Esther Castello Branco Mello Miranda

Prevalência de genótipos e de mutantes pré-core A-1896 do vírus da hepatite B e suas implicações na hepatite crônica, em uma população da Amazônia oriental

A infeccao pelo virus da hepatite B apresenta amplo espectro de manifestacoes clinicas. Objetivando conhecer os genotipos do HBV mais prevalentes e determinar a ocorrencia da mutacao pre-core A-1896, em uma populacao da Amazonia oriental, correlacionando com o diagnostico clinico, foram selecionados 51 pacientes portadores cronicos de HBsAg e HBV-DNA positivos e divididos em tres grupos: grupo A (n=14, pacientes assintomaticos); grupo B (n=20, sintomaticos HBeAg positivos) e grupo C (n=17, sintomaticos HBeAg negativos), sendo usado o sequenciador automatico ABI modelo 377 para identificacao de genotipos e mutantes pre-core. Os resultados evidenciaram o genotipo A como o mais prevalente, 81,8%, 89,5% e 93,7%, nos grupos A, B e C, respectivamente. A mutacao pre-core A-1896 foi encontrada em 11,5% (3/26), sendo todos assintomaticos. Concluiu-se que na populacao estudada o genotipo A foi o mais prevalente e houve baixa ocorrencia do mutante pre-core A-1896, ambos nao se constituindo fatores agravantes da doenca hepatica.

Mannose-binding lectin gene polymorphisms are not associated with susceptibility to hepatitis C virus infection in the Brazilian Amazon region

The present study compares the genotype frequencies between two population groups composed by 73 hepatitis C virus (HCV)-infected patients and 92 seronegative controls and investigates the role of allele variants as a possible factor in the susceptibility to HCV infection and the influence on disease progression. The identification of MBL*B and MBL*C alleles was performed by restriction fragment length polymorphism analysis of the 349-bp product using BanI and MboII restriction enzymes, respectively, and a polymerase chain reaction-sequence-specific polymorphism for discrimination of MBL*D. The analysis of allele and genotype frequencies between an HCV-infected group and seronegative controls did not indicate significant differences. The comparison of chronically infected subjects with and without liver cirrhosis was also not statistically significant. The odds ratio estimations were not significant, and the values obtained cannot suggest that the presence of allele variant MBL*B could have some influence in the risk of HCV infection progression to liver cirrhosis and that the presence of allele MBL*D could confer some protection against disease progression, but a larger sample size is necessary to confirm the present results.

Infecções pelos vírus das hepatites B e C e o carcinoma hepatocelular na Amazônia oriental

Com o objetivo de contribuir para um melhor conhecimento do envolvimento das infeccoes pelos virus das hepatites B e C, na etioepidemiologia do CHC na Amazonia Oriental, estudou-se 36 pacientes em Belem-PA. Foram avaliados marcadores sorologicos e a pesquisa do HBV-DNA e HCV-RNA pela reacao em cadeia da polimerase. Observou-se etilismo em 33,3% e cirrose em 83,3%. Marcadores sorologicos das infeccoes pelo HBV e HCV foram encontrados respectivamente em 88,9% e 8,3%. O HBsAg foi encontrado em 58,3%; anti-HBc em 86%; anti-HBe em 85,7; HBeAg em 9,5%; anti-HBc IgM em 57,1%. O HBV-DNA foi detectado em 37,7% e em 65% dos HBsAg positivos; o HCV-RNA em 8,5% e em 100% dos anti-HCV positivos. AFP esteve alterada em 88,9% e acima de 400ng/ml em 75% dos casos. Conclui-se que a infeccao pelo HBV parece ter importância na etiologia do CHC e ressalta-se a importância de implementar programas de vacinacao e deteccao precoce do tumor.

