies in their blood against HBV, while among the different age groups, the highest incidences of HBV antibodies were found in the age of 21-30 groups (10.73%). Furthermore, the ICT positive samples were screened by nested polymerase chain reaction to detect the existence of active HBV-DNA. It was observed that 169 (7.04%) out of (2399) male of the total population (4803) tested was positive. On the other hand, the female 463 (19.25%) possessed antibodies in their blood against HBV. Accumulatively, our results showed a higher percentage of HBV prevalence in males than females in the age group 21-30 years. The total HCV infected in Mardan general population was recorded at 5.7% comprising both male and female.

Resumo A infecção pelo vírus da hepatite B é perigosa entre os cinco tipos de hepatite, pois permanece clinicamente assintomática. O presente estudo traça a prevalência atualizada do vírus da hepatite B (HBV) na população geral de Mardan, Khyber Pakhtunkhwa, no Paquistão. Amostras de sangue de 4.803 indivíduos, incluindo 2.399 homens e 2.404 mulheres, foram investigadas. Todas as amostras suspeitas foram analisadas para o antígeno de superfície da hepatite B usando teste imunocromatográfico (ICT), enzyme-linked immunosorbent assay (ELISA), seguido por transcrição reversa-reação em cadeia da polimerase (RT-PCR). Os resultados mostraram que 312 (13,00%) de 2.399 indivíduos continham anticorpos no sangue contra o VHB, enquanto, entre as diferentes faixas etárias, as maiores incidências de anticorpos VHB foram encontradas nos grupos de 21 a 30 anos (10,73%). Além disso, amostras positivas para ICT foram rastreadas por reação em cadeia da polimerase aninhada para detectar a existência de HBV-DNA ativo. Observou-se que 169 (7,04%) de 2.399 homens do total da população (4803) testados foram positivos. Por outro lado, 463 mulheres (19,25%) possuíam anticorpos no sangue contra VHB. Acumulativamente, nossos resultados mostraram uma porcentagem maior de prevalência de HBV em homens do que em mulheres na faixa etária de 21 a 30 anos. O total de HCV infectados na população geral de Mardan foi registrado em 5,7%, incluindo homens e mulheres.

Evaluación de una reacción en cadena de la polimerasa en tiempo real simple y rápida para la cuantificación del ADN del virus de la hepatitis B / Evaluation of a simple and fast real time polymerase chain reaction assay for quantification of hepatitis B virus DNA

Introducción: Los ensayos para cuantificar el ADN del virus de la hepatitis B (VHB) o carga viral son imprescindibles en el diagnóstico y en el seguimiento de los pacientes con hepatitis B crónica; de ahí que estén disponibles estuches diagnósticos para esta función. En el presente estudio se muestra la validación de SUMASIGNAL VHB (un paso), el cual es un sistema de reacción en cadena de la polimerasa en tiempo real (RCP-TR) para la cuantificación del genoma del VHB, propuesto por el Centro de Inmunoensayo. Objetivo: Evaluar el desempeño analítico de SUMASIGNAL VHB (un paso). Métodos: Se utilizó un panel de 80 muestras de suero bien caracterizadas y el Tercer Estándar Internacional de la OMS para las técnicas de amplificación de ácidos nucleicos del virus de la hepatitis B. Se determinaron las características del ensayo como especificidad clínica, especificidad analítica (reactividad cruzada), rango lineal o linealidad y exactitud, precisión intraensayo y comparación con un ensayo de referencia. Resultados: La especificidad analítica y clínica fue del 100 por ciento. Al evaluar la linealidad y exactitud con un estándar de referencia de la OMS, se obtuvo que la totalidad de las diferencias entre los Log10 del valor obtenido y el de referencia resultaron inferiores a 0,5 Log10 (r= 0,9977 y r2= 0,9954). Además, se obtuvieron bajos coeficientes de variación intraensayo. La evaluación comparativa con el estuche comercial Artus HBV RG PCR kit mostró una correlación fuerte (r= 0,8882). Conclusiones: SUMASIGNAL VHB (un paso) es un ensayo fácil de realizar manualmente, es rápido e incluye reactivos de extracción de ácidos nucleicos. Teniendo en cuenta la validez del método para el uso previsto, puede ser recomendado para su introducción en el diagnóstico, la vigilancia y la indicación de tratamiento en los pacientes con hepatitis B crónica(AU)

Introduction: Assays to quantify hepatitis B virus (HBV) DNA or viral load are indispensable for the diagnosis and follow-up of patients with chronic hepatitis B, hence the availability of diagnostic kits for this purpose. The present study deals with the validation of HBV SUMASIGNAL (one step), a real time polymerase chain reaction (RT-PCR) system for quantification of the HBV genome proposed by the Immunoassay Center. Objective: Evaluate the analytical performance of HBV SUMASIGNAL (one step). Methods: Use was made of a panel of 80 well characterized serum samples and the Third WHO International Standard for hepatitis B virus nucleic acid amplification techniques. Determination was performed of assay characteristics such as clinical specificity, analytical specificity (cross-reactivity), linear range or linearity and accuracy, intra-assay precision and comparison with a reference assay. Results: Analytical and clinical specificity was 100 percent. Evaluation of linearity and accuracy with a WHO reference standard revealed that all the differences between the log10 of the value obtained and the reference value were lower than 0.5 log10 (r= 0.9977 and r2= 0.9954). The intra-assay variation coefficients obtained were low. Comparative evaluation with the commercial Artus HBV RG PCR kit showed a strong correlation (r= 0.8882). Conclusions: The assay HBV SUMASIGNAL (one step) is easy to conduct manually, fast and includes reagents for nucleic acid extraction. Based on the validity of the method for the use in mind, it may be recommended for incorporation into the diagnosis, surveillance and treatment of patients with chronic hepatitis B(AU)

Modelo de Cascada de Atención para la co-infección de las hepatitis virales para el cuidado continuo en personas con VIH/Sida / Care Continuum Model for Coinfection of Viral Hepatitis for the Continuing Care in people living with HIV / AIDS

