Made available in DSpace on 2014-06-11T19:28:01Z (GMT). No. of bitstreams: 0 Previous issue date: 2001Bitstream added on 2014-06-13T19:15:50Z : No. of bitstreams: 1 gabriel_gfcp_me_botfm.pdf: 271018 bytes, checksum: fda89419fe6178194c119a6733ea76fd (MD5) / A hepatite aguda pelo vírus da hepatite tipo A (VHA) é uma causa comum de doença hepática em crianças em nosso meio, sendo o tipo mais freqüente entre as de causa viral. Usualmente, diante de um paciente com quadro clínico e dados epidemiológicos sugestivos de hepatite aguda, a presença de doença hepática é confirmada e a evolução é acompanhada utilizando-se as chamadas “provas de função hepática” (PFH), cujos resultados habitualmente são conhecidos antes do resultado do exame sorológico, que define a etiologia. Diante do número relativamente grande de PFH que podem ser utilizadas, das implicações fisiopatológicas diferentes que podem ter e do custo de sua execução, procuramos verificar quais delas poderiam ser substituídas por outra(s) e quais as possíveis relações entre os mecanismos de suas alterações. Para isso estudamos as correlações entre os níveis das seguintes PFH – concentração sérica bilirrubina total (BT), concentração sérica de bilirrubina de reação direta (BD), atividades séricas de aspartato aminotransferase (AST), de alanina aminotransferase (ALT), de fosfatase alcalina (FA) e de γ-glutamiltransferase (γGT) em crianças com hepatite do tipo A (HA), que evoluíram para cura, em diferentes fases de sua evolução – do 1o ao 7o dia (G 0-7), do 8o ao 14o dia (G 8-14), do 15o ao 30o dia (G 15-30), do 31o ao 60o dia (G 31-60) e após os 60 dias (G > 60). Foi aplicada análise de correlação múltipla efetuando-se as seguintes análises: 1) correlação entre BD (variável dependente - VD) e BT, AST, ALT, FA e γGT (variáveis independentes - VI) nos grupos G 0-7 e G 8-14; 2) correlação entre BT (VD) e AST, ALT, FA e γGT (VI), nos demais grupos; 3) correlação entre AST (VD) e BT, ALT, FA e γGT (VI) em todos os grupos e 4) correlação entre... / Acute type A hepatitis (HA) is a common disease in children in Brazil. And is the most frequent cause of viral hepatitis. Usually when the clinical picture and epidemiological data are suggestive of acute hepatitis the diagnosis of hepatic damage and the follow-up is made using the so called “liver function tests” (LFT), besides the serological confirmation of a recent infection by the hepatitis type A virus (HAV). Considering that: 1) the number of available LFT is relatively large: 2) the ordering of many tests repeatedly over the course or disease would be expensive, and 3) the physiopathological mechanisms of their alterations may be different one from the other we aimed at determining which test(s) could be substituted by other(s) and which are the possible relations among the physiopathological mechanisms of their alterations. To fulfil these objectives, we studied, in children with type A hepatitis, which eventually cured, the multiple correlations among combinations from the following group of tests: total serum bilirubin concentration (TB), direct reactant bilirubin concentration (DB), serum aspartate aminotransferase activity (AST), serum alanine aminotransferase activity (ALT), serum alkaline phosphatase activity (AP) and serum γglutamiltranspeptidase activity (γGT). The correlations were calculated from data taken during different periods after jaundice was noticed – from 0 to 7 days (G 0-7), from 8 to 14 days (G 8-14), from 15 to 30 days (G 15-30), from 31 to 60 days (G 31-60) and after 60 days. A multiple correlation test was applied to carry out the following analyses: 1) correlation between DB ( dependent variable – DV) and TB, AST, ALT, AP and γGT (independent variable – IV) for the groups G 0-7 and... (Complete abstract, click electronic access below)

Introdução. Hepatite B oculta é caracterizada pela presença do HBV-DNA em pacientes que não expressam o antígeno B de superfície (HBsAg) e é relatada com maior freqüência em pacientes infectados pelo vírus da hepatite C (HCV). Nesse estudo avaliamos a prevalência de hepatite B oculta em transplantados renais infectados ou não pelo HCV e avaliamos a função hepática nos diferentes grupos. Material e métodos. Amostras de soro de 101 pacientes transplantados renais foram avaliadas para testes de função hepática, marcadores sorológicos e reação de polimerização em cadeia (PCR) para o HBV-DNA. Todos os pacientes eram HBsAg negativos e havia 51 pacientes anti- HCV reagentes e 50 pacientes não reagentes. A pesquisa do HBV-DNA foi feita por técnica de PCR aninhado para os genes S e “core”. Resultados. A pesquisa do gene S do HBV-DNA resultou positiva em 2 pacientes, sendo um do grupo anti-HCV reagente e o outro do grupo não reagente. A pesquisa do gene da região do “core” foi positiva em um paciente do grupo anti-HCV não reagente. A análise demonstrou que os pacientes do grupo anti-HCV reagente apresentam maior tempo de tratamento dialítico (50,8 + 34,6 e 32,02 + 20,87; p<0,001). Da mesma forma o grupo anti-HCV reagente apresentou valores mais elevados de aminotransferases: ALT: 34.5 ± 26.7 x 20.9 ± 10.0; (P < 0.001); AST: 31.7 ± 17.7 x 24.9 ± 14.9; (P < 0.05); gama glutamiltranspeptidase : 66.1 ± 82.4 x 33.4 ± 44.6; (P < 0.02) e fosfatase alcalina : 307.9 ± 397.7 x 186.9 ± 63.4; (P< 0.04). Os níveis de ciclosporina sérica também mais elevados também foram encontrados no grupo anti-HCV reagente 170.9 ± 69.8 and 135.0 ± 48.1 respectivamente (P < 0.02). No modelo de análise multivariada evidenciou-se que apenas a presença de infecção pelo HCV é determinante das alterações nas provas de função hepática. Conclusão. Hepatite B oculta foi um achado infreqüente na nossa população de pacientes transplantados renais, não tendo sido encontrada diferença na sua prevalência em pacientes infectados ou não pelo HCV. Pacientes anti-HCV reagentes apresentam alterações significativas das provas de função hepática e dos níveis sangüíneos de ciclosporina. / Background: Occult hepatitis B (HB) is characterized by the presence of HBV-DNA in patients who do not present HB surface antigen (HBsAg) detectable in sera. This condition is frequently described in patients with hepatitis C virus (HCV) infection and its clinical implications are uncertain. Since transplant patients were at risk for hepatitis B and/or C infection by blood transfusions, dialysis treatment and the transplant procedure itself we aimed to evaluate the prevalence of occult HB either with or without HCV infection. Patients and Methods: One hundred and one HBsAg negative renal transplant patients were evaluated. Fifty-one were anti-HCV reagents (Elisa III). Sera was analyzed for the presence of the S and core genes of the HBV-DNA by a nested PCR technique. Serological markers of HBV infection, liver function testes and ciclosporine through levels were also analysed. Results: The core gene of the HBV-DNA was identified in one HCV infected patient and in one anti-HCV negative who also presented the S gene (prevalence: 2% and 1% for each gene respectivelly). HCV infected patients presented longer pre-transplant dialysis time (50.8 ± 34.6 versus 32.0 ± 20.9; p<0,001). Results of liver function tests were also increased in the HCV infected group: ALT: 34.5 ± 26.7 x 20.9 ± 10.0; (P < 0.001); AST: 31.7 ± 17.7 x 24.9 ± 14.9; (P < 0.05); GGT: 66.1 ± 82.4 x 33.4 ± 44.6; (P < 0.02) and alkaline phosphatase: 307.9 ± 397.7 x 186.9 ± 63.4; (P< 0.04). Ciclosporine through levels were also significantly higher in HCV infected patients 170.9 ± 69.8 and 135.0 ± 48.1 respectivelly (P < 0.02). Multivariate analysis revealed that only HCV infection was determinant of the increased results of the LFTs. Conclusion: We found that occult hepatitis B is infrequent condition in our population of renal transplant patients and that HCV infection seems not to be a risk factor. In accordance with our previous work HCV we showed that infected renal transplant patients present evidence of liver damage and altered metabolism evidenced by the elevated liver function testes a higher ciclosporine through levels.

