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Published: 4 June 2021
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1

Pajenčkovskytė, Karolina. "Sergančiųjų lėtiniu virusiniu C hepatitu genotipai." Master's thesis, Lithuanian Academic Libraries Network (LABT), 2004. http://vddb.library.lt/obj/LT-eLABa-0001:E.02~2004~D_20040608_165139-44050.

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2

Berg, Thomas. "Chronische Hepatitis C." Doctoral thesis, Humboldt-Universität zu Berlin, Medizinische Fakultät - Universitätsklinikum Charité, 2002. http://dx.doi.org/10.18452/13812.

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Die vorliegende Habilitationsschrift befasst sich schwerpunktmäßig vor allem mit der Klinik und Therapie der Hepatitis C. Evaluiert wurden: 1. verschiedene therapeutische Strategien, 2. die Ursachen der "Non-Response" auf eine anti-virale Therapie sowie 3. die klinische Relevanz der neu entdeckten Hepatitis-assoziierten Viren und 4. ihre Bedeutung bei Patienten mit akuter bzw. chronischer Lebererkrankung unklarer Ätiologie sowie bei Patienten vor und nach Lebertransplantation. Ad 1. Aus dem Vergleich verschiedener Therapie-Konzepte wie der Kurzzeit- Kombinationstherapie, Triple-Therapie, Hochdosis-Interferon?-Therapie und der Anwendung antiviraler Substanzen wie Ribavirin und Amantadin ergaben sich neue Erkenntnisse hinsichtlich relevanter prognostischer Parameter für die Therapieresponse. Ad 2. Analysiert wurden die möglichen molekularen Mechanismen der Therapieresponse bzw. Non-Response sowie der Stellenwert von Interaktionen bestimmter HCV-Proteine (NS5A, E2, sogenannte PKR-eIF2a Phosphorylisations-Homologie-Domäne [PePHD]) mit den Interferon? induzierten Effektorproteinen. Es konnte gezeigt werden, daß die Anzahl der Mutationen innerhalb des NS5A Proteins einen prognostischen Parameter darstellen hinsichtlich der Response auf eine Interferon?-Therapie. Dagegen spielen Mutationen innerhalb der PePHD-Region keine Rolle. Ad 3. Aus den Untersuchungen zur klinischen Relevanz der neu entdeckten Hepatitis-assoziierten Viren GB Virus-C/Hepatitis G Virus (GBV-C/HGV) und TT-Virus (TTV) ergaben sich keine Hinweise bzgl. eines Einflusses von GBV-C/HGV bzw. TTV-Infektionen auf den Verlauf der chronischen Hepatitis C. Die durchgeführten Verlaufsuntersuchungen bei koinfizierten Patienten sprechen dafür, daß es sich um Interferon-sensitive Viren handelt; jedenfalls beeinflussen sie nicht die IFN?-induzierte Response. Ad 4. Untersucht wurden ferner die Prävalenz, Transmission und Relevanz der GBV-C/HGV und TTV-Infektion im Hinblick auf ihre Hepatitis-induzierenden Eigenschaften. Die Ergebnisse belegen, dass beide Viren parenteral übertragen werden, und dass sie eine hohe Prävalenz bei Patienten mit parenteralen Risikofaktoren besitzen. Eine Hepatitis-induzierende Potenz dieser Viren konnten wir nicht beobachten; bei der Mehrzahl aller chronisch infizierter Personen ließen sich keine Zeichen einer chronischen Hepatitis finden.
The major goal of this thesis is the analysis of the clinical outcome of patients with Hepatitis C virus (HCV) infection and the response to therapy. Analysed were 1. different types of therapeutic strategies 2. causes responsible for ineffective antiviral therapy (non-response) 3. clinical relevance of the newly discovered hepatitis-associated viruses and 4. the role of these viruses in patients with acute or chronic hepatitis of unknown causes and in those receiving liver grafts. Ad 1. Compared were different therapeutic concepts such as short-term combination therapy, triple-therapy, high dose IFN?-therapy and the use of antiviral substances such as ribavirin and amantadine. It emerged that relevant prognostic parameters can be deduced with respect to the therapeutic response rate. Ad 2. Analysed were possible molecular mechanisms, which may interfere with response or non-response to antiviral therapy. In this respect, we focussed on the interaction of certain HCV-proteins as NS5A, E2, so-called PKR-eIF2a phosphorylisation-homology-domain (PePHD). with the interferon-?-induced effector proteins. There is evidence, that number of mutations within the NS5A proteins are of prognostic relevance with respect to the response to interferon?-therapy. In contrast, mutations within the PePHD-region do not play any role in this respect. Ad 3. We also studied the clinical relevance of the newly discovered viruses GBV-C/HGV and TTV, and found, that they have no impact concerning the course of chronic hepatitis C. These viruses are interferon-sensitive and do not influence the IFNa-response as it could be documented by following the course of co-infected patients. Ad 4. Our studies also focused on the prevalence, transmission and relevance of GBV-C/HGV and TTV infections with respect to their role as hepatitis-inducing agents. We can show that both virus types are parenterally transmitted. There is a high prevalence for both types in patients confronted with risk factors for parenteral factors. From analysis of many patients being chronically infected with these viruses it became quite clear that they lack any important potency to provoke chronic liver disease.
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3

Silva, Filho Hermes Pedreira da. "Estudo Molecular dos Vírus B e C das Hepatites nas Regiões Norte e Nordeste do Brasil." reponame:Repositório Institucional da FIOCRUZ, 2010. https://www.arca.fiocruz.br/handle/icict/4219.

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Submitted by Ana Maria Fiscina Sampaio (fiscina@bahia.fiocruz.br) on 2012-07-19T21:21:54Z No. of bitstreams: 1 Hermes Pedreira EStudo molecular dos vírus B e C...2010.pdf: 5589974 bytes, checksum: b86706272dbb22d0d349edae7d641ce1 (MD5)
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Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, Bahia, Brasil
Infecções pelos vírus B e C das hepatites constituem um significante problema de saúde pública em todo mundo. Mais de 350 milhões de pessoas estão cronicamente infectadas pelo VHB e 170 milhões pelo VHC. No Brasil, a prevalência de pessoas infectadas pelo VHB varia de baixa endemicidade (<2%) até alta, (>7%), e estima-se que 1,5% da população esteja infectada pelo VHC (WHO). Estudos recentes tem demonstrado consideráveis variações entre os isolados do VHB, confirmando a diversidade de genótipos do vírus circulantes e o surgimento de mutações no genoma viral que podem ter impacto na resposta terapêutica e imune. Informações sobre a diversidade genética do VHB serão de grande valor para determinar fatores de risco associados a disseminação do vírus e auxiliar na adoção de medidas de prevenção e terapêutica. A infecção pelo VHC tornou-se um sério problema de saude pública desde que não existe uma vacina disponível e o tratamento é extremamente caro para os órgãos públicos como desgastante para o paciente. Este trabalho utilizou as ferramentas moleculares e de epidemiologia no estudo destes vírus para caracterizar molecularmente os vírus B e C das hepatites nas Regiões Norte e Nordeste, particularmente na Bahia, através de sequenciamento de DNA e análises filogenéticas. Amostras de pacientes provenientes da Bahia, Acre, Rondonia, Amazonas, Maranhão e Tocantins foram analisadas. As amostras foram oriundas de outros estudos e de centros de referência para tratamento das hepatites, sendo avaliadas 635 amostras para o VHC e 335 de VHB. Sequencias das regiões pré-S/S e pré- Core/Core do VHB e NS5b, 5UTR, E1 e Core do VHC foram utilizadas para classificação genotípica e análise filogenetica. Os genótipos mais frequentes para o VHB foram A (57%), D (10%) e F(33%) na Bahia e nas amostras da região Norte. Nós encontramos em nosso estudo 55,6% de pacientes co-infectados com VHB/Delta. Não foi possível estabelecer uma ligação genótipo específico com a evolução da infecção, e determinar a presença de mutantes relacionados à resposta terapêutica e ao escape imunológico. Com relação ao VHC, a subtipagem dos isolados foi realizada através do sequenciamento da região NS5b e 5UTR (n=230). Os sub-genótipos mais frequentes foram 1a(45,6%), 1b (46,9%), 3a (6,5%) e 2a/b(0,8%). As regiões E1 e Core também foram sequenciadas e no futuro serão utilizadas para avaliar possiveis mutações. O presente estudo mostra que a aplicação de protocolos de sequenciamento, bioinformática e filogenia são indispensáveis para a compreensão da epidemiologia molecular dos vírus das hepatites.
Infections with hepatitis B and C viruses constitute a significant public health problem worldwide. More than 350 million people are chronically infected with HBV and 170 million by HCV. In Brazil, HBV remains endemic despite widespread vaccination with prevalence of infection ranging from (<2%) low endemicity, until high (>7%) in different regions. Prevalence of HCV infection in Brazil has been estimated at 1.5%. Recent studies have shown considerable genetic variation among HBV isolates, confirming the diversity of circulating genotypes of the virus and the emergence of mutations in the viral genome that may impact on therapeutic and immune response. Information on the genetic diversity of HBV is useful for molecular epidemiology to determine risk factors associated with the spread of the virus and to inform prevention strategies and for monitoring therapy. Because there is no vaccine available to prevent HCV infection and treatment is extremely expensive for public agencies, HCV is an emerging public health problem. The treatment efficiency is directly related to viral genotype. In this study molecular epidemiology tools were used to characterize HBV and HCV in the North and Northeast, particularly in Bahia, through DNA sequencing and phylogenetic analysis. Samples from Bahia, Acre, Rondônia, Amazonas, Maranhão and Tocantins were analyzed. The samples were collected in collaboration with other studies and centers of references for hepatitis treatments. 635 samples from HCV infected patients and 335 samples from HBV infected were evaluated. Sequences of the regions pre-S / S, HBV core / pre-core, NS5B, 5UTR, HCV Core and E1 were used for genotypic classification and phylogenetic analysis. The most frequent HBV genotypes were A (57%), D (10%) and F (33%) in Bahia and in the samples from the North region. Fifty five percent of the patients from Rondônia were coinfected with HBV and HDV. In this study, we were unable to establish a connection with the particular genotype evolution of the infection and determine the presence of mutants related to therapeutic response and immune escape. In the North region co-infection with HBV genotype F and D virus is strongly associated with poor outcome of the disease as informed by the physicians and literature. Regarding HCV, the subtyping of isolates was performed by sequencing the NS5B region and 5UTR (n=230). The sub-genotypes more frequent were 1a (45.6%), 1b (46.9%), 3a (6.5%) and 2a / b (0.8%). The Core and E1 regions were also sequenced and in the future could be used to evaluate possible mutations. This study shows that the implementation of protocols for sequencing, bioinformatics and phylogenetic are essential for understanding the molecular epidemiology of hepatitis.
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4

Valente, Vanderleia Barbaro. "Estudo da distribuição dos marcadores sorológicos das hepatites B e C entre doadores de sangue do Hemocentro de Ribeirão Preto, SP." Universidade de São Paulo, 2002. http://www.teses.usp.br/teses/disponiveis/17/17139/tde-29052003-193717/.

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Este estudo, que envolveu todos os doadores de sangue (25.891) que compareceram pela primeira vez ao Hemocentro de Ribeirão Preto, de junho de 1996 a junho de 2001, teve os seguintes objetivos: 1) Estudar a positividade de marcadores sorológicos das hepatites B e C em testes da triagem dos doadores. 2) Analisar o fluxo dos doadores positivos para os marcadores das hepatites B e C ao Ambulatório de Hepatites (AH) do Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto. 3) Estimar a prevalência de infecção atual ou pregressa pelos vírus das hepatites B e C entre os doadores, através da análise dos resultados de testes confirmatórios para essas doenças. 4) Avaliar a importância da determinação da transaminase glutâmico-pirúvica (TGP) como marcador indireto de infecção pelos vírus das hepatites B e/ou C. Foram levantados dados registrados no Hemocentro, no Núcleo de Vigilância Epidemiológica (NVE) e no AH, coletando-se informações referentes ao doador, ao tipo de doação e ao resultado de teste da triagem sorológica (HBsAg, anti-HBc, anti-HCV, TGP, anti-HIV, anti-HTLV, doença de Chagas e sífilis). Foram estudados ainda: os resultados dos testes de repetição – realizados no Hemocentro – dos doadores positivos para os marcadores das hepatites B e C na triagem sorológica; o comparecimento ao NVE; e a confirmação, no AH, dos resultados para esses marcadores. A população dos doadores foi composta majoritariamente por homens (83,6%) e indivíduos de 26 a 45 anos de idade (64,0%). Predominaram as doações vinculadas (85,4%), e as maiores motivações foram solicitação e estímulo familiar ou de amigos. Os valores da prevalência, nos testes da triagem sorológica, foram iguais a 0,63% (IC95%: 0,54 – 0,72), para o HBsAg e 1,15% (IC95%: 1,02 – 1,28), para o anti-HCV. O total de doadores positivos que deveriam ser avaliados no AH, sofreu uma perda de 55,5% entre os suspeitos de ter hepatite B e de 58,7% entre os suspeitos de ter hepatite C, totalizando 266 doadores perdidos quanto ao acompanhamento. Os valores da prevalência, nos testes confirmatórios, foram iguais a 0,22% (IC95%: 0,16 – 0,28), para a hepatite B, e 0,31% (IC95%: 0,24 – 0,38), para a hepatite C. As co-positividades entre os valores de TGP e os marcadores de hepatites, nos testes de triagem sorológica, foram de 8,8%, para o vírus C, e de 0,5%, para o vírus B, indicando que a determinação dessa enzima não auxilia na seleção de doadores em bancos de sangue.
This study, which involved all blood donors (25.891) that attended the Blood Center of Ribeirão Preto for the first time from June 1996 to June 2001 had the following objectives: 1) To study the positiveness for hepatitis B and C serologic markers in donors screening tests. 2) To analyze the flow of positive donors for hepatitis B and C markers to the Hepatitis Ambulatory (HA) in the Clinical Hospital of the Faculty of Medicine of Ribeirão Preto of the University of São Paulo. 3) To estimate the predominance of present or former infection by hepatitis B and C viruses among donors, by analyzing results of screening tests that confirm these diseases. 4) To evaluate the importance of determining the glutamic-piruvic transaminase (GTP) as an indirect marker of infection by hepatitis B and C viruses. Registered data from the Blood Center as well as from the Epidemiological Surveillance Nucleus (ESN) and HA were used with the purpose of collecting information about donors, type of donation and results in serologic screening tests (HBsAg, anti-HBc, anti-HCV, GTP, anti-HIV, anti-HTLV, Chagas disease and syphilis). In addition, a study was performed on the results in repetition tests – that took place in the Blood Center – of positive donors for hepatitis B and C markers in serologic tests as well as on their attendance at the ESN and the confirmation in the HA of the results for these markers. The population of donors was composed in its majority by men (83,6%) and individuals from 26 to 45 year-old (64,0%). Linked donations predominated (85,4%), and the greatest reasons for donation arose from solicitation and stimulus coming from family and friends. The value of prevalence in serologic screening tests was 0,63% (IC95%: 0,54 – 0,72) for HBsAg and 1,15% (IC95%: 1,02 – 1,28) for anti-HCV. The total of positive donors that should have been evaluated in the HA suffered a loss of 55,5% among the suspects of having hepatitis B and of 58,7% among the suspects of having hepatitis C, reaching a total of 266 donors lost during follow-up. The value of prevalence in confirmatory tests was 0,22% (IC95%: 0,16 – 0,28) for hepatitis B and 0,31% (IC95%: 0,24 – 0,38) for hepatitis C. The copositiveness between GPT and hepatitis markers in serologic screening tests was 8.8% for hepatitis C virus and 0.5% for hepatitis B virus, indicating that determination of this enzyme is not helpful in selection of donors in blood banks.
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5

Silva, Edvaldo Ferreira da. "Prevalência de marcadores sorológicos das hepatites A e B em pacientes com hepatite C crônica atendidos no ambulatório de hepatites do serviço de Gastroenterologia Clínica do Hospital das Clínicas da Faculdade de Medicina da Universidade." Universidade de São Paulo, 2014. http://www.teses.usp.br/teses/disponiveis/5/5168/tde-04022015-153903/.

