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Epidemiologia da infecção pelo vírus da hepatite b em assentados em Goiás: subsídios para ações de prevenção e controle em populações emergentes / Epidemiology of infection by hepatitis B virus in settlments in Goiás: grants for prevention and control in emerging populationsCaetano, Karlla Antonieta Amorim 22 July 2014 (has links)
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Previous issue date: 2014-07-22 / Conselho Nacional de Pesquisa e Desenvolvimento Científico e Tecnológico - CNPq / Estimates indicate a total of 240 million chronic hepatitis B carriers worldwide. In
Brazil, rural settlements present adverse life conditions that favor the acquisition of
health problems, such as the hepatitis B virus (HBV). The objective of the present
study was to investigate the epidemiology of the infections caused by the hepatitis B
and D viruses in people living in settlements in the southwest region of the state of
Goiás. This is an observational, analytical, cross-sectional study, with a subsequent
cohort of susceptible subjects for vaccination against HBV, assessment of adherence
and vaccine response. In the period from May to July of 2011, 467 subjects were
selected from seven settlements in the southwest of Goiás. All subjects were
interviewed and tested for the detection of the serological markers HBsAg, anti-HBc
and anti-HBs, by means of the enzyme-linked immunosorbent assay (ELISA).
Reactive HBsAg samples were tested for total anti-HDV and IgM, by means of the
ELISA, submitted to the detection of the HBV DNA by semi-nested PCR and
genotyped by sequencing. Chemiluminescent microparticle immunoassay was used
for the quantitative determination of anti-HBs. The research proposal was approved
by the Research Ethics Committee of the Federal University of Goiás. Of the total
sample, 52.2% were men, 57.8% were married and 49% had less than five years of
education. Most subjects were from cities in the midwest region (81.6%) and were
older than 19 years of age (73.7%). Overall prevalence for infection by the HBV was
10.9% (51/467), being 0.8% (4/467) for HBsAg, 7.9% (37/467) for anti-HBc and anti-
HBs, and 2.1% (10/467) for anti-HBc. Moreover, 19.3% of the people living in
settlements presented isolated positivity for the anti-HBs marker, which indicates
they were previously vaccinated against hepatitis B. The four reactive HBV DNA
samples were classified as subgenotype A1 (3/4) and D3 (1/4). The male gender
(adjusted OR: 2.65; p= 0.007), age (adjusted OR: 1.07; p= 0.000), history of
transfusion (adjusted OR: 2.52; p= 0.025) and greater period of time living in the
settlements (adjusted OR: 1.10; p= 0.026) were variables associated with the HBV. A
total of 181 subjects susceptible to the infection started vaccine against hepatitis B,
but only 106 (58.6%; 106/181) completed the vaccine scheme. Of these, it was
possible to assess the vaccine response in 77 subjects, and 68.8% (53/77)
presented protective titers of anti-HBs. Of those subjects living in the settlements
who did not respond to the vaccine, a greater proportion was male, had more than 40
years and was smokers (p< 0.001). No subject presented positivity for the anti-HDV
marker. The results of this study evidence the need for effective strategies to prevent
hepatitis B in the studied settlements, emphasizing vaccine against hepatitis. In light
of the low vaccine response against this infection in older subjects, more
immunogenic schemes are suggested, so as to induce a protective vaccine
response. / Estima-se em 240 milhões o número de portadores crônicos de hepatite B. No
Brasil, as comunidades rurais de assentamentos apresentam condições de vida
adversas que favorecem a aquisição de agravos, como do HBV. O objetivo do
presente estudo foi investigar a epidemiologia das infecções pelos vírus das
hepatites B e D em assentados do sudoeste de Goiás. Trata-se de um estudo
observacional, analítico, de corte transversal, em que posteriormente foi formada
uma coorte de indivíduos suscetíveis para a vacinação contra HBV, avaliação da
adesão e resposta vacinal. No período de maio a julho de 2011, foram recrutados
467 indivíduos de sete assentamentos do sudoeste goiano. Todos foram
entrevistados e testados para a detecção dos marcadores sorológicos HBsAg, anti-
HBc e anti-HBs pelo ensaio imunoenzimático (ELISA). As amostras HBsAg
reagentes foram testadas para o anti-HDV total e IgM, pelo ELISA, submetidas à
detecção do HBV DNA por semi-nested PCR e genotipadas por sequenciamento.
Para a determinação quantitativa do anti-HBs empregou-se o imunoensaio de
micropartículas por quimioluminescência. O presente estudo foi aprovado pelo
Comitê de Ética em Pesquisa da Universidade Federal de Goiás. Do total, 52,2%
eram do sexo masculino, 57,8% casados e 49% possuía menos de cinco anos de
estudo. A maioria era natural de municípios da Região Centro-Oeste (81,6%) e
possuía mais de 19 anos de idade (73,7%). A prevalência global para a infecção
pelo HBV foi de 10,9% (51/467), sendo 0,8% (4/467) para HBsAg, 7,9% (37/467)
para anti-HBc e anti-HBs, e 2,1% (10/467) para anti-HBc. Também, 19,3% dos
assentados apresentaram positividade isolada para o marcador anti-HBs, indicando
vacinação prévia contra hepatite B. As quatro amostras HBV DNA reagentes foram
classificadas como subgenótipo A1 (3/4) e D3 (1/4). Observou-se que sexo
masculino (OR ajustado: 2,65; p= 0,007), idade (OR ajustado: 1,07; p= 0.000),
história de transfusão (OR ajustado: 2,52; p= 0,025) e maior tempo de moradia nos
assentamentos (OR ajustado: 1,10; p= 0,026) foram variáveis associadas ao HBV.
Um total de 181 assentados suscetíveis à infecção iniciaram a vacinação contra
hepatite B, mas apenas 106 (58,6%; 106/181) completaram o esquema vacinal.
Desses, em 77 foi possível avaliar a resposta vacinal, sendo que 68,8% (53/77)
apresentaram títulos protetores de anti-HBs. Verificou-se uma proporção maior de
não respondedores nos assentados do sexo masculino, com mais de 40 anos e
tabagistas (p< 0,001). Nenhum indivíduo apresentou positividade para o marcador
anti-HDV. Os resultados evidenciam a necessidade de estratégias efetivas de
prevenção da hepatite B nos assentamentos estudados, com ênfase na vacinação
contra hepatite. Ainda, diante da baixa resposta vacinal contra esta infecção em
indivíduos mais velhos, sugere-se esquemas mais imunogênicos, que induzam uma
resposta vacinal protetora.
