Fulminant hepatitis failure in adults and children from a Public Hospital in Rio de Janeiro, Brazil

Fulminant hepatic failure (FHF) is characterized by massive hepatocellular injury, whose physiopathology is still unclear. Hepatitis B (HBV) is probably the most common viral cause of FHF, while hepatitis A (HAV) virus seem occurs less frequently. However, the host and viral factors that determine the outcome of these infections are poorly understood. In the present study, viral load and genotyping determining regions of HAV and HBV genomes were sequenced. Eight FHF patients and one patient with severe acute hepatitis (SAH) were included. Liver and blood samples were collected during liver transplantation or necropsy procedures. HAV-RNA and HBV-DNA were extracted from serum, biopsy and paraffin liver. Nucleotide sequencing of HAV-RNA was performed from VP1/2A and HBV-DNA from PreS/S region. The amplified samples were quantified by Real-Time PCR. The cases of HAV infection were due to subgenotype IA. The cases of HBV infection were due to genotype A2 and D4. The case of HAV/HBV coinfection was infected by genotype IA and D3. Hepatitis A and B infection were associated with genotypes most prevalent in Brazil. In hepatitis A infection the mean of period evolution was 13 days. In hepatitis B, FHF patients infected by genotype D have a shorter period of evolution than FHF patients infected by genotype A (mean 15 v. 53 days). There was no association with genotype-determining region with the severity of hepatitis, however nucleotide differences and high viral load could be observed among FHF.

Fulminant hepatitis failure in adults and children from a Public Hospital in Rio de Janeiro, Brazil.

Fulminant hepatic failure (FHF) is characterized by massive hepatocellular injury, whose physiopathology is still unclear. Hepatitis B (HBV) is probably the most common viral cause of FHF, while hepatitis A (HAV) virus seem occurs less frequently. However, the host and viral factors that determine the outcome of these infections are poorly understood. In the present study, viral load and genotyping determining regions of HAV and HBV genomes were sequenced. Eight FHF patients and one patient with severe acute hepatitis (SAH) were included. Liver and blood samples were collected during liver transplantation or necropsy procedures. HAV-RNA and HBV-DNA were extracted from serum, biopsy and paraffin liver. Nucleotide sequencing of HAV-RNA was performed from VP1/2A and HBV-DNA from PreS/S region. The amplified samples were quantified by Real-Time PCR. The cases of HAV infection were due to subgenotype IA. The cases of HBV infection were due to genotype A2 and D4. The case of HAV/HBV coinfection was infected by genotype IA and D3. Hepatitis A and B infection were associated with genotypes most prevalent in Brazil. In hepatitis A infection the mean of period evolution was 13 days. In hepatitis B, FHF patients infected by genotype D have a shorter period of evolution than FHF patients infected by genotype A (mean 15 v. 53 days). There was no association with genotype-determining region with the severity of hepatitis, however nucleotide differences and high viral load could be observed among FHF.

Mecanismos inflamatórios de imunidade inata associados com extensa lesão do fígado na falência hepática fulminante / Inflammatory mechanisms of innate immunity associates with extensive injury of the liver in the fulminant hepatic failure

A falência hepática fulminante (FHF) é uma síndrome clínica resultante da morte maciça das células hepáticas, podendo ser induzida por agentes como vírus, drogas além de resposta autoimune, com taxa de mortalidade extremamente alta. Esta grave doença é caracterizada principalmente pelo rápido aparecimento de encefalopatia e coagulopatia, em indivíduos com função hepática previamente normal, sendo o transplante de fígado o tratamento de escolha. Os mesmos agentes envolvidos na FHF podem induzir formas menos graves de doença hepática, podendo o resultado clínico ser relacionado à resposta imunológica do hospedeiro, a qual envolve um sistema de moléculas sinalizadoras e células inflamatórias. Contudo, os elementos chave que determinam esta forma de doença hepática ainda não foram esclarecidos. Nossa contribuição foi identificar e quantificar marcadores de fenótipos celulares, citocinas e outros mediadores inflamatórios no parênquima hepático e sangue periférico de pacientes com FHF nos períodos pré e pós-transplante. Amostras de fígado de doadores saudáveis e pacientes com hepatite crônica, além do sangue de indivíduos saudáveis, foram utilizados como controle. Métodos histoquímicos, imunofluorescência, citometria de fluxo e tecnologia multiplex foram usados para identificar e quantificar fenótipos celulares, assim como citocinas e outros mediadores inflamatórios em amostras de fígado, sangue total periférico e plasma. Pacientes com FHF apresentaram um inesperado aumento do número de eosinófilos no ambiente intrahepático e no sangue periférico, concomitantemente detectou-se um aumento na expressão de IL-6 nos mesmos territórios, com ausência de IL-5 intrahepática. No sangue periférico, foi também observado um aumento no percentual de células Natural Killer (NK) expressando os marcadores de ativação/citotoxidade (CD16(mais) e CD38(mais)), ativação precoce (CD69(mais) and HLADR(mais)) e a molécula de adesão (CD44(mais)), além de um aumento de células Natural...FHF.

