Avaliação do perfil epidemiológico das hepatites virais no Brasil - 2010 A 2021 / Evaluation of the epidemiological profile of viral hepatitis in Brazil - 2010 to 2021

As hepatites virais são doenças que apresentam elevado impacto de morbimortalidade no mundo, sendo assim, consideradas um grave problema para a saúde pública. Nos últimos anos o enfrentamento das hepatites virais tem sido um grande desafio, principalmente para os países com alta prevalência de vulnerabilidades sociais. Medidas de controle e prevenção da doença devem ser tomadas, por isso torna-se necessário a realização de estudos que contemplem conhecimentos sobre a dinâmica epidemiológica das hepatites para demonstrar sua importância em relação a saúde pública. Objetivo: O objetivo nesta pesquisa foi analisar o perfil epidemiológico das hepatites virais no Brasil, no período de 2010 a 2021. Método: Realizou-se um estudo transversal, descritivo, retrospectivo e qualiquantitativo que utilizou como unidades de análise as unidades federativas brasileiras. Os dados foram coletados a partir das informações disponíveis no site TABNET/DATASUS, DCCI, e a estimativa da população anual absoluta foi obtida no Instituto Brasileiro de Geografia e Estatística (IBGE). Resultados: No período analisado foram registrados 476.981 casos de hepatites virais no Brasil, destacando-se a notificação de casos de hepatite C, seguida pela hepatite B, A e D. Com relação a taxa de incidência, a Região Norte destacou-se para hepatite A e D, e a Região Sudeste para hepatite B e C. O sexo do indivíduo acometido em todos os tipos de hepatite virais analisados que se destacou foi o masculino, mas com pouca diferença do feminino. Foram registrados 25.553 óbitos, sendo 78,3% devido à hepatite C. A presente pesquisa nos permitiu concluir que o tipo de hepatite mais relatada no Brasil é a tipo C, assim como a que mais provoca óbitos. Todas as hepatites virais apresentaram queda nas notificações no ano de 2020 e 2021 e por isso este fato deve ser analisado pelos setores de vigilância pois pode se tratar de subnotificações, principalmente devido a situação do país neste período, que enfrentava a pandemia de COVID-19

Viral hepatitis is a disease with a high impact on morbidity and mortality worldwide and hence considered a serious problem for public health. Fighting viral hepatitis has been a major challenge in recent years, especially for countries with a high prevalence of social vulnerabilities. Measures to control and prevent the disease must therefore be taken, so studies that include knowledge about the epidemiological dynamics of hepatitis are warranted to demonstrate its importance to public health. In the objective of the present study was to analyze the epidemiological profile of viral hepatitis in Brazil in the period from 2010 to 2021. A cross-sectional, descriptive, retrospective, and qualitative-quantitative investigation was carried out using the federative units of Brazil as units of analysis. Data were collected from information available on the TABNET/DATASUS, DCCI website, and the absolute annual population estimate was obtained from the Brazilian Institute of Geography and Statistics (IBGE). In the analyzed period, 476,981 cases of viral hepatitis were recorded in Brazil, the majority of which referred to hepatitis C, followed by hepatitis B, A, and D. As regards the incidence rate, the north region stood out with hepatitis A and D; and the southeast region with hepatitis B and C. Males prevailed between the genders of individuals affected, considering all types of viral hepatitis analyzed, but with little difference from females. A total of 25,553 deaths were recorded, 78.3% of which were due to hepatitis C. Conclusions: The present study allowed us to conclude that the most reported type of hepatitis in Brazil is type C, which is also the most death-causing. There was a drop in notifications of all viral hepatitis in 2020 and 2021, and this fact should be analyzed by surveillance sectors as it may be a situation of underreporting, due mainly to the COVID-19 pandemic crisis the country was facing in the period

Hepatitis D: advances and challenges / 中华医学杂志(英文版)

Hepatitis D virus (HDV) infection causes the most severe form of viral hepatitis with rapid progression to cirrhosis, hepatic decompensation, and hepatocellular carcinoma. Although discovered > 40 years ago, little attention has been paid to this pathogen from both scientific and public communities. However, effectively combating hepatitis D requires advanced scientific knowledge and joint efforts from multi-stakeholders. In this review, we emphasized the recent advances in HDV virology, epidemiology, clinical feature, treatment, and prevention. We not only highlighted the remaining challenges but also the opportunities that can move the field forward.

Tendências e distribuição espacial da hepatite D no Norte do Brasil, 2009-2018: um estudo ecológico / Tendencias y distribución espacial de Hepatitis D en el Norte de Brasil, 2009-2018: un estudio ecológico / Trends and spatial distribution of Hepatitis D in the North of Brazil, 2009-2018: an ecological study

Objetivo: Analisar a incidência anual de hepatite D no Brasil e na região Norte, no período 2009-2018. Métodos: Estudo ecológico de casos de hepatite D notificados no Sistema de Informação de Agravos de Notificação (Sinan), analisados por sexo, idade e estados do Norte. Realizou-se análise de tendência temporal pelo método de Prais-Winsten, para estimar a variação percentual anual (VPA) das taxas de incidência. Resultados: No período, foram reportados 2.710 casos no Brasil, 74,5% na região Norte e 71,5% somente no Amazonas, Acre e Rondônia. Houve tendência de queda da VPA no país (-21,6% - IC95% -3,8;-36,2%), região Norte (-28,5% - IC95% -5,2;-46,1%,), Amazonas (-34,1% - IC95% -0,8;-56,2%) e Acre (-37,6% - IC95% -18,0;-52,6%). Verificou-se diminuição de casos nos estratos etários abaixo de 40 anos. Conclusão: Houve tendência de queda da incidência de hepatite D na Amazônia Ocidental, que impactou na incidência no país. Essa redução foi puxada pelos mais jovens, provavelmente resultado da vacinação para hepatite B.