Introdução: As hepatites virais causadas pelo VHB e VHC são um importante problema de saúde pública, representando, juntas, mais de 530 milhões de indivíduos no mundo inteiro, que desenvolveram hepatites crônicas ao serem expostos a esses vírus. No entanto, grande parte da população infectada desconhece sua condição, pois frequentemente encontra-se assintomática. O diagnóstico dessas viroses muitas vezes se dá de forma ocasional, geralmente após procedimentos clínicos rotineiros ou após a realização de doações voluntárias de sangue. Entretanto, já foi demonstrado que mesmo assintomáticos, ou com a presença de sintomas mínimos, os portadores do VHB ou do VHC podem apresentar distúrbios de ordem emocional, social ou mesmo físicos, que repercutem na queda de sua QVRS. Objetivos: O principal objetivo desse estudo foi o de avaliar o impacto que a informação do diagnóstico da presença do VHB ou do VHC poderia causar na QVRS de doadores voluntários de sangue. Método: Participaram do estudo 105 doadores com sorologias alteradas ou para o VHB ou para o VHC nos exames de triagem das doações de sangue, sendo que 65 (62%) eram do sexo masculino e 40 (38%) eram do sexo feminino. Deste total, 32 (30,5%) apresentaram confirmação do diagnóstico para o VHB e 35 (33,3%) apresentaram confirmação do diagnóstico para o VHC. Entretanto, 38 doadores de sangue (36,2%), não tiveram a confirmação dessas viroses após a realização de exames confirmatórios, sendo que seus exames de triagem alterados na doação de sangue foram considerados falso-positivos. Os doadores com diagnóstico sorológico confirmado foram divididos em 2 grupos: um grupo formado por 32 doadores com diagnóstico de hepatite B e um grupo de 35 doadores com diagnóstico de hepatite C. Foram estabelecidos 2 grupos controles para as comparações. O primeiro, um grupo controle negativo, composto de doadores com sorologias negativas em doações de sangue sucessivas, pareados por sexo, cor e idade, e em igual número para cada grupo de doadores infectados. O segundo, um grupo controle falso-positivo, composto por 38 doadores que apresentaram sorologias falso-positivas na doação de sangue. As avaliações da QVRS nos indivíduos infectados foram realizadas em 3 etapas: a) 1ª Etapa: quando compareciam no banco de sangue para a repetição dos exames alterados na doação, contudo sem saberem qual alteração sorológica estava sendo investigada. b) 2ª Etapa: Quando o médico do banco de sangue informava ao doador qual era o seu diagnóstico. c) 3ª Etapa: No momento em que o doador iniciava o acompanhamento clínico ambulatorial. As comparações foram feitas seguindo-se quatro abordagens: a) Comparando-se o nível de percepção das diferenças na QVRS, conforme a evolução das etapas do estudo, através de uma análise longitudinal de cada grupo infectado. b) Comparando-se as diferenças na QVRS entre os grupos infectados com o VHB ou com o VHC e doadores do grupo controle negativo. c) Comparando-se as diferenças na QVRS entre os grupos infectados com o VHB ou com o VHC e doadores do grupo controle falsopositivo. d) Comparando-se a QVRS do grupo de doadores com diagnóstico de hepatite B com a QVRS do grupo de doadores com diagnóstico de hepatite C, no momento em que iniciaram o acompanhamento ambulatorial. As avaliações foram realizadas utilizando-se o questionário SF-36, genérico, de aplicação na população geral, e o questionário LDQOL, de aplicação específica nas doenças hepáticas. Resultados: Nas análises longitudinais, utilizando-se o questionário SF-36, somente o grupo de doadores com diagnóstico de hepatite C demonstrou diferenças estatisticamente significantes da QVRS, nos domínios Dor (p = 0,011), Estado Geral da Saúde (p < 0,001), Aspectos Sociais (p = 0,019), Saúde Mental (p = 0,033) e no Componente Físico da escala sumarizada do SF-36, à custa do aumento nos escores dos questionários. Diferentemente, o grupo de doadores com diagnóstico de hepatite B não apresentou diferenças estatisticamente significantes na análise longitudinal. Nas comparações do grupo de doadores com diagnóstico de hepatite B com seu grupo-controle negativo, utilizando-se o questionário SF-36, foram encontradas diferenças estatisticamente significantes: a) Fase 1 do estudo: nos domínios Dor (p = 0,036), Estado Geral de Saúde (p = 0,007) e no Componente Físico (p = 0,004) da escala sumarizada do SF-36. b) Fase 2 do estudo: nos domínios Capacidade Funcional (p = 0,034), Limitação por Aspectos Físicos (p = 0,048), Dor (p = 0,035), Estado Geral de Saúde (p = 0,002), Saúde Mental (p = 0,047) e no Componente Físico (p = 0,007) da escala sumarizada do SF-36. Fase 3 do estudo: nos domínios Capacidade Funcional (p = 0,028), Dor (p = 0,002), Estado Geral de Saúde (p = 0,006), Vitalidade (p = 0,046) e no Componente Físico (p = 0,006). Nas comparações do grupo de doadores com diagnóstico de hepatite B com o grupo controle falso-positivo, utilizando-se o questionário SF-36, foram encontradas diferenças estatisticamente significantes: a) Fase 1 do estudo: nos domínios Limitação por Aspectos Físicos (p = 0,032). b) Fase 2 do estudo: nos domínios Capacidade Funcional (p = 0,006), Limitação por Aspectos Físicos (p = 0,006), Dor (p = 0,006), Vitalidade (p = 0,017), Limitação por Aspectos Emocionais (p = 0,038), Saúde Mental (p = 0,030), no Componente Físico (p = 0,019) e no Componente Mental (p = 0,022) da escala sumarizada do SF-36.Nas comparações do grupo de doadores com diagnóstico de hepatite C com o seu grupo controle negativo, utilizando-se o questionário SF-36, foram encontradas diferenças estatisticamente significantes: a) Fase 1 do estudo: nos domínios Capacidade Funcional (p = 0,038), Dor (p = 0,003), Estado Geral de Saúde (p<0,011), Vitalidade (p = 0,034), Aspectos Sociais (p = 0,006), Limitação por Aspectos Emocionais (p = 0,024), Saúde Mental (p = 0,007) , no Componente Físico (p = 0,002) e no Componente Mental da escala sumarizada do SF-36. b) Fase 2 do estudo: nos domínios Limitação por Aspectos Físicos (p = 0,040), Dor (p = 0,017), Estado Geral de Saúde (p < 0,001), Vitalidade (p = 0,019), Aspectos Sociais (p = 0,005), Limitação por Aspectos Emocionais (p = 0,025), Saúde Mental (p = 0,034) e no Componente Físico (p = 0,008) da escala sumarizada do SF-36. c) Fase 3 do estudo: nos domínios Dor (p = 0,041), Estado Geral de Saúde (p = 0,003), Vitalidade (p = 0,030) e Limitação por Aspectos Emocionais (p = 0,027). Nas comparações entre o grupo de doadores com diagnóstico de hepatite C e o grupo controle falso-positivo, utilizando-se o questionário SF-36, foram encontradas diferenças estatisticamente significantes : a) Fase 1 do estudo: nos domínios Limitação por Aspectos Físicos (p = 0,040) e Limitação por Aspectos Emocionais (p = 0,042). b) Fase 2 do estudo: Limitação por Aspectos Físicos (p = 0,010), Vitalidade (p = 0,037), Aspectos Sociais (p = 0,010) e Limitação por Aspectos Emocionais (p = 0,005). Nas comparações da QVRS entre o grupo dos doadores com