Introducción: las coinfecciones con hepatitis virales y el VIH representan un riesgo por su alta transmisibilidad y complicaciones. Es de vital importancia que se puedan identificar las barreras de acceso y manejo de las coinfecciones del VIH y la Hepatitis B y C. El propósito del estudio es describir la cascada de atención para la coinfección de las hepatitis virales en personas viviendo con VIH/SIDA. Métodos: se delimitaron los indicadores de manejo y seguimiento de los pacientes monitoreados actualmente en clínicas de primer nivel de atención en Santo Domingo y Santiago. Los datos recopilados fueron analizados a partir de los registros escritos de los pacientes en seguimiento, para evaluar los datos epidemiológicos y serológicos que se obtuvieron de los archivos clínicos. Resultados: se demostró que un 100 % de los pacientes fueron enrolados, 85.7 % se consideraron como retenidos en el manejo de la coinfección VIH/VHB y solamente 71.4 % recibieron TARV basado en Tenofovir. La cascada de atención para la coinfección VIH/VHC muestra un vínculo de 87.5 % de los pacientes, 75 % fueron retenidos y ninguno recibió tratamiento. Conclusión: la identificación de los factores de riesgo que influyen en las brechas de la cascada es fundamental para optimizar el manejo y monitoreo de los pacientes coinfectados, teniendo en cuenta que es preciso poder reconocer aquellos infectados para iniciar tratamiento de inmediato y así prever secuelas citopatológicas hepáticas

Introduction: Co-infections of viral hepatitis and HIV represent a risk due to their high transmissibility and complications. It is vitally important that barriers to access and management of HIV and Hepatitis B and C co-infections can be identified. The purpose of the study is to describe the cascade of attention for the preparation of viral hepatitis in people living with HIV/AIDS. Methods: The management and follow-up indicators of the patients currently monitored in first-level care clinics in Santo Domingo and Santiago were delimited. The data collected was analyzed from the written records of the patients in follow-up to evaluate the epidemiological and serological data that was obtained from the clinical files. Results: It was demonstrated that 100% of the patients were enrolled, 85.7% were considered as retained in care of HIV / HBV coinfection and only 71.4% received ARTbased on Tenofovir. The cascade of care for HIV / HCV coinfection shows a linkage to care of 87.5% of patients, 75% were retained and none received treatment. Conclusions: Identifying the risk factors that influence the gaps in the cascade of care is essential to optimize the management and monitoring of coinfected patients, with special interest in those that might receive immediate treatment to prevent liver cytopathological sequelae

Prevalencia de Hepatitis B y C en Pacientes con Cirrosis / Prevalence of Hepatitis B and C in cirrhotic patients in a general hospital

Introducción: A nivel mundial la cirrosis representa una causa importante de morbi-mortalidad. En Guatemala no se cuenta con datos sobre las etiologías de la misma ni su frecuencia. Además, se ha demostrado que los pacientes infectados por virus hepatotropos, progresan más rápido hacia la muerte que los pacientes con enfermedad hepática crónica de otras etiologías. Estos pacientes son el principal interés del estudio, ya que la progresión podría desacelerarse con el tratamiento antiviral adecuado. Objetivos: Evaluar la prevalencia de infección crónica por hepatitis B y C en pacientes cirróticos, las principales causas de la misma, motivos de consulta en la EMA (Emergencia de Medicina de Adultos) y coinfección con VIH. Metodología: Se llevó a cabo un estudio prospectivo de 143 records médicos en la EMA (Emergencia de Adultos) de Gastroenterología del Hospital General San Juan de Dios, en los meses de octubre del 2017 a enero del 2018. Resultados: La ingesta excesiva de alcohol fue la principal causa de cirrosis, mientras que, los VHB y VHC son las principales causas de hepatopatía crónicas en países de primer mundo. Palabras clave: cirrosis, VHB, VHC, virus hepatotropos, progresión

Introduction: Worldwide, liver cirrhosis represents an important cause of morbimortality. There is no available data in Guatemala, regarding its etiologies or frequency and since patients infected with hepatotropic viruses, such as HBV or HCV and cirrhosis, progress faster to death than patients with chronic hepatic disease of different etiologies it is a most to know its prevalence . Objectives: To know the prevalence of HBV and HCV and other causes of chronic hepatic disease as HIV coinfection in patients consulting the ER. Methods: A prospective of study 143 patient files was conducted at the Adult ER and the Gastroenterology Outpatient Clinic at Hospital General San Juan de Dios, from October 2017 to January 2018. Results: Excessive alcohol intake was the main cause of cirrhosis amongst our patients, meanwhile HBV and HCV are the main etiologies of chronic liver disease in first world countries. Key words: cirrhosis, HBV. HCV, hepatotropic viruses, progression

Co-expression of β-glucosidase and Vitreoscilla hemoglobin in Escherichia coli / 生物工程学报

In producing recombinant β-glucosidase in Escherichia coli by high-cell density cultivation (HCDC), insufficient soluble oxygen is always a problem. To address it, Vitreoscilla hemoglobin (VHb) was introduced into Escherichia coli by the bicistron and T₇ promoter expression systems, to improve soluble oxygen by bacterial cells and thereby to enhance the biomass and recombinant β-glucosidase production. In the case of bicistron expression system, cell density in shaking flask reached OD₆₀₀=(4.24±0.29), 35.03% higher than that of the control without VHb. Correspondingly, the maximum activity of β-glucosidase co-expressed with VHb was (9.78±0.55) U/mL, 25.38% higher than that of the control. In a 3-L fermentor, the maximum activity of β-glucosidase was 141.23 U/mL, 35.57% higher than that of the control. In contrast, the activity of β-glucosidase co-expressed with VHb under T₇ promoter was lower than that of the control, either in flask or in fermentor. Co-expressing β-glucosidase with VHb using the bicistron expression system may improve the tolerance of E. coli to insufficient soluble oxygen and thus promote the bacterial biomass and the enzyme yield.