Objetivo: Evaluar la incidencia anual de casos de hepatitis D en Brasil y en la Región Norte, entre 2009-2018. Métodos: En este estudio ecológico, se utilizaron casos notificados al Sistema Nacional de Agravamiento de de Enfermedades (Sinan), analizados por sexo, edad y estados del Norte. Se utilizó la regresión de Prais-Winsten para análisis de la tendencia temporal y el cálculo de la variación porcentual anual (VPA) de tasas de incidencia. Resultados: En el periodo, se notificaron 2.710 casos, siendo 74,5% en el Norte e 71,5% en Amazonas, Acre y Rondônia. Hubo tendencia a disminución de la VPA en Brasil (-21,6% - IC95% -3,8;-36,2%), región Norte (-28,5% - IC95% -5,2;-46,1%,), Amazonas (-34,1% - IC95% -0,8;-56,2%) y Acre (-37,6% - IC95% -18,0;-52,6%). Hubo disminución de casos entre los menores de 40 años. Conclusión: Hubo tendencia a la disminución de la incidencia en la Amazonía Occidental, impactando en la incidencia en Brasil. Esta baja está relacionada con los más jóvenes, probablemente debido a la vacunación contra la hepatitis B.

Objective: To analyze the annual incidence of hepatitis D cases in both Brazil and the Brazilian Northern region between 2009 and 2018. Methods: This was an ecological study of hepatitis cases notified on the Notifiable Health Conditions Information System (SINAN), analyzed by sex, age groups, and Northern region states. Temporal trend analysis was performed using the Prais-Winsten method to estimate incident rate annual percent change (APC). Results: In the period studied, 2,710 cases were reported in Brazil, 74.5% of them in the Northern region and 71.5% in Amazonas, Acre and Rondonia alone. APC showed a downward trend in Brazil as a whole (-21.6% - 95%CI -3.8;-36.2%), in the Northern region (-28.5% - 95%CI -5.2;-46.1%,), in Amazonas (-34.1% - 95%CI -0.8;-56.2%) and in Acre (-37.6% - 95%CI -18.0;-52.6%). Cases decreased in age groups below 40 years old. Conclusion: There was a downward trend in incidence in the Western Amazon, impacting incidence in Brazil as a whole. This fall was led by younger people, probably due to hepatitis B vaccination.

Reducción en la infección por VHB y VHD en dos poblaciones indígenas de la Amazonia peruana después de la vacunación contra la hepatitis B / Reduction of HBV and HDV infection in two indigenous peoples of Peruvian Amazon after the vaccination against hepatitis B

Resumen: Objetivo: Conocer el resultado de la vacunación contra la hepatitis B en las comunidades hiperendémicas Kandozi y Chapra de la Amazonia Peruana a partir de la prevalencia de infecciones por los virus de la hepatitis B (VHB) y Delta (VHD), ocho años después de iniciada la vacunación. Material y métodos: Se realizó un estudio transversal en 2 944 pobladores de 67 comunidades indígenas Kandozi y Chapra en abril de 2010. El tamizaje serológico para el antígeno de superficie del VHB (HBsAg), anticuerpos anti-HBc IgM e IgG, anticuerpos anti-HBs y anti-VHD se determinaron mediante pruebas de ELISA. Resultados: Las tasas de prevalencia del HBsAg, anti-HBc IgG, anti-HBs ≥10 mlUI/ml y anti-VHD fueron 2.3, 39.13, 50.95 y 2.11%, respectivamente. La prevalencia del HBsAg en niños <11 años fue cero. Entre los portadores del HBsAg, las tasas de prevalencia de sobreinfeccion por el VHD e infección aguda por el VHB fueron 2.11% (todos fueron >14 años) y 11.94%, respectivamente. Conclusiones: Estos hallazgos muestran la eliminación de portadores de VHB en niños <11 años, ocho años después de iniciada la vacunación contra el VHB.

Abstract: Objective: To determine the outcome of the vaccination against hepatitis, we determined the prevalence of hepatitis B virus (HBV) and hepatitis D virus (HDV) infections, eight years after introduction of the vaccination. Materials and methods: A cross-sectional study was performed in 2 944 participants of 67 Kandozi and Chapra indigenous peoples in April 2010. Serological screening for hepatitis B surface antigen (HBsAg), antibody anti-HBc IgM and IgG, antibody anti-HBs and anti-HDV were determined by ELISA tests. Results: The prevalence rates of HBsAg, anti-HBc total, anti-HBs ≥10 mlUI/ml and anti-HDV were 2.3, 39.13, 50.95 and 2.11%, respectively. The prevalence rate of HBsAg in children <11 years was 0%. Among carriers of HBsAg, the prevalence rates of HDV and acute HBV infections were 2.11% (all were >14 years) and 11.94%, respectively. HBsAg and anti-HBc total were associated with individuals ≥10 years (p<0.001). Conclusions: These findings show the elimination of HBV carriers in children <11 years, eight years following introduction of the vaccination against HBV.