diagnóstico de hepatite B e o grupo dos doadores com diagnóstico de hepatite C no momento em que iniciavam o acompanhamento clínico, utilizando-se o questionário LDQOL, não foram observadas diferenças estatisticamente significantes. Conclusões: A análise longitudinal dos doadores com diagnóstico de hepatite C, as comparações com o seu grupo-controle negativo e com o grupo controle falso-positivo, demonstraram alteração na QVRS. Segundo a análise longitudinal, os doadores com o VHC, ao evoluírem nas etapas do estudo, apresentaram um aumento em seus escores, sugerindo que as informações prestadas pela equipe médica sobre a doença e a perspectiva de um atendimento clínico adequado causaram uma tranquilização que melhorou o impacto inicial do diagnóstico da doença, promovendo melhora relativa da QVRS. Ainda que houvesse melhora dos escores na análise longitudinal, os doadores com o diagnóstico de hepatite C tiveram queda de sua QVRS, demonstrada quando comparados ao seu grupo-controle negativo e com o grupo-controle falso-positivo. Nos doadores do grupo com o diagnóstico de hepatite B, ao contrário, não houve alteração da QVRS que pôde ser demonstrada na análise longitudinal. Este achado sugere a baixa QVRS nestes indivíduos mesmo antes do diagnóstico, e que não houve alteração perceptível de sua queda neste grupo de infectados durante a evolução do estudo. Entretanto, quando comparados ao grupocontrole de doadores negativos e ao grupo-controle falso-positivo, foi demonstrada queda na sua QVRS, que pôde ser associada ao impacto do diagnóstico da infecção pelo VHB / Introduction: Viral hepatitis caused by HBV and HCV are an important public health problem. Together they represent around 530 million individuals who have been exposed to these viruses all over the world. Much of that infected population is unaware of their condition, because they are often asymptomatic. Diagnosing these viral infections often comes only occasionally, usually after clinical routine procedures or after volunteer blood donations. However, it has been shown that even asymptomatic, or even in the presence of minimum symptoms, carriers living with HBV or HCV virus can show emotional, social or even physical disturbs, which echoes in the fall of their Health Related Quality of Life (HRQOL). Aims: The main goal of this study was to evaluate the impact of the diagnosis information of the HBV or HCV presence could cause on HRQOL of voluntary blood donors. Method: The study included 105 donors with altered serology to HBV or HCV tests in blood donations screening. 65 (62%) blood donors were male and 40 (38%) were female. From this total, 32 (30.5%) blood donors were submitted to HBV diagnosis confirmation and 35 (33.3%) were submitted to HCV diagnosis confirmation. However 38 (36.2%) blood donors had no confirmation of these infections after conducting confirmatory tests, and were considered as false positive result tests. Donors with a confirmed serological diagnosis were divided into 2 groups: a group of 32 blood donors with hepatitis B diagnosis and 35 blood donors with hepatitis C diagnosis. Two control groups have been established for comparisons. The first, a negative control group, composed of donors with negative serology, matched by sex, race and age, and in equal numbers for each group of infected donors. The second, a false-positive control group composed by 38 blood donors who had false-positive serology in their blood donation. Assessments of HRQOL in individuals infected were performed in 3 phases: a) Phase 1: When they went to the blood bank for collecting blood samples to new confirmatory tests, however, they werent informed about which serological test was specifically being investigated. B) Phase 2: When the blood banks doctor informed what the donors diagnosis was. C) Phase 3: At the moment the donor started his clinical follow-up. Comparisons were performed according to 4 approaches: A) Comparing the level of perceived HRQOL differences according to the evolution of the studys phases, through a longitudinal analysis of each group infected. B) Comparing the HRQOL differences between the infected donor groups with HBV or HCV and their negative control group. C) Comparing the HRQOL differences between the infected donor groups with HBV or HCV and the false-positive control group. C) Comparing the HRQOL differences between the infected groups with HBV or HCV virus with the false-positive control group. D) Comparing the HRQOL in the group of donors with diagnosis of hepatitis B and the HRQOL in the group of donors with diagnosis of hepatitis C at the time they started the ambulatory monitoring. Evaluations were performed using the SF-36, the generic form applied for the general population, and the LDQOL, specific form applied in liver diseases. Results: In the longitudinal analysis in patients with HBV or HCV using the SF-36, only the group of donors diagnosed with hepatitis C showed significant differences in HRQOL, which occurred in the domains: Bodily Pain (p = 0.011), General Health (p <0.001), Social Function (p = 0.019), Mental Health (p = 0.033) and in the Physical Component of the summarized SF-36 scale, at the costs of increasing in the questionnaire scores. On different way, the hepatitis B group did not show statistically significant differences in longitudinal analysis. Comparing the hepatitis B diagnosis donors group with their negative control group using the SF-36, were found the following statistically significant differences, in the domains: A) Phase 1 Study: Bodily Pain (p = 0.036), General Health (p = 0.007) and in the Physical Component (p = 0.004) of the summarized SF-36 scale. B) Phase 2 Study: Physical Function (p = 0.034), Role Physical (p = 0.048), Bodily Pain (p = 0.035), General Health (p = 0.002), Mental Health (p = 0.047) And in the Physical Component (p = 0.007) of the summarized SF-36 scale. C) Phase 3 Study = Physical Function (p = 0.028), Bodily Pain (p = 0.002), General Health (p = 0.006), Vitality (p = 0.046), and in the Physical Component (p = 0.006) of the summarized SF-36 scale. Comparisons between the hepatitis B diagnosis donors group and their false positive control using the SF-36, were found statistically significant differences in the domains: A) Phase 1 Study : Role Physical (p = 0.032). B) Phase 2 Study = Physical Function (p = 0.006), Role Physical (p = 0.006), Bodily Pain (p = 0.006), Vitality (p = 0.017), Role Emotional (p = 0.038), Mental Health (p = 0.030), and in the Physical Component (p = 0.019) and Mental Component (p = 0,022) of the SF-36 summarized scale. In comparisons of the group of donors with a diagnosis of hepatitis C with their negative control group, using the SF-36 were found statistically significant differences in the domains: A) Phase 1 Study: Physical Function (p = 0.038), Bodily Pain (p = 0.003), General Health (p <0.011), Vitality (p = 0.034), Social Function (p = 0.006), Role Emotional (p = 0.024), Mental Health (p = 0.007), Physical Component (P = 0.002) and Mental Component of the SF-36 summarized scale. B) Phase 2 study: Role Physical (p = 0.040), Bodily Pain (p = 0.017), General Health (p <0.001), Vitality (p = 0.019), Social Function (p = 0.005), Role Emotional (p = 0.025), Mental Health (p = 0.034) and Physical Component (p = 0.008) of the SF-36 summarized scale. C) Phase 3 Study: Bodily Pain (p = 0.041), General Health (p = 0.003), Vitality (p = 0.030) and Role Emotional (p = 0.027). Comparisons between the group of donors diagnosed with hepatitis C and the control group false-positive, using the SF-36 were statistically significant differences: A) Phase 1 Study: Role Physical (p = 0.040) and Role Emotional (p = 0.042). b) Phase 2 Study: Role Physical (p = 0.010), Vitality (p = 0.037), Social Function (p = 0.010) and Role Emotional (p = 0.005). In comparisons of HRQOL between the group of donors with a diagnosis of hepatitis B and the group of donors diagnosed with hepatitis C at the time of beginning the clinical follow-up, using the questionnaire LDQOL, there were no statistically significant differences. Conclusion: The longitudinal analysis of donors diagnosed with hepatitis C, the comparisons with their negative control group and the control group false-positive, showed changes in HRQOL. According to the longitudinal analysis, donors with HCV, when evoluting in the phases of the study showed an increase in their scores, suggesting that the information provided by the medical team about the disease and the prospect of an appropriate clinical care caused a tranquilization that has improved the initial impact diagnose of the disease, promoting a relative improvement on HRQOL. Although there were improvement in scores on the longitudinal analysis, the donors with the diagnosis of hepatitis C had a reduction of their HRQOL, as demonstrated when compared to their negative control group and the control group false-positive. In the donor group with the diagnosis of hepatitis B, in contrast, there was no change in HRQOL that could be demonstrated in longitudinal analysis. But when compared to their control groups negative and false-positive, statistically significant differences were identified. This finding suggests a poor HRQOL in these individuals even before the diagnosis, and that there was no noticeable change to its fall in this group infected during the course of the study. However, when compared to the negative control group of donors and the false-positive control group it was demonstrated decrease in HRQOL of these donors, which might be associated with the impact of the diagnosis of HBV infection

Introdução. Hepatite B oculta é caracterizada pela presença do HBV-DNA em pacientes que não expressam o antígeno B de superfície (HBsAg) e é relatada com maior freqüência em pacientes infectados pelo vírus da hepatite C (HCV). Nesse estudo avaliamos a prevalência de hepatite B oculta em transplantados renais infectados ou não pelo HCV e avaliamos a função hepática nos diferentes grupos. Material e métodos. Amostras de soro de 101 pacientes transplantados renais foram avaliadas para testes de função hepática, marcadores sorológicos e reação de polimerização em cadeia (PCR) para o HBV-DNA. Todos os pacientes eram HBsAg negativos e havia 51 pacientes anti- HCV reagentes e 50 pacientes não reagentes. A pesquisa do HBV-DNA foi feita por técnica de PCR aninhado para os genes S e “core”. Resultados. A pesquisa do gene S do HBV-DNA resultou positiva em 2 pacientes, sendo um do grupo anti-HCV reagente e o outro do grupo não reagente. A pesquisa do gene da região do “core” foi positiva em um paciente do grupo anti-HCV não reagente. A análise demonstrou que os pacientes do grupo anti-HCV reagente apresentam maior tempo de tratamento dialítico (50,8 + 34,6 e 32,02 + 20,87; p<0,001). Da mesma forma o grupo anti-HCV reagente apresentou valores mais elevados de aminotransferases: ALT: 34.5 ± 26.7 x 20.9 ± 10.0; (P < 0.001); AST: 31.7 ± 17.7 x 24.9 ± 14.9; (P < 0.05); gama glutamiltranspeptidase : 66.1 ± 82.4 x 33.4 ± 44.6; (P < 0.02) e fosfatase alcalina : 307.9 ± 397.7 x 186.9 ± 63.4; (P< 0.04). Os níveis de ciclosporina sérica também mais elevados também foram encontrados no grupo anti-HCV reagente 170.9 ± 69.8 and 135.0 ± 48.1 respectivamente (P < 0.02). No modelo de análise multivariada evidenciou-se que apenas a presença de infecção pelo HCV é determinante das alterações nas provas de função hepática. Conclusão. Hepatite B oculta foi um achado infreqüente na nossa população de pacientes transplantados renais, não tendo sido encontrada diferença na sua prevalência em pacientes infectados ou não pelo HCV. Pacientes anti-HCV reagentes apresentam alterações significativas das provas de função hepática e dos níveis sangüíneos de ciclosporina. / Background: Occult hepatitis B (HB) is characterized by the presence of HBV-DNA in patients who do not present HB surface antigen (HBsAg) detectable in sera. This condition is frequently described in patients with hepatitis C virus (HCV) infection and its clinical implications are uncertain. Since transplant patients were at risk for hepatitis B and/or C infection by blood transfusions, dialysis treatment and the transplant procedure itself we aimed to evaluate the prevalence of occult HB either with or without HCV infection. Patients and Methods: One hundred and one HBsAg negative renal transplant patients were evaluated. Fifty-one were anti-HCV reagents (Elisa III). Sera was analyzed for the presence of the S and core genes of the HBV-DNA by a nested PCR technique. Serological markers of HBV infection, liver function testes and ciclosporine through levels were also analysed. Results: The core gene of the HBV-DNA was identified in one HCV infected patient and in one anti-HCV negative who also presented the S gene (prevalence: 2% and 1% for each gene respectivelly). HCV infected patients presented longer pre-transplant dialysis time (50.8 ± 34.6 versus 32.0 ± 20.9; p<0,001). Results of liver function tests were also increased in the HCV infected group: ALT: 34.5 ± 26.7 x 20.9 ± 10.0; (P < 0.001); AST: 31.7 ± 17.7 x 24.9 ± 14.9; (P < 0.05); GGT: 66.1 ± 82.4 x 33.4 ± 44.6; (P < 0.02) and alkaline phosphatase: 307.9 ± 397.7 x 186.9 ± 63.4; (P< 0.04). Ciclosporine through levels were also significantly higher in HCV infected patients 170.9 ± 69.8 and 135.0 ± 48.1 respectivelly (P < 0.02). Multivariate analysis revealed that only HCV infection was determinant of the increased results of the LFTs. Conclusion: We found that occult hepatitis B is infrequent condition in our population of renal transplant patients and that HCV infection seems not to be a risk factor. In accordance with our previous work HCV we showed that infected renal transplant patients present evidence of liver damage and altered metabolism evidenced by the elevated liver function testes a higher ciclosporine through levels.