Infección oculta por el virus de la hepatitis B en pacientes hemodializados cubanos / Occult hepatitis B virus infection in hemodialysis patients

Introducción: la infección oculta por el virus de la hepatitis B se caracteriza por la presencia en suero o plasma del genoma viral y anticuerpos contra la proteína de la cápsida (anti-HBc) en ausencia del marcador de infección.Objetivos: detectar la IOB en los pacientes hemodializados e identificar la posible relación de la IOB con la infección por el virus de la hepatitis C y variables sociodemográficas y epidemiológicas.Métodos: se estudiaron 709 muestras de pacientes provenientes de 18 unidades de hemodiálisis de Cuba. Se determinaron marcadores de infección, exposición e inmunidad al virus de la hepatitis B. Las muestras con HBsAg negativo, anti-HBc positivo y niveles de anti-HBs < 50 UI/L se les analizó la detección de ADN del virus de la hepatitis B y marcadores de lvirus de la hepatitis C.Resultados: las prevalencias de la infección y la exposición al virus de la hepatitis B fueron de 6,9 por ciento y 28,6 por ciento, respectivamente. El 4,3 por ciento de las muestras tuvieron criterio de infección oculta por el virus de la hepatitis B ; esta se detectó en el 58,1 por ciento (18/31) de los casos, con cargas virales menores de 105 UI/mL. La prevalencia global de infección oculta por el virus de la hepatitis B fue de 2,5 por ciento (18/709). No se encontró asociación significativa entre las variables analizadas.Conclusiones: la infección oculta por el virus de la hepatitis B fue frecuente en pacientes hemodializados con bajos niveles de anti-HBs, principalmente en aquellos con concentraciones no protectoras. Este estudio ratifica la necesidad de mantener la estrategia de prevención contra las hepatitis virales de transmisión parenteral en las unidades de diálisis(AU)

Introduction: occult hepatitis B virus infection is characterized by the presence of the viral genome and antibodies to the capside protein in serum or plasma (anti-HBc) that test negative for the infection marker.Objectives: to detect the occult hepatitis B virus in hemodialysis patients and to identify the possible relationship between occult hepatitis B infection and hepatitis C virus infection and the epidemiological and demographic variables.Methods: seventy thousand and nine serum samples from patients treated in 18 hemodialysis units were included. Serological markers for HBV infection, exposure and immunity were tested. Samples with negative HBsAg , positive anti-HBc and anti-HBs titers <50 IU/L were tested for detection of HBV-DNA and HCV markers.Results: the prevalence of HBV infection and exposure were 6.9 percent and 28.6 percent respectively. In the group, 4.3 percent of samples met occult hepatitis B infection criteria, the HBV-DNA was detected in 58.1 percent (18/31) of the samples, with viral loads below 105 IU/mL. Overall occult hepatitis B infection prevalence was 2.5 percent (18/709). There was no significant association among the analyzed variables.Conclusions: occult hepatitis B infection was frequent in hemodialysis patients with low levels of anti-HBs mainly in those with non protected titers. This study supports the need of keeping the prevention strategies against parenterally transmitted viral hepatitis in dialysis units(AU)

Genetic diversity of hepatitis B virus and mutations associated to hepatocellular carcinoma in patients from Venezuela, with different stages of liver disease / Diversidad genética del virus de la hepatitis B y mutaciones asociadas con carcinoma hepatocelular en pacientes de Venezuela, con diferentes estados de la enfermedad del hígado

Globally, about 50% of liver cancer originates as a result of long term infection with hepatitis B virus (HBV), and some genotypes and mutations have been associated with an increased severity of infection. The aim of this study was to evaluate the genetic diversity of HBV in patients from Venezuela, with chronic infection, cirrhosis and hepatocellular carcinoma (HCC) and to compare the occurrence of mutations in all patient groups. Samples from patients with different pathologies of the liver, associated with HBV infection, were collected. The HBV S region was analyzed for genotype determination and, when available, the whole genome sequence was examined for mutations analysis. Genotype F was the most common genotype (87%). While the HBV subgenotype F3 was the most frequent genotype in the whole group of samples (44%), the subgenotype F2 predominated in HCC patients (56%). Mutations were more common in HCC and cirrhosis cases (p=0.01). The A1762T mutation was significantly associated with the advanced stage of liver disease (p=0.008). Additionally, mutations were more common in early stages of liver disease in HBV subgenotype F2- infected patients, and a significant association between this subgenotype and the emergence of T1753C, A1762T, A1762T/G1764A (p=0.04) and C1773T (p=0.001) mutations in chronic patients was found, when compared to the HBV subgenotype F3. By comparing F2 with all other HBV subgenotypes, a positive association for the three basal core promoter (BCP) mutants (A1762T, A1762T/G1764A p=0.01, G1764A p=0.04) was found. These results suggest that the HBV subgenotype F2 might be associated to more severe forms of liver disease in comparison with the HBV subgenotype F3.

Mundialmente, alrededor del 50% del cáncer de hígado se origina como consecuencia de la infección a largo plazo con el virus de la hepatitis B (VHB), y algunos genotipos y mutaciones han sido asociados con severidad incrementada de la infección. El objetivo de este estudio fue evaluar la diversidad genética del VHB en pacientes de Venezuela con infección crónica, cirrosis y carcinoma hepatocelular (CHC) y comparar la ocurrencia de mutaciones en los tres grupos de pacientes. Se reunieron muestras de pacientes con diferentes patologías de la enfermedad del hígado asociada a la infección por VHB. La región S del VHB fue analizada para la determinación del genotipo y cuando estuvo disponible, la secuencia del genoma completo fue examinada para análisis de mutaciones. El genotipo F de VHB fue el más frecuente (87%). Mientras que el F3 fue el subgenotipo más encontrado en el grupo completo de muestras (44%), el F2 fue predominante en pacientes con CHC (56%). Las mutaciones fueron más comunes en casos de pacientes con cirrosis y CHC (p=0,01). La mutación A1762T estuvo asociada significativamente con estado avanzado de la enfermedad del hígado (p=0,008). Adicionalmente, las mutaciones fueron más comunes en estados tempranos de la enfermedad del hígado en pacientes infectados con el subgenotipo F2, encontrándose una asociación significativa entre este subgenotipo y la ocurrencia de las mutaciones T1753C, A1762T, A1762T/ G1764A (p=0,04) y C1773T (p=0,001) en pacientes crónicos, en comparación con el subgenotipo F3. Por otro lado, al comparar F2 con los demás subgenotipos de VHB, se encontró una asociación positiva para las tres mutantes del promotor basal de la cápside (PBC) (A1762T, A1762T/G1764A p=0,01, G1764A p=0,04). Estos resultados sugieren que el subgenotipo F2 de VHB puede estar asociado a formas más severas de la enfermedad del hígado en comparación al subgenotipo F3.