Seroepidemiological markers of enterically transmitted viral hepatitis A and E in individuals living in a community located in the North Area of Rio de Janeiro, RJ, Brazil.

We investigated the seroprevalence of hepatitis A virus (HAV) and hepatitis E virus (HEV) infection in subjects living in the community of Manguinhos, Rio de Janeiro, Brazil, and assisted at the Health Unit of Escola Nacional de Saúde Pública, Fundação Oswaldo Cruz. After formal consent, individuals were submitted to an interview using a standardized questionnaire. Anti-HAV and anti-HEV antibodies were detected by ELISA. Statistical analysis was carried out using the Epi-Info 6.04b software, to investigate possible associations between serological markers and risk factors. Results were regarded as significant when p value < 0.05. Although a high prevalence of anti-HAV was observed (87%), almost 50% of subjects under the age of 10 were susceptible to HAV infection, an unexpected rate in endemic areas. This fact could be attributed to improvements in environmental sanitation, occurring in this area in the last years. The increasing proportion of susceptible people may result in outbreaks of HAV infection, since the virus still circulates in this area, as verified by the detection of anti-HAV IgM in some individuals. No statistical association was met between HAV infection and the risk factors here assessed. The anti-HEV IgG prevalence found in this population was 2.4%, consistent with the one found in non-endemic areas.

Seroepidemiological markers of enterically transmitted viral hepatitis A and E in individuals living in a community located in the North Area of Rio de Janeiro, RJ, Brazil

We investigated the seroprevalence of hepatitis A virus (HAV) and hepatitis E virus (HEV) infection in subjects living in the community of Manguinhos, Rio de Janeiro, Brazil, and assisted at the Health Unit of Escola Nacional de Saúde Pública, Fundaçäo Oswaldo Cruz. After formal consent, individuals were submitted to an interview using a standardized questionnaire. Anti-HAV and anti-HEV antibodies were detected by ELISA. Statistical analysis was carried out using the Epi-Info 6.04b software, to investigate possible associations between serological markers and risk factors. Results were regarded as significant when p value < 0.05. Although a high prevalence of anti-HAV was observed (87 percent), almost 50 percent of subjects under the age of 10 were susceptible to HAV infection, an unexpected rate in endemic areas. This fact could be attributed to improvements in environmental sanitation, occurring in this area in the last years. The increasing proportion of susceptible people may result in outbreaks of HAV infection, since the virus still circulates in this area, as verified by the detection of anti-HAV IgM in some individuals. No statistical association was met between HAV infection and the risk factors here assessed. The anti-HEV IgG prevalence found in this population was 2.4 percent, consistent with the one found in non-endemic areas

Avaliação da freqüência das hepatites virais de transmissão entérica A e E em indivíduos atendidos em um centro de saúde da região de Manguinhos, Rio de Janeiro, RJ / Evaluation of the frequency of the hepatitis A and E virais enteric transmission in individuals taken care of in a center of health of the region Manguinhos, Rio de Janeiro, RJ

As hepatites virais representam um problema de saúde pública mundial. Entre os agentes que causam hepatite no homem dois são entericamente transmitidos: O vírus da hepatite A (HAV) e o vírus da hepatite E (HEV). Nos últimos anos, melhorias no saneamento básico têm sido responsáveis por uma diminuição do nível de endemicidade da hepatite A em diversos países. No Brasil, a hepatite A é considerada uma doença endêmica, embora sua prevalência não seja bem conhecida em todo o País. O presente estudo teve como objetivo avaliar a prevalência da infecção pela HAV e a circulação do HEV em indivíduos moradores da comunidade de Manguinhos, localizada na Zona Norte do Município do Rio de Janeiro. Amostras de sangue destes indíviduos foram coletadas durante atendimento ambulatorial no Centro de Saúde da Escola Nacional de Saúde Pública (FIOCRUZ) e submetidas à pesquisa de anticorpos para o HAV (IgM e IgG anti-HAV) e HEV (igG anti-HEV) por teste imunoenzimático. Os dados epidemiológicos foram obtidos por meio de entrevista e posteriormente analisados pelo programa epi-info )CDC - Atlanta, 1996). Embora a prevalência total de anti-HAV nesta população tenha sido alta (87 por cento), quase 50 por cento dos indivíduos abaixo de 10 anos eram suscetíeis à infecção pelo HAV, uma taxa não esperada para áreas endêmicas para a hepatite A. Este fato poderia ter sido decorrente de melhorias no saneamento básico que vêm sendo implementadas nesta região nos últimos anos. O aumento no número de pessoas suscetíveis pode resultar na ocorrência de surtos da infecção, uma vez que o vírus ainda circula nesta área pela detecção de anti-HAV IgM em alguns indivíduos. A análise da prevalência de anti-HAV de acordo com os fatores de risco não demonstrou significado estatístico, provavelmente devido a alta prevalência de anti-HAV nesta população.