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Introduction and aims: In the United Kingdom hepatitis B virus (HBV) and hepatitis C virus (HCV) disproportionately affect migrants and people who inject drugs (PWID). Ascertainment rates of HBV and HCV are 10-40% and screening is recommended in at risk groups. Treatment uptake for HCV in PWID is low at 2-18%, and the most effective way to increase uptake is not known. This research aims to evaluate methods to address the low ascertainment and treatment rates of HBV and HCV in these populations. Methods: A pilot observational cohort study of screening for chronic viral hepatitis in primary care. A retrospective observational cohort study into outcomes of HCV treatment in PWID. A prospective cluster randomised trial of nurse versus doctor initiated treatment for HCV in PWID and a qualitative analysis exploring the engagement with treatment for HCV of PWID. Results: Direct testing results in a greater uptake of screening than opportunistic testing in migrants in primary care (21% versus 1.9%, p = < 0.0001). PWID have SVR rates of 55%, re-infection rates of 2.4 per 100 person years, and crack cocaine use reduces over treatment (90% to 49%, p= < 0.0001). Nurse initiation of treatment does not result in a higher uptake of therapy (9.6 % versus 7.8%, p=0.53). Treatment engagement themes included the normalisation and stigmatisation of HCV and the perception of HCV treatment as a transformative process. Discussion: Direct testing for HBV and HCV appears to result in a greater uptake of testing in migrants in primary care and should be investigated in a randomised controlled trial. HCV treatment in PWID is safe and effective, and illicit drug use may reduce over treatment. Further service development is unlikely to result in a greater uptake of antiviral therapy for HCV in PWID and other options should be explored to improve treatment uptake.

Globally, it is estimated that 240 million people are infected with chronic viral hepatitis B and in excess of 185 million people with chronic hepatitis C. The burden of disease from hepatitis is concentrated in developing countries where transmission of HBV occurs predominantly from mother to child (vertical transmission) and transmission of HCV through unsafe medical procedures and the transfusion of unscreened blood products. Global patterns of migration favour the movement of individuals from countries with medium or high risk prevalence of chronic viral hepatitis to countries with traditionally low prevalence among their indigenous populations, including the United Kingdom (UK). In excess of 3.2% of the global population are international migrants, posing important implications for healthcare systems in host nations. It is predicted that up to 7 million first and second generation immigrants, originating from high prevalence countries for viral hepatitis now reside permanently in the UK. However, as a result of deficiencies in screening initiatives, the prevalence and associated burden of these diseases in these high-risk populations residing in the UK is yet to be determined. In order to establish the feasibility of inviting first and second generation immigrant populations to participate in viral hepatitis testing in primary care, as well to determine the prevalence and demography of viral hepatitis in four areas of the UK, a randomised controlled cross sectional cluster trial was conducted. In HepFree clinical computer systems in general practice surgeries were interrogated to identify the target population that was then approached using a variety of different invitations to determine the most appropriate method for engaging this population. The outcomes of viral hepatitis testing from practices in one area of the UK are described in this thesis. Despite multiple challenges encountered both in engaging practices and individuals in trial participation, results of this investigation suggest that if it is found to be cost effective, then viral hepatitis screening is feasible and the burden of disease in the UK is concentrated in first generation immigrants.

Globally, policy recommendations on vaccines as provided by the Strategic Group of Experts on Immunization (SAGE) rely on a number of factors including burden of disease. In the scope of this thesis, two studies were conducted in order to inform the World Health Organization Hepatitis E Virus (HEV) working group and ultimately the SAGE: 1) a systematic review and meta-analysis of the global incidence, prevalence and mortality associated with all genotypes of HEV; and 2) a global subgroup analysis of incidence, prevalence and mortality on special populations and high risk populations. Circulation of HEV was documented in all global regions. Severe disease was observed among pregnant women and fulminant hepatic failure patients in both studies conducted. Poor data quality was observed in both studies, this poses a serious challenge for estimating the burden of disease. Countries should consider the implementation of an HEV surveillance system to improve data quality and ultimately to inform decision-making.