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Introdução: Pacientes com infecção crônica pelo VHC e superinfecção pelo vírus da hepatite A (VHA) ou o vírus da hepatite B (VHB), têm maior morbi-mortalidade quando comparados com pacientes que apresentam infecção aguda somente pelo VHA ou VHB. A mortalidade associada à hepatite A aguda pode estar particularmente elevada em pacientes com pré-existência de hepatite crônica causada pelo VHC. Por esta razão, a imunização ativa com vacinas contra o VHA e o VHB vem a ser obrigatória nesta população, e consequentemente esta sorologia deve ser determinada. Objetivos: O objetivo deste trabalho foi avaliar a prevalência de marcadores sorológicos da hepatite A e hepatite B em 1.000 pacientes com infecção crônica pelo VHC atendidos no Ambulatório de Hepatites da Divisão de Gastroenterologia e Hepatologia Clínica do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo. Resultados: O anti-VHA IgG foi positivo em 923 de 1000 pacientes (92,3%). Quando estratificados por idade, o anti-VHA IgG foi encontrado em 61% dos pacientes entre 20 e 29 anos, 70% entre 30 e 39 anos, 85% entre 40 e 49 anos, 94% entre 50 e 59 anos e 99% nos pacientes com mais de 60 anos . O anti-HBc total foi positivo em 244 pacientes (24%). Estratificados por idade, em 4,3% dos pacientes entre 20 e 29 anos, 17% entre 30e 39 anos, 21% entre 40 e 49 anos, 24% entre 50 e 59 anos, e 28% dos pacientes com mais de 60 anos. Dos 244 pacientes anti-HBc IgG positivos, 0,8% são HBsAg positivo, 8,5% anti-HBc IgG isolado e 16% anti-HBs positivo. Conclusões: A prevalência de anti-VHA IgG nod nossos pacientes com hepatite C crônica foi semelhante à da população geral no município de São Paulo. No entanto, o anti-HBc totaI foi maior em nossos pacientes, quando comparada historicamente à população geral dos países ocidentais, sugerindo fatores de risco semelhantes para as hepatites B e C, o que enfatiza a importância dos programas de imunização nesta população
Background and Aims: Patients with chronic HCV and superinfection by hepatitis A virus (HAV) or hepatitis B virus (HBV) have higher morbidity and mortality when compared with those without HCV. For this reason, HAV and HBV active immunization has become mandatory in this population and hence their serological markers must be determined. The aim of this study was to evaluate the prevalence of serological markers of HAV and HBV infection in patients with chronic HCV. Methods: 1.000 chronic HCV infected patients at the University of Sao Paulo School of Medicine outpatient Liver Clinic were evaluated for the prevalence of serological markers of HAV and HBV infection. Results: Anti-HAV IgG was positive in 923 of 1000 patients (92.3%). When stratified by age, the anti-HAV IgG was found in 61% of patients between 20-29 years, 70% between 30-39 years, 85% between 40-49 years, 94% between 50-59 years, and 99% over 60 years of age. Anti-HBc IgG was positive in 244 patients (24%). Stratified by age, anti-HBc IgG was found in 4.3% of patients between 20-29 years, 17% between 30-39 years, 21% between 40 -49 years, 24% between 50-59 years, and 28% of patients over 60 years of age. Of the 244 anti-HBc IgG positive patients, 0.8% were also HBsAg positive, 8.5% were anti-HBc IgG isolated and 16% were also anti-HBs positive. Conclusions: The prevalence of anti-HAV IgG was similar to the general population in the city of São Paulo. However, anti-HBc IgG was higher in our chronic HCV patients, when compared historically to the general population of western countries, suggesting similar risk factors for HBV and HCV acquisition, so emphasizing the importance of immunization programs in this population. Keywords: Hepatitis C, Chronic; Hepatitis C; Hepacivirus, Prevalence; Hepatitis A; Hepatitis B Título: Prevalência de Marcadores Sorológicos das Hepatites A e B em Pacientes com Hepatite C Crônica atendidos no Ambulatório de Hepatites do Serviço de Gastroenterologia Clínica do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo - HCFMUSP Background and Aims: Patients with chronic HCV and superinfection by hepatitis A virus (HAV) or hepatitis B virus (HBV) have higher morbidity and mortality when compared with those without HCV. For this reason, HAV and HBV active immunization has become mandatory in this population and hence their serological markers must be determined. The aim of this study was to evaluate the prevalence of serological markers of HAV and HBV infection in patients with chronic HCV. Methods: 1.000 chronic HCV infected patients at the University of Sao Paulo School of Medicine outpatient Liver Clinic were evaluated for the prevalence of serological markers of HAV and HBV infection. Results: Anti-HAV IgG was positive in 923 of 1000 patients (92.3%). When stratified by age, the anti-HAV IgG was found in 61% of patients between 20-29 years, 70% between 30-39 years, 85% between 40-49 years, 94% between 50-59 years, and 99% over 60 years of age. Anti-HBc IgG was positive in 244 patients (24%). Stratified by age, anti-HBc IgG was found in 4.3% of patients between 20-29 years, 17% between 30-39 years, 21% between 40 -49 years, 24% between 50-59 years, and 28% of patients over 60 years of age. Of the 244 anti-HBc IgG positive patients, 0.8% were also HBsAg positive, 8.5% were anti-HBc IgG isolated and 16% were also anti-HBs positive. Conclusions: The prevalence of anti-HAV IgG was similar to the general population in the city of São Paulo. However, anti-HBc IgG was higher in our chronic HCV patients, when compared historically to the general population of western countries, suggesting similar risk factors for HBV and HCV acquisition, so emphasizing the importance of immunization programs in this population
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6

Thiel, Jens. "Einfluss von Immunsuppression auf Hepatitis-C-assoziierte Immunphänomene und Hepatitis-C-Quasispezies." [S.l.] : [s.n.], 2003. http://deposit.ddb.de/cgi-bin/dokserv?idn=969417918.

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7

Shen, Hong. "Hepatitis C infection models." Thesis, Paris 5, 2012. http://www.theses.fr/2012PA05T016.

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L'hépatite C (VHC) est l'une des causes principales de maladies du foie dans le monde, qui représentent un risque élevé d'évoluer vers la cirrhose et le carcinome hépatocellulaire. Actuellement, le traitement standard de l’infection par le VHC est l'interféron pégylé-(peg-IFN) et la ribavirine. Bien que le taux de la réponse virale soutenue (RVS) au traitement se soit améliorée au cours de ces années, cette thérapie n'est pas efficace chez tous les patients. En outre, plusieurs effets secondaires toxiques, de complications et le coût élevé limitent la compliance du patient et l'efficacité du traitement. Il n'existe pas de modèle simple d'infection par le VHC et il est nécessaire de développer des modèles in vitro et in vivo utiles pour étudier la physiopathologie de l'infection par le VHC, y compris les événements précoces de l'infection aiguë (l'entrée du virus, des mécanismes immunologiques et génétiques prédictifs) ainsi que l'évaluation de la puissance des médicaments antiviraux contre le VHC. Nous rapportons ici, nos efforts visant à développer des modèles appropriés de l'infection par le VHC. Dans un premier temps, nous avons établi un modèle de petit animal pour étudier l'infection par le VHC. Tupaia est un petit animal, apparenté aux primates et peu couteux. Dans notre travail, nous avons étudié la susceptibilité du tupaia à l'infection par VHC. Douze tupaias adultes ont été inoculés avec le VHC provenant de sérum de patient et d'ARN du VHC (génotype 1a). Trois jeunes tupaias ont été artificiellement nourris pendant un mois et ensuite inoculés par le VHC provenant de sérum du patient. L'ARN du VHC, les anticorps anti-VHC et l’évolution des quasi-espèces du VHC ont été déterminées chez l'animal avant et après l'inoculation. L'infection transitoire et intermittente s'est produite chez deux des 3 jeunes tupaias et l’infection chronique par le VHC s’est produite chez quatre tupaias sur 12 tupaias adultes. Le tupaia devrait représenter un modèle utile pour l'étude de l’infection chronique par le VHC. Dans une deuxième étape, un système de culture in vitro d'hépatocytes primaires de Tupaia a été établi, dans lequel l'infection par le VHC ne pouvait être bloquée ni par le CD81 soluble ni par des anticorps dirigés contre le CD81. Pour comprendre ces résultats, nous avons cloné, séquencé la grande boucle extracellulaire (LEL) du CD81 chez le Tupaia et analysé l'interaction de la protéine d’enveloppe E2 du VHC avec la LEL du CD81 chez le Tupaia par un test « enzyme-linked immunosorbent assay » (EIA). Nous avons constaté que chez le Tupaia, la séquence d'acides aminés du LEL de CD81 qui se lie au VHC présentait en 6 résidus d'acides aminés différents par rapport à la séquence humaine et la capacité de LEL de CD81 à se lier à la proteine d’enveloppe E2 du VHC a également diminuée. La structure différente de CD81 chez l’homme et chez le tupaia pourrait expliquer l'altération de l'interaction entre CD81 et la proteine E2 du VHC. Ce résultat démontre un rôle important de LEL du CD81 pour l'entrée du VHC. Dans une troisième étape, nous avons développé un modèle ex vivo de culture de tranches de foie humain et leur infection par le VHC. Le développement de lignées cellulaires provenant d’hepatocarcinome, permissives à la réplication du VHC, a fourni d'importants nouveaux outils virologiques pour étudier les mécanismes de l'infection par le VHC, mais ce modèle expérimental reste relativement éloigné des conditions physiologiques et pathologiques. Nous rapportons ici le développement d'un nouveau modèle ex vivo utilisant la culture de tranches de foie humain adulte, démontrant, pour la première fois, la capacité d’isolats primaires ainsi que JFH -1, H77/C3, Con1/C3 (HCVcc), de répliquer et de produire de novo des particules virales infectieuses ayant un titre viral élevé…
Hepatitis C virus (HCV) is one of the major causes of liver disease all over the world which has a high risk to progress to cirrhosis and hepatocellular carcinoma. Currently, the licensed standard treatment of HCV infection is Pegylated-interferon (peg-IFN) and ribavirin. Although the sustained viral response (SVR) rate of treatment has improved during these years, this therapy is not effective in all patients. In addition, several toxic side effects, complication and high cost limit the patient compliance and the efficacy of the treatment. There is no easy model of HCV infection and it is necessary to develop useful in vitro and in vivo models to study the pathobiology of HCV infection, including early events of acute infection (viral entry, immunological mechanisms, and genetic predictors) as well as the evaluation of the potency of the HCV antiviral drugs. We report here in our efforts in developing suitable models of HCV infection. In a first step, we preliminary established a small animal model to study HCV infection. Tupaia is a small, closed related to primate and cost-effective animal. In our work, we investigated the susceptibly of tupaia to HCV infection. Twelve adult tupaias were inoculated with native HCV from patient serum and full-length HCV RNA (Genotype 1a). Three young tupaias were artificially breeded for a month and then inoculated by native HCV from patient serum. HCV RNA, anti-HCV and HCV quasi species evolution were determined in the animal before and after inoculation. Transient and intermittent infection occurred in two among 3 young tupaias and HCV chronic infection occurred in four among 12 adult tupaias. Tupaia should represent a useful model for study HCV chronic infection. In a second step, an in vitro culture system of primary tupaia hepatocytes has been established in which HCV infection could be blocked neither by the soluble CD81 nor by antibodies against CD81. To understand these results, we cloned, sequenced the large extracellular loop (LEL) of tupaia CD81 and analyzed the interaction of HCV E2 with the tupaia CD81 LEL by enzyme-linked immunosorbent assay (EIA). We found that in the tupaia the amino acids sequence of HCV CD81 LEL presented in 6 different amino acid residues compared with human CD81 LEL sequence and the CD81 LEL ability to bind to HCV E2 was also decreased. The different structure of CD81 between human and tupaia could explain the alteration of the interaction between HCV E2 and CD81. This result demonstrated an important role of CD81 LEL for HCV entry. In a third step, we developed an ex vivo model of human liver slices culture and their infection with HCV. The development of human cultured HCV-replication-permissive hepatocarcinoma cell lines has provided important new virological tools to study the mechanisms of HCV infection; however this experimental model remains distantly related to physiological and pathological conditions. Here, we report the development of a new ex vivo model using human adult liver slices culture, demonstrating, for the first time, the ability of primary isolates to undergo de novo viral replication with the production of high titer infectious virus, as well as JFH-1, H77/C3, Con1/C3 (HCVcc). This experimental model was validated by demonstrating the HCV neutralization or HCV inhibition, in a dose-dependent manner, either by CD81 or E2 specific antibodies or convalescent serum from a recovered HCV patient, or by anti-viral drugs. This new ex vivo model represents a powerful tool for studying the viral life cycle, dynamics of virus spread in the liver and also for evaluating the efficacy of the new antiviral drugs. In the last step, we evaluated the efficacy of the new antiviral drugs with our ex vivo model of human adult liver slices. HCV NS3/4A protease is essential for viral replication and has been one of the most important target for developing specific antiviral drug
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8

Hopwood, Maxwell Norman. "Living with Hepatitis C." Maastricht : Maastricht : Universiteit Maastricht ; University Library, Universiteit Maastricht [host], 2007. http://arno.unimaas.nl/show.cgi?fid=9171.