Avaliação de mutações de resistência ao tratamento com análogos de nucleos(t)ídeos e de escape vacinal do vírus da hepatite B (VHB) em pacientes com hepatite crônica / Evaluation of treatment resistance mutations with nuclei analogues (t) ide and vaccine escape the hepatitis B virus (HBV) in patients with chronic hepatitis

INTRODUÇÃO: A hepatite B (VHB) é uma infecção dinâmica crônica, que apesar de existir programas de imunização e tratamento antiviral disponível, existe o risco de emergência de mutações de resistência aos análogos de núcleos(t)ídeos (AN) que devem ser rastreadas, devido as suas implicações clínicas. O Brasil disponibiliza pelo SUS cinco drogas para o tratamento antiviral: IFN, LAM, ADF, ETV e TDF e um guia de conduta clínica para orientar o tratamento no território nacional, o Protocolo de Diretrizes Terapêuticas para Hepatite B e co-infecções. OBJETIVO: O objetivo do presente estudo foi avaliar as mutações de resistência aos AN, mutações de escape vacinal e genótipos circulantes em pacientes com hepatite B crônica em dois centros de referencia em Hepatites, na Bahia (região Nordeste) e no Acre (região Norte) do Brasil. MATERIAL E MÉTODOS: Foi utilizadas ferramentas de biologia molecular e bioinformática, através de nested PCR e sequenciamento direto das amostras, para rastrear as mutações de resistência, a região alvo foi a transcriptase reversa (RT) do gene P e as mutações de escape vacinal foi a região do gene S do VHB, como também os genótipos e subgenotipos do VHB. RESULTADOS: Foram incluídos 527 pacientes durante o período de 2011-2015, sendo 320 pacientes do HUPES/BA e 207 do FUNDHACRE/AC. Os pacientes que representam a região Nordeste foram 59,3 % do sexo masculino e uma média de idade de 44,75±12,4 DP, os pacientes da região Norte 42% foram do sexo masculino e a média de idade foi de 40,36±13,9 DP. Todos os pacientes incluídos apresentaram AgHBs persistente por mais de seis meses e 86,1% apresentaram AgHBe negativo. Foram sequenciadas 296 amostras dos pacientes com VHB crônica. Foram encontradas mutações de resistência aos AN na Região Norte 1,2% (2), Região Nordeste 7,4%(8) e no global 3,8%(20). Os padrões de mutações de resistência primária encontrados foram: rtA194T, (3) rtL180M+M204V, rtL180M+M204I, rtS202I, rtM204I, rtA181S, rtA181E e rtA184S. Em relação ao escape vacinal a frequencia para a Região Norte foi de 7,1% (11), Região Nordeste 8,4% (9) e no global 7,6% (20). Nos pacientes virgens de tratamento (n=189), a frequência de mutações de resistência foi de 6%, somente nas amostras da região Nordeste. Não houve diferença estatisticamente significante entre o grupo com ou sem mutação dos pacientes virgens de tratamento. Não foram encontradas mutações de resistência nas amostras da região Norte. Os genótipos circulantes nas duas regiões foram A, D e F, e a região Nordeste foi encontrada o genótipo C (C2). CONCLUSÃO: Os resultados demonstram a importância de rastrear e monitorar as mutações de resistência aos AN e de escape vacinal devido a importância epidemiológica e clínica na conduta terapêutica.

INTRODUTION: Hepatitis B virus (HBV) is a chronic dynamic infection, which although there immunization programs and antiviral therapy available, there is a risk of emergence of resistance mutations cores analogs (t) ide to be screened, because of their implications clinics. The Brazil offers the SUS five drugs for antiviral treatment: IFN, LAM, ADF, ETV and TDF and clinical guide of conduct to guide treatment in the country, the Therapeutic Guidelines Protocol for Hepatitis B and coinfections. AIM: The aim of this study was to evaluate the resistance mutations core analogues (t) ide, vaccine escape mutations and circulating genotypes in patients with chronic hepatitis B in two reference centers in Hepatitis, Bahia (Northeast) and Acre (Northern region) of Brazil. MATERIAL AND METHODS: Was used tools of molecular biology and bioinformatics by nested PCR and direct sequencing of samples to track resistance changes, the target region is the reverse transcriptase (RT) P gene and vaccine escape mutations was region of the gene S of HBV, as well as the HBV genotypes and subgenotipos. RESULTS: 527 patients were included during the period 2011-2015, with 320 patients HUPES / BA and 207 FUNDHACRE / AC. Patients representing the Northeast were 59.3% male and an average age of 44.75 ± 12.4 PD patients in the northern region 42% were male and the average age was 40, 36 ± 13.9 DP. All patients had persistent HBsAg for more than six months and 86.1% were HBeAg negative. We were sequenced 296 samples from patients with chronic HBV. the cores of similar resistance mutations were found (t) ide in the North 1.2% (2), Northeast 7.4% (8) and 3.8% overall (20). The patterns of primary resistance mutations were: rtA194T (3) rtL180M + M204V, M204I + rtL180M, rtS202I, rtM204I, rtA181S, and rtA181E rtA184S. Regarding vaccine escape the frequency for the Northern Region was 7.1% (11), Northeast 8.4% (9) and the global 7.6% (20). In treatment-naïve patients (n = 189), the frequency of resistance mutations was 6%, only the samples in the Northeast. There was no statistically significant difference between the groups with or without mutation of naive patients. There were no resistance mutations in samples from the North. Circulating genotypes in the two regions A, D and F, and the Northeast found the C genotype (C2). CONCLUSION: The results demonstrate the importance of tracking and monitoring the resistance mutations similar cores (t) ide and vaccine escape due to epidemiological and clinical importance in the therapeutic approach.

Serorreactividad al antígeno de superficie del virus de la hepatitis B en mujeres que acudieron al laboratorio central de salud pública. Asunción, Paraguay / Seroreactivity against the hepatitis B virus surface antigen in women who attended the central public health laboratory. Asunción, Paraguay

La hepatitis B es un grave problema de salud pública a nivel mundial, aproximadamente cerca de 2 billones de personas tienen evidencia serológica de infección por el virus de la hepatitis B. El objetivo de este trabajo fue describir la frecuencia de hepatitis B e identificar los factores de riesgo asociados en mujeres en edad fértil que acudieron al Laboratorio Central de Salud Pública entre diciembre de 2013 y junio de 2014. Fue un estudio observacional analítico de corte transverso que, previo consentimiento informado, analizó suero de mujeres entre 15 y 44 años con una edad promedio de 26,6 (±6,8) años. Mediante la detección del antígeno de superficie de la hepatitis B por ELISA se identificaron seis casos positivos (0,4%), indicando una endemicidad baja; cifra que ha variado según perfil socio demográfico: según edad, las de 20 y más años presentaron una frecuencia mayor en comparación a las demás (p>0,05). No se observaron diferencias significativas al evaluar la seropositividad según el estado civil, el nivel de escolaridad, la condición de gravidez, los antecedentes de transfusiones, sin embargo, la seropositividad era mayor en las portadoras de tatuajes/piercing que entre las no portadoras, lo que representaba un riesgo 6,2 veces mayor (OR:6,2 IC95%:1,3-31,3). En conclusión, la frecuencia del HBsAg en nuestra población es baja, y el factor de riesgo asociado a su detección fue la presencia de tatuajes y/o piercing.