Thesis ( M Med (Virological Pathology))--University of Limpopo, 2010. / Introduction: Hepatitis B virus (HBV) is a serious problem worldwide causing various liver diseases such as chronic hepatitis and hepatocellular carcinoma (HCC). The pathogenesis of HBV related HCC is not well established. Hepatitis B X protein (HBx) plays an important role in the pathogenesis of HCC. HBx coded by HBV X gene enhances several cellular pathways in hepatocytes which may lead to HCC. The genetic variability of other HBV genomic regions plays a significant role in diagnosis, vaccine development and drug resistance. However, the genetic variability of HBV X gene is not well understood. In addition the dual basal core promoter mutations found within the X gene have been implicated in the inhibition of hepatitis B e antigen (HBeAg) expression. Studies focusing on HBV X gene are scarce in South Africa. Consequently HBV X gene variability may reveal interesting mutations and substitutions that are important in chronic liver diseases or HCC. This study aimed at characterising HBV X gene at a molecular level isolated from patients with different serological profiles. Methods: This was an exploratory study which used 20 stored sera (-70°C) collected from adult patients at Dr George Mukhari hospital, Pretoria. The samples were already tested for HBsAg, anti-HBs, anti-HBc and HBeAg serological markers (Elecsys, Roche Diagnostics, Penzburg, Germany). HBV DNA extraction was performed from serum using High Pure Viral Nucleic Acid Assay (Roche Diagnostics, Penzburg, Germany). Nested PCR assay was used for the amplification of 465 nucleotide HBV X gene. Sequencing of PCR positive samples was done using spectruMedix SCE2410 genetic analysis system. Six samples selected, were cloned into the pGEM®-T Easy vector system (Promega, Madison, USA). Three clones of each sample were selected and their plasmids purified using Pure Yield™ Plasmid Miniprep System (Promega, Madison, USA). The plasmid DNA was recovered using optimised nested PCR assay and sequenced. A total of 38 sequences were generated from the study and compared with reference strains retrieved from GenBank. Phylogenetic analysis based on HBV X gene sequences was done using MEGA 4 software to determine different genotype clusters. vi Results: HBV X gene was successfully detected and amplified in 20 study samples. The sequenced HBV X gene products revealed mutations and insertions. Particularly a six nucleotide insertion, GCATGG between nucleotides 1611 and 1618 which was detected in five samples. In addition, the six cloned samples confirmed the six nucleotide insertion and other mutations associated with inhibition of hepatitis B e antigen (HBeAg) detected in the study. The substitutions within HBx were detected in the N (1-50 amino acids) and C (51-154) terminals by comparing our sequences with archival sequences from GenBank. Important substitutions found within the N and C terminals were S31A, P38S, A42P, F73L, H94Y, P101S, K118T, D119N, I127T/N, K130M and V131I. These substitutions are associated with various biological functions and pathogenesis. Other substitutions with unknown functions detected in the study include A2G, A3G, A4G, C6W, P42S and V116L. Further mutations of T1753M, A1762T and G1764A associated with inhibition of HBeAg expression were detected in most samples and only one sample had C1766T mutation. Phylogenetic analysis resulted in A, C and D HBV genotypes. Five samples and 11 clones clustered with genotype D, two samples and four clones clustered with genotype C and finally 13 samples and 3 clones clustered with genotype A. Conclusion: HBV X gene was successfully characterised using various molecular methods. HBx substitutions detected are involved in various pathogenic effects and may present a risk of HCC for patients infected with HBV. Genotype D samples displayed most mutations/substitutions and this can be regarded as an important genotype with high risk of HCC. The detection of a six nucleotide insertion (GCATGG) in 5 samples may emerge as a new variant of genotype D. Furthermore triple mutations of T1753M/A1762T/G1764A within basal core promoter region were detected mostly in HBeAg negative samples. However further analysis of HBV X gene variability is needed.

Diss. (sammanfattning) Stockholm : Karol. inst., 2004. / Härtill 4 uppsatser.

Diss. (sammanfattning) Stockholm : Karol. inst., 2004. / Härtill 5 uppsatser.