Prevalencia de infección por los virus de la hepatitis B, D y por retrovirus en la etnia Matsés (Loreto, Perú) / Prevalence of retrovirus, hepatitis B and D infection in the Matsés ethnic group in Loreto, Peru

RESUMEN Para determinar la prevalencia de infección por los virus de la hepatitis B y D (VHB y VHD, respectivamente), VIH y HTLV-1/2 en la etnia matsés, después de la inmunización contra el VHB se realizó un estudio transversal y poblacional, utilizando pruebas de ELISA y qPCR en 963 pobladores. Las prevalencias de HBsAg, anti-HBc y anti-HBs fueron 3,3%, 36,0% y 58,7%, respectivamente. En el 3,1% de la población la carga viral fue mayor a 2000 UI/mL. En menores de 10 años, la prevalencia de HBsAg y anti-HBc fue 0,0% y 2,6%, respectivamente, mientras que en el 94,4% se encontraron anticuerpos protectores. La prevalencia de infección por el VIH y el HTLV-1/2 fue 1,5% y 0,6%, respectivamente. Se concluye que existen tasas bajas de infección por el VHB y el VHD en la población infantil de la etnia matsés. Asimismo, se confirma la presencia de infección por el VIH y el HTLV-1/2.

ABSTRACT Observational, cross-sectional, populational study to determine the prevalence of infection by hepatitis B virus (HBV), hepatitis D virus (HDV), human immunodeficiency virus (HIV) and human T-lymphotropic virus type 1 and 2 (HTLV-1/2) in the Matsés ethnic group, after immunization against HBV. ELISA and qPCR tests were used in 963 residents. The prevalence of HBsAg, Anti-HBc and Anti-HBs was 3.32%, 36.03% and 58.67% respectively. In 3.1% of the population the viral load was greater than 2000 IU/mL. In children under 10 years, the prevalence of HBsAg and anti-HBc was 0.0% and 2.6%, respectively, while protective antibodies were found in 94.4%. The prevalence of HIV and HTLV-1/2 infection was 1.5% and 0.6%, respectively. It is therefore concluded that there are low rates of HBV and HDV infection in the Matsés child population. Likewise, the presence of HIV and HTLV-1/2 infection is confirmed.

Prevalence of hepatitis B and D virus infection in a district of Mato Grosso, bordering Amazonas and Rondônia states

Abstract INTRODUCTION: Brazil's western Amazon basin has the highest prevalence of hepatitis B virus (HBV) infection in the country. Coinfection with hepatitis D virus (HDV) is also endemic. To estimate the prevalence of HBV and HDV markers in a population inhabiting the northwest portion of Mato Grosso state in the western Amazon. METHODS: We performed a cross-sectional study of the seroprevalence of antibodies against HBV core antigen (anti-HBc) in the Três Fronteiras District northwest of Mato Grosso. Anti-HBc-positive subjects were tested for HBV surface antigen (HBsAg). Those positive for this marker were tested for HDV antibodies. Anti-HBc-negative participants were tested for anti-HBsAg. All tests were performed by EIA. RESULTS: A total of 623 individuals in the community were assessed; the majority (67.6%) were male, with a mean age of 30.8 ± 15.4 years. Two hundred and fourteen individuals (34.3%) were anti-HBc-positive, and 47 (7.5%) were HBsAg carriers. Only one individual was anti-HDV-positive. Among the 409 individuals without HBV infection, 18.3% were anti-HBsAg-positive. There was no association between HBV infection and known risk factors. CONCLUSIONS: The study area had intermediate-to-high endemicity for HBV infection, but a low prevalence of HDV. Our serological results suggesting low vaccination-induced protection indicate a need for reinforced immunization programs in the populations of northwest Mato Grosso.

Hepatitis B and Delta: clinical aspects of patients in the Brazilian Western Amazonia / Hepatitis B y Delta: aspectos clínicos de pacientes en el Amazonas brasileño Occidental / Hepatite B e Delta: aspectos clínicos de pacientes na Amazônia Ocidental brasileira

ABSTRACT Objective: to analyze clinical, serological, biochemical and hematological aspects in patients infected with the hepatitis B (HBV) and Delta (HDV) viruses. Method: cross-sectional, descriptive and retrospective study, performed with patients chronically infected with HBV and superinfected with HDV. Results: among the 112 patients selected, 74% were monoinfected with HBV (Group HBV) and 26% were superinfected with HDV (Group HBV+HDV). There was no difference in gender distribution. The average age was 36 years with standard deviation of ±12 years. The symptoms and signs presented a higher proportion in Group HBV+HDV (p=0.001). In both groups, most patients had non-reactive AgHBe. The records of biochemical and hematologic changes showed highest proportion in Group VHB+VHD Group (p<0.05). Conclusion: the study found that patients were in clinical stages of the disease different from those in the initial examination for monitoring their chronic condition. The clinical profile suggests greater severity of liver disease among the patients superinfected with HDV.