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Epidemiologia da hepatite B em indivíduos em situação de rua abrigados em casa de passagem de Goiânia, Goiás / Epidemiology of hepatitis B among homeless people attended in the public shelter of Goiania, GoiásCarvalho, Paulie Marcelly Ribeiro dos Santos 18 February 2016 (has links)
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Previous issue date: 2016-02-18 / Infection caused by the hepatitis B virus (HBV) continues to have a major impact on global public health, even while being vaccine-preventable. People living on the streets, homeless, are at high risk for sexually transmitted infections (STIs), including hepatitis B. To investigate the epidemiology of HBV infection among homeless people in Goiania, Goias, from August 2014 to June 2015, 353 individuals served by a public shelter at the capital were interviewed using a structured questionnaire containing questions about socio-demographic characteristics, clinical and risk factors for HBV infection. Next, all were tested for serologic markers of HBV. It was observed the predominance of males (81.3%), mixed race selfdeclared (61%), single (59.8%), low income (70%) and low level of education (53,3%). The global prevalence of HBV was estimated at 21.81% (95% CI 17.82 to 26.41): two individuals were HBsAg / anti-HBc positive, 61 were anti-HBc / anti-HBs, and 16 showed reactivity to only the anti-HBc marker. Additionally, 19.55% (CI: 95%: from 15.75 to 24.00) tested positive for isolated anti-HBs, suggesting immunity to HBV. Analyzing potential risk factors to HBV showed that: age over 50 years, being gay or bisexual, and being mixed race/blackselfdeclared were independently associated of exposure to HBV. The results confirm the vulnerability of this populational subgroup and a high prevalence of exposure to HBV. Still. the low frequency of serological evidence of immunization against HBV, specially among older subjects, makes evident the need of drawing up strategies of vaccination at the support places to homeless. / A infecção causada pelo vírus da hepatite B (HBV) continua apresentando grande impacto na saúde pública mundial, mesmo sendo imunoprevenível. Populações em situação de rua (PSR) apresentam um risco elevado para infecções sexualmente transmissíveis (IST), incluindo a hepatite B. Para investigar a epidemiologia da infecção pelo HBV em indivíduos em situação de rua em Goiânia, Goiás, durante agosto de 2014 a junho de 2015, 353 indivíduos atendidos em um albergue público da capital foram entrevistados utilizando-se um roteiro estruturado, contendo questões sobre características sociodemograficas, clínicas e fatores de risco para a infecção pelo HBV. A seguir, todos foram testados para os marcadores sorológicos do HBV. Observou-se predomínio de indivíduos do sexo masculino (81,3%), de cor/raça parda autodeclarada (61%), solteiros (59,8%), de baixa renda (70%) e baixo nível de escolaridade (53,3%). Estimou-se uma prevalência global para o HBV de 21,81% (IC 95%: 17,82 - 26,41): dois indivíduos foram HBsAg/anti-HBc positivos, 61 foram anti-HBc/anti-HBs e 16 apresentaram reatividade do marcador anti-HBc isolado. Ainda, 19,55% (IC: 95%: 15,75 - 24,00) apresentaram positividade isolada para o anti-HBs, sugerindo imunidade para o HBV. A análise de potenciais fatores de risco para HBV mostrou que: idade > 50 anos, ser homossexual ou bissexual e ser de cor preta/negra autodeclarada foram independentemente associados a exposição ao HBV. Os resultados ratificam a vulnerabilidade desse subgrupo populacional e uma elevada prevalência de exposição ao HBV. Ainda, a baixa freqüência de evidência sorológica de imunização contra o HBV, especialmente nos indivíduos mais velhos, evidencia a necessidade de elaboração de estratégias de vacinação nos locais de apoio a PSR.
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HIV-1 and coinfection with hepatitis B and delta viruses: What is the impact of HIV-1 infection on hepatitis B chronic carriage and the sero-prevalence of delta virus in Uganda?Opio, Alex Achol January 1994 (has links)
No description available.
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The prevalence of Hepatitis B virus infection in an HIV-exposed paediatric cohort from the Western Cape, South AfricaChotun, Bibi Nafiisah 12 1900 (has links)
Thesis (MScMedSc))--Stellenbosch University, 2012. / Includes bibliography / ENGLISH ABSTRACT: Despite the availability of Hepatitis B virus (HBV) vaccination for over three decades, this infection remains a major public health problem. Whilst the WHO recommends giving a birth dose of the vaccine, in South Africa, routine infant HBV vaccination commences at six weeks of age. This schedule is based on data from the pre-HIV era which showed transmission occurred via the horizontal, rather than the vertical route. In the era of HIV however, maternal HIV co-infection may release HBV from immune control, resulting in higher HBV loads and increasing the risk of vertical transmission. The aim of this study was to determine the prevalence and character of HBV infection in HIV-exposed infected and uninfected infants.
Residual plasma samples from routine HIV nucleic acid testing of 1000 HIV-exposed infants aged between 0 and 18 months from the Western Cape were tested. Samples were tested for HBsAg by ELISA (Murex HBsAg Version 3) and confirmed by neutralisation. HBV DNA was quantified using an in-house real-time PCR assay. Infants with HBsAg positive samples were followed up and a blood sample was collected from mother and child. Those HBsAg positive samples were tested for HBeAg/antiHBe (Diasorin) and HBsAg negative samples were tested for antiHBs. HBV DNA was quantified. The surface gene was sequenced and the HBV genotype determined by phylogenetic analysis using HepSEQ (www.hepseq.org.uk). Whole genome sequencing was also performed.
Of 1000 samples tested, four samples were positive for HBsAg and/or HBV DNA, indicating a prevalence of HBV transmission of 0.4%. At follow-up, two of three infected infants were positive for HBsAg, with HBV viral loads of greater than 108 IU/ml. The third infant was found to have cleared his infection and the fourth child was lost to follow up. These infected infants had all received HBV vaccination. All four mothers were HBeAg positive. Sequencing analysis showed the HBV strains from the two infants and four mothers belonged to subgenotype A1. The two mother-child paired sequences were identical.