Hepatitis B is a serious public health problem worldwide; approximately about 2 billionpeople have serologic evidence of infection with hepatitis B virus. The aim of this analyticcross-sectional study was to describe the frequency of hepatitis B and identify risk factorsin women of child bearing age who attended the Central Public Health Laboratory in theperiod 2013 to 2014. Prior informed consent, antigen detection of hepatitis B surface wasperformed by ELISA in women between 15 and 44 years with a mean age of 26.6 (±6.8)years. The identification of six serologic positive cases (0.4%) indicates low endemicity.This figure varied according to socio-demographic profile: according to age, those whowere 20 years old or older had an increased frequency compared to the others (p> 0.05). No significant differences were observed in seropositivity by marital status, level ofeducation, pregnancy, history of transfusion, while seropositivity was higher amongcarriers of tattoos/piercing than among non-carriers, which represented a 6.2 times higherrisk (OR 6.2 95% CI 1.3 to 31.3). In conclusion, the frequency of HBsAg in our populationwas low. The risk factor associated with its detection was the presence of tattoos and / or piercings.

Coinfección de hepatitis B y/o hepatitis C en pacientes infectados por virus de inmunodeficiencia humana (VIH) / Hepatitis B and/or hepatitis C co-infection in patients infected by the human immunodefficiency virus (HIV)

La coinfección con los virus de hepatitis B (VHB) y/o hepatitis C (VHC) puede provocar complicaciones en el paciente VIH+. El objetivo de este estudio fue evaluar la frecuencia de marcadores serológicos en la coinfección del VHB y/o VHC en plasmas de pacientes infectados por VIH y su correlación con el estatus virológico del VIH e inmunológico del paciente. Se evaluaron 1.846 plasmas positivos para VIH, referidos al Instituto Nacional de Higiene “Rafael Rangel” para la determinación de marcadores serológicos del VHB y VHC. Se realizaron análisis de carga viral del VIH-1 y recuento de linfocitos T CD4+/CD8+ para evaluar el estatus virológico e inmunológico, respectivamente de la población estudiada. La frecuencia de coinfección por VHB ó VHC fue de 15% y 5%, respectivamente mientras que la coinfección VHB/VHC fue de 0,16% (3/1.846) en pacientes infectados por VIH. No se observó asociación entre presencia de marcadores serológicos del VHB ó el VHC y bajos ó elevados niveles de ARN genómico del VIH (p=0,81 y p=0,31, respectivamente) ni valores bajos ó normales del índice CD4/CD8 (p=0,75 y p=0,06, respectivamente). Estos resultados sugieren que la coinfección con VHB o VHC no parece influir en los estatus virológico e inmunológico de la población evaluada.

Co-infection with hepatitis B (HBV) virus and/or hepatitis C (HCV) virus can induce complications in HIV+ patients. The purpose of this study was to evaluate the frequency of serologic markers in HBV and/ or HCV in plasma of HIV infected patients, and its correlation with the HIV viral status and the immunological status of the patient. The study included the evaluation of 1,846 HIV positive plasmas referred to the Instituto Nacional de Higiene “Rafael Rangel” for the determination of HBV and HCV serologic markers. The evaluation of the viral and immunological status was done by the analysis of the HIV-1 viral load and CD4+/CD8+ T lymphocyte counts, respectively, in the population studied. The frequency of HBV or HCV co-infection was 15% and 5%, respectively, while HBV/HCV co-infection was 0.16% (3/1,846) in HIV infected patients. There was no association between the presence of HBV or HCV serologic markers and low or normal values of the HIV genomic RNA (p=0.81 and p=0.31, respectively) nor low or normal values of the CD4/CD8 index (p=0.75 and p=0.06, respectively). These results suggest that HBV or HCV co-infection does not seem to influence the viral and immunological status of the evaluated population.

Mecanismos moleculares involucrados en la mutagenicidad inducida por aflatoxina B1 / Molecular mechanism involved in the mutagenicity induced by Aflatoxin B1 / Mecanismos moleculares envolvidos na mutagenicidade induzida pela aflatoxina B1

La aflatoxina B1 (AFB1) es una micotoxina identificada como el más potente hepatocarcinógeno. El metabolito que resulta del proceso de detoxificación de la AFB1 en el hígado tiene la capacidad de reaccionar con el ADN genómico, generando el aducto AFB1-ADN; durante la replicación del ADN este aducto induce la transversión G:C—>T:A. Polimorfismos en los genes que codifican las enzimas encargadas de la activación y detoxificación de la AFB1 y enzimas de reparación del ADN han sido asociados con el riesgo de desarrollar carcinoma hepatocelular (CHC). Adicionalmente, en poblaciones con alta exposición a aflatoxina y alta prevalencia de infección por el virus de la hepatitis B (VHB) se ha demostrado un sinergismo entre estos dos factores de riesgo para el desarrollo de CHC.

The aflatoxin B1 (AFB1) is a mycotoxin that has been identified as the most potent hepatocarcinogen. The metabolite resulting from detoxification process of AFB1 in liver, has the ability to react with the genomic DNA, generating AFB1-DNA adducts; during DNA replication process, this adduct induced the G:C—>T:A transversion. Polymorphism in genes encoding for enzymes involved in the activation and detoxification of AFB1 and DNA repair enzymes has been associated with the risk of hepatocellular carcinoma (HCC) development. Additionally, in populations of high exposure to aflatoxin and high prevalence of hepatitis B virus (HBV) infection, has been demonstrated a synergism between these two risk factors for the development of HCC.