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9

Montes, Teves Pedro. "Hepatitis C: retos pendientes." Sociedad de Gastroenterología del Perú, 2014. http://hdl.handle.net/10757/331937.

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10

Winckler, Fernanda Cristina. "Influência da Resposta inflamatória na resposta virológica sustentada em pacientes com hepatite C crônica genótipo 1 durante o tratamento antiviral com terapia tripla." Botucatu, 2016. http://hdl.handle.net/11449/144991.

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Orientador: Giovanni Faria Silva
Coorientador: Marjorie de Assis Golim
Resumo: A hepatite C é uma doença infecciosa que torna-se crônica em cerca de 85% dos infectadosque poderão desenvolver cirrose e carcinoma hepato celular. O tratamento antiviral em muitosdos pacientes não é eficaz, principalmente quando estes portam o genótipo 1 e fibroseavançada, a resposta inflamatória também desempenha seu papel sobre a resposta virológicasustentada (RVS) durante o tratamento com Interferon Peguilado (PegIFN) associado aRibavirina (RBV). Nesse estudo nosso objetivo principal foi avaliar a influência da respostainflamatória através de células e citocinas/quimiocinas sobre a resposta virológica do pacienteem tratamento antiviral com terapia tripla. Incluimos pacientes com RNA VHC+, nuncatratados (naive), portadores do genótipo 1, ambos os sexos e com fibrose avançada F3 (n=6);F4 (n=21) candidatos ao tratamento em regime triplo. Os pacientes tiveram suas amostrascoletadas e analizadas nas semanas 0 e 12 do tratamento e os seguintes parâmetros foramanalisados: IL-2, IL-4, IL-6, IL-8, IL-10, IL-17A, TNF-α, IFN-γ, RANTES, MCP-1, MIG, IP-10, através de citometria de fluxo (método CBA). Foram incluídos 15 voluntários saudáveis(grupo controle) e 27 pacientes que foram separados em G1(RVS) e G2 (não RVS), a taxa deRVS foi de 63%. Os pacientes com hepatite C crônica tiveram os níveis circulantes de IP10,MCP-1, MIG, RANTES, IL-8 e IL-6 mais elevados quando comparados com voluntáriossaudáveis, quando comparados G1xG2 os níveis de RANTES (p=0,04... (Resumo completo, clicar acesso eletrônico abaixo)
Mestre
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11

Machado, Danusa de Almeida. "Qualidade de vida e morbidade psicológica de pacientes portadores de hepatite C em tratamento com interferon peguilado e ribavirina /." Botucatu, 2009. http://hdl.handle.net/11449/98430.

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Resumo: O presente estudo teve por objetivo descrever características sóciodemográficas, psicossociais, clínicas, índices de qualidade de vida, ocorrência de transtorno mental comum, de sintomas depressivos de pacientes portadores de Hepatite C crônica, em tratamento no Ambulatório de Hepatites Virais da Disciplina de Gastroenterologia Clínica do HC da FMB-UNESP, em três momentos de seu tratamento com Interferon Peguilado e Ribavirina: antes do início, nas 12ª e 24ª semanas de tratamento. Foram também estudadas as associações das variáveis sócio-demográficas e clínicas, de transtorno mental comum (TMC), sintomas depressivos, da forma de tratamento com índices de qualidade de vida (QV) nos três momentos estudados e com os resultados de exames indicativos da resposta virológica ao tratamento (detecção do RNA do vírus da Hepatite C pelo método de PCR). Método: Realizou-se estudo transversal e de seguimento. Uma amostra de conveniência foi estabelecida, tendo-se estudado 82 pacientes no estudo transversal e feito o seguimento de 46 no terceiro e sexto mês após o início do tratamento. Utilizou-se formulário estruturado para investigar aspectos sócio-demográficos e clínicos. Sintomas depressivos foram avaliados pelo Beck Depression Inventory (BDI). Utilizou-se o Self Reporting Questionnaire (SRQ) para avaliar Transtorno Mental Comum e o uso nocivo de álcool foi avaliado por meio do Alcohol Use Disorders Identification Test (AUDIT). A qualidade de vida foi estudada por meio do The Medical Outcomes Study 36 item Short-Form Health Survey (SF-36). O estudo das associações entre variáveis categoriais foi feito pelo teste do Qui-quadrado (ou Fisher, se adequado). Os Testes de Mann-Whitney e de Kruskal Wallis foram utilizados para comparar as distribuições dos vários domínios do SF-36. Para comparação entre os dados nos momentos subseqüentes foram... (Resumo completo, clicar acesso eletrônico abaixo)
Abstract: This study aimed at describing socio-demographic, psychosocial and clinical characteristics as well as quality of life indexes, occurrence of common mental disorder and depressive symptoms of patients with chronic hepatitis C undergoing treatment at the Viral Hepatitis Outpatient Unit of the Botucatu Medical School - UNESP, at three different moments of their treatment with Peguilated Interferon and Ribavirin: immediately before treatment, 12 and 24 weeks after its introduction. The association of socio-demographic and clinical variables as well as those for common mental disorder (CMD), depression symptoms and form of treatment with quality-of-life (QL) indexes was evaluated at the three studied moments. The association of such variables with test results indicating virological response to treatment (detection of the hepatitis C virus RNA by the PCR method) was also investigated. Method: A convenience sample was established, and 82 patients were studied in a cross-sectional and follow-up investigation. Forty-six patients were followed 3 and 6 months after the beginning of treatment. A structured questionnaire was used to investigate socio-demographic and clinical aspects. Depression symptoms were evaluated by the Beck Depression Inventory (BDI). The Self Reporting Questionnaire (SRQ) was utilized to evaluate common mental disorder, and harmful use of alcohol was evaluated by the Alcohol Use Disorders Identification Test (AUDIT). Quality of life was assessed by the Medical Outcomes Study 36-item Short-Form Health Survey (SF-36). The study of the associations between categorial variables was performed by the chi-square test (or Fisher, if adequate). The Mann-Whitney and Kruskal Wallis tests were used to compare the distribution of various domains of SF-36. McNemar's Exact Test was used for category variables to compare the data at the subsequent moments, and Friedman's Test was... (Complete abstract click electronic access below)
Orientador: Ana Teresa de Abreu Ramos-Cerqueira
Coorientador: Giovanni Faria Silva
Banca: Fani Eta Korn Malerbi
Banca: Carlos Antonio Caramori
Mestre
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Gryninger, Gabriela [UNESP]. "Influência do vírus da hepatite B na infecção crônica pelo vírus da hepatite C: perfil das séricas e histopatologia hepática." Universidade Estadual Paulista (UNESP), 2008. http://hdl.handle.net/11449/89937.

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Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
Universidade Estadual Paulista (UNESP)
O vírus da hepatite C é uma das principais causas de doença hepática no mundo inteiro. O estudo histopatológico é de grande importância no prognóstico e indicação de tratamento. A coinfecção com o vírus da hepatite B oculta pode agravar a lesão hepática e diminuir a resposta ao tratamento. As citocinas IL-2, INF, TNF- induzem lesão hepática e fibrose. A IL-10 apresenta atividade antiinflamatória e o TGF- induz o desenvolvimento e depósito de matriz extracelular causando fibrose. Este estudo avaliou, em pacientes com HCC, a presença da hepatite B oculta, a dosagem das citocinas IL-2, INF, TNF , TGF e IL-10, correlacionando com o estágio de fibrose em pacientes tratados e não tratados com interferon, comparando também com indivíduos saudáveis. Foram estudados 55 pacientes com HCC crônica, atendidos na Faculdade de Medicina de Botucatu, excluindo-se pacientes imunossuprimidos e gestantes. O grupo controle foi constituído de 20 indivíduos doadores de sangue. O vírus da hepatite B oculto foi pesquisado por de PCR in house, segundo técnica de Kaneno, com limite de detecção menor que 100 cópias/ml. A dosagem de citocinas foi determinada por método de Elisa. A avaliação da fibrose hepática seguiu aquela proposta pela Sociedade Brasileira de Patologia. Os resultados mostraram predominância do gênero masculino, adulto jovem, 36,4% foram usuários de drogas endovenosas e 41,8% haviam sido hemotransfundidos. Nenhum paciente apresentou coinfecção pelo vírus da hepatite B oculto. Na biópsia hepática predominou fibrose leve ou ausência de fibrose (47,2%). As citocinas analisadas não discriminaram o grau de fibrose nos indivíduos com HCC crônica, mesmo quando separados em pacientes que foram submetidos ao tratamento e pacientes que não receberam o tratamento. Não houve também discriminação das citocinas...
The Hepatitis C virus is one of the major causes of hepatic diseases worldwide. Histopathological analyses play a leading role in determining disease outcome and treatment. Co-infection with occult Hepatitis B can aggravate liver injury and diminish treatment response. Cytokines such as IL-2, INF and TNF- induce liver injury and fibrosis. IL-10 has an antiinflamatory action and TGF- induces extracellular matrix development and deposition causing fibrosis. In this study, the presence of occult Hepatitis B and the expression of IL-2, INF, TNF , TGF and IL-10 were assessed in HCC patients and correlated with fibrosis stage in patients treated and non-treated with interferon, as well as healthy individuals. A total of 55 patients with chronic HCC seen at Botucatu Medical School were included. Immunosuppressed or pregnant patients were excluded. The control group consisted of 20 blood donors. The occult Hepatitis B virus was detected by in-house PCR according to the technique of Kaneno with a detection limit < 100 clones/ml. Cytokine levels were determined by the Elisa method. Hepatic fibrosis was assessed as proposed by the Brazilian Society of Pathology. The results showed a predominance of male young adults of whom 36.4% had used endovenous drugs and 41.8% had been hemotransfused. No patient showed occult Hepatitis B co-infection. Hepatic biopsy revealed that fibrosis was either absent or mild in most cases (47.2%). The cytokines under study did not correlate with fibrosis stage in individuals with chronic HCC no matter whether they had or not received treatment. In addition, no correlations with cytokine levels were observed when VHC patients were separated into groups of individuals treated and non-treated with interferon . However, cytokine expressions were significantly increased in all cases in comparison with the control group.
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13

Roy, Kirsty McLiver. "Hepatitis C virus in saliva." Thesis, University of Glasgow, 1996. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.297005.

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14

Buckton, Andrew John. "Multitypic hepatitis C virus infection." Thesis, Open University, 2006. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.435903.

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15

Ciaccia, Maria Celia Cunha. "Aspectos epidemiológicos, sorológicos e moleculares das hepatites A, B e C em crianças e adolescentes matriculados em creches e escolas do ensino infantil e fundamental da rede municipal na cidade de Santos." Universidade de São Paulo, 2012. http://www.teses.usp.br/teses/disponiveis/5/5141/tde-14012013-120337/.

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As hepatites virais continuam sendo uma preocupação em nível de saúde pública no Brasil e no Mundo, tanto pelo número de indivíduos atingidos, como pela possibilidade de complicação das formas agudas e crônicas. Segundo a Organização Mundial de Saúde (OMS), 170 milhões de pessoas são portadoras crônicas de hepatite C e 350 milhões portadoras crônicas de hepatite B. No Brasil, a estimativa de portadores de hepatite B crônica é de aproximadamente 600 mil pessoas e de hepatite C crônica, 1,5 milhão. Quanto à hepatite aguda A foram confirmados no país, em 2010, 5943 casos. O objetivo deste estudo foi conhecer a prevalência de marcadores sorológicos dos vírus das hepatites A, B e C em crianças e adolescentes matriculados em creches e escolas de ensino infantil e fundamental da rede municipal na cidade de Santos; conhecer os aspectos moleculares dos vírus das hepatites B e C, identificando o genótipo dos dois agentes e estudar modo de aquisição nos casos com sorologias positivas. Tratou-se de um estudo transversal realizado no período de 28 de Junho a 14 de Dezembro de 2007 onde foram coletadas 4680 amostras de sangue colhidas através de punção capilar e ao mesmo tempo aplicado um questionário nos familiares das crianças e adolescentes. Os exames sorológicos foram realizados utilizando a técnica de ELISA. O estudo molecular foi realizado pela técnica de reação em cadeia de polimerase \"in House\". A idade da população estudada variou de 7 meses a 18 anos e 1 m. A prevalência geral do anti-HVA IgG reagente foi de 9,7% e desses 74,6% foi anti-HVA IgM reagente. A prevalência de anti-HVA IgG foi maior entre as crianças mais velhas, meninas, aquelas que brincavam em córregos, sem esgoto em sua moradia, de pais com baixa instrução, de baixa renda familiar e aquelas que não eram moradoras da Orla. A prevalência de anti-HVA IgM, não foi diferente entre as diferentes categorias, exceção feita à faixa etária (pico no primeiros anos e posterior queda) e morro e Zona Noroeste foi mais baixa. A prevalência geral do anti-HBc reagente foi de 0,1%, do AgHBs de 0,02% e do anti-HVC foi de 0,02%. Conclui-se que a prevalência geral em crianças dos marcadores sorológicos para hepatites A, B e C na cidade de Santos foi baixa, quando comparada com os dados de literatura. Apesar dos nossos dados confirmarem uma mudança no perfil epidemiológico da hepatite A, as medidas preventivas atuais quanto ao saneamento, grau de instrução, habitação, ainda permanece com uma deficiência em Santos, cidade balneária com o maior porto do Brasil. A vacinação para hepatite B foi altamente eficaz com a baixa prevalência encontrada dos marcadores sorológicos. A utilização do papel de filtro em estudos epidemiológicos para hepatite A foi eficaz. Entretanto para o vírus da hepatite C ainda necessita de estudos comparativos utilizando sangue venoso, uma vez que a prevalência de crianças infectadas com hepatite C foi muito baixa na cidade de Santos.
Viral hepatitis are still a concern in the public health level in Brazil and around the Word, due both to the number of affected subjects and the possibility of complication in the acute and chronic forms. According to the World Health organization (WHO), 170 million people are chronic carriers of hepatitis C and 350 million chronic carriers of hepatitis B. In Brasil, the estimate of people with chronic hepatitis B is approximately 600 thousand people and chronic hepatitis C, 1,5 million. It has been confirmed in the country, in 2010, 5943 cases of acute hepatitis A. The The aim of this study was to learn the prevalence of serological markers of hepatitis A, B and C virus in children and teenagers enrolled at the municipal education network in the city of Santos, to learn molecular aspects of hepatitis B and C, identifying the genotype of the two agents and to study the acquisition mode in cases with positive serology. Cross-sectional study carried out over the period from June 28 to December 14, 2007, in which 4680 fingerprick blood samples were collected; at the same time, a survey questionnaire was applied to the family members of the children and teenagers. The serological tests were performed using the ELISA technique. The molecular analysis was performed using the technique of polymerase chain reaction \"in House\". Age of the population studied ranged from 7 months to 18 years and 1 month. . The general prevalence of serological markers anti-HAV IgG reagent was 9.7% and between them 74,7% was anti-HAV IgM reagent. There was higher prevalence among older children, females, those who used to play in streams near their home, the absence of a sewage system in home, parents with low education, low household income and among those who did not live in the seashore. The prevalence of anti-HAV IgM was not different between the categories, except for the age (peak in the early years and subsequent fall) and lower on the Hills and Northweast Zone. The general prevalence of anti-HBc reagent was 0,1%, AgHBs was 0,02% and anti-HCV was 0,02%. It is concluded that, in children, the general prevalence of serological markers for hepatitis A, B and C in the city of Santos was low when compared with literature data. Although our data confirm a change in the epidemiological profile of hepatitis A, the current preventive measures regarding sanitation, education level and housing still remain with a deficiency in Santos, the coastal city with the largest harbor in Brazil. Vaccination for hepatitis B was highly effective because it found a low prevalence of serological markers. The use of filter paper in epidemiological studies for hepatitis A was effective. However for the vírus of hepatitis C still requires comparative studies using venous blood because the prevalence of infected children was very low in the city of Santos.
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16