RESUMEN Objetivo: Analizar los aspectos clínicos, serológicos, bioquímicos y hematológicos de pacientes infectados por el virus de las hepatitis B (VHB) y Delta (VHD). Método: Se trata de un estudio transversal, descriptivo, retrospectivo, realizado entre pacientes crónicos infectados de VHB y sobre infectados de VHD. Resultados: Entre los 112 pacientes seleccionados, el 74% estaba mono infectado por VHB (Grupo VHB) y el 26%, sobre infectado por VHD (Grupo VHB+VHD). No se encontró diferencia en la distribución por género. La edad promedio era 36 años, con desviación típica de ±12 años. Los síntomas y signos sobresalían en mayor proporción en el grupo VHB+VHD (p=0,001). Para ambos grupos, la mayoría de los pacientes estaba con AgHBe no reactivo. El registro de alteraciones bioquímicas y hematológicas atribuyó proporción más grande al grupo VHB+VHD (p<0,05). Conclusión: El estudio demostró que los pacientes, en la consulta inicial para el seguimiento de la condición crónica, estaban en diferentes estadios clínicos de la enfermedad. El perfil clínico sugiere que la gravedad de la enfermedad hepática es mayor entre pacientes sobre infectados de VHD.

RESUMO Objetivo: Analisar aspectos clínicos, sorológicos, bioquímicos e hematológicos entre pacientes infectados por vírus das hepatites B (VHB) e Delta (VHD). Método: Estudo transversal, descritivo, retrospectivo, realizado com pacientes cronicamente infectados por VHB e superinfectados por VHD. Resultados: Entre os 112 pacientes selecionados, 74% estavam monoinfectados por VHB (Grupo VHB) e 26% superinfectados por VHD (Grupo VHB+VHD). Não houve diferença na distribuição por gênero. A idade média foi de 36 anos, com desvio padrão de ±12 anos. Os sintomas e sinais apresentaram maior proporção no grupo VHB+VHD (p=0,001). Para ambos os grupos, a maioria dos pacientes estava com AgHBe não reagente. O registro de alterações bioquímicas e hematológicas apresentou maior proporção no grupo VHB+VHD (p<0,05). Conclusão: O estudo revelou que os pacientes estavam em diferentes estágios clínicos da doença na consulta inicial para acompanhamento de condição crônica. O perfil clínico sugere maior gravidade da doença hepática entre os pacientes superinfectados por VHD.

Hepatitis delta prevalence in South America: a systematic review and meta-analysis

Abstract Hepatitis delta virus (HDV) has been associated with acute or chronic hepatitis in Latin America, but there is no prevalence study covering South American countries. This meta-analysis aimed to estimate anti-HDV prevalence through a systematic review of published articles in English, Portuguese and Spanish until December 2017. Searches were conducted in Health Virtual Library, Capes, Lilacs, PubMed, and SciELO, according to defined criteria regarding participant selection and geographical setting. Study quality was assessed using the GRADE guidelines. Pooled anti-HDV prevalence was calculated using the DerSimonian-Laird random-effects model with Freeman-Tukey double arcsine transformation. Out of the 405 identified articles, only 31 met the eligibility criteria for inclusion in the meta-analysis. In South America, pooled anti-HDV prevalence among hepatitis B virus carriers was 22.37% (95% confidence interval: 13.72-32.26), though it appeared less frequently in some countries and populations, according to the data collection date. The findings indicated significant successive reductions in anti-HDV prevalence over thirty years. However, there was a scarcity of HDV epidemiological studies outside the Amazon Basin, notably in the Southwest continent and absence of target population standardization. There was a high HDV prevalence in South American countries, despite differences in methodological characteristics and outcomes, highlighting a drastic decline in the last decades. Future studies should identify HDV prevalence estimates in other regions of the continent and identify risk factors.

Chronic hepatitis B and D: prognosis according to Child-Pugh score / Hepatitis crónicas B y D: pronóstico según escore Child-Pugh / Hepatites crônicas B e D: prognóstico segundo escore Child-Pugh

ABSTRACT Objective: compare chronic hepatitis B patients to those superinfected with hepatitis D virus, according to Child-Pugh score regarding disease severity. Method: retrospective descriptive study, performed with 59 patients followed in the ambulatory, of which 22 (37.3%) were chronically infected with hepatitis B virus (Group HBV) and 37 (62.7%) superinfected with Delta virus (Group HBV+HDV); variables of sex, age and items of Child-Pugh score were collected by consulting medical records. Results: out of the patients, 57.6% were male, with a mean age of 30.5 years. Score A, which indicates lesser severity, was found in 100% of group HBV and 78.4% of group HBV+HDV. Score B, which indicates greater severity, was found only in group HBV+HDV in 21.6% of the patients. Conclusion: by means of the Child-Pugh score, it was observed that patients with superinfection by HDV tended to present a worse prognosis.

RESUMEN Objetivo: comparar los pacientes con hepatitis B crónica con superinfectados por el virus D según escore de Child-Pugh cuanto a la gravedad de la enfermedad. Método: estudio descriptivo retrospectivo, realizado con 59 pacientes acompañados en ambulatorio, siendo 22 (37,3%) crónicamente infectados por el virus de hepatitis B (Grupo VHB) y 37 (62,7%) con superinfección por virus Delta (Grupo VHB+VHD); fueron colectadas variables cuanto al sexo, edad y referentes al escore de Child-Pugh por medio de consulta a prontuarios. Resultados: entre los pacientes 57,6% era de varones, con edad media de 30,5 años. El escore A, que indica menor gravedad, fue encontrado en 100% del grupo VHB y 78,4% del grupo VHB+VHD. El escore B, que indica mayor gravedad, fue encontrado apenas en el grupo VHB+VHD en 21,6% de los pacientes. Conclusión: por medio del escore de Child-Pugh, se observó que los pacientes con superinfección por VHD tienden a presentar peor pronóstico.