Aflatoxina B1 (AFB1) é uma micotoxina identificado como o hepatocarcinogen mais potente. O metabolito resultante do processo de desintoxicação de AFB1 no fígado, tem a capacidade de reagir com o ADN genómico, gerando AFB1 DNA-aducto; transversão durante a replicação do ADN deste aducto induz G:C—>T:A. Polimorfismos em genes que codificam as enzimas envolvidas na activação e na desintoxicação de AFB1 e enzimas de reparação do ADN têm sido associados com o risco de desenvolvimento de carcinoma hepatocelular (HCC). Além disso, em populações com elevada exposição a aflatoxina e elevada prevalência da infecção com vírus da hepatite B (VHB) tem sido mostrado um sinergismo entre estes dois factores de risco para o desenvolvimento de carcinoma hepatocelular.

Molecular epidemiology of hepatitis B virus among the indigenous population of the Curuçá and Itaquaí Rivers, Javari Valley, State of Amazonas, Brazil / Epidemiologia molecular do vírus da hepatite B em população indígena em torno dos Rios Curuçá e Itaquaí, Vale do Javari, Estado do Amazonas, Brasil

INTRODUCTION: Hepatitis B virus (HBV) infection is one of the most serious public health problems in the world. In Brazil, HBV endemicity is heterogeneous, with the highest disease prevalence in the North region. METHODS: A total of 180 samples were analyzed and subjected to polymerase chain reaction (PCR) and semi-nested PCR of the HBV S-gene, with the aim of determining the prevalence of HBV-DNA (deoxyribonucleic acid) in indigenous groups inhabiting the areas near the Curuçá and Itaquaí Rivers in the Javari Valley, State of Amazonas, Brazil. RESULTS: The prevalence of the HBV-DNA S-gene was 51.1% (92/180). The analysis found 18 of 49 (36.7%) samples from the Marubo tribe, 68 of 125 (54.4%) from the Kanamary, and 6 of 6 (100%) from other ethnic groups to be PCR positive. There was no statistically significant difference in gender at 5% (p=0.889). Indigenous people with positive PCR for HBV-DNA had a lower median age (p<0.001) of 23 years. There was no statistical difference found in relation to sources of contamination or clinical aspects with the PCR results, except for fever (p<0.001). The high prevalence of HBV-DNA of 75% (15/20) in pregnant women (p=0.009) demonstrates an association with vertical transmission. CONCLUSIONS: The results confirm the high prevalence of HBV-DNA in the Javari Valley, making it important to devise strategies for control and more effective prevention in combating the spread of HBV.

INTRODUÇÃO: A infecção pelo vírus da hepatite B (VHB) é um dos mais sérios problemas de saúde pública do mundo. No Brasil, a endemicidade do VHB é heterogênea, sendo a doença mais prevalente na região norte do país. MÉTODOS: Neste estudo, foram investigadas 180 amostras de sangue por meio da técnica da reação em cadeia da polimerase (PCR) e PCR semi-nested para o vírus da hepatite B, gene S, com o intuito de determinar a prevalência do DNA (ácido desoxirribonucléico) do vírus da hepatite B em povos de etnias indígenas habitantes dos Rios Curuçá e Itaquaí no Vale do Javari, Estado do Amazonas, Brasil. RESULTADOS: A prevalência encontrada para o DNA-VHB gene S foi de 51,1% (92/180). Entre as amostras positivas 18/49 (36,7%) pertenciam à etnia Marubo, 68/125 (54,4%) à Kanamary e 6/6 (100%) a outras etnias. Não houve diferença significante ao nível de 5% em relação ao gênero (p=0,889). Os indígenas com PCR positiva para DNA-VHB apresentaram mediana de idade menor de 23 anos (p<0,001). Não foi constatado nenhuma diferença estatística em relação às fontes de contágio e o resultado da PCR, como também aos aspectos clínicos, com exceção da febre (p<0,001). A alta prevalência do DNA-VHB de 75% (15/20) em gestantes (p=0,009) demonstra associação com a transmissão vertical. CONCLUSÕES: Os resultados comprovam a alta prevalência do DNA-VHB no Vale do Javari, tornando-se importante traçar estratégias de controle e prevenção mais eficazes no combate à disseminação do VHB.

Efecto de Phyllanthus orbicularis sobre la viabilidad celular y el antígeno de superficie de la hepatitis B en células PLC/PRF/5 / Effect of Phyllanthus orbicularis on the cell viability and the hepatitis B surface antigen in PLC/PRF/5 cells

La actividad antiviral de Phyllanthus orbicularis Kunth, planta endémica de Cuba, frente al virus de la hepatitis B, fue estudiada in vitro. Se determinó la capacidad del extracto acuoso y 2 fracciones químicas ricas en taninos y flavonoides (acético-acuosa y butanólica) para inhibir la producción o bloquear la detección del antígeno de superficie de la hepatitis B (AgsHB) en las células PLC/PRF/5, una línea celular de hepatoma humano que expresa este marcador constitutivamente. El extracto acuoso fue efectivo al inhibir el AgsHB producido a las 24 y 48 h con índices selectivos superiores a 10, con una acción inhibitoria dependiente de la concentración. La evaluación de la actividad de las fracciones obtenidas a partir de esta planta mostró que ambas eran efectivas con índices selectivos superiores a 10. Estos resultados sugieren que existe una actividad inhibitoria del antígeno estudiado y que esta planta posee algunos compuestos fenólicos que podrían actuar sobre el AgsHB y reducir su producción en las células, lo que indica una posible actividad in vivo. Este trabajo corrobora el potencial de acción antiviral del extracto acuoso de P orbicularis, además de avalar el empleo de la línea PLC/PRF/5 para futuras evaluaciones o ensayos encaminados a valorar la actividad antihepatitis B de diferentes productos. De igual forma abre el camino para la determinación de aquel o aquellos componentes químicos responsables de la actividad de la planta frente al virus de la hepatitis B

The antiviral activity of Phyllanthus orbicularis, an endemic Cuban plant, against the hepatitis B virus was evaluated in vitro. The ability of the aqueous extract and 2 tannin- and flavonoid-rich chemical fractions (aqueous-acetic and buthanolic) to inhibit the hepatitis B surface antigen (HBsAg) production was determined in PLF/PRC/5 cellas, a human hepatoma cell line that constitutively expresses this antigen. The aqueous extract was effective in inhibiting the HBsAg at 24 and 48 hours of treatment, being the selective index (SI) above 10, with concentration-dependent inhibitory activity. The evaluation of the inhibitory action of the two fractions from the plant proved that both were effective and their selective indexes were also higher than 10. These results indicated the inhibitory activity against HBsAg of the plant and the presence of phenolic compounds that could reduce the antigen production. This may contribute to an in vivo antiviral action. This paper also corroborated the antiviral potential of the aqueous extract from Phyllanthus orbicularis Kunth, in addition to supporting the use of PLC/PRF/5 for future evaluations or trials directed towards assessing the anti-hepatitis B activity of various products. Likewise, it paved the way for the detection of the chemical component(s) responsible for the plant's action against hepatitis B virus