The data from this study shows that vertical transmission of HBV infection in HIV-exposed infants from the Western Cape is occurring, despite vaccination. Data from the Western Cape, showing an HBV prevalence of 3.4% in HIV-infected pregnant women, and those presented here suggest a vertical transmission rate of HBV of 12%. This is despite the widespread use of tenofovir and lamivudine in HIV-infected women with low CD4 counts. This study provides data supporting calls to bring HBV vaccination closer to the time of birth. Further work is urgently needed to confirm these findings and to determine the rates of transmission in HIV-unexposed infants. / AFRIKAANSE OPSOMMING: Ten spyte van die beskikbaarheid van die Hepatitis B virus (HBV) inenting vir meer as drie dekades, hierdie infeksie bly 'n groot openbare gesondheid probleem. Terwyl die WGO aan beveel dat'n geboorte dosis van die entstof, in Suid-Afrika, roetine baba HBV inenting op die ouderdom van ses weke gegee word. Hierdie skedule is gebaseer op data van die pre-MIV era wat getoon het dat die oordrag plaasgevind het via die horisontale, eerder as die vertikale roete. In die era van MIV egter, moeder MIV ko-infeksie kan HBV vrylaat van immuun beheer, wat lei in hoër HBV vlakke en die verhoging van die risiko van vertikale oordrag. Die doel van hierdie studie was om die voorkoms en karakter van die HBV infeksie in MIV-besmette en onbesmette babas te bepaal.
Residuele plasma monsters van roetine-MIV-nukleïensuur toetse van 'n 1000 MIV-blootgestelde babas tussen die ouderdomme van 0 en 18 maande van die Wes-Kaap was getoets. Monsters was getoets vir HBsAg deur ELISA (Murex HBsAg Version 3) en bevestig deur neutralisering. HBV DNA is gekwantifiseer deur gebruik te maak van 'n in-huis real-time PCR assay. Babas met HBsAg positiewe monsters was opgevolg en 'n bloedmonster is versamel van moeder en kind. Die HBsAg positiewe monsters was getoets vir HBeAg/antiHBe (Diasorin) en HBsAg negatiewe monsters was getoets vir antiHBs. HBV DNA was gekwantifiseer. Die oppervlak gene volgorde en genotipes was bepaal deur filogenetiese analise met behulp van HepSEQ (www.hepseq.org.uk). Die hele genoom-volgordebepaling was ook uitgevoer.
Van die 1000 monsters wat getoets was, was vier monsters positief vir HBsAg en of HBV DNA, dit dui op 'n voorkoms van HBV oordrag van 0.4%. By op volg, twee van die drie besmette babas was positief vir HBsAg, met HBV virale vlakke van groter as 108 IE/ml. Die derde baba was gevind dat sy infeksie opgeklaar het en die vierde kind was verlore as gevolg van op volg. Hierdie besmette babas het almal HBV inenting ontvang. Al vier moeders was HBeAg positief. Volgordebepaling analise het getoon die HBV stamme van die twee babas en vier moeders behoort aan subgenotype A1. Die twee moeder-kind gepaarde rye was homoloë.
Die data van hierdie studie toon dat die vertikale oordrag van HBV infeksie in MIV-blootgestelde babas van die Wes-Kaap vind plaas, ten spyte van inenting. Data van die Wes-Kaap, wat 'n HBV voorkoms van 3.4% in MIV-besmette swanger vroue, en dié wat hier aangebied is dui op 'n vertikale oordrag koers van 12% van die HBV. Dit is ten spyte van die wydverspreide gebruik van tenofovir en lamivudine in MIV-geïnfekteerde vroue met 'n lae CD4-telling. Hierdie studie bied data wat ondersteunende oproepe van HBV inenting nader aan die tyd van die geboorte bring. Verdere werk is dringend nodig om die bevindinge te bevestig en die pryse van die oordrag in MIV-blootgestelde babas te bepaal. / National Health Laboratory Service Research Trust / Poliomyelitis Research Foundation (PRF) / Harry Crossley Foundation / Stellenbosch University
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Hepatitis B prevention and control : knowledge, attitudes and vaccination status of registered nurses at Nyangabgwe hospital in Francistown, BotswanaKapungumberi, Leighton Taurai 11 1900 (has links)
The study investigated knowledge, attitudes and vaccination status of registered nurses regarding prevention and control of hepatitis B (HB). An analytical, cross-sectional study was conducted, and data was collected using self-administered questionnaires. 53.0% of the respondents (n=219) had good knowledge and 96.3% had positive attitudes regarding HB prevention and control. 86.8% had received at least 1 dose of the HB vaccine, but only 54.7% had received the 3 doses for complete vaccination. A positive attitude score was a significant predictor of HB vaccination uptake (OR=1.424, p=0.003). Female registered nurses were 3.479 times (95% CI: 1.495-8.098; p=0.004) more likely to be vaccinated than male registered nurses. Registered nurses are aware that hepatitis B virus infection can be prevented by a safe and effective vaccine, however, there is need to improve awareness and encourage complete HB vaccination uptake among all registered nurses to ensure their protection against the risk of HBV infection. / Health Studies / M. P. H. (Health Studies)