RESUMO Objetivo: comparar os pacientes com hepatite B crônica com superinfectados pelo vírus D segundo escore de Child-Pugh quanto à gravidade da doença. Método: estudo descritivo retrospectivo, realizado com 59 pacientes acompanhados em ambulatório, sendo 22 (37,3%) cronicamente infectados pelo vírus da hepatite B (Grupo VHB) e 37 (62,7%) com superinfecção por vírus Delta (Grupo VHB+VHD); foram coletadas variáveis quanto ao sexo, idade e referentes ao escore de Child-Pugh por meio de consulta a prontuários. Resultados: entre os pacientes 57,6% era do sexo masculino, com idade média de 30,5 anos. O escore A, que indica menor gravidade, foi encontrado em 100% do grupo VHB e 78,4% do grupo VHB+VHD. O escore B, que indica maior gravidade, foi encontrado apenas no grupo VHB+VHD em 21,6% dos pacientes. Conclusão: por meio do escore de Child-Pugh, observou-se que os pacientes com superinfecção por VHD tendem a apresentar pior prognóstico.

Acquired hepatocerebral degeneration in a patient with hepatitis B and hepatitis delta virus coinfection

Abstract Acquired hepatocerebral degeneration is a neurological syndrome with typical clinical (extrapyramidal and neuropsychiatric) symptoms and brain magnetic resonance imaging findings (high T1 signal in the globus pallidus). It occurs mainly in patients with advanced liver disease, such as in patients co-infected with hepatitis B virus (HBV) and hepatitis delta virus (HDV). However, there are no reports relating HBV/HDV coinfection and acquired hepatocerebral degeneration. This report presents the case of a 49-year-old woman with characteristics of acquired hepatocerebral degeneration and liver cirrhosis due to HBV/HDV coinfection, and presents the main theories of the physiopathology of this condition.

Acute hepatitis A, B and C but not D is still prevalent in Mongolia: a time trend analysis

BACKGROUND/AIMS: Mongolia has one of the highest hepatitis A, C, B and D infection incidences worldwide. We sought to investigate changes in the proportion of acute viral hepatitis types in Mongolia over the last decade. METHODS: The cohort comprised 546 consecutive patients clinically diagnosed with acute viral hepatitis from January 2012 to December 2014 in Ulaanbaatar Hospital, Mongolia. A time trend analysis investigating the change in proportion of acute hepatitis A virus, hepatitis C virus (HCV), hepatitis B virus (HBV) and hepatitis delta virus (HDV) infection among the cohort with respect to a previous published study was undertaken. RESULTS: Acute hepatitis A, B and C was diagnosed in 50.9%, 26.2% and 6.0% of the cohort. Notably, 16.8% of the cohort had a dual infection. The etiologies of acute viral hepatitis were varied by age groups. The most common cause of acute viral hepatitis among 2-19 year olds was hepatitis A, HBV and superinfection with HDV among 20-40 year olds, and HCV among 40-49 year olds. Patients with more than one hepatitis virus infection were significantly older, more likely to be male and had a higher prevalence of all risk factors for disease acquisition. These patients also had more severe liver disease at presentation compared to those with mono-infection. CONCLUSIONS: Acute viral hepatitis is still prevalent in Mongolia. Thus, the need for proper infection control is increasing in this country.

Expression and Purification of Recombinant Hepatitis Delta Virus (HDV) Antigen for Use in a Diagnostic ELISA for HDV Infection Using the High-Density Fermentation Strategy in Escherichia coli / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>Hepatitis Delt a Virus (HDV) antigen is widely used as a capture antigen in ELISAs for the identification of HDV infection; large amounts of recombinant HDV antigen with active antigenicity are required for this purpose.</p><p><b>METHODS</b>Reconstruct the gene of HDV antigen based on the bias code of Escherichia coli, the recombinant protein expresses by high-density fermentation with fed-batch feeding strategy, and purify by immobilized metal chromatography. The sensitivity and specificity of this antigen detect by ELISA method.</p><p><b>RESULTS</b>The expression of HDV antigen can reach 20% of the total cell mass in the soluble form. The recombinant HDV antigen can be conveniently purified (98%) by immobilized metal ion affinity chromatography (IMAC) using the interaction between a His-tag and nickel ions. Production of recombinant HDV antigen can reach 0.5 g/L under conditions of high-density cell fermentation. Applied to the diagnostic ELISA method, the recombinant HDV antigen shows excellent sensitivity (97% for IgM and 100% for IgG) and specificity (100% for IgG and IgM) for the detection of anti-HDV antibodies.</p><p><b>CONCLUSION</b>Expression and purification the recombinant HDV antigen as a candidate protein for application in a diagnostic ELISA for HDV infection. Large-scale production of the protein can be achieved using the high-density fermentation strategy.</p>

Liver transplantation in a patient with hepatitis B, C and D coinfection associated with hepatocellular carcinoma: a management strategy for a rare condition. Case report / Transplante hepático em paciente com coinfecção pelos vírus B, C e D associada a carcinoma hepatocelular: uma estratégia de tratamento para uma condição rara. Relato de caso

CONTEXT: Orthotopic liver transplantation (OLT) is the treatment of choice for end-stage liver disease. Cirrhosis due to hepatitis C infection is the leading indication for liver transplantation worldwide. However, patients who are given transplants because of viral liver diseases often present clinical coinfections, including hepatitis B together with hepatitis D. Currently, different strategies exist for patient management before and after liver transplantation, and these are based on different protocols developed by the specialized transplantation centers. CASE REPORT: We present a rare case of a 58-year-old man with chronic hepatitis B, C and D coinfection. The patient developed cirrhosis and hepatocellular carcinoma. His treatment comprised antiviral therapy for the three viruses and OLT. The patient's outcome was satisfactory. CONCLUSION: OLT, in association with antiviral therapy using entecavir, which was administered before and after transplantation, was effective for sustained clearance of the hepatitis B and D viruses. A recurrence of hepatitis C infection after transplantation responded successfully to standard treatment comprising peginterferon alfa-2A and ribavirin.