Hepatitis B and C virus infection among Brazilian Amazon riparians / Infecção pelo virus da hepatite B e C em ribeirinhos da Amazônia brasileira

INTRODUCTION: Viral hepatitis is a major public health concern in Brazil. There are few past studies on this issue, especially among riparian communities. This study aims at determining the seroprevalence of viral hepatitis B and C in the riparian community of Pacuí Island, within the Cametá municipality of Pará State, Brazil. Moreover, this study aims to investigate the principal risk factors that this community is exposed to. METHODS: The current study has accessed blood samples from 181 volunteers who have answered an epidemiological questionnaire. Analyses on serological markers have been tested with commercial ELISA kits for detecting HBsAg, total anti-HBc, anti-HBs, and anti-HCV. Within seroreactive patients for HCV, RT-PCR and line probe assay have been performed to identify the viral genotype. RESULTS: In the serological marker analysis for hepatitis B, no reactivity for HBsAg, rate of 1.1 percent for total anti-HBc, and rate of 19.3 percent for anti-HBs have been observed. On hepatitis C, 8.8 percent seroprevalence has been found, in which 62.5 percent have gotten viral RNA. Among the risk factors studied, the following have been highlighted: non-use of condoms, sharing of cutting instruments, use of illicit drugs, and reports of family disease with HBV or HCV. CONCLUSIONS: The vaccination coverage against HBV is low, and the high prevalence of HCV within this community has been observed.

INTRODUÇÃO: As hepatites virais constituem um importante problema de saúde pública no mundo. No Brasil existem poucos estudos sobre esta questão, especialmente entre as comunidades ribeirinhas. O objetivo deste estudo foi determinar a soroprevalência das hepatites B e C virais na comunidade ribeirinha da Ilha do Pacuí, no Estado do Pará, Brasil, e investigar os principais fatores de risco principal a que está comunidade está exposta. MÉTODOS: O presente estudo avaliou amostras de sangue de 181 voluntários que responderam a um questionário epidemiológico. Análises de marcadores sorológicos foram testados com kits comerciais de ELISA para detecção de HBsAg, anti-HBc total, anti-HBs e anti-VHC. Nos pacientes reagentes para VHC, RT-PCR e um line probe assay foi realizado para identificar o genótipo viral. RESULTADOS: Na análise dos marcadores sorológicos para hepatite B, observou-se taxas de 1,1 por cento para anti-HBc total e 19,3 por cento para anti-HBs, o marcador sorológico HBsAg não foi encontrado nesta população. Para a hepatite C foi encontrada um soroprevalência de 8,8 por cento, destes 62,5 por cento tinham RNA viral. Entre os fatores de risco estudados se destacaram: a não-utilização de preservativos, o compartilhamento de instrumentos cortantes, uso de drogas ilícitas e relatos de doença na família com VHB ou VHC. CONCLUSÕES: Observamos que a cobertura de vacinação contra o VHB é baixa e uma alta prevalência da hepatite C nesta comunidade.

Artículo de revisión: hepatitis viral B y su manejo / Review article: viral hepatitis B and its handling

La Hepatitis B es causada por el virus del mismo nombre (VHB). El paciente presenta ictericia, acolia, coluria, astenia, adinamia, anorexia, distensión abdominal, lienteria, náuseas y vómitos sin fiebre. Blumberg y colaboradores detectaron y caracterizaron al nuevo Virus. Además de hepatitis postranfusional puede causar epidemias por trasnmisión sexual, alimentos y en las zonas endémicas, perinatal. Trabajos en Asia, América y África demostraron relación del VHB con cirrosis macro y micronodular, hepatocarcinoma. Se presenta una parte de nuestra modesta contribución en Colombia. Varias vacunas están en uso clínico y se describen en el artículo. El tratamiento con Inmunomoduladores como interferones y antivirales inespecíficos como rivabirina, isoprinosine, lamivudina, adefovir, entecavir, tenofovir, emtricitabina, clevudina, alamifovir se comenta en el artículo. La respuesta a antivirales depende del subtipo y genotipo del VHB y mutaciones inducidas por el tratamiento. Esto y progresos en métodos diagnósticos en los cinco últimos años renovaron el interés por estudiar las mutaciones naturales y espontáneas del VHB, sus genotipos, subtipos y respuesta inmune que se revisan.

Hepatitis B is caused by the virus with the same name (HBV). The patient has symptoms of jaundice, acolia, dark urine, fatigue, weakness, anorexia, abdominal distension, lienteria, nausea and vomiting without fever. Blumberg and his colleagues identified and characterized the new virus. Besides postranfusional hepatitis, it can cause epidemics by sexual transmission, food, and in endemic areas, perinatal. Studies in Asia, America and Africa showed a relationship between the HBV and macro and micronodular cirrhosis, hepatocellular carcinoma. We present a part of our modest contribution in Colombia. Several vaccines are being used clinically and they are described in the article. In the article, we discuss the treatment with immunomodulators such as interferons and non-specific antiviral drugs such as isoprinosine, lamivudina, adefovir, entecavir, tenofovir, emtricitabina, clevudina, alamifovir. The response to antiviral drugs depends on the HBV subtype, genotype and mutations induced by the treatment. This and advances in diagnostic methods in the last five years renewed the interest in studying the natural and spontaneous mutations of HBV, its genotypes, subtypes, and the immune response that is analyzed here.

Hepatitis B / Hepatitis B

Resumen: el virus de la hepatitis B es un agente viral común que infecta de forma crónica casi 400 millones de personas en el mundo, las cuales tienen un riesgo permanente de desarrollar cirrosis y/o carcinoma hepatocelular. La historia natural de la infección por este virus es dinámica, ya que los pacientes pueden fluctuar entre periodos con inflamación hepática y periodos con enfermedad inactiva. En la progresión de la enfermedad participan varios factores como el genotipo viral infectante, la edad al momento de la infección y el sexo masculino, entre otros. Las personas con alto riesgo de infección por el virus de la hepatitis B, deben ser evaluadas serológicamente y de ser negativas para la infección, deben ser vacunadas. Si por el contrario, se encuentran infectadas, deberán ser monitorizadas hasta descartar una progresión a la infección crónica, y si ésta se presenta, deberán ser seguidas de por vida con el fin de tratar de controlar el desarrollo de una posible cirrosis, o en el peor de los casos, de un carcinoma hepatocelular.