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"去污名化"的政治: 中国乙肝携带者与公民社会组织的反歧视抗争. / 中国乙肝携带者与公民社会组织的反歧视抗争 / 去污名化的政治 / Politics of de-stigmatization: anti-discrimination social movements among HBVers and NGOs in China / CUHK electronic theses & dissertations collection / "Qu wu ming hua "de zheng zhi: Zhongguo yi gan xie dai zhe yu gong min she hui zu zhi de fan qi shi kang zheng. / Zhongguo yi gan xie dai zhe yu gong min she hui zu zhi de fan qi shi kang zheng / Qu wu ming hua de zheng zhiJanuary 2013 (has links)
近年来,针对就业和就学中遭遇歧视的困境,中国乙肝携带者发起一场要求消除歧视、维护合法权益的抗争运动。为什么乙肝携带者就业歧视问题在中国如此显著?面对国家和市场这两大最具权势的系统,公民社会将何以对抗?本文旨在从社会学的视角对这场“将‘乙肝’去除"的运动进行解读。 / 本文采用个案研究方法,以北京益仁平中心为主要研究对象,围绕 “乙肝"在中国的建构和重构过程,将研究聚焦于三个方面:第一,乙肝污名化过程以及国家、市场中的话语权;第二,反乙肝歧视维权运动的条件和动员机制;第三,“将‘乙肝’去除"中的政治和权力话语三角。 / 本文从社会运动理论中的资源动员、政治机会结构和框架理论出发解读中国乙肝携带者的维权运动;将运动中的微观景象与宏观社会结构结合起来,考察影响乙肝携带者维权运动的主要因素以及运动的动员机制。研究伊始分别从国家和市场两个领域审视乙肝歧视问题在中国的建构过程,阐明乙肝污名化是政府权威以及市场中医药商和医学权威共谋下的合力作用,从而为乙肝携带者反歧视抗争运动的后续研究选择一个合适的立足点。笔者在案例中发现,组织在维权运动中将乙肝携带者群体动员起来,采取有效的策略,充分利用其在资源获得方面的优势、建立乙肝维权组织网络、善于把握时机营造政治机会空间、并能够吸纳律师和媒体的专业力量是维权行动能取得成功的重要因素。 / 组织在维权行动中的话语框架对运动的发展至关重要。乙肝携带者群体对组织运动框架的认同是动员成功的基础;掌握定义“乙肝"的主动权、运动领袖的可信性、框架话语表达的日常化、与媒体的良好关系等策略有助于框架在动员中与参与者、旁观者产生共鸣;抗争精英通过话语框架为抗争活动提供合法性。 / 反乙肝歧视维权运动可以看作是一个“将‘乙肝’去除"的“去污名化"运动。一方面,中央政府与地方政府有着各自自主性利益;另一方面,乙肝携带者群体内部就抗争形式也难以统一,这两种分裂情况交叉形成了一个围绕“将‘乙肝’去除"的,以规则、效益和权利为话语的权力三角,支撑反歧视行动的抗争空间。权力三角的多变性决定去除“乙肝"的行动是有策略的、冒险的,但却相对稳定。 / Hepatitis B Virus carriers (HBVers) have launched series social movements targeting at eliminating discriminations against HBVers in job market and promoting fair employment in recent decade of years. Why does nowhere match the HBV discrimination in such country like China? How is contentious politics possible when the powerless engage in struggles with power holders, like state and market in China? The thesis attempts to learn the intricacies of body politics with sociological approaches. / Yirenping, a NGO located in Beijing, is selected as research object in this case study. Concentrating on the political nature of the HBV confrontations, this thesis is comprised of three parts: first, the stigmatization of HBV in China; second, tactics and strategies that employed against the system of discrimination; third, the politics of “Removing HBV" and the power triangle among state, market and civil society. / The analysis of the HBV movement is informed by three sociological theories of social movements: resource mobilization, political opportunity structure and framing, meanwhile macro structure and micro interaction are combined. It is postulated that this disease discrimination in China occurs when confronting an entrenched stigmatization conjoined from both state and market dedicated to keeping the HBVers excluded and marginalized, which serves as a departure point for further analysis of the struggles for power against this discrimination. Resources mobilized, leaderships and organizations, networks among HBVers and outside supporters, strategies in mobilization positively facilitate the anti-discrimination movements. Utilizing the institutional advocacies as well as informal networks with officials, NPC & CPCCC delegates open more political opportunities within the preexisting political environment. / Framing is essential to the movement mobilization. Identifying closely with the visions and missions in movements, the self conceptualization of HBV-discrimination, charismatic leaders, the everyday narrative of the frame, as well as strategic media coverage help promoting resonance among movement participants and standers-by. Framing strategies provide legitimacy for HBV selves in collective movements. / Finally, the thesis came to the conclusion that anti-discrimination-against-HBVers social movements in China can be interpreted as a process of struggle to “Removing HBV" power. Central government and local ones have their autonomies and interests respectively, while weak but observed divisions in protesting strategies also exist within the HBVers, which shape a triangle of power struggles among the dominant and dominated groups. The power triangle is flexible, and the “Removing HBV" movements are strategic, risk-taking, while being routinized. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / 郭娜. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2013. / Includes bibliographical references (leaves 137-156) / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstracts in Chinese and English. / Guo Nuo. / 中文摘要 --- p.i / 英文摘要 --- p.ii / 引言 --- p.1 / Chapter 第一章 --- 导论 乙肝:作为医学问题和作为社会问题 --- p.3 / Chapter 1.1 --- 作为医学问题的乙型肝炎及其全球地理分布 --- p.3 / Chapter 1.2 --- 乙型肝炎在中国 --- p.6 / Chapter 1.3 --- 作为社会问题的乙肝歧视 --- p.8 / Chapter 1.4 --- 研究方法 --- p.10 / Chapter 1.5 --- 小结 --- p.14 / Chapter 第二章 --- 研究问题与文献回顾 --- p.15 / Chapter 2.1 --- 社会运动理论的发展脉络 --- p.16 / Chapter 2.2 --- 认同与社会运动的动员 --- p.21 / Chapter 2.3 --- 中国底层社会与维权抗争研究回顾 --- p.24 / Chapter 2.4 --- 中国反乙肝歧视运动的分析框架 --- p.26 / Chapter 2.5 --- 小结 --- p.34 / Chapter 第三章 --- 政府与入职体检 --- p.35 / Chapter 3.1 --- 新中国成立之初的公共卫生政策 --- p.35 / Chapter 3.2 --- 中国人事制度改革和公务员职业声望 --- p.39 / Chapter 3.3 --- 体检标准与强制乙肝检测 --- p.43 / Chapter 3.4 --- 小结 --- p.47 / Chapter 第四章 --- 市场话语权与定义“乙肝" --- p.49 / Chapter 4.1 --- 市场中的虚假广告 --- p.50 / Chapter 4.2 --- 体检经济 --- p.54 / Chapter 4.3 --- 医药商与医学权威 --- p.56 / Chapter 4.4 --- 小结 --- p.58 / Chapter 第五章 --- 乙肝携带者的个人经验 --- p.61 / Chapter 5.1 --- 疾病的社会建构 --- p.62 / Chapter 5.2 --- 乙肝携带者的认知过程 --- p.66 / Chapter 5.3 --- 乙肝携带者的抗争选择 --- p.68 / Chapter 5.4 --- 小结 --- p.74 / Chapter 第六章 --- 从个体经验到集体行动:公民社会的回应 --- p.76 / Chapter 6.1 --- 从个人困境到集体行动 --- p.76 / Chapter 6.2 --- 反乙肝歧视运动中的资源动员 --- p.80 / Chapter 6.3 --- 反乙肝歧视组织网络 --- p.82 / Chapter 6.4 --- 反乙肝歧视运动中的机会空间 --- p.86 / Chapter 6.5 --- 小结 --- p.90 / Chapter 第七章 --- 框架策略:反乙肝歧视运动中的动员 --- p.91 / Chapter 7.1 --- 认同与社会运动 --- p.91 / Chapter 7.2 --- 反乙肝歧视运动的行动框架 --- p.95 / Chapter 7.3 --- 反乙肝歧视运动的动员策略 --- p.100 / Chapter 7.4 --- 小结 --- p.107 / Chapter 第八章 --- 身体的政治:将“乙肝"去除 --- p.108 / Chapter 8.1 --- 权力的维度 --- p.108 / Chapter 8.2 --- 反乙肝歧视行动的抗争轨迹 --- p.111 / Chapter 8.3 --- 国家、市场与公民社会:将“乙肝"去除 --- p.116 / Chapter 8.4 --- 小结 --- p.130 / Chapter 第九章 --- 总结与讨论 --- p.131 / 参考文献 --- p.137 / Chapter 附录A --- 访谈提纲 --- p.157 / Chapter 附录B --- 64名被访者基本信息概况 --- p.160 / 致谢 --- p.162
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Untersuchung der Dynamik von Resistenzvarianten des Hepatitis-B-Virus unter Drittlinientherapie mit Tenofovir mittels Tiefenpyrosequenzierung bei Patienten mit chronischer Hepatitis-B-Virusinfektion mit Schwerpunkt auf den Adefovir-Resistenzvarianten und Verlauf der HBV-QuasispeziesBock, Julia Friederike 30 March 2017 (has links) (PDF)
Eine Monotherapie mit Tenofovir disoproxil fumarate (TDF) stellt eine hoch effiziente Therapie-option für multipel vorbehandelte Patienten mit chronischer Hepatitis-B-Virusinfektion (HBV) dar. Eine Resistenz gegen TDF wurde bislang nicht beschrieben, jedoch wird ein möglicher negativer Einfluss von Adefovir dipivoxil (ADV)-Resistenzvarianten auf die TDF-Ansprechrate diskutiert. Diese retrospektive Kohortenstudie untersucht die Dynamik von Nukleos(t)id-Analoga (NA)-Resistenzvarianten im HBV-Polymerasegen mit Fokus auf ADV-Resistenzvarianten bei 18 chronisch HBV-infizierten Patienten mit Therapieversagen auf eine vorangegangene Lamivudin (LAM)- und ADV-Therapie, sowie nur partiellem Therapieansprechen auf eine TDF-Monotherapie. Zur Detektion von NA-Resistenzvarianten wird eine HBV-Genomsequenzierung mit Tiefenpyrosequenzierung (Genome Sequencer FLX, Roche Diagnostics, Germany) (UDPS), direkte Sequenzierung (TRUGENETM HBV Genotyping Kit, OpenGeneTM DNA Sequencing Sys-tem, Siemens Healthcare Diagnostic, USA) (TG) und Line Probe Assay (INNO-LiPa DRv2 und v3, Innogenetics, Belgium) (INNO-LiPA) durchgeführt. Unter TDF kommt es zu einer quantitati-ven Shift zugunsten der ADV-Resistenzvarianten mit konstant bleibendem Anteil und deutlich höher persistierender Virämie zu Monat 12 im Vergleich zu Patienten ohne ADV-Resistenzvarianten. Vor allem werden die Varianten rtA181V und rtN236T selektiert, jedoch nicht die Variante rtA181T. Die absolute Anzahl der LAM-Resistenzvarianten hingegen halbiert sich. Varianten mit einem initial per UDPS detektierten Anteil von >20% der patientenspezifi-schen HBV-Population werden meist selektiert und nehmen im Verlauf den Hauptanteil der Quasispezies ein. UDPS stellte ein potentes Medium der Detektion, Identifikation und Quantifi-zierung von HBV-Varianten dar und ist INNO-LiPa und TG überlegen. Es ergibt sich kein Hin-weis auf TDF-Resistenzvarianten, jedoch zeigt das Vorliegen von ADV-Resistenzvarianten ei-nen tendentiell negativen Einfluss auf die virale Kinetik. Weitere größere Langzeitstudien sind zur Bestätigung dieser Beobachtung notwendig. / Tenofovir disoproxil fumarate (TDF) is a highly efficient treatment option for nucleos(t)ide analogue (NA) pre-treated patients with chronic hepatitis B virus (HBV) infection. Little is known about the reasons for persistent virus replication in some rare cases. As of today, no TDF resistance variants have been identified, but a possible linkage to Adefovir dipivoxil (ADV) resistance associated variants negatively influencing HBV-DNA suppression by TDF has been suspected, based on the similarity of the chemical structure.
In this retrospective cohort study the dynamics of NA resistance variants in the HBV polymerase gene with focus on ADV resistance variants were assessed. For this, we have chosen a cohort including patients with multiple failures to treatment with different NAs. Thus, data of 18 patients with previous treatment failure to LAM and ADV was analysed, showing a persistent viremia (HBV-DNA >35 copies/mL) despite switch to TDF monotherapy (median HBV-DNA at month 12 3,5±0,8 (2,1-4,9) log10 copies/mL). Sequencing analysis was performed with ultra-deep pyrosequencing (UDPS) (Genome Sequencer FLX, 454 Life Science, Roche Diagnostic, Branford, CT), direct sequencing (TG) (TRUGENETM HBV Genotyping Kit, OpenGeneTM DNA Sequencing System, Siemens Healthcare Diagnostic, USA) and line probe assay (INNO-LiPA) (INNO-LiPa DRv2/v3, Innogenetics, Belgium).