Submitted by Marlene Santos (marlene.bc.ufg@gmail.com) on 2014-11-04T19:15:44Z No. of bitstreams: 2 Dissertação - Natália Alberto Alves Brandão.pdf: 2752228 bytes, checksum: f1f4834b88d60df4f5620fe3e16ff30d (MD5) license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5) / Approved for entry into archive by Jaqueline Silva (jtas29@gmail.com) on 2014-11-05T09:19:23Z (GMT) No. of bitstreams: 2 Dissertação - Natália Alberto Alves Brandão.pdf: 2752228 bytes, checksum: f1f4834b88d60df4f5620fe3e16ff30d (MD5) license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5) / Made available in DSpace on 2014-11-05T09:19:23Z (GMT). No. of bitstreams: 2 Dissertação - Natália Alberto Alves Brandão.pdf: 2752228 bytes, checksum: f1f4834b88d60df4f5620fe3e16ff30d (MD5) license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5) Previous issue date: 2013-05-06 / Hepatitis B and C viruses are responsible for the most common chronic viral infections worldwide. The prevalence of these viruses is higher among HIV-infected individuals, due to common route of transmission. Coinfections HBV / HIV and HCV / HIV seems to be associated with a worst liver disease prognosis. Studies evaluating these coinfections in the mid-western Brazil are scarce. Objectives: To estimate the prevalence and the risk factors associated with HBV and HCV coinfections in HIV-positive patients in Goiânia – Goiás. Methods: A cross-sectional study was conducted including 495 adults, recruited from the Centro de Referência em Diagnóstico e Terapêutica de Goiânia in 2011. After signing the informed consent, participants were interviewed and material was collected for research markers for HBV (anti-HBc, HBsAg, anti-HBs and HBV DNA) and HCV (anti-HCV and HCV RNA). Prevalence of HBV and HCV infection was estimated. Univariate and multivariate analysis to evaluate factors associated with positivity for both viruses were performed. Odds and adjusted odds ratios were calculated with 95% confidence intervals (CI95%) and a significance level of p<0.05. Results: Participants mean age was 40.2 years (standard deviation =10. 4) with a male predominance (73.9%). Injecting drugs usage was reported by 3.6% of participants. The prevalence of markers for hepatitis B exposure was 33.5% (CI95% 29.4-37.9). Nineteen patients (3.8%, CI95% 2.4-6.0) were diagnosed as hepatitis B carriers. Prevalence of anti-HCV was 9.7% (CI95% 7.3-12.7). The distribution of HCV genotypes was: 1a (72.7%), 3 (13.6%) and 1b (9.1%). Coinfection by the three viruses was 4.4% (CI95% 2.9-6.8). Male, age ≥ 40 years, previous history of sexually transmitted disease (STD) and homo or bisexuality were associated with exposure to HBV. History of injecting drugs and STD were associated with HCV seropositivity. Over half of the coinfected patients were not aware of being HBV or HCV positive. Conclusion: Seromarkers for previous HBV and/or HCV infections are common among individual HIV positives in Goiânia. A significant proportion of them are unaware of their serological status. These findings suggest the need for better screening and guidance improvements for this population / Os vírus das hepatites B (HBV) e C (HCV) são responsáveis pelas infecções crônicas virais mais comuns em todo o mundo. A prevalência dessas infecções é maior entre indivíduos infectados pelo HIV, devido às vias comuns de transmissão desses vírus. As coinfecções HBV/HIV e HCV/HIV parecem estar associadas a um pior prognóstico da doença hepática. Estudos avaliando essas coinfecções, na região centro-oeste do Brasil, são escassos. Objetivos: Estimar a prevalência e analisar fatores sócio-demográficos e comportamentais associados às infecções pelo HBV e HCV em pacientes HIV positivos. Métodos: Estudo transversal, com inclusão de 495 pacientes adultos, recrutados no Centro de Referência em Diagnóstico e Terapêutica de Goiânia, em 2011. Após assinatura do termo de consentimento livre e esclarecido, os participantes foram entrevistados e coletouse material para pesquisa de marcadores para o HBV (anti-HBc, HBsAg, anti-HBs e HBV DNA) e HCV (anti-HCV e HCV RNA). Estimou-se a prevalência das infecções pelo HBV e HCV. Foi realizada análise uni e multivariada para avaliar fatores associados com a positividade para os dois vírus. Foram calculados os Odds Ratios brutos e ajustados com respectivos intervalos de 95% de confiança (IC95%) e nível de significância de p<0,05. Resultados: A média de idade dos participantes foi de 40,2 anos (desvio padrão=10,4), com predomínio de homens (73,9%). O relato de uso de drogas injetáveis foi feito por 3,6% dos participantes. A prevalência de exposição ao vírus da hepatite B foi de 33,5% (IC95% 29,4-37,9). Dezenove pacientes (3,8%, IC95% 2,4-6,0) foram diagnosticados como portadores do vírus da hepatite B. A prevalência de anti-HCV foi 9,7% (IC95% 7,312,7). A distribuição dos genótipos do HCV nessa população foi: 1a (72,7%), 3 (13,6%) e 1b (9,1%). A coinfecção pelos três vírus foi de 4,4% (IC95% 2,9-6,8). Sexo masculino, idade ≥ 40 anos, relato de doença sexualmente transmissível (DST) e homo ou bissexualismo mostraram-se associados à presença de marcadores de exposição ao HBV. Antecedentes de drogas injetáveis e DST mostraram associação com soropositividade para HCV. Cerca da metade dos pacientes coinfectados não sabia ser HBV ou HCV positivos. Conclusões: Marcadores de exposição prévia ao HBV e ao HCV são frequentes entre os pacientes HIV positivos, em Goiânia. Uma parcela significativa dessa população desconhece seu status sorológico, sugerindo a necessidade de medidas de triagem e de orientação mais efetivas.