Aisyah, Dewi Nur. "Assessing the epidemiology of hepatitis C to inform public health strategies towards hepatitis C elimination." Thesis, University College London (University of London), 2018. http://discovery.ucl.ac.uk/10058645/.

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Background: Major advances in hepatitis C virus (HCV) treatment suggest that HCV might be eliminated in the future. In this thesis, I have undertaken a series of studies (systematic review, secondary analysis of existing cohort study, modelling) to investigate factors that are likely to impact on the feasibility of achieving HCV elimination. Overarching Aim: To improve our understanding of the epidemiology and natural history of hepatitis C in order to inform public health strategies working towards HCV elimination. Methods: Systematic review and meta-analysis assessing HCV spontaneous clearance rate and its predictors (Chapters 2&3). Prevalence surveys to assess the burden of and risk factors for HCV in Guernsey (Chapter 4) and in vulnerable populations in London (Chapter 5). Development of a mathematical model to estimate the required scale-up of DAA treatment that would be required to eliminate HCV in PWID in London by 2030 (Chapter 6). Findings: • HCV prevalence was high in people screened in homeless centres, a prison and drug treatment centres. Increased case finding is needed in these settings. • 35% of patients spontaneously clear HCV by 12 months - it may be appropriate to have a year observation before instigating treatment for recently infected patients in low and middle-income countries with low healthcare budgets. • A wide range of risk factors predict spontaneous clearance. Notably drug users and those with HIV are less likely to spontaneously clear than other groups. Thus, early treatment for high risk groups is recommended for those who are less likely to achieve clearance and pose a higher risk of onward transmission. • IL28B rs8103142, IL28B rs12979860, and IL28B rs8099917 are important host genetics predictors of clearance. • Treatment prioritisation with "watch and wait" approach is probably more appropriate to be implemented for developing and less developed countries, where large number of HCV patients were infected by iatrogenic transmission and usually those settings have limited DAAs drugs supply. However, for developed countries such as UK, treatment prioritisation is probably less relevant as the majority of HCV infection came from PWID and DAA's treatment are available. • The modelling suggests that elimination of HCV in PWID in London by 2030 would require 46% annual treatment coverage of those infected - this represents a major scale up from current activity. Retreatment of treatment failures lowers the coverage needed to 29.5%. The model is highly sensitive to: SVR (Sustained Virologic Response - suggesting need to support adherence and prevent resistance) and injecting duration (suggesting the need for drug treatment services). Conclusion: Hepatitis C elimination would require substantial additional investment to raise treatment coverage and prevent transmission through injecting drug use. My work has identified a number of approaches would could support efforts to achieve this goal.
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Oliveira, Célia Figueiredo de. "Detecção de marcadores sorológicos para hepatite A, B e C associados ao perfil epidemiológico em uma população de estudantes universitários no interior de São Paulo-SP." [s.n.], 2010. http://repositorio.unicamp.br/jspui/handle/REPOSIP/311371.

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Orientadores: Neiva Sellan Lopes Gonçales, Fernando Lopes Gonçales Júnior
Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas
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Resumo: As hepatites virais constituem um importante problema de saúde pública. São doenças provocadas por agente etiológicos com tropismo primário pelo tecido hepático com características epidemiológicas, clínicas e laboratoriais semelhantes com importantes particularidades. O objetivo desta pesquisa foi determinar a prevalência das hepatites A, B e C em estudantes universitários utilizando marcadores sorológicos. Avaliar seus fatores de risco, o nível de conhecimento dos estudantes sobre as vias de transmissão e prevenção e caracterizar a proteção vacinal pelo marcador anti-HBs. O estudo foi realizado em 685 estudantes universitários. Foi aplicado um questionário para avaliar os aspectos sócio-econômicos, epidemiológicos e laboratoriais dos estudantes quanto às hepatites A, B e C. Foi coletado sangue para análise dos marcadores sorológicos anti-HBc, anti-HBs, HBsAg, Anti-HCV, anti-VHA IgG. A prevalência da hepatite A foi de 19,5%, da hepatite B 1,17% e da hepatite C 0,15%. O marcador sorológico anti-HBs com títulos superiores a 10mUI/ml, o qual confere soroproteção, estava presente em 61,2% dos universitários. A análise dos questionários mostrou que os fatores de risco relevantes entre a população estudada foram: o contato com material biológico em atividades laboratoriais (45,1%), com pacientes (38,6%), acupuntura (14,8%), tatuagem (13,5%), droga inalatória (8,09%) e droga injetável (0,73%). Quanto ao comportamento sexual, 71,5% já tiveram de 1 a 3 relacionamentos regulares e 42,9% usavam preservativos e 7,7% nunca fizeram uso. Dos estudantes universitários analisados, 88,7% relataram ter conhecimento das vias de transmissão e prevenção das hepatites. A análise dos dados mostra que é de extrema importância quando os estudantes universitários iniciam sua jornada acadêmica, independente do curso ser da área da saúde deveriam ser vacinados (vacina para VHA e VHB) uma vez que se trata de uma população exposta aos fatores de risco para aquisição de hepatites. Seria interessante incluir no calendário escolar, palestras que possibilite sempre a atualização sobre o conhecimento das hepatites principalmente sobre transmissão parenteral e sexual, da prevenção, da importância do conhecimento do seu status vacinal
Abstract: The objective this study was to determinate the prevalence of the hepatitis A, B and C among graduate students using serological markers. To evaluate their risk factors, the knowledgement level of the students about the transmission pathways and prevention and to characterize the vaccine-related protection by the anti-Hbs marker. Six hundred eighty five graduate students were enrolled in this study. The students were submitted to enquiry about to evaluate the socio economic, epidemiological and laboratorial aspects of the students concerning hepatitis A, B and C. Peripheral blood was collected from students to perform the following serological marker: anti-HBc, anti-HBs, HBsAg, anti-HCV and HAV IgG. The prevalence of hepatitis A was 19.5%, hepatitis B was 1.17% and hepatitis C was 0.15%. The anti-HBs marker with titles higher than 10 mUI/mL which is consistent with protection was present in 61.2% of the students. The analysis of enquires showed that the relevant risk factors among the studied cohort were: contact to biological materials during laboratorial proceedings (45.1%), contact to patients (38.6%), acupuncture (14.8%), tattoo (13.5%), inhalatory drug (8.09%) and injectable drugs (0.73%). Whereas sexual practices, 71.5% already had from 1 to 3 regular relationship, 42.9% of them used condom and 7.7% had never used. Among the students enrolled in this study, 88.7% reported to have knowledge about the transmission pathways and prevention of the hepatitis. The data analysis showed that is extremely important to the students to have access to lectures concerning general knowledge about hepatitis and about pathways of transmission, prevention and about the importance of vaccine-related prophylaxis. Access to that lectures should begin when the students start their academic journey, independently if the course is or not included among health courses. In addition, vaccination should be included in their academic programming
Mestrado
Ciencias Basicas
Mestre em Clinica Medica
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18

Moraes, Camila Fernanda Verdichio de [UNESP]. "Antígeno plaquetários humanos (HPA) em portadores do vívus da hepatite c (HCV)." Universidade Estadual Paulista (UNESP), 2009. http://hdl.handle.net/11449/102625.

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Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
A Hepatite C é uma das principais causas de doença crônica hepática. A combinação entre o interferon peguilado e a ribavirina tem sido considerado o padrão-ouro de tratamento para Hepatite C. A resposta ao tratamento vem sendo associada a fatores ambientais, do vírus e também do paciente, tais como polimorfismos genéticos dos antígenos leucocitários humanos (HLA), da interleucina-10 e do fator de necrose tumoral-a. Plaquetas possuem em suas membranas glicoproteínas que expressam segmentos protéicos polimórficos, os quais são chamados de antígenos plaquetários humanos (HPA). Os sistemas HPA-1, -3, -4 e -5 residem em integrinas, proteínas que possuem interações com interferon. O objetivo desse estudo foi avaliar a associação entre freqüência dos HPA-1, -3, -4 e -5 e a resposta ao tratamento, em 138 pacientes tratados para Hepatite C. A genotipagem dos HPA-1, -3 e -4 foi realizada pela técnica de PCR-SSP e do HPA-5 pela PCR-RFLP. A genotipagem do HCV foi realizada através do Kit comercial INNO-LiPA® v.1.0 (Innogenetics, Ghent, Belgium), segundo as instruções do fabricante. Os pacientes foram divididos em grupos e subgrupos de acordo com o esquema terapêutico, a resposta ao tratamento e o genótipo do HCV. Os pacientes que possuíam o genótipo do HCV não-1 e que foram tratados com IFN-a+RBV, com falha terapêutica, apresentaram uma diferença estatística significante (p<0.05) nas freqüências alélicas e genotípicas do sistema HPA-3, com aumento do alelo 3b. O sistema HPA-3 está localizado em uma integrina que se liga a fibronectina, um receptor de interferon. Nesse contexto, a alteração conformacional glicoprotéica decorrente da presença do alelo HPA-3b, poderia estar associada à falha ao tratamento com IFN-a+RBV em pacientes portadores de genótipo viral não-1.
Hepatic fibrosis leading cirrhosis in 20 to 30% of patients with chronic hepatitis C virus (HCV) infection. Rapid progression to fibrosis has been related to environmental, viral and host factors. However, genetic polymorphisms have recently been associated with this progression, including the expression of integrins. Platelet membrane glycoproteins express several polymorphic antigenic determinants on their surface, which are called human platelet antigens (HPA). HPA-1, -3, -4 and -5 reside in integrins. The association between HPA antigens and stage of fibrosis can determine if HPA is related to progression of fibrosis. Thus, the goal of this study was to determine the association between the HPA-1, -3, -4 and -5 and the liver fibrosis stage in 175 HCV-infected patients. HPA-1, -3 and -4 genotyping was performed by PCR-SSP and, HPA-5 by PCR-RFLP. Fibrosis progression was evaluated using the METAVIR scoring system. There were no significant differences (p>0.05) in allelic and genotypic frequency distribution of HPA-1, -3 and -5, residing in integrins.
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19

Nogueira, Camila Tita [UNESP]. "Estudo da influência dos genótipos 1 e 3 do vírus da hepatite C sobre os indicadores do metabolismo lipídico em hepatopatas crônicos." Universidade Estadual Paulista (UNESP), 2009. http://hdl.handle.net/11449/93604.