Association of killer cell immunoglobulin-like receptor polymorphisms with chronic hepatitis C and responses to therapy in Brazil

Soroprevalence for Hepatitis C virus is reported as 2.12% in Northern Brazil, with about 50% of the patients exhibiting a sustained virological response (SVR). Aiming to associate polymorphisms in Killer Cell Immunoglobulin-like Receptors (KIR) with chronic hepatitis C and therapy responses we investigated 125 chronic patients and 345 controls. Additionally, 48 ancestry markers were genotyped to control for population stratification. The frequency of the KIR2DL2 and KIR2DL2+HLA-CAsp80 gene and ligand was higher in chronic infected patients than in controls (p < 0.0009, OR = 3.4; p = 0.001, OR = 3.45). In fact, KIR2DL3 is a weaker inhibitor of NK activity than KIR2DL2, which could explain the association of KIR2DL2 with chronic infection. Moreover, KIR2DS2 and KIR2DS2+HLA-CAsp80 (p < 0.0001, OR = 2.51; p = 0.0084, OR = 2.62) and KIR2DS3 (p < 0.0001; OR = 2.57) were associated with chronic infection, independently from KIR2DL2. No differences in ancestry composition were observed between control and patients, even with respect to therapy response groups. The allelic profile KIR2DL2/KIR2DS2/KIR2DS3 was associated with the chronic hepatitis C (p < 0.0001; OR = 3). Furthermore, the patients also showed a higher mean number of activating genes and a lower frequency of the homozygous AA profile, which is likely secondary to the association with non-AA and/or activating genes. In addition, the KIR2DS5 allele was associated with SVR (p = 0.0261; OR = 0.184).The ancestry analysis of samples ruled out any effects of population substructuring and did not evidence interethnic differences in therapy response, as suggested in previous studies.

Coinfection caused by the human immunodeficiency virus and hepatitis C virus (HIV-1/HCV): a case study in the Brazilian Amazon

INTRODUCTION: Since highly active antiretroviral therapy was developed in 1996, liver injury has become an important cause of morbidity and mortality in individuals infected by the human immunodeficiency virus-1 (HIV-1). OBJECTIVE: To report the demographic and laboratory findings of 62 patients coinfected with HIV-1/HCV. METHODS: This cross-sectional study analyzed HIV patients , confirmed serologically by ELISA and indirect immunofluorescence or Western Blot, with positive anti-HCV by ELISA and confirmed by RT-PCR. These patiens were treated at the Liver Department of the Fundação Santa Casa de Misericórdia do Pará from August 2004 to April 2008. RESULTS: A total of 49 (79%) male and 13 female patients were analyzed. Their age median was 42.6 years and they were single (66.1%, n=41), heterosexual (59.7%, n = 37), bisexual (27.4%, n = 17), man who have sex with man MSM (12.9%, n = 8); the lymphocytes T CD4+ count median 3 was 327 cells/mm , HIV serum viral load median was 2.54 log HIV RNA copies/mL, HCV viral load (RNA-HCV) was 5.9 10 log UI/mL. The HCV genotype 1 was found in 60.87% of the patients. Forty-one (66.12%) patients were submitted to liver 10 biopsies and the histopathology results according to METAVIR were F0 (12%), F1 (24.4%), F3 (17%), F4 (14.6%). CONCLUSION: Patients were predominantly single, with high viral load. They presented with moderate to severe fibrosis in more than 50% of cases without significant changes in their laboratory findings.

Coinfecção provocada pelos vírus da imunodeficiência humana e hepatite C (HIV-1/HCV): uma casuística da Amazônia brasileira