CONTEXTO: O transplante ortotópico de fígado (TOF) é o tratamento de escolha em pacientes com doença hepática terminal. A cirrose por hepatite C é a principal indicação de transplante hepático no mundo. No entanto, pacientes transplantados por hepatopatias virais frequentemente apresentam coinfecções, como hepatite B associada a hepatite D. Atualmente, existem diferentes estratégias de manejo em pacientes pré e pós-transplantados conforme diferentes protocolos de conduta de serviços especializados em transplante. RELATO DE CASO: Apresentamos o raro caso de um homem de 58 anos diagnosticado com as hepatites crônicas B, C e D. O paciente evoluiu com cirrose e carcinoma hepatocelular. O tratamento consistiu de terapia antiviral para os três vírus e de transplante ortotópico de fígado. O desfecho do paciente foi satisfatório. CONCLUSÃO: O transplante ortotópico de fígado, associado à terapia antiviral com entecavir antes e após o procedimento, foi eficaz na depuração sustentada dos vírus B e D. A recidiva do vírus C após o transplante respondeu com sucesso ao tratamento padrão com alfapeginterferon 2A e ribavirina.

Delta hepatitis in Rondônia: epidemiological analysis from 1999 to 2012 / Hepatite Delta em Rondônia: análise epidemiológica de 1999 a 2012

O vírus da hepatite Delta (VHD) é considerado um importante causador de doença hepática grave. Objetivo: Este estudo objetivou realizar uma análise epidemiológica dos casos diagnosticados em Rondônia. Métodos: Foi feito um estudo retrospectivo de 1999 a 2012, por meio de dados cedidos pela Agência Estadual de Vigilância em Saúde de Rondônia (AGEVISA RO). As variáveis analisadas foram: ano de diagnóstico, gênero, faixa etária, contato com paciente sabidamente portador do vírus da hepatite B (VHB), cor, vacinação, exposição aos fatores de risco, mecanismo de infecção e forma clínica. Resultados: Foram notificados 149 casos da doença, tendo uma incidência média de 0,7 casos/100.000 habitantes/ano; destes, 62,4% são do gênero masculino e 5,3% são gestantes. A faixa etária mais comum foi entre 20 e 39 anos. Sobre a vacinação da hepatite B, a mioria não tomou nenhuma dose da vacina. A forma mais comum de aquisição do vírus foi a sexual (71,8%), estando a grande maioria dos pacientes na fase crônica de doença (95,9%). Conclusão: A população acometida pelo vírus constituiu-se, principalmente, de homens na faixa etária sexualmente ativa, tendo como principal meio de transmissão a relação sexual. Observou-se baixa aderência da população acometida à vacinação; com isso, medidas de educação e conscientização da populaçãose fazem necessárias.

Hepatitis Delta virus (HDV) is considered an important cause of severe liver disease. Objective: This study aimed at an epidemiological analysis of cases diagnosed in Rondônia. Methods: A retrospective study from 1999 to 2012 was done through data provided by the State Agency of Health Surveillance of Rondônia (AGEVISA-RO). The variables analyzed were: year of diagnosis, gender, age, contact with patients known to have hepatitis B virus (HBV), ethnicity, caccination, exposure to risk factors, mechanism of infection and clinical manifestation. Results: 149 cases have been reported, with an average incidence of 0.7 cases per 100.000 inhabitants/year; 62,4% of these were males and 5,3%, females. The most common agre group was between 20 and 39 years. About hepatitis B vaccination, the majority took no vaccine dose. The most common route of transmission was sexual (71.8%), and most patients were in the chronic phase of the disease (95.9%). Conclusion: The population affected by the virus is mainly composed of men in the sexually active age group, with sexual intercourse as the main mode of transmission. Low adherence to vaccination by the population affected was observed; thereby, measures of education and public awareness are needed.

Hepatitis: know it confront it

Like last year, the World Hepatitis Day will be celebrated across the world including in the Eastern Mediterranean Region [EMR] of WHO on 28 July. The global theme of the campaign continues to be: This is hepatitis. Know it. Confront it

Effects of counseling and education to patients presenting with hepatitis at a tertiary care hospital