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Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
Os perfis metabólicos correlacionam-se com a infecção pelo VHC e são prognósticos da resposta viral em pacientes crônicos. Porém, pouco se sabe a respeito da associação entre perfis lipídicos e carga viral do VHC entre infecções dos genótipos 1, 2 ou 3. Portanto, o objetivo deste trabalho foi estudar a influência da viremia e dos genótipos do VHC sobre o metabolismo lipídico através das variações de lipoproteínas séricas (colesterol total, LDL, HDL, VLDL, triglicérides) e apolipoproteína B (Apo B) em hepatopatas crônicos, avaliando se o VHC predispõe os indivíduos ao aparecimento de complicações vasculares. O grupo amostral constituiu-se de um total de 150 pacientes crônicos do VHC com genótipos 1, 2 ou 3, e de um grupo controle de 20 indivíduos saudáveis (10 homens e 10 mulheres) em idade adulta (20 à 50 anos). Os níveis séricos de HDL (28%), VLDL (26%) e triglicérides (26%) nos portadores crônicos do VHC se mostraram diminuídos em relação ao grupo controle, enquanto os níveis de LDL (25%) e Apo B (29%) se mostraram elevados, resultados que foram mais importantes nos portadores do genótipo 3a. Observou-se correlação positiva entre a viremia e alterações nos níveis de apo B (r = 0,5763) nos portadores do genótipo 1b. Assim, foi pressuposto que o risco de pacientes portadores do VHC desenvolverem complicações vasculares é elevado, pois 1% de redução nos níveis de LDL está associado com uma redução de 2-3% no risco de desenvolvimento de doenças cardíacas, e como cerca de 90% da proteína na LDL se constitui de apo B, sua concentração plasmática indica o número total de partículas potencialmente aterogênicas. Desta forma, o perfil lipídico auxilia no diagnóstico da severidade da infecção hepática causada pelo VHC e ainda atua como um bom sinal prognóstico.
The metabolic profiles correlate with the hepatitis C virus infection and are prognostics for the viral reply in chronic patients. However, little is known regarding the distinguishing association between lipid profiles and hepatitis C viral load in patients carrying genotypes 1, 2 or 3. Therefore, the objective of this work was to study viremia and genotypes on the lipid metabolism through the serum lipoprotein variations (total cholesterol, LDL, HDL, VLDL, triglycerides) and apolipoprotein B (Apo B) in chronic carriers of this infection, evaluating if the HCV premakes the individual to the lipidic disequilibrium and favors the appearance of vascular complications. The amostral group consisted of 150 HCV chronic patients with genotypes 1, 2 or 3, and a control group consisted of 20 healthful individuals (10 men and 10 women) in adult age (20 to 50 years). The levels of HDL (28%), VLDL (26%) and triglycerides (26%) of the HCV chronic patients were lower than the control group, while the LDL levels (25%) and the Apo B levels (29%) were higher. These findings were more significant in the genotype 3a carrying patients. Positive correlation occurred between the viremia and the alterations in the Apo B levels (r = 0.5763) in the genotype 1b carrying patients. Consequently it was inferred that the risk of HCV patients to develop vascular complication is elevated. In general, 1% of reduction in the LDL levels is associated with a reduction of 2-3% in the risk of development of cardiac illnesses, and, as about 90% of the protein in the LDL is constituted of apo B, its plasmatic concentration indicates the total potentially atherogenics particles number. The lipid profile aids in the diagnosis of the severity of the hepatic infection and equally acts as a good signal prognostic, therefore its analysis must be carried through in all the cases of advanced hepatic infection.
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20

Lima, Lais Roncalho de [UNESP]. "Imunossensores à base de filmes nanoestruturados de fibroína da seda - peptídeo antigênico NS5A-1-vanadato de ítrio: európio para detecção de Hepatite C." Universidade Estadual Paulista (UNESP), 2014. http://hdl.handle.net/11449/110709.

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Neste trabalho foram investigados a fibroína da seda (silk fibroin, SF) com o peptídeo antigênico da proteína NS5A-1 derivado do vírus da hepatite C (HCV) e nanopartículas de vanadato de ítrio dopadas com európio em filmes nanoestruturados. Dois foram os tópicos abordados: i) interação e organização estrutural do peptídeo com a fibroína. ii) imobilização do peptídeo, da fibroína e nanopartículas em filmes automontados (Layer-by-Layer, LbL), visando estudar a interação específica peptídeo antigênico-anticorpo e a produção de protótipos de imunossensores. As interações fibroína-peptídeo foram estudadas em solução e em filmes LbL pelas técnicas espectroscópicas de dicroísmo circular e luminescência. Os resultados indicaram que há uma mudança conformacional da fibroína em solução para a fibroína em filmes, de aleatória para folha-β, respectivamente, e que o filme de fibroína induz a estrutura secundária do peptídeo que não possui uma conformação bioativa em solução. O crescimento dos filmes LbL foi monitorado por espectroscopia UV-visível, e pôde-se observar um crescimento linear a cada deposição realizada. Além do estudo fundamental das interações a nível molecular, os sistemas foram utilizados para o desenvolvimento de protótipos de imunossensores. A interação peptídeo antigênico-anticorpo foi estudada por medidas de detecção eletroquímica, elétrica e óptica. Para a detecção eletroquímica realizou-se medidas de voltametria cíclica, indicando uma diminuição na corrente quando em presença dos anticorpos anti-HCV e testes em amostras reais soropositivas para o vírus, que indicaram uma maior densidade de elétrons nos voltamogramas referentes às amostras infectadas. A detecção elétrica foi analisada por espectroscopia de impedância elétrica, e observou-se que há um aumento no sinal da capacitância e das perdas dielétricas de acordo com o aumento da concentração...
The present study investigated the silk fibroin (SF) with the antigenic peptide of the NS5A-1 protein of the hepatitis C virus (HCV) and nanoparticles of yttrium vanadate doped with europium immobilized on nanostructured films. Two main topics were explored: i) interaction and structural organization of the peptide with fibroin. ii) immobilization of the peptide together with fibroin and nanoparticles in LbL films (Layer- by- Layer), in order to study the specific interaction peptide antigen-antibody and production of prototype immunosensors. The fibroin-peptide interactions were studied in solution and in LbL films by spectroscopic techniques of circular dichroism and luminescence. The results indicate that there is a conformational change of fibroin in the fibroin solution in film, sheet to random coil-B, respectively, and that the fibroin film induces the secondary structure of the peptide does not possess a bioactive conformation in solution. The growth of the LbL films was monitored by UV-visible spectroscopy, and could observe a linear growth every deposit made. Besides the fundamental study of interactions at the molecular level, the systems were used for the development of prototype immunosensors. The peptide antigen-antibody interaction was studied by electrochemical, electrical and optical detection measures. For electrochemical detection, were made cyclic voltammetry measurements indicating a decrease in current when in the presence of anti-HCV antibodies, and were made tests on real samples seropositive for the virus, which indicated a higher density of electrons in voltammograms respect to infected samples. The electrical detection was analyzed by electrical impedance spectroscopy, and it was observed that there is an increase in the signal of capacitance and the dielectric losses in accordance with the increase in antibody concentration. This increase in signal is higher for films containing smaller number of bilayers and...
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21

Gryninger, Gabriela. "Influência do vírus da hepatite B na infecção crônica pelo vírus da hepatite C : perfil das séricas e histopatologia hepática /." Botucatu : [s.n.], 2009. http://hdl.handle.net/11449/89937.

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Orientador: Jussara Marcondes Machado
Banca: Sueli Aparecida Calvi
Banca: Maria Cassia Jacintho Mendes Correa
Resumo: O vírus da hepatite C é uma das principais causas de doença hepática no mundo inteiro. O estudo histopatológico é de grande importância no prognóstico e indicação de tratamento. A coinfecção com o vírus da hepatite B oculta pode agravar a lesão hepática e diminuir a resposta ao tratamento. As citocinas IL-2, INF, TNF- induzem lesão hepática e fibrose. A IL-10 apresenta atividade antiinflamatória e o TGF- induz o desenvolvimento e depósito de matriz extracelular causando fibrose. Este estudo avaliou, em pacientes com HCC, a presença da hepatite B oculta, a dosagem das citocinas IL-2, INF, TNF , TGF e IL-10, correlacionando com o estágio de fibrose em pacientes tratados e não tratados com interferon, comparando também com indivíduos saudáveis. Foram estudados 55 pacientes com HCC crônica, atendidos na Faculdade de Medicina de Botucatu, excluindo-se pacientes imunossuprimidos e gestantes. O grupo controle foi constituído de 20 indivíduos doadores de sangue. O vírus da hepatite B oculto foi pesquisado por de PCR in house, segundo técnica de Kaneno, com limite de detecção menor que 100 cópias/ml. A dosagem de citocinas foi determinada por método de Elisa. A avaliação da fibrose hepática seguiu aquela proposta pela Sociedade Brasileira de Patologia. Os resultados mostraram predominância do gênero masculino, adulto jovem, 36,4% foram usuários de drogas endovenosas e 41,8% haviam sido hemotransfundidos. Nenhum paciente apresentou coinfecção pelo vírus da hepatite B oculto. Na biópsia hepática predominou fibrose leve ou ausência de fibrose (47,2%). As citocinas analisadas não discriminaram o grau de fibrose nos indivíduos com HCC crônica, mesmo quando separados em pacientes que foram submetidos ao tratamento e pacientes que não receberam o tratamento. Não houve também discriminação das citocinas... (Resumo completo, clicar acesso eletrônico abaixo)
Abstract: The Hepatitis C virus is one of the major causes of hepatic diseases worldwide. Histopathological analyses play a leading role in determining disease outcome and treatment. Co-infection with occult Hepatitis B can aggravate liver injury and diminish treatment response. Cytokines such as IL-2, INF and TNF- induce liver injury and fibrosis. IL-10 has an antiinflamatory action and TGF- induces extracellular matrix development and deposition causing fibrosis. In this study, the presence of occult Hepatitis B and the expression of IL-2, INF, TNF , TGF and IL-10 were assessed in HCC patients and correlated with fibrosis stage in patients treated and non-treated with interferon, as well as healthy individuals. A total of 55 patients with chronic HCC seen at Botucatu Medical School were included. Immunosuppressed or pregnant patients were excluded. The control group consisted of 20 blood donors. The occult Hepatitis B virus was detected by in-house PCR according to the technique of Kaneno with a detection limit < 100 clones/ml. Cytokine levels were determined by the Elisa method. Hepatic fibrosis was assessed as proposed by the Brazilian Society of Pathology. The results showed a predominance of male young adults of whom 36.4% had used endovenous drugs and 41.8% had been hemotransfused. No patient showed occult Hepatitis B co-infection. Hepatic biopsy revealed that fibrosis was either absent or mild in most cases (47.2%). The cytokines under study did not correlate with fibrosis stage in individuals with chronic HCC no matter whether they had or not received treatment. In addition, no correlations with cytokine levels were observed when VHC patients were separated into groups of individuals treated and non-treated with interferon . However, cytokine expressions were significantly increased in all cases in comparison with the control group.
Mestre
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22

Lima, Lais Roncalho de. "Imunossensores à base de filmes nanoestruturados de fibroína da seda - peptídeo antigênico NS5A-1-vanadato de ítrio: európio para detecção de Hepatite C /." Araraquara, 2014. http://hdl.handle.net/11449/110709.

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Orientador: Sidney José Lima Ribeiro
Co-orientador: Marli Leite de Moraes
Banca: Eduardo Maffud Cilli
Banca: Orlando Fatibello Filho
Resumo: Neste trabalho foram investigados a fibroína da seda (silk fibroin, SF) com o peptídeo antigênico da proteína NS5A-1 derivado do vírus da hepatite C (HCV) e nanopartículas de vanadato de ítrio dopadas com európio em filmes nanoestruturados. Dois foram os tópicos abordados: i) interação e organização estrutural do peptídeo com a fibroína. ii) imobilização do peptídeo, da fibroína e nanopartículas em filmes automontados (Layer-by-Layer, LbL), visando estudar a interação específica peptídeo antigênico-anticorpo e a produção de protótipos de imunossensores. As interações fibroína-peptídeo foram estudadas em solução e em filmes LbL pelas técnicas espectroscópicas de dicroísmo circular e luminescência. Os resultados indicaram que há uma mudança conformacional da fibroína em solução para a fibroína em filmes, de aleatória para folha-β, respectivamente, e que o filme de fibroína induz a estrutura secundária do peptídeo que não possui uma conformação bioativa em solução. O crescimento dos filmes LbL foi monitorado por espectroscopia UV-visível, e pôde-se observar um crescimento linear a cada deposição realizada. Além do estudo fundamental das interações a nível molecular, os sistemas foram utilizados para o desenvolvimento de protótipos de imunossensores. A interação peptídeo antigênico-anticorpo foi estudada por medidas de detecção eletroquímica, elétrica e óptica. Para a detecção eletroquímica realizou-se medidas de voltametria cíclica, indicando uma diminuição na corrente quando em presença dos anticorpos anti-HCV e testes em amostras reais soropositivas para o vírus, que indicaram uma maior densidade de elétrons nos voltamogramas referentes às amostras infectadas. A detecção elétrica foi analisada por espectroscopia de impedância elétrica, e observou-se que há um aumento no sinal da capacitância e das perdas dielétricas de acordo com o aumento da concentração...
Abstract: The present study investigated the silk fibroin (SF) with the antigenic peptide of the NS5A-1 protein of the hepatitis C virus (HCV) and nanoparticles of yttrium vanadate doped with europium immobilized on nanostructured films. Two main topics were explored: i) interaction and structural organization of the peptide with fibroin. ii) immobilization of the peptide together with fibroin and nanoparticles in LbL films (Layer- by- Layer), in order to study the specific interaction peptide antigen-antibody and production of prototype immunosensors. The fibroin-peptide interactions were studied in solution and in LbL films by spectroscopic techniques of circular dichroism and luminescence. The results indicate that there is a conformational change of fibroin in the fibroin solution in film, sheet to random coil-B, respectively, and that the fibroin film induces the secondary structure of the peptide does not possess a bioactive conformation in solution. The growth of the LbL films was monitored by UV-visible spectroscopy, and could observe a linear growth every deposit made. Besides the fundamental study of interactions at the molecular level, the systems were used for the development of prototype immunosensors. The peptide antigen-antibody interaction was studied by electrochemical, electrical and optical detection measures. For electrochemical detection, were made cyclic voltammetry measurements indicating a decrease in current when in the presence of anti-HCV antibodies, and were made tests on real samples seropositive for the virus, which indicated a higher density of electrons in voltammograms respect to infected samples. The electrical detection was analyzed by electrical impedance spectroscopy, and it was observed that there is an increase in the signal of capacitance and the dielectric losses in accordance with the increase in antibody concentration. This increase in signal is higher for films containing smaller number of bilayers and...
Mestre
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23

Mandalou, Paraskevi. "Molecular mechanisms of protection from hepatitis C infection." Thesis, University of Plymouth, 2018. http://hdl.handle.net/10026.1/11610.

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Hepatitis C virus (HCV) infection is a major global health burden affecting 1-2% of the world’s population. The majority of infected individuals will develop chronic infection and are at risk of cirrhosis and hepatocellular carcinoma. There is currently no preventative vaccine available for HCV. In the developed world, the highest HCV incidence and prevalence rate is amongst intravenous drug users (IDU). The duration, frequency of IDU, and sharing of drug injecting equipment contribute to particularly high rates of HCV infection in this population. Individuals at high risk of recurrent exposure to HCV infection from long term IDU have been recruited in Plymouth, UK, from 2003 onwards and if they remain negative for HCV infection are termed exposed uninfected (EU). Understanding the factors that prevent HCV infection in this cohort could give valuable insight into the mechanisms of natural resistance to HCV infection. The EU cohort was previously shown to have characteristics attributable to the activation of both the adaptive and the innate arms of the immune system with no known dominant, immune or non- immune, mechanism of HCV protection. The aim of this thesis was to attempt and identify this mechanism and for that purpose a comparative transcriptional profile study was initially performed between 3 groups: EU, individuals who spontaneously cleared HCV infection (SR) and patients with chronic HCV infection (CHCV). Of the differentially regulated genes, the association with resistance to HCV was strongest for Interleukin-27 (IL-27) which was significantly upregulated in EU compared to the 2 other groups and C X C motif chemokine 7 (CXCL7) which was significantly upregulated in EU relative to the CHCV group. The CD28 mediated T-helper cell signalling pathway was significantly upregulated in SR relative to the 2 other groups. We attempted to corroborate the above findings and we demonstrated that IL-27 is overexpressed in EU, compared to SR and CHCV. The possible role of IL-27 in natural protection from HCV infection remains to be elucidated and requires further study.
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24

Ferreira, Ana Rita Filgueiras. "Hepatitis C virus and peroxisomes : evasion from the cellular antiviral response." Master's thesis, Universidade de Aveiro, 2015. http://hdl.handle.net/10773/14348.