Using TDF monotherapy, a quantitative shift in favour to ADV resistance variants was observed in this cohort. The percentage of substitutions conferring resistance to ADV at baseline (BL) and at the time of the last sequencing endpoint (EP) of the HBV genome remained constant (BL 35%, 13/37, EP 36%, 9/25). The variants rtA181V and rtN236T were mostly selected, whereas rtA181T was not selected. The total amount of substitutions conferring resistance to Lamivudin (LAM) showed a strong decline, however remained the majority part of all NA resistance variants (BL 51% (19/37), EP 40% (10/25)). The percentage of ETV resistance variants increased slightly (BL 14% (5/37), EP 24% (6/25)). Known ADV, Lam and ETV resistance variants emerged in variable abundance (1,0-99,6%) of quasispecies during TDF therapy. A homogenization of HBV quasispecies took place. Especially mutations occurring in higher abundance (>20% of viral population) were mostly selected (BL 51% (19/37), EP 80% (20/25)). No new HBV variants with possible association to resistance against TDF were identified, but patients with ADV resistance variants showed the highest HBV-DNA level at month 12 of TDF therapy (median HBV-DNA 3,57±0,72 (2,14-3,96) log10 copies/mL, not significant). A negative influence of ADV resistance variants on viral suppression with TDF monotherapy may be assumed, however more long-term studies are needed to confirm the role of ADV resistance variants in TDF therapy. UDPS is a potent medium for detection, identification and quantification of dominant to low level variants in HBV-DNA. It is superior to direct sequencing and line probe assay in the detection of variants.
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Estudo de títulos protetores para o vírus de hepatite B após esquema vacinal de três doses e \"booster\" em crianças com HIV / Study of protective titles for hepatitis B virus after a three-dose and booster vaccination schedule in HIV-infected childrenFilgueira, Fabiana Ariston 10 September 2008 (has links)
INTRODUÇÃO: A hepatite B é uma enfermidade para a qual não existe tratamento curativo efetivo e que pode determinar graves conseqüências, como o desenvolvimento de cirrose e carcinoma hepático. Segundo dados da OMS, mais de dois bilhões de pessoas estão infectadas pelo vírus da hepatite B e esta doença é responsável por 500.000 a um milhão de óbitos por ano, em todo o mundo. Em pacientes com infecção pelo HIV, é freqüente a co-infecção pelo vírus da hepatite B, pelo fato de serem vírus que compartilham modos semelhantes de transmissão. Em vista dessa problemática, a adequada imunização dos pacientes infectados pelo vírus HIV é fundamental para a prevenção da hepatite B. A recomendação atual do Ministério da Saúde para vacinação de crianças HIV-positivas é a realização do esquema de quatro doses (zero, um, seis e doze meses), com dose dupla. OBJETIVOS: Estudar a resposta sorológica ao booster com vacina da hepatite B em crianças HIV-positivas, previamente vacinadas com três doses duplas que não apresentaram títulos protetores. Estudar a associação dos níveis de CD4 e carga viral no momento do booster. Estudar a associação do intervalo de tempo entre a primovacinação e a primeira avaliação sorológica com a presença de títulos protetores, bem como a associação do intervalo de tempo entre a terceira dose vacinal e o booster com a presença de títulos protetores. METODOLOGIA: O presente trabalho é um estudo prospectivo descritivo de uma coorte de 70 crianças com HIV do total de 187 matriculadas em seguimento no ambulatório de Infectologia do Instituto da Criança (HCFMUSP), no período de agosto de 2005 a novembro de 2006. Em um primeiro momento, realizou-se a dosagem sorológica do anti-HBs dos pacientes que preencheram os critérios de inclusão. Em um segundo momento, nos pacientes que não apresentaram títulos de anti-HBs maiores que 10 mUI/mL, aplicou-se a dose booster da vacina (20 g). Realizou-se dosagem sorológica nos pacientes que receberam a dose booster, no período de um a três meses depois. RESULTADOS: Observou-se que a maioria dos pacientes (50 = 71,4%) não apresentava títulos de anti-HBs >10 mUI/mL no momento da primeira avaliação laboratorial. A média do intervalo de tempo entre a terceira dose da vacina e a dosagem sorológica nos pacientes que apresentaram títulos protetores foi de 53,8 meses, enquanto que a média de tempo no grupo que não apresentou títulos protetores foi de 74,0 meses (p = 0,007). A freqüência de títulos não protetores após dose booster foi de 68%, enquanto apenas 32% apresentaram sorologia protetora após booster. Os dados deste estudo não mostraram associação estatisticamente significante entre níveis de CD4 e carga viral com resposta à dose booster. CONCLUSÕES: O estudo do intervalo de tempo entre a última dose da primovacinação e a feitura da sorologia sugere haver uma tendência à queda de títulos protetores (anti-HBs) ao longo do tempo. Após a dose dupla do booster, ainda se manteve uma predominância de não-resposta sorológica ou resposta com títulos não protetores à vacina da hepatite B nas crianças com HIV, neste estudo. / INTRODUCTION: Hepatitis B is a disease for which there is no effective healing treatment and which can bring about such severe consequences as cirrhosis and hepatocellular carcinoma . According to the World Health Organization (WHO), more than two billion people are currently infected with the hepatitis B virus and the disease is responsible for half a million to one million deaths a year worldwide. Coinfection with hepatitis B virus is common in HIV-infected patients, since both viruses share similar transmission means. Within this context, adequate immunization of HIV-infected people is crucial for hepatitis B prevention. The current recommendation from the Ministry of Health in Brazil for HIV-positive children vaccination is the four-dose schedule (0, 1,6 and 12months) with a double dose. OBJECTIVES: Study the serologic response to a booster dose with the hepatitis B vaccine in HIV-infected children who had been previously vaccinated with three double doses but did not present protective titles. Study the relationship of CD4 levels and the viral load with protective titles at the time of the booster. Study the relationship between the time gap from the first vaccination to the first serologic evaluation and the presence of protective titles, as well as the relationship between the time gap from the third vaccine dose to the booster and the presence of protective titles. METHODOLOGY: The present research consists of a prospective descriptive study of a sample of 70 HIV-infected children out of a total of 187 children enrolled in a follow-up program at the Infectology sector of the Instituto da Criança (Childrens Institute HCFMUSP) from August 2005 through November 2006. First of all, the patients who met the admission criteria had their anti-HBs serologic titles tested. Then the ones whose anti-HBs serologic titles were lower than 10 mUI/mL received a vaccine booster (20 g). Those patients who received the booster had their serologic titles tested again between one and three months after that. RESULTS: It was found that most patients (50=71.4%) did not present anti-HBs serologic titles > 10 mUI/mL at the moment of the first laboratory evaluation. The average time gap between the third dose of the vaccine and the serologic testing of the patients who presented protective titles was of 53.8 months, while the average time in the group who lacked protective titles was of 74 months (p=0.007). The rate of no protective titles after the booster dose in those patients was 68%; on the other hand, only 32% presented protective serology after the booster. The studys data did not show a statistically significant relationship between CD4 levels and viral load with the response to the booster dose. CONCLUSIONS: The study of the time gap between the last dose of the first vaccination and the serology testing suggests that the protective titles (anti-HBs) tend to decrease with time. The serologic lack of response or the nonprotective titles response to hepatitis B vaccine prevailed in the study sample of HIV-infected children even after they received the booster double dose.