Hepatitis is an escalating problem in Pakistan due to lack of awareness about its risk factors. To create awareness about risk factors for hepatitis in patients coming for its treatment at a tertiary care hospital using a counseling intervention. The study was conducted at civil hospital, Karachi. Patients having hepatitis B or C were enrolled. Each patient filled a pre and post counseling questionnaire [after 6 months]. A total of 153 hepatitis positive patients were counseled. There were 108 females and 45 males. Majority [83] had hepatitis C virus, 56 had hepatitis B virus, 08 had co-infection of hepatitis B virus and hepatitis D virus and 06 had hepatitis B virus with hepatitis C virus. Counseling was done on multiple parameters. Pre counseling figures for using brand new syringes were 32% which improved to 81% after counseling, for using screened blood these changed from 22% to 81%, for sterilized dental instruments they improved from 21% to 65% and for avoiding road side barbers they improved from 58% to 78%. The figures for hepatitis B virus vaccination in hepatitis C virus patients rose from 3% to 36.6% and for families rose from 2.6% to 43.1%. Great improvements were seen in the awareness and health seeking behavior of hepatitis cases following behavior change communication. More stress should be given on preventive strategies through mass awareness and counseling programs to control disease spread

Prevalência de anticorpos anti-vírus da hepatite D (HDV) em pacientes com hepatite B no Rio de Janeiro e caracterização molecular do genoma completo do HDV / Prevalence of antibodies to hepatitis D virus (HDV) in patients with hepatitis B in Rio de Janeiro and molecular characterization of the complete genome of HDV

O vírus da hepatite D (Hepatitis D Virus ou HDV) é um vírus defectivo que necessita da presença do vírus da hepatite B (HBV) para completar seu ciclo infeccioso. A infecção pelo HDV está associada a uma forma mais grave de hepatite e com aumento do risco de progressão para complicações, tais como, cirrose e carcinoma hepatocelular. No Brasil, a Bacia Amazônica é uma área endêmica para a infecção pelo HDV, no entanto, poucos dados foram avaliados em outras regiões do país. Este estudo avaliou a prevalência de HDV em pacientes com infecção aguda ou crônica pelo HBV, acompanhados no Ambulatório Hepatites Virais, Rio de Janeiro, Brasil, entre 2006 e 2011. Um total de 368 amostras de soro de pacientes positivos para o antígeno de superfície do vírus da hepatite B (HBsAg) foi testado para a presença de anticorpos anti-HD utilizando o ensaio comercial ETI-AB-DELTAK-2, de acordo com as instruções do fabricante. Amostras com resultados reagentes ou indeterminados foram retestadas em duplicata, para confirmação ou não do resultado. Amostras anti-HD positivos foram testadas por PCR para amplificar um fragmento da região genômica do antígeno delta (HDAg). As amostras positivas para HDV RNA foram submetidas ao sequenciamento de nucleotídico, a fim de identificar o genótipo do HDV. As sequências obtidas foram alinhadas utilizando o programa Clustal X e a análise filogenética foi realizada usando o programa MEGA v.5. A carga viral do HBV foi quantificada por meio do ensaio comercial COBAS ® TaqMan ® HBV e o genótipo do HBV foi determinado pelo ensaio INNO-LIPA. Nossa população de estudo consistiu de 243 homens e 125 mulheres, com média de idade de 43 anos (1-82 anos), sendo 138 e 230 pacientes com infecção aguda e crônica pelo HBV, respectivamente. Cinco pacientes foram positivos para anticorpos anti-HD (infecção aguda pelo HBV, n = 1; infecção crônica pelo HBV, n = 4) e um dos pacientes com infecção crônica pelo HBV apresentou amostras com HDV RNA detectável. A análise filogenética mostrou que a sequência do HDV se agrupou com o genótipo 3. Dos quatro pacientes que tiveram HBV DNA detectado, três apresentaram baixos níveis de HBV DNA. Em relação ao genótipo de HBV, o genótipo A foi mais prevalente (n = 4). A fim de caracterizar a variabilidade genética de todo o genoma de HDV, o genoma completo foi sequenciado e as sequências de aminoácidos deduzidas foram inferidas utilizando o programa MEGA v.5. O genoma da amostra identificado no presente estudo é constituído por 1673 nucleotídeos e mostrou apenas 88,7% de similaridade com as sequências de genótipo 3 caracterizadas até o momento. A região LHDAg (large HDAg) da amostra brasileira contém múltiplas substituições de aminoácidos, que são conservadas em todas as sequências completas de genótipo 3, cujo significado ainda não foi estabelecido. Este trabalho constitui o primeiro estudo sobre a caracterização da variabilidade genética do genoma completo do HDV no Brasil. Em conclusão, apesar da soroprevalência de HDV ser considerada baixa em nossa coorte, este resultado destacou a importância da investigação infecção pelo HDV em áreas não endêmicas.

Hepatitis D virus infection in the Western Brazilian Amazon - far from a vanishing disease / Infecção pelo vírus da hepatite D na Amazônia brasileira - longe de uma doença em declínio

INTRODUCTION: A decline in hepatitis D virus (HDV) occurrence was described in Europe and Asia. We estimated HDV prevalence in the Brazilian Amazon following hepatitis B vaccination. METHODS: This is a cross-sectional survey of HDV measured by total antibodies to HDV (anti-HD T). RESULTS: HDV prevalence was 41.9% whiting HBsAg carries and was associated with age (PR = 1.96; 95% CI 1.12-3.42; p = 0.01), hepatitis B virus (HBV) infection (PR = 4.38; 95% CI 3.12-6.13; p < 0.001), and clinical hepatitis (PR =1.44; 95% CI 1.03-2.00; p = 0.03). Risk factors were related to HDV biology, clinical or demographic aspects such as underlying HBV infection, clinical hepatitis and age. CONCLUSIONS: Our study demonstrated that HDV infection continues to be an important health issue in the Brazilian Amazon and that the implementation of the HBV vaccination in rural Lábrea had little or no impact on the spread of HDV. This shows that HDV has not yet disappeared from HBV hyperendemic areas and reminding that it is far from being a vanishing disease in the Amazon basin.