Abstract: Hepatitis B virus is a common viral pathogen that chronically infects almost 400 million people worldwide, who have a permanent risk of developing cirrhosis and/or hepatocellular carcinoma. The natural history of hepatitis B virus infection is dynamic, and patients can fluctuate between periods of active liver inflammation and periods of inactive disease. Disease progression is influenced by various factors, including viral genotype, age at the time of infection, and male gender, among others. Persons with high risk of infection by hepatitis B virus should be serologically evaluated and if found negative, should be vaccinated; if found positive, they should be monitored until a chronic infection is ruled out. If chronic infection is developed, patients should be monitored for life to try to control the appearance of cirrhosis, or even worst, hepatocellular carcinoma.(AU)

Sangre segura en ausencia de infecciones virales por VHB, VHC y VIH en período de ventana serológica de donadores

OBJETIVO: Determinar la prevalencia de infecciones virales (VHB, VHC y VIH) en período de ventana serológica en donadores de sangre evaluados con la prueba de ácidos nucleicos (NAT). MATERIALES Y MÉTODOS: Se incluyeron donadores de sangre evaluados de 2008 a 2009 con pruebas serológicas y moleculares del VHB, VHC y VIH. El período de ventana serológica se definió con la prueba de NAT positiva y la prueba serológica negativa. RESULTADOS: Durante un año se evaluaron 47 847 donadores de sangre; no se identificó ningún caso con infección viral (VHB, VHC y VIH) en período de ventana serológica; únicamente se demostró NAT positivo en donadores con pruebas serológicas positivas: 26 de 78 con VHB, 56 de 318 con VHC y 16 de 155 con VIH. CONCLUSIÓN: Este es el primer estudio en México que demostró en donadores de sangre la ausencia de infecciones virales (VHB, VHC y VIH) en período de ventana serológica con la prueba de NAT.

OBJECTIVE: To determine the prevalence of viral infections (HBV, HCV and HIV) in serological window period in blood donors screened with nucleic acid testing (NAT). MATERIALS AND METHODS: We assessed all blood donors from July 2008 to June 2009 at the Central Blood Bank of the Mexican Institute of Social Security. Medical history was made and provided an information brochure and self-exclusion questionnaire. All blood donors were tested with serological tests (Ag-HBVs, Anti-HCV and Anti-HIV) and molecular testing with NAT for HBV, HCV and HIV. The window period was defined with the positive NAT and negative serological test. RESULTS: During one year, we evaluated 47 847 blood donors. None subject was identified with viral infection (HBV, HCV and HIV) in serological window period. Positive serological testing were found for HBV in 78 (0.2 percent), 318 (0.7 percent) for HCV and 155 (0.3 percent) for HIV. Positive NAT was demonstrated only in donors with positive serology: 26 of 78 with HBV, 56 of 318 with HCV and 16 of 155 with HIV. CONCLUSION: This is the first study in México showed no viral infections (HBV, HCV and HIV) during serological window period in blood donors; The medical history and the self-exclusion questionnaire help to improve blood transfusion safety.

La tolerancia inmunológica a 50 años del premio nobel en medicina y fisiología: una perspectiva como mecanismo de respuesta inmune frente a patógenos: [revisión] / Immune tolerance at 50 years from the nobel prize in medicine and physiology: a perspective as a mechanism of immune response against pathogens: [review]

El sistema inmune es responsable de proteger al organismo contra agentes extraños mediante el desarrollo de un repertorio de receptores, capaces de reconocer antígenos de toda etiología, diferenciando moléculas propias de extrañas, estableciendo además fundamentos para la identidad biológica del individuo. Para ello dispone de una red compleja de mecanismos celulares y moleculares que son los responsables de la llamada tolerancia inmune. La regulación de la interacción entre el sistema inmune y los antígenos que eventualmente puede conducir al desarrollo de tolerancia, es crítica tanto en condiciones fisiológicas como en diferentes estados de patología. Desde las primeras descripciones de Medawar, las cuales mostraron que el fenómeno de tolerancia es adquirido y central para la homeóstasis del sistema inmune, un número importante de mecanismos se han propuesto para explicar la tolerancia inmune. Sin embargo, un mecanismo único de autotolerancia ha surgido: la generación de linfocitos T reguladores antígeno específicos, también conocidos como células T reguladoras (Treg), de origen central o periférico. Esta subpoblación de linfocitos con funciones supresoras ha mostrado un papel muy importante no solo en el control de enfermedades autoinmunes, sino además en la inmunopatogenia de enfermedades infecciosas crónicas, ya sean inducidas por el patógeno como mecanismo de escape o por el hospedador para mitigar el daño tisular consecuencia de la activación de la respuesta inmune. Esta revisión tiene como propósito actualizar los conceptos modernos en tolerancia inmune, con especial énfasis en el papel de las células Treg en la tolerancia inducida durante el curso de infecciones crónicas.

The immune system has the capability of protection against infectious disease which is accomplished by an enormous repertoire of receptors specifically reactive to foreign antigens, but it is tolerant to self-antigens, establishing biological identity. The ability to discriminate between self and non-self is a central property of the immune system, by using complex network of cellular and molecular mechanisms in order to prevent autoimmunity; this function is called immune tolerance. Thus, the Interaction between immune system and antigens is required for the generation of tolerance and it is critical in different physiological and pathological conditions in order to limit the damage to self tissues. Since Medawar description, who showed that the tolerance is an acquired property playing a central role in the homeostasis, several mechanism has been proposed to explain it. It is accepted today that an important group of antigen specific cells called regulatory T cell, both natural and induced, are critical as a unifying mechanism to maintain self-tolerance. These suppressor lymphocyte subpopulations had shown to play an important role not only by controlling autoimmune disease but also in the pathogenesis of many chronic infectious diseases, either manipulated by the microorganism to escape from the immune system, or induced by the host to reduce inflammatory damage. This review has the intention of updating about modern concepts in immune tolerance mechanisms, with special emphasis played by Treg cell in the tolerance which is unquestionable induced during the course of chronic infections diseases.