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Mestrado em Biomedicina Molecular
Hepatitis C virus (HCV) causes the most prevalent viral infection worldwide. Upon infection, the HCV genome is detected by the RIG-I-MAVS signalling pathway leading to the production of direct antiviral effectors. NS3/4A protease is the main inhibitor of innate immunity against HCV and it was found to inhibit the mitochondrial signalling protein (MAVS). MAVS was recently found to localize at peroxisomes coordinating with mitochondria the activation of effective antiviral response. Peroxisomal MAVS is responsible for inducing a rapid but short termed antiviral response that is IFNindependent, contrary to mitochondrial MAVS which is associated with the activation of an IFN-dependent antiviral response with delayed kinetics. With this work we aimed at evaluating the effect of NS3/4A over the peroxisomal– MAVS pathway. Our results showed that the MAVS localizing exclusively at peroxisomes is targeted by the HCV NS3/4A protease. We also show that the MAVS cleavage by NS3/4A impaired the antiviral response mediated by peroxisomal-MAVS. These results reaffirm the importance of peroxisomes for viral-host interaction and in antiviral defences. Further studies are proposed in order to better understand the role of this organelle in innate immunity. These may lead to the improvement of therapy against HCV infection.
O vírus da hepatite C (VHC) provoca a infeção viral mais prevalente em todo o mundo. Após infeção, o genoma do VHC é detetado pela via de sinalização RIGI- MAVS levando à produção de efetores diretos da resposta antiviral. A protease NS3/4A é o principal inibidor da resposta imune produzido pelo VHC e foi descrito como inibidor da proteína MAVS. A proteína MAVS foi recentemente localizada nos peroxissomas que, juntamente com a mitocôndria, coordenam a resposta antiviral. A MAVS peroxisomal é responsável pela indução de uma resposta antiviral rápida mas de curta duração que é independente de interferões, mas pelo contrário, a MAVS mitocondrial está associada a uma ativação da resposta antiviral que é dependente de interferões mas que se caracteriza por uma cinética retardada. O nosso objetivo com este trabalho consistiu em avaliar o efeito da NS3/4A na via de sinalização coordenada pelos peroxissomas. Os nossos resultados mostram que a MAVS localizada nos peroxissomas é alvo da protease NS3/4A do VHC. Também mostramos que a clivagem da proteína MAVS pela NS3/4A inibe a resposta antiviral mediada pela MAVS peroxissomal. Estes resultados reafirmam a importância dos peroxissomas na interação vírushospedeiro e na defesa antiviral. Futuros estudos são aconselhados para que se compreenda a função dos peroxissomas na imunidade inata. Estes podem levar a uma melhoria na terapia da infeção pelo VHC.
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25

Brandão, Natália Alberto Alves. "Prevalência e fatores associados às infecções pelos vírus das hepatites B e C em pacientes HIV positivos, atendidos na rede pública de Goiânia - Goiás." Universidade Federal de Goiás, 2013. http://repositorio.bc.ufg.br/tede/handle/tede/3534.

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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.
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26

Erup, Louise, Alice Lettius, and Elisabeth Mollberg. "Sjuksköterskans bemötande till patienter med hepatit B och hepatit C : En litteraturstudie." Thesis, Högskolan i Halmstad, Akademin för hälsa och välfärd, 2019. http://urn.kb.se/resolve?urn=urn:nbn:se:hh:diva-41342.

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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.
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Ariede, Jovita Ramos. "Avaliação da carga viral do virus da hepatite C em diferentes compartimentos biológicos : influência na predição da recidiva virológica /." Botucatu, 2013. http://hdl.handle.net/11449/88063.

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Orientador: Rejane Maria Tommasini Grotto
Coorientador: Maria de Moura Campos Pardini
Banca: Giovanni Faria Silva
Banca: Ana Flavia Nacif Pinto coelho Pires
Resumo: A detecção do RNA viral do VHC tem sido documentada em outros compartimentos biológicos além do soro e plasma de pacientes infectados pelo vírus, como nas plaquetas. No entanto, sua influência na terapia antiviral é desconhecida. Poucos estudos têm sido realizados na tentativa de avaliar a quantificação do RNA viral em outros compartimentos biológicos e a significância deste achado no resultado da terapia antiviral. Considerando que o VHC é carreado pelas plaquetas na circulação, a avaliação quantitativa do RNA viral neste compartimento biológico pode se mostrar distinta da observada no plasma.Realizar a avaliação comparativa in vitro do RNA do VHC plasmático e do RNA do VHC carreado à plaqueta e, realizar a avaliação comparativa da quantificação do RNA viral do VHC em plasma e plaquetas de pacientes com recidiva ao tratamento antiviral.Amostras de sangue periférico provenientes de pacientes infectados pelo VHC foram utilizadas para realização de dois experimentos. Experimento in vitro (repetido em triplicata) consistiu na separação de quatro alíquotas da mesma amostra, as quais foram submetidas a incubação a 37oC por 30xg por diferentes intervalos de tempo (0, 48, 96, 144h) e, posteriormente separadas para obtenção de plasma e pellet de plaquetas. A partir de cada uma destas frações foi extraído RNA viral, o qual foi utilizado como fonte para qPCR. Experimento in vivo: Foram acompanhados pacientes que iniciaram e finalizaram a terapêutica entre janeiro de 2011 a julho de 2012 e, dentre estes, os que apresentaram recidiva virológica ao tratamento antiviral estabelecido. Dos pacientes em recidiva virológica foram processadas amostras para a obtenção do plasma e pellet de plaquetas em dois momentos: no momento da recidiva virológica e, no momento imediatamente anterior (12 semanas anteriores... (Resumo completo, clicar acesso eletrônico abaixo)
Abstract: Treatment for chronic hepatitis C is effective in about 50% of patients treated with exogenous interferon, which induces interferon-stimulated genes leading to endogenous interferon production. Integrins are involved in interferon production and structural modifications of them can be associated with altered function. Some integrins, expressed on the platelet membrane, show polymorphic antigenic determinants called human platelet antigens (HPA). The association between HCV infection and HPA-5b has already been demonstrated, in the same way the HPA profile could be associated with therapeutic response. This study aimed evaluates the association between the HPA-1, -3, -5 frequencies and therapy response in HCV-infected patients. HPA genotyping was performed in 168 HCV-infected patients by PCRSSP or PCR-RFLP. The patients were on interferon- (48.8%: 43.9% carriers of HCV genotype 1 and 56.1% non-1) or peginterferon (51.2%; 87.2% carriers of HCV genotype 1 and 12.8% non-1), both combined with ribavirin. Statistical analysis was performed using the proportional odds model. The genotypic frequency of HPA-1a/1b was significantly higher in the patients with therapeutic failure (odds ratio=3.58, 95% CI -1.18 - 10.82). The results suggest that the HPA-1a/1b genotype is associated with therapy failure... (Complete abstract click electronic access below)
Mestre
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28

Bengsch, Bertram. "CD8+ T Zelldifferenzierung bei der Hepatitis B- und Hepatitis C-Virusinfektion." [S.l. : s.n.], 2007. http://nbn-resolving.de/urn:nbn:de:bsz:25-opus-60765.

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29

Moraes, Camila Fernanda Verdichio de. "Antígeno plaquetários humanos (HPA) em portadores do vívus da hepatite c (HCV) /." Botucatu : [s.n.], 2009. http://hdl.handle.net/11449/102625.

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Resumo: A Hepatite C é uma das principais causas de doença crônica hepática. A combinação entre o interferon peguilado e a ribavirina tem sido considerado o padrão-ouro de tratamento para Hepatite C. A resposta ao tratamento vem sendo associada a fatores ambientais, do vírus e também do paciente, tais como polimorfismos genéticos dos antígenos leucocitários humanos (HLA), da interleucina-10 e do fator de necrose tumoral-a. Plaquetas possuem em suas membranas glicoproteínas que expressam segmentos protéicos polimórficos, os quais são chamados de antígenos plaquetários humanos (HPA). Os sistemas HPA-1, -3, -4 e -5 residem em integrinas, proteínas que possuem interações com interferon. O objetivo desse estudo foi avaliar a associação entre freqüência dos HPA-1, -3, -4 e -5 e a resposta ao tratamento, em 138 pacientes tratados para Hepatite C. A genotipagem dos HPA-1, -3 e -4 foi realizada pela técnica de PCR-SSP e do HPA-5 pela PCR-RFLP. A genotipagem do HCV foi realizada através do Kit comercial INNO-LiPA® v.1.0 (Innogenetics, Ghent, Belgium), segundo as instruções do fabricante. Os pacientes foram divididos em grupos e subgrupos de acordo com o esquema terapêutico, a resposta ao tratamento e o genótipo do HCV. Os pacientes que possuíam o genótipo do HCV não-1 e que foram tratados com IFN-a+RBV, com falha terapêutica, apresentaram uma diferença estatística significante (p<0.05) nas freqüências alélicas e genotípicas do sistema HPA-3, com aumento do alelo 3b. O sistema HPA-3 está localizado em uma integrina que se liga a fibronectina, um receptor de interferon. Nesse contexto, a alteração conformacional glicoprotéica decorrente da presença do alelo HPA-3b, poderia estar associada à falha ao tratamento com IFN-a+RBV em pacientes portadores de genótipo viral não-1.
Abstract: Hepatic fibrosis leading cirrhosis in 20 to 30% of patients with chronic hepatitis C virus (HCV) infection. Rapid progression to fibrosis has been related to environmental, viral and host factors. However, genetic polymorphisms have recently been associated with this progression, including the expression of integrins. Platelet membrane glycoproteins express several polymorphic antigenic determinants on their surface, which are called human platelet antigens (HPA). HPA-1, -3, -4 and -5 reside in integrins. The association between HPA antigens and stage of fibrosis can determine if HPA is related to progression of fibrosis. Thus, the goal of this study was to determine the association between the HPA-1, -3, -4 and -5 and the liver fibrosis stage in 175 HCV-infected patients. HPA-1, -3 and -4 genotyping was performed by PCR-SSP and, HPA-5 by PCR-RFLP. Fibrosis progression was evaluated using the METAVIR scoring system. There were no significant differences (p>0.05) in allelic and genotypic frequency distribution of HPA-1, -3 and -5, residing in integrins.
Orientador: Maria Inês de Moura Campos Pardini
Coorientador: Giovanni Faria Silva
Banca: Rejane M. T. Grotto
Banca: Paula Rahal
Banca: Ricardo Alberto Moliterno
Banca: Fernando Lopes Gonçalves Junior
Doutor
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30

Mohamed, Gibrial Saleh. "Hepatitis C virus infection in Libya." Thesis, King's College London (University of London), 1996. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.518840.

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31

Glacken, Michèle. "Fatigue in the hepatitis C population." Thesis, University of Ulster, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.268535.

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Sweeting, Michael John. "Statistical modelling in hepatitis C epidemiology." Thesis, University of Cambridge, 2008. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.612187.

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33

Cramer, Janina. "Funktionelle Charakterisierung der RNA-abhängigen RNA-Polymerase des Hepatitis-C-Virus Untersuchung molekularer Mechanismen der Substratspezifität von DNA-abhängigen DNA-Polymerasen /." [S.l. : s.n.], 2004. http://deposit.ddb.de/cgi-bin/dokserv?idn=971700796.

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34

Yuen, King-tai, and 袁敬弟. "A study of pharmacogenomics for therapeutic and prognostic guidance towards hepatitis C virus (HCV) for patients co-infected with HIV." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2013. http://hdl.handle.net/10722/193555.

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The cost effectiveness of using novel HCV treatment option, telaprevir and boceprevir, should depend on patients’ respond to conventional PEG-INFα and ribavirin therapy. The study of pharmacogenomics, interleukin-28B (IL-28B) polymorphisms, accompanied with the information of HCV genotypes are suggested to have the strongest predictive value of treatment outcomes and prognosis of disease in individuals infected with HCV who are undergoing conventional PEG-INFα and ribavirin therapy. It is extremely valuable in HCV/HIV co-infected patients as these groups of patients require a complex treatment regimen and demonstrate poor sustained viral response (SVR) rate. The development of a fast and promising IL-28B genotyping assay is urgently needed. A total of 47 blood samples randomly selected from HCV and HIV co-infected patients were used in this investigation. The aims of this study are to evaluate and compare the performance of newly developed IL-28B HybProbe real-time PCR assay using LightCycler® system against Sanger Sequencing method in determining IL-28B polymorphisms on rs12979860 and rs8099917 and to estimate the prevalence of IL-28B polymorphisms among HCV/HIV co-infected patients in Hong Kong. In addition, the genotypic distribution of HCV among the same patient group is identified by using in-house Sanger Sequencing method. It was found that the newly developed IL-28B real-time HybProbe assay resulted in 100% concordance with the traditionally used Sanger Sequencing method. The allele frequencies of C and T were 96% and 4% in rs12979860 and T and G were 97% and 3% in rs8099917 respectively. The CC and TT wild type are predominating in rs12979860 and rs8099917 with frequencies of 93.62% and 95.74% respectively. The most favorable compound genotype CC/TT with both homozygous wild types on both SNPs was the most predominant type with a high prevalence of 93.61%. Among all the samples, 50% samples were found to be HCV genotype 1, 41.18% were genotype 6 and 8.82% were genotype 3. A simple and efficient IL-28B real-time HybProbe assay was developed in this study and proved to show excellent performance on IL-28B genotyping although further optimization is suggested before it can be applied in the clinical setting. The favourable wild type genotypes of rs12979860 and rs8099917 accounted for the most predominant genotypes which is similar to other findings obtained from an Asian population. A comparatively high prevalence of HCV genotype 6 was found in the HCV/HIV co-infected group. Future study with the information of treatment outcomes (HCV viral load) can further evaluate the predictive value of IL-28B polymorphisms on SVR in different HCV genotypes.
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35

Verbaan, Hans. "Chronic hepatitis C infection with special reference to prevalence, aggravating factors and longterm outcome /." Lund : Gastroenterology and Hepatology Division, Dept. of Medicine, University Hospital, Lund University, 1997. http://books.google.com/books?id=SBdrAAAAMAAJ.