Orientador: Cláudio Antonio Rabello Coelho / Resumo: A hepatite aguda pelo vírus da hepatite tipo A (VHA) é uma causa comum de doença hepática em crianças em nosso meio, sendo o tipo mais freqüente entre as de causa viral. Usualmente, diante de um paciente com quadro clínico e dados epidemiológicos sugestivos de hepatite aguda, a presença de doença hepática é confirmada e a evolução é acompanhada utilizando-se as chamadas "provas de função hepática" (PFH), cujos resultados habitualmente são conhecidos antes do resultado do exame sorológico, que define a etiologia. Diante do número relativamente grande de PFH que podem ser utilizadas, das implicações fisiopatológicas diferentes que podem ter e do custo de sua execução, procuramos verificar quais delas poderiam ser substituídas por outra(s) e quais as possíveis relações entre os mecanismos de suas alterações. Para isso estudamos as correlações entre os níveis das seguintes PFH - concentração sérica bilirrubina total (BT), concentração sérica de bilirrubina de reação direta (BD), atividades séricas de aspartato aminotransferase (AST), de alanina aminotransferase (ALT), de fosfatase alcalina (FA) e de γ-glutamiltransferase (γGT) em crianças com hepatite do tipo A (HA), que evoluíram para cura, em diferentes fases de sua evolução - do 1o ao 7o dia (G 0-7), do 8o ao 14o dia (G 8-14), do 15o ao 30o dia (G 15-30), do 31o ao 60o dia (G 31-60) e após os 60 dias (G > 60). Foi aplicada análise de correlação múltipla efetuando-se as seguintes análises: 1) correlação entre BD (variável dependente - VD) e BT, AST, ALT, FA e γGT (variáveis independentes - VI) nos grupos G 0-7 e G 8-14; 2) correlação entre BT (VD) e AST, ALT, FA e γGT (VI), nos demais grupos; 3) correlação entre AST (VD) e BT, ALT, FA e γGT (VI) em todos os grupos e 4) correlação entre... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Acute type A hepatitis (HA) is a common disease in children in Brazil. And is the most frequent cause of viral hepatitis. Usually when the clinical picture and epidemiological data are suggestive of acute hepatitis the diagnosis of hepatic damage and the follow-up is made using the so called "liver function tests" (LFT), besides the serological confirmation of a recent infection by the hepatitis type A virus (HAV). Considering that: 1) the number of available LFT is relatively large: 2) the ordering of many tests repeatedly over the course or disease would be expensive, and 3) the physiopathological mechanisms of their alterations may be different one from the other we aimed at determining which test(s) could be substituted by other(s) and which are the possible relations among the physiopathological mechanisms of their alterations. To fulfil these objectives, we studied, in children with type A hepatitis, which eventually cured, the multiple correlations among combinations from the following group of tests: total serum bilirubin concentration (TB), direct reactant bilirubin concentration (DB), serum aspartate aminotransferase activity (AST), serum alanine aminotransferase activity (ALT), serum alkaline phosphatase activity (AP) and serum γglutamiltranspeptidase activity (γGT). The correlations were calculated from data taken during different periods after jaundice was noticed - from 0 to 7 days (G 0-7), from 8 to 14 days (G 8-14), from 15 to 30 days (G 15-30), from 31 to 60 days (G 31-60) and after 60 days. A multiple correlation test was applied to carry out the following analyses: 1) correlation between DB ( dependent variable - DV) and TB, AST, ALT, AP and γGT (independent variable - IV) for the groups G 0-7 and... (Complete abstract, click electronic access below) / Mestre

Made available in DSpace on 2014-06-11T19:32:13Z (GMT). No. of bitstreams: 0 Previous issue date: 2009-08-12Bitstream added on 2014-06-13T21:03:39Z : No. of bitstreams: 1 zornoff_dcm_dr_botfm.pdf: 1383521 bytes, checksum: 0cce38030a5b43ad346b2ed91fbbb2e1 (MD5) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / Os profissionais da saúde necessitam de métodos efetivos de educação continuada, com estratégias de capacitação objetivas, flexíveis e dinâmicas. Desse modo, proposta de ensino/aprendizado baseadas na Web podem ser bem sucedidas na sua atualização. Levantamos a hipótese de que o emprego da plataforma Moodle de educação on-line pode viabilizar a criação de portal eletrônico para educação médica continuada e pode ser uma ferramenta viável e simples para a formulação de segunda opinião em saúde nas hepatites virais. Assim, este trabalho descreve a criação de plataforma voltada ao aprendizado em hepatites virais, empregando o sistema Moodle de gerenciamento de cursos. O portal foi desenvolvido de acordo com proposta de Cook & Dupras, que descreve 10 recomendações na elaboração de sites educacionais: análise das necessidades, metas e objetivos; determinação de recursos técnicos e necessidades; avaliação de sistemas similares pré-existentes; assegurar compromisso de todos os participantes e identificar potenciais barreiras à implantação do projeto; desenvolvimento de conteúdo em íntima coordenação com o design do site; criação de materiais que estimulem o aprendizado ativo; encorajamento no uso do site pelo usuário; avaliação dos usuários e do curso; promoção de estudo piloto; monitoração da comunicação on-line e atualização periódica. O conteúdo incluiu consensos científicos nacionais e internacionais, aulas, animações, tutoriais, suporte para segunda opinião médica e links de interesse na Web. Acredita-se que esta ferramenta ofereça uma alternativa interativa de educação e ratifique a necessidade de se promover estudos adicionais para validar estratégias efetivas de educação continuada. / Health workers need effective methods of continuing education, with objective, flexible and dynamic strategies. Thus, teaching and learning based on Web can be successful in upgrading those professionals. We hypothesized that the use of Moodle for online education can facilitate the creation of an electronic portal for continuing medical education and it is a viable tool to formulate queries for viral hepatitis second opinion. This paper describes the creation of a learning platform focused on viral hepatitis, using the Moodle system of course management. The portal was developed according to Cook & Dupras proposal, following ten recommendations: perform a needs analysis and specify goals and objectives; determine technical resources and needs; evaluate preexisting software; secure commitment from all participants and identify potential barriers to implementation; develop content in close coordination with website design; encourage active learning; facilitate use by the learner; evaluate learners and course; pilot the website, and plan to monitor online communication periodically. The contents include national and international guidelines, presentations, support for second medical opinion and links of interest on the Web. It is expected that this tool offers an interactive alternative for education and encourage further studies to validate effective strategies for continuing education.

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