INTRODUÇÃO: É descrito declínio na ocorrência do vírus da hepatite D (VHD) na Europa e Ásia. Estimamos a prevalência de infecção pelo VHD na Amazônia Ocidental, após a introdução da vacinação contra hepatite B. MÉTODOS: Este é um estudo de corte transversal da prevalência do VHD medido pela ocorrência de anticorpos totais (anti-HD T). RESULTADOS: A prevalência do VHD encontrada foi 41,9% entre os portadores do HBsAg, e esteve associado à idade (RP = 1,96; IC 95% 1,12-3,42; p = 0,01), infecção pelo HBV (RP = 4,38; IC 95% 3,12-6,13; p < 0,001) e história clínica de hepatite (RP =1,44; IC 95% 1,03-2,00; p = 0,03). Fatores de risco mostraram-se associados à biologia do HDV, aspectos clínicos e demográficos como infecção prévia pelo VHB e idade. CONCLUSÕES: O estudo demonstra que a infecção pelo VHD continua sendo um importante problema de saúde pública na região, e que a implantação da vacinação contra o VHB na área rural de Lábrea teve um impacto pouco significativo no controle do VHD, percebe-se que este ainda não desapareceu de áreas hiperendêmicas do VHB, e está longe de poder ser classificado como uma doença em declínio na bacia Amazônica.

Hepatites virais: B, C e D: atualização / Viral hepatitis: B, C and D: an update

JUSTIFICATIVA E OBJETIVOS: As hepatites causadas pelos vírus da hepatite B (VHB), vírus da hepatite C (VHC) e vírus da hepatite (VHD) têm como aspecto comum a transmissão por via parenteral e a possibilidade de cronificação. Revisar os aspectos clínico-epidemiológicos, diagnósticos, terapêuticos e profiláticos das infecções virais por tais agentes é o escopo do presente artigo. Realizou-se pesquisa bibliográfica nas bases de dados Scielo e Pubmed empregando-se os descritores hepatite B (hepatitis B); hepatite C (hepatitis C); hepatite D (hepatitis D) e hepatite G (hepatitis G), assim como livros texto, consensos e diretrizes relacionadas ao tema.CONTEÚDO: As formas agudas das hepatites B, C e D são usualmente benignas, podendo, sem embargo, ocorrerem quadros de hepatite fulminante. Em situações nas quais o sistema imunológico não é capaz de depurar o VHB e/ou VHC, há cronificação da infecção, com risco de desenvolvimento de cirrose e consequente insuficiência hepática crônica, bem como carcinoma hepatocelular. As hepatites B e D são imunopreveníveis, graças à vacina parao vírus B, mas, até o momento, não há imunoprofilaxia disponível para o vírus C.CONCLUSÃO: As hepatites pelos VHB e VHC constituem importantes desafios para a medicina atual, especialmente pela prevalência das infecções no planeta e pelo risco de desenvolvimento das complicações crônicas. Neste contexto, destaque-se a importância da avaliação diagnóstica, da instituição da terapêutica adequada e do emprego das medidas preventivas para tais infecções, elementos que devem ser solidamente conhecidas pelo clínico.

BACKGROUND AND OBJECTIVES: Hepatitis caused by hepatitis B virus (HBV), hepatitis C virus (HCV) and hepatitis D virus (HDV) have in common the transmission by parenteral route and the possibility of chronification. Reviewing the clinic, epidemiology, diagnose, therapeutics and prophylaxis of viral infections by these agents is the scope of this work. Bibliographic research was conducted both at databases Scielo and Pubmed through the chosen descriptors: hepatitis B, hepatitis C, hepatitis D and hepatitis G, and text books, consensus and guidelines related to the subject.CONTENTS: The acute viral B, C and D hepatitis are usually benign, though acute liver failure, fulminant hepatitis, may occur. In the cases when the immune system is unable to debug HBV and HCV the infection becomes chronic, cirrhosis with consequent chronic liver insufficiency and hepatocellular carcinomamay develop. HBV and HDV are immunopreventable, thanks to the hepatitis B virus vaccine, but at this point there's no immunoprophylaxis available for hepatitis C virus. CONCLUSION: HBV and HCV hepatitis are great challenges for medicine, particularly due to the prevalence of infections worldwide and the risk of chronic complications. In this context, diagnostic evaluation, adequate therapeutic care, and preventive measures must be soundly known by the physician.

Gene optimization, protein expression, purification and characterization of the HDV antigen for diagnosis / 中华实验和临床病毒学杂志

<p><b>OBJECTIVE</b>To prepare HDAg with biological activities as a candidate of diagnostic reagent.</p><p><b>METHODS</b>To synthesize HDV gene fragment after codon optimization. To construct a thio-fused recombinant plasmid based on M48 expression vector. To express in E. coli induced by IPTG. To purify the protein by affinity chromatography followed by characterization in ELISA:</p><p><b>RESULTS</b>Plasmid construction was verified by enzyme digestion. SDS-PAGE indicated the molecular weight of the protein was the same as we expectation. ELISA proved its affinity with HDV antibodies.</p><p><b>CONCLUSION</b>HDAg was obtained successfully and it will pave the road to the research of HDV diagnostic reagent.</p>