Bakgrund: Hepatit B och hepatit C räknas i dag som de största infektionssjukdomarna i världen med dödlig utgång. Sjukdomarna rapporteras som en världsomfattande börda och mellan år 2018 och 2019 uppgavs 1,9 miljoner människor avlidit. I omvårdnadsarbetet ska sjuksköterskan värna om patienten och arbeta personcentrerat, visa respekt och inte kränka patienten. Patienter med hepatit B och C har uttryckt sig känna av stigmatisering och förutfattade meningar om hur de smittats, de kände även av att bemötandet i omvårdnaden kunde påverkas negativt. Syftet med litteraturstudien var att utforska sjuksköterskors bemötande till patienter med hepatit B och C. Metoden utgick från en allmän litteraturstudie där 13 vetenskapliga artiklar presenterade resultat på hur sjuksköterskor bemöter patienter med blodsmitta. Resultatet visade att sjuksköterskor bemöter patienter med hepatit B och C olika med både positiva och negativa attityder. Det fanns signifikanta samband mellan låg kunskap och ett sämre bemötande. Det berodde bland annat på rädsla och förutfattade meningar som speglades i omvårdnadsarbetet. Det fanns även signifikanta samband mellan korrekt tillämpning i basala hygienrutiner och ett tryggt omvårdnadsarbete för sjuksköterskan. Konklusion: Bemötandet till patienter med hepatit B och C var övergripande positivt men det förekom sjuksköterskor med ett stigmatiserande synsätt och motvillighet till att bemöta dessa patienter. / Background: Hepatitis B and C are currently considered to be the largest infectious diseases with lethal repercussions. The diseases are considered a worldwide burden, which between 2018 and 2019, caused the death of an estimated 1,9 million people. In nursing, nurses are meant to shield patients, work on a personal basis with them, show the respect and not offend them. Patients with hepatitis B and C have expressed a feeling of stigmatization and prejudice towards how they were infected. Therefore, they feel their care could be affected in a negative way. The aim of this literature study was to explore nurses’ attitudes towards patients with hepatitis B and C. The method emanated from a literature study where 13 scientific articles showed results for how nurses’ attitudes towards patients with blood diseases varies. The results showed that nurses’ attitudes towards patient infected with hepatitis B and C can be both positive and negative. Statistically significant associations occurred between a lack of knowledge and worsened attitude in nursing, the reason was often because of fear and preconceptions. Findings showed a relation between using correct safe precautions and confidence in nursing. Conclusion: The attitude towards patients with hepatitis B and C was positive over all but there were some nurses with a stigmatized perception and reluctance to handle those patients.

Chronic haemodialysis patients have a high prevalence of Hepatitis B and C virus infections both of which are associated with chronic liver disease and hepatocellular carcinoma Hepatitis B virus (HBV) was identified as a frequent cause of hepatitis during the early years of chronic haemodialysis therapy and strict adherence to infection control measures alone proved inadequate to control the transmission of infection between patients. A policy of regular screening of all patients and blood donations for hepatitis B surface antigen together with isolation of positive patients to separate dialysis units resulted in a significant decline in the incidence of new infections. Hepatitis B vaccination provided an important new means of protection. Despite the finding that haemodialysis patients did not respond to the vaccine as well as normal adults, randomized controlled trials showed significant protection in units with a previously high incidence of infection. Studies have identified both monocyte dysfunction and B cell inhibition by elevated levels of parathyroid hormone (PTH) as possible mechanisms for the reduced response in dialysis patients. Other factors which have been associated with this poor response include increased age, male gender, specific human leukocyte antigens, shorter time on a dialysis programme and poor nutritional status. One study has shown an increased response in patients receiving recombinant human erythropoietin and. there is in vitro evidence that nifedipine improves B cell proliferation in dialysis patients with hyperparathyroidism. Hepatitis C virus (HCV) infection in haemodialysis patients has been associated with blood transfusions in many studies. However, evidence exists that transmission between patients also occurs. There is disagreement as to what measures are necessary to prevent possible nosocomial spread. Some authors recommend isolation of HCV -infected patients to separate dialysis machines or units. There is also concern over the potential of dialyzer reuse to transmit the virus. A protocol for surveillance 0f hepatitis B and C infections was established in the dialysis unit at Groote Schuur Hospital while HCV positive patients were not isolated and reuse of dialyzers was continued for all patients. HBV -infected patients are dialyzed in a separate unit and their dialyzers are not reused. A trial of hepatitis B vaccination of all antibody negative patients was undertaken using four doses of a plasma-derived vaccine given intramuscularly at month 0,1 ,2 and 4.

Background: In 2019, hepatitis is seen as one of the deadliest virus infections in the world and is seen as a global health problem. Hepatitis is a DNA-virus that can lead to chronic hepatitis and liver cirrhosis. Both hepatitis B and C are blood infections which means that they are transmitted through contact with damaged skin, mucus membrane or the eyes. Aim: The aim of this study was to describe how patients with hepatitis B and C experience the treatment from healthcare professionals. Method: The method used in this study was a review of literature research. The study was conducted through examination of 10 research articles. The chosen articles were found on the databases PubMed and CINAHL. The differences and the similarities were noted to create a larger understanding of the results. Results: The results consist of four categories which shows how patients with hepatitis B and C experience the treatment from healthcare professionals. The four categories are, a lack of information, faulty information, withholding of the diagnosis hepatitis and dismissive treatment. Patients were in need of support in the form of information and understanding. The negative experience received from healthcare professionals could be derived from lack of information. Conclusion: The conclusion of this study is that patients with hepatitis B and C experience negative treatment from healthcare professionals. The negative treatment is often connected to information and lack thereof. This study may have significance for future treatment of patients with hepatitis by highlighting the existing response. / Bakgrund: År 2019 anses hepatit vara den näst dödligaste virusinfektionen i världen. Det är ett globalt folkhälsoproblem. Hepatit är ett DNA-virus som kan leda till kronisk hepatit och levercirros. Både hepatit B och C är blodsmittor vilket innebär att de smittar genom att blod kommer i kontakt med skadad hud, slemhinna eller öga. Syfte: Syftet med studien var att beskriva hur patienter med hepatit B och C upplever bemötandet från omvårdnadspersonal. Metod: Studien är en litteraturöversikt med beskrivande design. Studien har genomförts genom granskning av 10 vetenskapliga artiklar. Valda artiklar har hittats genom sökningar på PubMed och CINAHL. Skillnader och likheter har noterats för att skapa större förståelse för resultatet. Resultat: Resultatet består av fyra kategorier som påvisar hur patienter med hepatit B och C upplever bemötandet från omvårdnadspersonal. De fyra kategorierna är otillräcklig- och felaktig information, undanhållande av diagnosen hepatit och avvisande bemötande från omvårdnadspersonalen. Patienterna hade ett stort behov av stöd i form av information och förståelse. Det negativa bemötandet från omvårdnadspersonalen kunde ofta härledas till okunskap. Slutsats: Slutsatsen av denna studie är att patienter med hepatit B och C upplever negativt bemötande från omvårdnadspersonal. Det negativa bemötandet är ofta kopplat till information och brist på sådan. Det finns en kunskapslucka hos omvårdnadspersonal när det gäller hepatit vilket får konsekvenser för patientens behandling och hälsa. Denna studie kan komma att få betydelse för den framtida vården för patienter med hepatit genom att konsekvenser av det befintliga bemötandet belyses.