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Monitoramento do anticorpo anti-HBs em indivíduos renais crônicos vacinados contra hepatite B de um município do interior paulista / Monitoring of anti-HBs in individuals with chronic renal failure who were vaccinated against hepatitis B in a city in the interior of the state of São PauloLopes, Leticia Pimenta 10 August 2011 (has links)
A vacinação é o método mais importante, barato e eficaz que se tem para a prevenção da transmissão do vírus da hepatite B (VHB). A vacina é indicada para indivíduos renais crônicos devido ao risco acrescido para aquisição do VHB durante a hemodiálise e a transfusão de sangue ou derivados. É indicado que a vacina seja administrada o mais precocemente possível ao entrar no programa de diálise, enquanto os indivíduos são bons respondedores. Este estudo teve como objetivo avaliar o monitoramento do anticorpo anti-HBs vacinal contra a hepatite B em pacientes renais crônicos, que iniciaram hemodiálise no ano de 2005 e permaneceram em seguimento por até quatro anos, em Ribeirão Preto-SP. Trata-se de um estudo de coorte retrospectivo, desenvolvido em quatro unidades de hemodiálise que atendiam indivíduos portadores de DRC na cidade de Ribeirão Preto. A fonte de informação foi composta pela revisão de prontuários de saúde e a população do estudo foi constituída por 102 indivíduos renais crônicos. Dos 102 (100%) participantes, 58,8% eram do sexo masculino e a faixa etária predominante foi <= 45 anos; 52,3% foram a óbito; 18,5% foram submetidos a transplante renal; 20% transferidos; e, em 9,2% dos casos, as razões da interrupção do seguimento não estavam descritas nos prontuários. A proporção de indivíduos que receberam o esquema vacinal completo contra hepatite B foi de 35,3%; em 94,4% dos indivíduos, o tipo de esquema vacinal realizado foi de três doses de 40 mcg e, em 5,6%, o de quatro doses de 40 mcg; o esquema vacinal foi realizado antes do início da hemodiálise em 13,9% dos indivíduos. Em relação à realização da dose de reforço da vacina, 16,7% receberam-na, e o número de doses variou de uma a três doses. A taxa de soroconversão da vacina contra hepatite B, nos hemodialisados que receberam o esquema vacinal completo, foi de 72,2%. Quanto ao teste anti-HBs, no período da admissão na unidade de hemodiálise, 29,4% dos pacientes possuíam registros desse teste. Os títulos de anti-HBs não foram realizados semestralmente em 62,7% dos indivíduos. Ao avaliar a persistência da imunidade da vacina contra hepatite B nos hemodialisados, 39,2% dos indivíduos permaneceram com os títulos de anti-HBs sempre reagentes ao longo do estudo, sendo, portanto, respondedores à vacina contra hepatite B. Conclui-se que a análise dos dados permitiu evidenciar índices insatisfatórios da vacinação contra hepatite B durante o tratamento hemodialítico, bem como dificuldades em seguir o protocolo com esquema vacinal implementado, realização de doses reforço e solicitação de sorologia para anti-HBs. Desta forma, identifica-se a necessidade da equipe de profissionais que atuam em unidades de hemodiálise de adotar, na sua prática, a aplicação de instrumentos que visem facilitar e possibilitar um maior controle e monitoramento da vacinação contra hepatite B e dos títulos de anti-HBs. / Vaccination is the most important, inexpensive and effective method to prevent the transmission of hepatitis B virus (HBV). The vaccine is indicated for individuals with chronic renal failure due to the increased risk for acquiring HBV during hemodialysis and transfusion of blood or derivatives. It is recommended that the vaccine be administered as early as possible to patients entering the dialysis program, while individuals are good responders. This study aimed to evaluate the monitoring of anti- HB antibodies in patients with chronic renal failure who initiated hemodialysis in 2005 and remained in follow-up for up to four years in the city of Ribeirão Preto, state of São Paulo, Brazil. It is a retrospective cohort study which was developed in four hemodialysis units that assist individuals with chronic renal failure in Ribeirão Preto. The source of information was composed of the review of health records and the sample was consisted of 102 individuals with chronic renal failure. Of the 102 (100%) participants, 58.8% were male and the predominant age group was <= 45 years; 52.3% of them died; 18.5% were undergone to kidney transplantation; 20% were transferred; and in 9.2% of the cases, the reasons for discontinuing follow up were not described in the records. The proportion of individuals who received the complete vaccination against hepatitis B was of 35.3%; the vaccination scheme used for immunization in 94.4% of the individuals was of three doses of 40 mcg; and in 5.6% was of four doses of 40 mcg; the vaccination was performed before initiating hemodialysis in 13.9% of individuals. 16.7% of them received the booster dose of vaccine and the number of doses ranged from one to three doses. The seroconversion rate of hepatitis B vaccine in hemodialysis patients who received the full vaccination schedule was of 72.2%. Related to the anti-HBs test in the period of admission to the hemodialysis unit, 29.4% of the patients had records of this test. The titers of anti-HBs were not accomplished every six months in 62.7% of the individuals. Evaluating the persistence of vaccine immunity against hepatitis B virus in hemodialysis patients, 39.2% of the them remained with the titers of anti-HBs always reagents throughout the study, being therefore, responders to the vaccine against hepatitis B. Data analysis highlighted unsatisfactory rates of vaccination against hepatitis B during the hemodialysis treatment as well as difficulties to follow the vaccination protocol implemented, give a booster dose, and request serology for anti-HBs. Thus, it was observed the need for professional staff who works at hemodialysis units to adopt, in their practice, the use of instruments to facilitate and enable greater control and monitoring of hepatitis B vaccination and titers of anti- HBs.