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36

Maia, Sarah Cristina Oliveira Machado. "Análise de custo-efetividade do tratamento da hepatite C crônica genótipo 1: comparação da adição do boceprevir a terapia padrão (interferon-α peguilado e ribavirina)." Universidade de São Paulo, 2015. http://www.teses.usp.br/teses/disponiveis/9/9139/tde-16062015-140318/.

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A hepatite C afeta cerca de 150 milhões de pessoas no mundo e é a razão mais comum de transplantes de fígado. A erradicação viral, por meio de tratamento medicamentoso, é a única intervenção que pode deter a progressão da doença, reduzir a mortalidade e melhorar a qualidade de vida dos pacientes. Em 2011, foi aprovado o boceprevir, um inibidor de protease, que passou a ser adicionado à terapia padrão dupla (interferon peguilado e ribavirina) pelo Protocolo Clínico brasileiro para tratamento de Hepatite C genótipo 1 em pacientes com grau de fibrose maior que F2. Devido ao alto custo de aquisição deste medicamento e à produção cada vez maior de novas tecnologias para essa área terapêutica, foi proposta essa pesquisa que tem como objetivo analisar o custo-efetividade da terapia tripla em relação à terapia dupla, no tratamento da hepatite C crônica genótipo 1 em pacientes virgens de tratamento para todos os graus de fibrose. Para tanto, foi construído um modelo de Markov com 15 estados de saúde representando a história natural da Hepatite C crônica. O modelo seguiu uma coorte hipotética pela vida toda, em que os custos foram expressos em Reais e os desfechos em anos de vida ganhos. A perspectiva adotada foi a do SUS. A RCEI calculada, com taxa de desconto de 5% para custos e desfechos, foi R$ 201.504,92 por ano de vida ganho. Considerando um limiar de custo efetividade de 3 vezes o valor do PIB per capita, segundo recomendação da OMS, a adição do boceprevir não foi custo-efetiva no tratamento de pacientes virgens em todos os graus de fibrose. Pela análise de sensibilidade, nenhuma variável teve grande impacto na RCEI, exceto quando a taxa de desconto aplicada em desfechos foi zerada, em que a terapia tripla passou a ser custo-efetiva.
The Hepatitis C virus affects around 150 million of people worldwide and it is the most common reason for liver transplantation. Viral eradication, by drug treatment, is the only therapeutic intervention that may halt the disease progression, reduce HCV-related mortality and improve the quality of life of infected patients. Boceprevir, a protease inhibitor, was approved in 2011, being to be added to standard of care (peguilated interferon-α and ribavirin) by the Brazilian Protocol of treatment of genotype 1 Hepatitis C, in patients with degree of fibrosis greater than F2. Due to the high cost of acquisition of this drug and the increasing production of new technologies in this therapeutic area, the aim of this work was develop a cost-effectiveness analysis, comparing the triple therapy with the standard of care (double therapy) for treatment of genotype 1 chronic hepatitis C in treatment-naïve patients of all degrees of fibrosis. It was constructed a Markov Model with 15 health states representing the natural history of chronic Hepatitis C. The model followed a hypothetic cohort by lifetime, where costs were expressed in Reais and outcomes in life-years gained, under the perspective of Brazilian public health system. The calculated ICER, with discount rate of 5% to costs and outcomes, was R$201.504, 92 by life-years gained. Considering three times GDP per capita for cost-effectiveness threshold, according WHO recommendation, boceprevir was not cost-effective, when considered treatment-naïve patients of all degrees of fibrosis. By sensitivity analysis, none of the variables had a big impact in the ICER, except when it was stopped applying the discount rate in outcomes, in which the triple therapy became cost-effective.
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37

Tyler, Darlene Fay. "Knowledge about hepatitis C virus infection and health care utilization for hepatitis C infection among homeless adults." Diss., Restricted to subscribing institutions, 2009. http://proquest.umi.com/pqdweb?did=1835641801&sid=1&Fmt=2&clientId=1564&RQT=309&VName=PQD.

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38

Barbosa, Alexandre Naime [UNESP]. "Avaliação das citocinas (ELISA e RT-PCR) e da fibrose hepática na coinfecção pelo HIV e vírus da hepatite C." Universidade Estadual Paulista (UNESP), 2010. http://hdl.handle.net/11449/101466.

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Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Universidade Estadual Paulista (UNESP)
A aids e a hepatite C crônica são infecções caracterizadas por importante processo inflamatório contínuo, regulado por uma complexa interação entre citocinas. A persistência da atividade inflamatória crônica está intimamente relacionada com a progressão da patogênese da aids, bem como na indução de fibrose na hepatite C. Com o objetivo de avaliar o padrão de citocinas na infecção pelo HIV e na hepatite C crônica, as citocinas IL-2, IL-4, IL-10, TNF-α, INF-γ, TGF-β foram dosadas por Elisa e RT-PCR em cinco grupos: pacientes coinfectados pelo HIV/VHC (n=22), monoinfectados pelo HIV com supressão virológica pelo tratamento, e sem supressão virológica (n=17), monoinfectados pelo VHC (n=22) e um grupo controle composto por indivíduos doadores de sangue (n=10). IL-4 e IL-10 estiveram aumentadas consistentemente nos quatro grupos de estudo, determinando predomínio do perfil Th-2. INF-γ, TNF-α e TGF-β estiveram aumentados apenas nos grupos com infecção pelo VHC, com ou sem coinfecção pelo HIV. No grupo de monoinfectados pelo HIV com supressão virológica, a IL-2 dosada por RT-RCR esteve aumentada, porém os níveis séricos dosados por Elisa estavam normais. A alta produção de citocinas pró-inflamatórias INF-γ, TNF-α e TGF-β nos dois grupos de pacientes com infecção pelo VHC refletem o processo progressivo de acúmulo de inflamação e fibrose hepática. Já o predomínio de IL-4 e IL-10 em todos os grupos, citocinas ligadas ao perfil Th-2, demonstram a incapacidade de produção de uma resposta citotóxica Th-1, perpetuando a infecção e a inflamação crônica, mesmo naqueles indivíduos com supressão virológica pelo tratamento. Além de drogas antivirais, novos tratamentos imunomoduladores têm sido propostos para a erradicação viral, ou a interrupção das lesões causadas pelo estado inflamatório crônico...
Both AIDS and chronic hepatitis C (HCV) are characterized by continuous inflammatory process, regulated by a complex interaction between cytokines. The persistence of chronic inflammatory activity is closely related to the progression of the pathogenesis of AIDS, as well as the induction of fibrosis in HCV. In order to analyze the role of cytokines in HIV/HCV coinfection and the fibrosis progression, IL-2, IL-4, IL-10, TNF- α, INF-γ, TGF-β were measured by ELISA and RT -PCR in five groups: HIV/HCV coinfected patients (n = 22), HCV monoinfected patients (n = 22), HIV monoinfected patients with and without virological suppression (n = 17) and a control group composed by blood donors (n = 10). Hepatic biopsy and METAVIR classification were performed in all HCV patients (n=44). The baseline characteristics (sex, age and race) of all groups were similar. No correlations were found between cytokines and hepatic fibrosis. IL-4 and IL-10 were consistently increased in the four study groups, findings associated to a Th-2 profile. INF- γ, TNF-α and TGF-β were increased only in groups with HCV infection. In the group of HIV monoinfected patients with virological suppression, IL-2 measured by RT-RCR was increased, but serum levels measured by ELISA were normal. The high production of proinflammatory cytokines INF-γ, TNF-α and TGF-β in two groups of patients with HCV infection reflect the gradual process of inflammation and liver fibrosis. The predominance of IL-4 and IL-10 in all study groups demonstrates an inability to promote a cytotoxic Th-1 response. Even in HIV monoinfected patients with virological suppression with increased IL-2 expression, Th-2 cytokines were the predominant, perpetuating the chronic inflammation. In addition to antiviral drugs, new immunomodulatory treatments have been proposed... (Complete abstract click electronic access below)
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39

Barbosa, Alexandre Naime. "Avaliação das citocinas (ELISA e RT-PCR) e da fibrose hepática na coinfecção pelo HIV e vírus da hepatite C /." Botucatu : [s.n.], 2010. http://hdl.handle.net/11449/101466.

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Orientador: Domingues Alves Meira
Banca: Alexandrina Sartori
Banca: Ricardo Sobhie Diaz
Banca: Fernando Lopes Gonçalves Júnior
Resumo: A aids e a hepatite C crônica são infecções caracterizadas por importante processo inflamatório contínuo, regulado por uma complexa interação entre citocinas. A persistência da atividade inflamatória crônica está intimamente relacionada com a progressão da patogênese da aids, bem como na indução de fibrose na hepatite C. Com o objetivo de avaliar o padrão de citocinas na infecção pelo HIV e na hepatite C crônica, as citocinas IL-2, IL-4, IL-10, TNF-α, INF-γ, TGF-β foram dosadas por Elisa e RT-PCR em cinco grupos: pacientes coinfectados pelo HIV/VHC (n=22), monoinfectados pelo HIV com supressão virológica pelo tratamento, e sem supressão virológica (n=17), monoinfectados pelo VHC (n=22) e um grupo controle composto por indivíduos doadores de sangue (n=10). IL-4 e IL-10 estiveram aumentadas consistentemente nos quatro grupos de estudo, determinando predomínio do perfil Th-2. INF-γ, TNF-α e TGF-β estiveram aumentados apenas nos grupos com infecção pelo VHC, com ou sem coinfecção pelo HIV. No grupo de monoinfectados pelo HIV com supressão virológica, a IL-2 dosada por RT-RCR esteve aumentada, porém os níveis séricos dosados por Elisa estavam normais. A alta produção de citocinas pró-inflamatórias INF-γ, TNF-α e TGF-β nos dois grupos de pacientes com infecção pelo VHC refletem o processo progressivo de acúmulo de inflamação e fibrose hepática. Já o predomínio de IL-4 e IL-10 em todos os grupos, citocinas ligadas ao perfil Th-2, demonstram a incapacidade de produção de uma resposta citotóxica Th-1, perpetuando a infecção e a inflamação crônica, mesmo naqueles indivíduos com supressão virológica pelo tratamento. Além de drogas antivirais, novos tratamentos imunomoduladores têm sido propostos para a erradicação viral, ou a interrupção das lesões causadas pelo estado inflamatório crônico... (Resumo completo, clicar acesso eletrônico abaixo)
Abstract: Both AIDS and chronic hepatitis C (HCV) are characterized by continuous inflammatory process, regulated by a complex interaction between cytokines. The persistence of chronic inflammatory activity is closely related to the progression of the pathogenesis of AIDS, as well as the induction of fibrosis in HCV. In order to analyze the role of cytokines in HIV/HCV coinfection and the fibrosis progression, IL-2, IL-4, IL-10, TNF- α, INF-γ, TGF-β were measured by ELISA and RT -PCR in five groups: HIV/HCV coinfected patients (n = 22), HCV monoinfected patients (n = 22), HIV monoinfected patients with and without virological suppression (n = 17) and a control group composed by blood donors (n = 10). Hepatic biopsy and METAVIR classification were performed in all HCV patients (n=44). The baseline characteristics (sex, age and race) of all groups were similar. No correlations were found between cytokines and hepatic fibrosis. IL-4 and IL-10 were consistently increased in the four study groups, findings associated to a Th-2 profile. INF- γ, TNF-α and TGF-β were increased only in groups with HCV infection. In the group of HIV monoinfected patients with virological suppression, IL-2 measured by RT-RCR was increased, but serum levels measured by ELISA were normal. The high production of proinflammatory cytokines INF-γ, TNF-α and TGF-β in two groups of patients with HCV infection reflect the gradual process of inflammation and liver fibrosis. The predominance of IL-4 and IL-10 in all study groups demonstrates an inability to promote a cytotoxic Th-1 response. Even in HIV monoinfected patients with virological suppression with increased IL-2 expression, Th-2 cytokines were the predominant, perpetuating the chronic inflammation. In addition to antiviral drugs, new immunomodulatory treatments have been proposed... (Complete abstract click electronic access below)
Doutor
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40

Schweller, Mariana Salhab Dall' Aqua 1986. "Prevalência e características clínico epidemiológicas de gestantes com hepatite C atendidas no CAISM - UNICAMP = Prevalence and clinical epidemiological features of hepatitis C infection among pregnant women at CAISM - UNICAMP." [s.n.], 2015. http://repositorio.unicamp.br/jspui/handle/REPOSIP/312687.