Lamivudin war der erste Inhibitor der Hepatitis-B-Virus(HBV)-Polymerase, der für die Therapie der chronischen HBV-Infektion in Deutschland zugelassen wurde und seitdem zu einer signifikanten Senkung der HBV-assoziierten Letalität beigetragen hat. Aufgrund des hohen Resistenzrisikos unter Lamivudin wird der Einsatz der Substanz jedoch in den aktuellen HBV-Leitlinien nicht mehr empfohlen. Stattdessen sollen hochpotente Nukleos(t)id-Analoga wie Entecavir oder Tenofovir angewendet werden, die jedoch gerade in den ärmeren Endemiegebieten nur selten verfügbar sind. Zudem gibt es auch in den westlichen Industrieländern Patienten, die seit Jahren resistenzfrei mit Lamivudin behandelt wurden. Ob diese von einer prophylaktischen Therapieumstellung profitieren, ist bislang unklar. Ziel dieser Studie war es, die Langzeiteffektivität der Lamivudin-Therapie sowie die Häufigkeit und die prädiktiven Faktoren der Lamivudin-Resistenz zu ermitteln. In einer retrospektiven Untersuchung wurden hierzu die Verläufe von 147 HBeAg-positiven und 80 HBeAg-negativen Patienten aus 3 hepatologischen Zentren in Deutschland analysiert. Zur Sicherung der Lamivudin-Resistenz erfolgte eine genetische Resistenztestung. Zusätzlich wurde der klinische Nutzen einer hoch-sensitiven Real-Time-PCR zur Bestimmung der HBV-DNA evaluiert. Im Langzeitverlauf zeigte sich bei einer bestimmten Subgruppe von Patienten ein gutes virologisches, serologisches und biochemisches Ansprechen. Die vorliegende Studie bestätigte jedoch auch das hohe Resistenzrisiko unter einer Langzeittherapie mit Lamivudin, welches nach 7 Jahren 55% erreichte. Maßgeblicher prädiktiver Faktor für eine spätere Resistenzentwicklung war das virologische Ansprechen im Therapieverlauf. Entgegen den Ergebnissen früherer Studien stellte die Höhe der HBV-DNA zum Zeitpunkt des Therapiebeginns keinen prädiktiven Faktor der Resistenzentwicklung dar, sondern beeinflusste die Wahrscheinlichkeit des virologischen Ansprechens. Der Einsatz hoch-sensitiver Verfahren zur Bestimmung der HBV-DNA zur Therapiekontrolle oder Prädiktion der Lamivudin-Resistenz ist unseren Beobachtungen nach nicht erforderlich. Bei HBeAg-positiven Patienten hatte zudem ein HBeAg-Verlust einen günstigen Einfluss auf die Resistenzwahrscheinlichkeit. Auffällig war außerdem, dass HBeAg-positive Patienten nach einem virologischen Ansprechen nur noch ein sehr geringes Resistenzrisiko aufwiesen, während bei HBeAg-negativen Patienten trotz eines virologischen Ansprechens im gesamten Therapiezeitraum neue Fälle von Lamivudin-Resistenz beobachtet wurden. Auch durch die Kombination verschiedener Merkmale, die die Resistenzwahrscheinlichkeit nachweislich beeinflussten, konnte letztlich keine Subgruppe identifiziert werden, die im Verlauf resistenzfrei blieb oder nur ein sehr geringes Resistenzrisiko aufwies. Zusätzlich wurden diverse weitere Wirts-, virale und therapieassoziierte Charakteristika untersucht, die jedoch keinen prädiktiven Wert in Hinblick auf eine Resistenzentwicklung aufwiesen. Insbesondere natürlich vorkommende HBV-Mutationen, die mit einer Lamivudin-Resistenz assoziiert sind, wurden bei 9% der unvorbehandelten Patienten nachgewiesen, ohne dass dieser Befund einen signifikanten Einfluss auf das virologische Ansprechen oder die Resistenzwahrscheinlichkeit zeigte. Zusammenfassend ist festzustellen, dass wir in unserer Studie Parameter definieren konnten, die mit einem Langzeitansprechen assoziiert sind und damit die Grundlage einer individualisierten Therapie darstellen könnten. Die Ergebnisse sind vor allem für Länder mit eingeschränkten Therapiemöglichkeiten von Relevanz. Sofern höher potentere Nukleos(t)idanaloga zur Verfügung stehen, sollte in Anbetracht des hohen Resistenzrisikos allerdings von einer Therapie mit Lamivudin abgesehen werden. Liegt bereits eine langjährige Lamivudin-Therapie ohne Zeichen einer Resistenzentwicklung vor, so erscheint die Fortsetzung jedoch gerechtfertigt. Dennoch sind regelmäßige Kontrollen erforderlich, da Lamivudin-Resistenzen auch nach mehr als 10 Jahren auftreten können.

Hintergrund: Von circa 240-260 Millionen Hepatitis-B-Virus-(HBV)-Infizierten sind schätzungsweise circa 15-20 Millionen Menschen mit dem Hepatitis-D-Virus (HDV) koinfiziert. Das HDV benötigt für seine Replikation zwingend das Oberflächenprotein des HBV (HBsAg) und ist damit als sogenannter Satellitenvirus ohne HBV nicht überlebensfähig. Als mögliche Therapieoptionen steht derzeit das Interferon-alpha (IFNα) zur Verfügung. Zum Therapiemonitoring werden HBV-spezifische Marker (HBsAg, anti-HBs, anit-HBe, anti-HBc-IgM, HBV-DNA), HDV-spezifische Marker (HDV-RNA, anti-HDAg) als auch Marker für die Leberfunktion (ALT, AST, AP, gGT, Bilirubin, Quick) bestimmt. Jedoch fehlen aktuell für die HDV-Infektion noch aussagekräftige Marker, um frühzeitig einen Therapieerfolg bzw. –misserfolg abzuschätzen und darauf reagieren zu können. Fragestellung: In dieser Studie wurden erstmalig aktuelle experimentelle Marker der HBV-Replikation hinsichtlich einer Assoziation mit dem Therapieverlauf bei HBV/HDV-Infektion untersucht: die HBVfl-RNA mittels RT-qPCR und die Komposition des HBsAg (SHBs, MHBs und LHBs) mittels Sandwich-ELISA. Methodik: Es konnten insgesamt 50 Patienten aus Deutschland, Italien und Spanien mit nachgewiesener HBV/HDV-Koinfektion rekrutiert werden. Diese wurden nach der Therapieform, die der Patient erhalten hat, in eine Gruppe unter IFN-Therapie, eine Gruppe unter NA-Therapie und eine therapienaive Kontrollgruppe unterteilt. Desweiteren wurden die Gruppen an Hand des Verlaufes der