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Avaliação de fatores virológicos associados ao desenvolvimento de carcinoma hepatocelular (CHC) em pacientes com hepatite B crônica / Virological evaluation factors associated with the development of hepatocellular carcinoma (HCC) in patients with chronic hepatitis BLima, Livia de Souza Botelho 02 March 2016 (has links)
O objetivo principal deste estudo foi avaliar fatores virais associados com a evolução para o carcinoma hepatocelular (CHC) em pacientes com hepatite B crônica. Para tanto caracterizamos os subgenótipos do HBV, investigamos a ocorrência de mutações nos genes pré-core/core do HBV associadas à presença de CHC avaliamos por análise filogenética a associação de linhagens virais com a ocorrência de CHC e por fim a associação de outros fatores de risco com o desenvolvimento de CHC. Foram incluídos 119 amostras de soro de pacientes com infecção crônica pelo HBV, destas amostras 60 pertencem ao grupo 1 (CHC), que são pacientes com diagnóstico confirmado de carcinoma hepatocelular e 59 amostras pertencem ao grupo 2 (sem CHC) que são pacientes com hepatite crônica sem detecção prévia de nódulos hepáticos. Foram obtidas informações acerca da idade, sexo e naturalidade. Além disso, os pacientes responderam a um questionário sobre fatores de riscos associados ao desenvolvimento de CHC. Foram realizados exames bioquímicos, sorológicos, determinação da carga viral, e amplificação por nested PCR e sequenciamento das regiões S/polimerase e pré-core/core do genoma viral para posterior caracterização dos genótipos/subgenótipos do HBV e pesquisa de mutações associadas com evolução da doença hepática. Em relação à idade e sexo não houve grande variação entre os grupos. Quanto à naturalidade a maioria era procedente da região sudeste, seguido pela região nordeste; e por fim seis pacientes eram procedentes de outros países. Com base no sobrenome dos pacientes avaliou-se também a frequência de etnia oriental na casuística estudada, que foi similar nos 2 grupos. O perfil sorológico HBeAg negativo foi o mais frequente nos dois grupos de pacientes, assim como níveis de carga viral abaixo de 2.000 UI/mL. Em relação aos exames bioquímicos foram observadas diferenças estatisticamente significantes nos níveis séricos de AFP (p= 0,0013), FA (p= 0,0003) e GGT (p= 0,005). Dentre os fatores de risco analisados neste estudo, o consumo de amendoim foi o único que apresentou significância estatística (p= 0,003). A região S/pol foi amplificada e sequenciada com sucesso em 58 amostras (28 do grupo 1 e 30 do grupo 2). Entre as 58 amostras analisadas 4 genótipos e 8 subgenótipos do HBV foram identificados, sendo o subgenótipo A1 o mais frequente nos dois grupos. Não se observou diferença estatisticamente significante na distribuição dos subgenótipos entre os dois grupos de pacientes. Na topologia da árvore filogenética construída com sequências do HBV isoladas dos pacientes incluídos neste estudo e sequências disponíveis no GenBank não se observou padrões de agrupamento associados com o perfil clinico do paciente (com e sem CHC). Foram obtidas sequências de boa qualidade da região précore/ core em 44 amostras, sendo 20 amostras do grupo 1 e 24 do grupo 2. Diversas das mutações investigadas foram identificadas na região précore/ core, as quais foram avaliadas estatisticamente para verificar a existência de diferença na frequência das mesmas entre os grupos de pacientes estudados. Entre as mutações identificadas se destacaram com significância estatística as seguintes mutações: T1768A (p= 0,006), a combinação das mutações C1766T + T1768A (p= 0,043) e G1888H (p= 0,05). Na análise de regressão logística simples foi possível identificar que a chance de um paciente do grupo 2 desenvolver CHC aumenta 14,7 vezes na presença de infecção por cepas do HBV com a mutação T1768A, enquanto que a infecção com cepas do HBV que albergam a mutação G1888H reduz tal chance 2,5 vezes / The aim of this study was to evaluate viral factors associated with the progression to hepatocellular carcinoma (HCC) in patients with chronic hepatitis B. For this goal, we characterized HBV subgenotypes, investigated the occurrence of mutations in pre-core/core genes associated with progression to HCC, characterized HBV strains through phylogenetic analyzes and evaluated risk factors associated with HCC. Were included 119 serum samples from patients with chronic HBV infection that were classified in 2 groups: 60 patients with confirmed HCC diagnosis (group 1) and 59 patients with advanced hepatitis B liver disease without the detection of nodular liver lesions and without HCC (group 2). Data about the age, sex and geographic precedence were obtained from medical records. The patients also answered a questionnaire on risk factors for developing HCC. Biochemical, serological and viral load testing were performed in all samples. Moreover, S/polymerase and precore /core regions of HBV DNA were amplified by nested PCR and sequenced by Sanger method. Sequences were analyzed to identify HBV genotypes and subgenotypes and to detect mutations in the precore/core gene. Patient\'s age and sex did not differ between the two groups. Most of the patients came from the Southeast region, followed by the Northeast region; and six patients were from other countries. Based on the patient\'s surname, they were evaluated concerning Eastern ethnicity, which was similar in the 2 groups. Most of the patients included in this study were HBeAg negative and showed viral load bellow 2,000 IU/mL. Concerning the biochemistry assays, statistically significant differences in serum levels of AFP (p = 0.0013), AP (p = 0.0003) and GGT (p = 0.005) were found. Among the risk factors analyzed in this study, peanut consumption was the only one statistically significant (p = 0.003). The S/pol region was successfully amplified and sequenced in 58 samples (28 from Group 1 and 30 from Group 2). Among the 58 samples analyzed, 4 genotypes and 8 subgenotypes were identified, subgenotype A1 was the most frequent in both groups and there was no statistically significant difference in the distribution of them between the two groups. In the phylogenetic tree topology built with HBV sequences isolated from patients included in this study and sequences available in GenBank, it was not observed any clustering associated with the clinical profile of the patients (with or without HCC). Sequences of good quality from pre-core/core region were obtained from 44 samples, 20 from group 1 and 24 from group 2. These sequences were analyzed and several mutations were found among which stood out with statistical significance: T1768A (p = 0.006) C1766T + T1768A (p = 0.043) and G1888H (p = 0.05). In addition to the comparative analysis, the changes were subjected to a simple logistic regression analysis which found that the chance of a patient in group 2 developed HCC increases 14.7 times in the presence of HBV infection strains with the T1768A mutation, while infection with HBV strains harboring the mutation G1888H reduces this chance by 2.5 times
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