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Orientador: Helaine Maria Besteti Pires Mayer Milanez
Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas
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Resumo: Introdução: A Hepatite C é um dos maiores problemas atuais de saúde pública, com mais de 150 milhões de pessoas contaminadas. A evolução da doença geralmente é assintomática e suas complicações são cirrose, fibrose hepática e hepatocarcinoma. Na gestação o tratamento não é recomendado, com possível piora da doença no período. Objetivo: identificar a prevalência de Hepatite C em gestantes que realizaram acompanhamento pré-natal no Hospital da Mulher Professor José Aristodemo Pinotti - Centro de Atenção Integral à Saúde da Mulher (CAISM) da UNICAMP, analisando dados clínicos, epidemiológicos e resultados perinatais. Metodologia: estudo de corte transversal cuja amostra foi composta por gestantes atendidas nos ambulatórios de pré-natal do CAISM entre 2005 e 2014 com sorologia positiva para Hepatite C. As pacientes foram identificadas através de listas informatizadas do serviço, e seus prontuários levantados para análise de dados sociodemográficos, epidemiológicos e desfechos perinatais. A análise dos dados foi feita através da distribuição percentual ou de médias. Resultados: na população de 29.327 gestantes atendidas pelo pré-natal entre 2005 e 2014, a prevalência de Hepatite C foi de 0,2%. Das 47 mulheres incluídas no estudo, a idade média foi de 32,5 anos, houve 49% de prevalência de baixa escolaridade, metade das participantes não planejaram a gestação, sendo que 38% destas não faziam uso de métodos contraceptivos. Além disso, 34% apresentaram coinfecção pelo HIV e 34% relataram uso de drogas. O número médio de gestações por paciente foi 3. Não se observou um pior desfecho perinatal, com peso médio de 2827,5 gramas ao nascimento e idade gestacional média de 39 semanas e 4 dias. Conclusões: Entre as pacientes infectadas pelo vírus C, observamos maior prevalência da raça branca, baixa escolaridade e coinfecção com HIV. Como principais fatores de risco para contaminação pela doença, foram identificados o uso de drogas, histórico de transfusões sanguíneas e a coinfecção com o HIV. Além disso, foram observadas maiores taxas de aborto, cesáreas e prematuridade neonatal em relação a outros estudos, fatores relacionados ao aumento da morbimortalidade materna, fetal e neonatal
Abstract: Introduction: Hepatitis C is a leading public health problem, with more than 150 million people infected. Disease evolution is usually asymptomatic, and complications are cirrhosis, liver fibrosis and hepatocellular carcinoma. Treatment is not recommended during pregnancy, but it may influence disease evolution. Objective: To identify Hepatitis C prevalence in pregnant women attended at Professor Doctor José Aristodemo Pinotti Women's Integrated Healthcare Center (CAISM) of the UNICAMP Medical School during prenatal period, analyzing clinical and epidemiological data, including perinatal outcomes. Methods: Authors performed a cross-sectional study with pregnant women who tested positive for Hepatitis C and gave birth at CAISM, between 2005 and 2014. Demographic, epidemiological and perinatal data were extracted from each patient¿s hospital records. Data analysis was made through media or percentage distribution. Results: Among 29.327 women treated at CAISM between 2005 and 2014, Hepatitis C prevalence was 0,2%. The mean maternal age at delivery was 32.5 years, 49% had low education and 49% did not plan the pregnancy. Among them, 38% did not use contraceptive methods. In addition, 34% had coinfection with HIV and 34% reported use of drugs. The average number of pregnancies per woman was 3, and there was no significant evidence of disease influence in pregnancy outcomes. Newborns¿ average weight was 2,827.5 grams, and the average of the gestational age was 39 weeks and 4 days. Conclusions: Among patients infected with Hepatitis C, there was predominance of the white race, low education and HIV coinfection. Drug addiction, blood transfusions and HIV co-infection were the main risk factors for contamination. When compared with other similar studies, this study found higher rates of abortion, cesarean sections and neonatal prematurity. These factors are associated with perinatal morbidity and mortality
Mestrado
Saúde Materna e Perinatal
Mestra em Ciências da Saúde
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41

Boner, Winifred. "HBV pre-C/C variation : geographical and functional aspects." Thesis, University of Glasgow, 1997. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.360172.

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42

Laestadius, Hanna, and Berfin Güven. "Hur patienter med hepatit B och hepatit C upplever bemötandet av omvårdnadspersonal." Thesis, Uppsala universitet, Institutionen för folkhälso- och vårdvetenskap, 2019. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-397661.

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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.
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43

Ariede, Jovita Ramos [UNESP]. "Avaliação da carga viral do virus da hepatite C em diferentes compartimentos biológicos: influência na predição da recidiva virológica." Universidade Estadual Paulista (UNESP), 2013. http://hdl.handle.net/11449/88063.

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A detecção do RNA viral do VHC tem sido documentada em outros compartimentos biológicos além do soro e plasma de pacientes infectados pelo vírus, como nas plaquetas. No entanto, sua influência na terapia antiviral é desconhecida. Poucos estudos têm sido realizados na tentativa de avaliar a quantificação do RNA viral em outros compartimentos biológicos e a significância deste achado no resultado da terapia antiviral. Considerando que o VHC é carreado pelas plaquetas na circulação, a avaliação quantitativa do RNA viral neste compartimento biológico pode se mostrar distinta da observada no plasma.Realizar a avaliação comparativa in vitro do RNA do VHC plasmático e do RNA do VHC carreado à plaqueta e, realizar a avaliação comparativa da quantificação do RNA viral do VHC em plasma e plaquetas de pacientes com recidiva ao tratamento antiviral.Amostras de sangue periférico provenientes de pacientes infectados pelo VHC foram utilizadas para realização de dois experimentos. Experimento in vitro (repetido em triplicata) consistiu na separação de quatro alíquotas da mesma amostra, as quais foram submetidas a incubação a 37oC por 30xg por diferentes intervalos de tempo (0, 48, 96, 144h) e, posteriormente separadas para obtenção de plasma e pellet de plaquetas. A partir de cada uma destas frações foi extraído RNA viral, o qual foi utilizado como fonte para qPCR. Experimento in vivo: Foram acompanhados pacientes que iniciaram e finalizaram a terapêutica entre janeiro de 2011 a julho de 2012 e, dentre estes, os que apresentaram recidiva virológica ao tratamento antiviral estabelecido. Dos pacientes em recidiva virológica foram processadas amostras para a obtenção do plasma e pellet de plaquetas em dois momentos: no momento da recidiva virológica e, no momento imediatamente anterior (12 semanas anteriores...
Treatment for chronic hepatitis C is effective in about 50% of patients treated with exogenous interferon, which induces interferon-stimulated genes leading to endogenous interferon production. Integrins are involved in interferon production and structural modifications of them can be associated with altered function. Some integrins, expressed on the platelet membrane, show polymorphic antigenic determinants called human platelet antigens (HPA). The association between HCV infection and HPA-5b has already been demonstrated, in the same way the HPA profile could be associated with therapeutic response. This study aimed evaluates the association between the HPA-1, -3, -5 frequencies and therapy response in HCV-infected patients. HPA genotyping was performed in 168 HCV-infected patients by PCRSSP or PCR-RFLP. The patients were on interferon- (48.8%: 43.9% carriers of HCV genotype 1 and 56.1% non-1) or peginterferon (51.2%; 87.2% carriers of HCV genotype 1 and 12.8% non-1), both combined with ribavirin. Statistical analysis was performed using the proportional odds model. The genotypic frequency of HPA-1a/1b was significantly higher in the patients with therapeutic failure (odds ratio=3.58, 95% CI -1.18 – 10.82). The results suggest that the HPA-1a/1b genotype is associated with therapy failure... (Complete abstract click electronic access below)
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44

Smith, Jennifer. "Viral diversity and dynamics of hepatitis C virus." Thesis, University of Oxford, 2011. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.559853.

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Complex patterns of HCV infection are increasingly reported, particularly in highly exposed individuals, with multiple and variable subtype profiles seen in many chronic patients. This study aims to address some of the questions arising from this increasingly diverse and dynamic picture, both within hosts and at a population level. In Chapter 2 I find evidence for a highly dynamic infection profile in acute HCV, both in terms of viral load and the dominant subtype. I extrapolate these observations from individual patients to formulate a model of HCV transmission across a high-risk population in order to predict the impact of current and anticipated interventions in Chapters 3 and 4. I show that antiviral therapy and a putative vaccination can still have a significant impact on HCV prevalence at the population level, even when the latter offers only partial protection and in the epidemiological background of ongoing exposure. Thus, in an epidemic with more than one circulating strain it will be crucial for any individual or combination of interventions to target all variants present. In Chapter 5 I demonstrate that early viral load kinetics of patients initiating treatment are indicative of treatment outcome. Strain differences are also evident in the virologic response to treatment with hard-to-treat genotype 1 exhibiting a slower rate of viral load decline than genotypes 2 and 3.
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45

Polis, Suzanne Public Health &amp Community Medicine Faculty of Medicine UNSW. "Hepatitis B and hepatitis C virus in an antenatal population : an epidemiological study." Awarded by:University of New South Wales. School of Public Health and Community Medicine, 2005. http://handle.unsw.edu.au/1959.4/22035.

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Although Australian epidemiology of HBV and HCV has been well described for populations groups at higher risk, but the information available for groups generally considered to be lower risk is much more limited. An understanding of the prevalence of these infections and their risk factors in antenatal women is important to guide testing policy and practice. A study was therefore conducted of the epidemiology of hepatitis B and hepatitis C infection in women. In addition, women were asked about their experience with antenatal testing. A total of 516 women participated in the survey, of these 479 (95%) women had been tested for HCV antibodies .The prevalence of HCV antibodies was 4% overall, and 2% among women who were unaware of their HCV status prior to their antenatal test. A history of injecting drug use and residing with a HCV positive person were significantly associated with HCV infection in multivariate analyses. HBV testing was conducted in 468 (99.6%) of women, and the overall prevalence was 2%. Risk factors identified were birthplace in countries of South East Asia. Women were asked about their perception of antenatal testing and pre-test information. Nearly a third (143, 30.5%) of women who had been tested for HCV infection either said that they did not know whether they had been tested, or said that they had declined testing. The corresponding proportion for HBV infection was 28.8% (135). Over 65% and 66% of women said that had not received any information about testing for HCV and HBV respectively. The finding that virtually all antenatal women were being tested for HCV was in contrast to government and non-government organisation policies of ???selective??? screening in place during the study period. Of concern was the substantial proportion of women who were tested despite reporting that they had declined their clinician???s offer to test for HCV and HBV, and the large number of women who reported an absence of pre-test information. Women who said they had received information reported the delivery and quality of information varied according to the antenatal clinician group, but perceived the overall quality as poor.
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46

Christie, John Michael Landale. "Viral persistence in hepatitis C virus infection." Thesis, University of Southampton, 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.268465.

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47

Jones, Louisa Alice School of Biotechnology And Biomolecular Sciences UNSW. "Aptamers to the hepatitis C virus polymerase." Awarded by:University of New South Wales. School of Biotechnology And Biomolecular Sciences, 2005. http://handle.unsw.edu.au/1959.4/32734.

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Treatments for the hepatitis C virus (HCV) are currently only partially effective. Research into antivirals directed at HCV viral proteins are commonly based and tested on a single genotype, namely genotype 1. This is despite the high level of variability of the RNA virus and the frequency of infection with genotypes other than 1. The systematic evolution of ligands by exponential enrichment (SELEX) is a novel in vitro approach for the isolation of antiviral agents. SELEX allows rapid screening of vast nucleic acid libraries to isolate sequences (termed aptamers) that bind to target proteins with high affinity. The SELEX approach was used in the present study to isolate DNA aptamers to the RNAdependent RNA polymerase (RdRp) [non-structural protein B (NS5B)] protein of HCV subtype 3a, with the aim of inhibiting polymerase activity. Ten rounds of selection were performed using a Biacore 2000 and resultant aptamers cloned from rounds 2, 4, 8 and 10. Sequences of aptamers were aligned to elucidate common motifs and a proportion of the aptamers from rounds 8 and 10 (29/48) were screened for binding ability using the Biacore. The five ???best binding??? aptamers were investigated for inhibition of 3a polymerase activity in an in vitro polymerase assay. Two aptamers, r10/43 and r10/47, were chosen for further studies based on their ability to inhibit polymerase activity. The inhibition constants (Ki) of r10/43 and r10/47 were estimated to be 1.4 + 2.4 nM and 6.0 + 2.3 nM respectively. The affinity (Kd) of these aptamers for the 3a polymerase was estimated to be 1.3 + 0.3 nM (r10/43) and 23.5 + 6.7 nM (r10/47). The estimated inhibition and dissociation constants of these two aptamers are among the best for inhibitory aptamers of the HCV enzymes (polymerase and protease). Inhibition of HCV 3a polymerase appeared to be specific for r10/47, whilst r10/43 also had some inhibitory effect on norovirus and ??6 polymerase activity. This study is the first description of an inhibitor to the HCV subtype 3a polymerase that investigates genotypic specificity of targeted antivirals.
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48

Post, Jeffrey John Medical Sciences Faculty of Medicine UNSW. "Primary hepatitis C virus infection in prisons." Awarded by:University of New South Wales. Medical Sciences, 2008. http://handle.unsw.edu.au/1959.4/41511.

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Infection with hepatitis C virus (HCV) causes significant morbidity and mortality. An understanding of the factors associated with both acquisition and clearance of HCV infection is critical to prevention strategies including vaccine development. Although research in the prison environment is logistically challenging, inmates are a premier risk group. Accordingly, a prospective cohort study of prisoners with monthly sampling for HCV viraemia was undertaken to assess the incidence of, and risk factors for, infection; and to assess the natural history of infection when detected by viraemia. The incidence of infection was 8 per 100 person years, with the incidence of "high risk" and "possible" HCV transmission risk events being 61 and 210 per 100 person years respectively. The first case of HCV infection in prison with tattooing as the probable route of acquisition was reported. A novel phenotype of HCV infection with HCV viraemia and subsequent clearance without the development of symptoms, biochemical hepatitis or seroconversion on HCV specific enzyme immunoassay (EIA), despite more than one year of follow-up, was reported. HCV-specific cell mediated immune responses were detected in the subjects analysed. These subjects also had indeterminate HCV serological responses directed against non-structural proteins detected on a recombinant immunob10t assay (RIBA) that were stable over time and typically predated HCV viraemia. The prevalence of such responses ranged from 29-79% in other relevant cohorts, including injecting drug users (IDUs) and multiply-transfused patients with thalassaemia. The antibody response against the non-structural protein, NS5 was the most reproducible. This reactivity was blocked in 57% of subjects when sera were pre-incubated with recombinant HCV proteins, suggesting HCV-specificity. A case-control study was undertaken to examine whether such responses predicted protection from "classical" HCV infection with EIA seroconversion. Cases that developed HCV viraemia and EIA seroconversion were more likely to have these responses at baseline (when aviraemic) than controls, demonstrating that they do not protect against acute infection. However, the rate of viral clearance in subjects with indeterminate RIBA responses that subsequently developed acute infection and were followed for viral clearance was high (88%), suggesting that such subjects have immune responses that are associated with viral clearance.
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49

Carlsson, Tony. "Hepatitis C virus kinetics during antiviral treatment /." Stockholm, 2004. http://diss.kib.ki.se/2004/91-7349-588-3/.

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50

Isherwood, Beverley Jane. "Hepatitis C virus : particle assembly and morphogenesis." Thesis, University of Glasgow, 2003. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.410179.

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