HDV-RNA in Responder, partielle Responder und Non-Responder eingeteilt. Desweiteren wurden Patienten nach HBsAg-Verlust analysiert, welcher als funktionelle Ausheilung der HBV-Infektion und somit auch der HBV/HDV-Koinfektion angesehen wird. Es erfolgte eine retrospektive Beurteilung der neuen HBV-Serummarker im Vergleich zu etablierten Serummarkern im Verlauf der IFN- bzw. NA-Therapie, wenn möglich bis sechs Monate nach Therapieende. Die therapienaiven Patienten wurden an Hand der zur Verfügung stehenden Proben ebenfalls in ihrem Verlauf beurteilt. Resultate: Die Komposition des HBsAg zeigte in der Gruppe der Responder unter IFN-Therapie nach ausführlicher Betrachtung der Einzelverläufe einen Verlust des MHBs, welcher zum Teil deutlich vor dem Verlust des Gesamt-HBsAg lag. Dies konnte auch bei Respondern unter NA-Therapie beobachtet werden, fehlte jedoch bei den therapienaiven Patienten. Insbesondere bei Patienten, die nicht nur eine Suppression der HDV-RNA sondern auch einen HBsAg-Verlust erreichten, kam es zu einer frühzeitigen Suppression von LHBs und MHBs unter die Nachweisgrenze. In der untersuchten Kohorte stellten sich außerdem die ALT-Spiegel bei den Respondern mit IFN-Therapie mit einem signifikanten Abfall zu mehreren Zeitpunkten im Verlauf dar, der bei den anderen Gruppen fehlte. Die HBVfl-RNA erwies sich nicht als geeignet zum Therapiemonitoring, da sie in fast allen gemessenen Serumproben negativ war. Dies könnte an der Suppression der HBV-Replikation durch das HDV liegen, weshalb auch die HBV-DNA bei Patienten mit einer HBV/HDV-Koinfektion oft nicht nachweisbar ist. Schlussfolgerung: MHBs könnte ein neuer Serummarker für einen HBsAg-Verlust sowie für ein Therapieansprechens auf eine IFN-Therapie bei HBV/HDV-Koinfizierten darstellen und somit zur Personalisierung und zur Steigerung der Effektivität der Therapie bei Patienten mit HBV/HDV-Koinfektion beitragen. Zur Bestätigung dieser Ergebnisse sind daher weiterführende Untersuchungen in größeren Patientenkollektiven notwendig.:I Inhaltsverzeichnis II Abkürzungsverzeichnis III Abbildungsverzeichnis IV Tabellenverzeichnis 1. Einführung 1.1. HBV/HDV 1.1.1. Epidemiologie und Genotypen 1.1.2. Aufbau 1.1.3. Replikation 1.1.4. Infektionsverlauf 1.1.5. Etablierte Diagnostik/ Biomarker 1.1.6. Neue potentielle HBV/HDV-Biomarker 1.1.7. Therapie 1.1.8. Prävention 2. Aufgabenstellung 3. Materialien und Methoden 3.1. Materialien 3.1.1. Kits 3.1.2. Chemikalien 3.1.3. Reagenzien zur Bestimmung des Gesamt-HBsAg, LHBs, MHBs 3.1.4. Geräte 3.1.5. Labormaterialien 3.1.6. Primer, Standardplasmid, In-vitro-Transkript und Sonden 3.1.7. Datenanalyse 3.2. Methoden und Datenanalyse 3.2.1. Nukleinsäure-Isolierung 3.2.2. Quantifizierung der HBVfl-RNA mittels RT-qPCR 3.2.3. Quantifizierung des Vox-Referenzplasmids 3.2.4. Datenanalyse RT-qPCR 3.2.5. Prinzip der Quantifizierung der HBsAg-Komposition mittels nicht-kompetetivem Sandwich-ELISA 3.2.6. Durchführung der Quantifizierung der HBsAg-Komposition 3.2.7. Testauswertung 3.2.8. Untersuchte Patientenkohorte 3.2.9. Statistische Auswertung 4. Ergebnisse 4.1. Untersuchungskohorte zu Studienbeginn 4.2. Evaluierung der untersuchten Biomarker während einer IFN-Therapie 4.2.1. Statistische Auswertung der analysierten Parameter unter IFN-Therapie 4.2.1.1. HDV-RNA als Grundlage der Kohorteneinteilung 4.2.1.2. Analyse der Blutbildparameter im Verlauf der IFN-Therapie 4.2.1.3. Analyse der Leber- und Nierenparameter im Verlauf der IFN-Therapie 4.2.1.4. Analyse der Transaminasen und Cholestaseparameter im Verlauf der IFN-Therapie…………… 4.2.1.5. Analyse der HBV-DNA und der HBVfl-RNA unter IFN-Therapie 4.2.1.6. Analyse des Gesamt-HBsAg, LHBs und MHBs unter IFN-Therapie 4.3. Einzelverlaufdarstellung ausgewählter Patienten unter IFN-Therapie 4.3.1. Exemplarischer Einzelverlauf eines Patienten mit partiellem Therapieansprechen auf IFN im ersten Therapiezyklus 4.3.2. Exemplarischer Einzelverlauf eines Patienten mit Therapieansprechen auf IFN 4.3.3. Exemplarischer Einzelverlauf eines zweiten Patienten mit Therapieansprechen auf IFN……….. 4.3.4. Exemplarischer Einzelverlauf eines dritten Patienten mit Therapieansprechen auf IFN…….. 4.4. Evaluierung der untersuchten Biomarker während einer NA-Therapie 4.4.1. Statistische Auswertung der analysierten Parameter unter NA-Therapie 4.5. Zusammenfassende Darstellung der Patienten mit HBsAg-Verlust unter IFN- bzw. NA-Therapie 4.6. Evaluierung der untersuchten Biomarker im therapienaiven Verlauf 4.6.1. Statistische Auswertung der analysierten Parameter der therapienaiven Patienten 5. Diskussion 5.1. Untersuchungskohorte 5.2. Methoden 5.2.1. RT-qPCR der HBVfl-RNA 5.2.2. Nicht-kompetetiver Sandwich-ELISA des Gesamt-HBsAg, MHBs und LHBs 5.3. Ergebnisse der Biomarkeranalyse 5.3.1. MHBs bzw. LHBs als mögliche neue Serummarker eines Therapieansprechens unter IFN- und NA-Therapie bei HBV/HDV-Koinfizierten 5.3.2. Gesamt-HBsAg als möglicher Marker eines Therapieansprechens unter IFN- und NA-Therapie bei HBV/HDV-Koinfizierten 5.3.3. HBVfl-RNA und HBV-DNA zum Therapiemonitoring bei HBV/HDV-Koinfizierten ungeeignet 5.3.4. ALT bzw. AST als möglicher Prädiktor einer Response auf eine IFN-Therapie bei HBV/HDV-Koinfizierten 5.3.5. Hämoglobin mit fraglicher Relevanz für das Therapiemonitoring bei HBV/HDV-Koinfizierten 5.4. Ergebnisse jenseits der Biomarkeranalyse 5.4.1. Wiederholte IFN-Therapie bei HBV/HDV-Koinfizierten potentiell sinnvoll 6. Zusammenfassung der Arbeit 7. Literaturverzeichnis 8. Anlagen 9. Erklärung über die eigenständige Abfassung der Arbeit 10. Lebenslauf 11. Danksagung