INTRODUCTION: Since highly active antiretroviral therapy was developed in 1996, liver injury has become an important cause of morbidity and mortality in individuals infected by the human immunodeficiency virus-1 (HIV-1). OBJECTIVE: To report the demographic and laboratory findings of 62 patients coinfected with HIV-1/HCV. METHODS: This cross-sectional study analyzed HIV patients , confirmed serologically by ELISA and indirect immunofluorescence or Western Blot, with positive anti-HCV by ELISA and confirmed by RT-PCR. These patiens were treated at the Liver Department of the Fundação Santa Casa de Misericórdia do Pará from August 2004 to April 2008. RESULTS: A total of 49 (79%) male and 13 female patients were analyzed. Their age median was 42.6 years and they were single (66.1%, n=41), heterosexual (59.7%, n = 37), bisexual (27.4%, n = 17), man who have sex with man MSM (12.9%, n = 8); the lymphocytes T CD4+ count median 3 was 327 cells/mm , HIV serum viral load median was 2.54 log HIV RNA copies/mL, HCV viral load (RNA-HCV) was 5.9 10 log UI/mL. The HCV genotype 1 was found in 60.87% of the patients. Forty-one (66.12%) patients were submitted to liver 10 biopsies and the histopathology results according to METAVIR were F0 (12%), F1 (24.4%), F3 (17%), F4 (14.6%). CONCLUSION: Patients were predominantly single, with high viral load. They presented with moderate to severe fibrosis in more than 50% of cases without significant changes in their laboratory findings.

Programa de hepatopatias do Hospital da Fundação Santa Casa de Misericórdia do Pará: infra-estrutura e epidemiologia clínica em 10 anos de atendimento

O Programa de Hepatopatias do Hospital da Fundacao Santa Casa de Misericordia do Para surgiu pela necessidade de prestar assistencia a hepatopatas na regiao amazonica priorizando assistencia qualificada, identificacao das etiologias, seguimento clinico, e tratamento direcionado. Este trabalho visa descrever dados relativos a epidemiologia clinica, fatores etiologicos e analise histopatologica. Dos 1469 pacientes avaliados, atraves de exames clinicos, laboratoriais, endoscopicos e de imagem e/ou histopatologico, foram considerados hepatopatas cronicos 935 (63,6%). Nesta casuistica, a media de idade foi 50 anos, 666 (71,2%) do sexo masculino e maior procedencia de Belem. Os agentes etiologicos mais prevalentes foram alcoolismo (53,7%) e hepatites virais (39,1%). Biopsia hepatica realizada em 403/935 (43,1%), demonstrou hepatite cronica (34%) e cirrose (34%) na maioria das amostras. Conclui-se, portanto, que a doenca hepatica cronica na regiao e mais prevalente no sexo masculino, sendo o alcoolismo a principal etiologia e mais da metade dos casos se encontravam em fase avancada no momento do diagnostico.

Assessment of the treatment of chronic hepatitis C virus infection: a case series from a hospital in the Brazilian Amazon region.

According to the World Health Organization, more than 170 million people worldwide are infected with HCV, corresponding to 3% of the world population, with an important impact on global public health.1 More than 20 years have elapsed since the discovery of the putative virus. The efficacy of chronic hepatitis C treatment has improved over the past decade, but treatment with interferon (IFN) is unable to eradicate HCV in chronically infected patients.2 In treatment-naive patients who are infected with HCV genotype 1 and present a high viral load, a sustained virological response (SVR) rate of 10% is obtained with conventional IFN and about 50% with the combination of pegylated IFN (PEG-IFN) and ribavirin.3 Promising results have been reported for patients infected with HCV genotype 1 when a protease inhibitor either telaprevir or boceprevir is added to PEG-IFN plus ribavirin, with an increase in SVR rates from 50% (PEG-IFN + ribavirin) to around 70% (PEG-IFN + ribavirin + protease inhibitor). In Brazil some studies evaluating the efficacy of the treatment for chronic hepatitis C have been published, such as the study conducted by Azevedo et al., who first demonstrated a SVR rate of 32.6% in the state of Mato Grosso, lower than rates found in the South and Southeast regions.4 I would like to share the preliminary results of a larger study of the treatment of the hepatitis C virus infection in which we are investigating the role of interleukin 28B and ancestrality as predictive factors of SVR. The treatment of hepatitis C virus (HCV) infection is provided free-of-charge by the national public health system (SUS) in Belém do Pará, northern Brazil, where conventional interferon or pegylated interferon combined with ribavirin was used in the study period. A total of 251 patients seen between 2002 and 2011 at the liver outpatient service of the of Fundação Santa Casa de Misericórdia do Pará (FSCMPA) Hospital, Belém, Pará, Brazil, were included in the study. Some patients were excluded because of incomplete information in the medical records. Data entry and statistical analysis of research data were carried on in EPI INFO 6.0 and 5.0 BioEstat softwares. Out of the 251 patients, 86 (34%) received conventional IFN and 165 (66%) received PEG-IFN, both combined with ribavirin. Table 1 summarizes the patient variables of the 251 HCV-infected patients treated with conventional IFN or PEG-IFN plus ribavirin. Among patients receiving conventional IFN, 52/86 (60%) had mild fibrosis (F1 and F2), 56/86 (65%) were infected with HCV non-genotype 1, and 41/86 (48%) achieved SVR. Patients infected with genotype 1 achieved 30% SVR compared to 58% of patients with non-genotype 1 (p = 0.01). Seventy-nine (48%) of the 165 patients receiving PEG-IFN had fibrosis stage F2. HCV genotype 1 was the most frequent (84.24%) and 88/165 (53%) patients achieved SVR whereas 52% (72/139) of patients infected with non-genotype 1 in this group achieved SVR. The SVR rate according to fibrosis stage, irrespective of HCV genotype, was 53.7% in patients with stage F2 and 8% in patients with stage F4 (p = 0.0068). The main objective of hepatitis C treatment is to eradicate the virus and to prevent cirrhosis and its complications, as well as hepatocellular carcinoma. The overall objective is not met in case of failure to eradicate the virus. In the present study, half of the patients chronically infected with HCV who were treated with conventional IFN and ribavirin did not achieve SVR. Analysis according to HCV genotype showed that only 31% of patients with genotype 1 achieved SVR. A study analyzing 87 patients with chronic hepatitis C seen at the Federal University of Paraná, who received conventional IFN plus ribavirin provided by the Ministry of Health, yielded an overall SVR of about 30%. This rate is similar to those reported in the international literature, although recent studies have achieved rates close to 40%.5 The introduction of protease inhibitors is expected to enhance SVR rates in Belem, Para.

Coinfección provocada por los virus de inmunodeficiencia humana y hepatitis C (VIH-1/VHC): una casuística de la Amazonía brasileña

INTRODUCTION: Since highly active antiretroviral therapy was developed in 1996, liver injury has become an important cause of morbidity and mortality in individuals infected by the human immunodeficiency virus-1 (HIV-1). OBJECTIVE: To report the demographic and laboratory findings of 62 patients coinfected with HIV-1/HCV. METHODS: This cross-sectional study analyzed HIV patients , confirmed serologically by ELISA and indirect immunofluorescence or Western Blot, with positive anti-HCV by ELISA and confirmed by RT-PCR. These patiens were treated at the Liver Department of the Fundação Santa Casa de Misericórdia do Pará from August 2004 to April 2008. RESULTS: A total of 49 (79%) male and 13 female patients were analyzed. Their age median was 42.6 years and they were single (66.1%, n=41), heterosexual (59.7%, n = 37), bisexual (27.4%, n = 17), man who have sex with man MSM (12.9%, n = 8); the lymphocytes T CD4+ count median 3 was 327 cells/mm , HIV serum viral load median was 2.54 log HIV RNA copies/mL, HCV viral load (RNA-HCV) was 5.9 10 log UI/mL. The HCV genotype 1 was found in 60.87% of the patients. Forty-one (66.12%) patients were submitted to liver 10 biopsies and the histopathology results according to METAVIR were F0 (12%), F1 (24.4%), F3 (17%), F4 (14.6%). CONCLUSION: Patients were predominantly single, with high viral load. They presented with moderate to severe fibrosis in more than 50% of cases without significant changes in their laboratory findings.