L’hépatite est une inflammation du foie pouvant être causée par divers agents. Elle reste un problème de santé publique majeur dans le monde, compte tenu du coût de plus en plus élevé des médicaments. Une meilleure compréhension des mécanismes d’action des plantes médicinales apparaît intéressante pour développer des traitements alternatifs. L’objectif de cette étude était donc d’évaluer les propriétés hépatoprotectrice, puis d’identifier les mécanismes qui pourraient soutendre l’action de Neoboutonia velutina (NV), une plante médicinale camerounaise.Les extraits aqueux (NVH) et éthanolique (NVE) de NV ont été préparés, se référant à la préparation traditionnelle. Les analyses phytochimique et toxicologique ont été effectuées et le potentiel antioxydant évalué in vitro et in vivo. De même, l’effet antiinflammatoire des deux extraits a été évalué sur les cellules et chez la souris. L’hépatite aiguë a été induite par le tétrachlorure de carbone (CCl4) ou la Concanavalin A (ConA), chez la souris qui recevait ou non différentes doses d’extrait par gavage. De plus, l’extrait aqueux a été fractionné pour l’identification des composés bioactifs.NVE contiendrait ainsi des stérols et polyterpènes. Cet extrait a présenté une capacité anti-radicalaire meilleure que celle de NVH. Mais, il s’est avéré plus toxique que NVH; ce qui a limité nos investigations sur cet extrait. En revanche, NVH contiendrait des saponines et glycosides et a révélé une très faible toxicité. De plus, un remarquable effet protecteur de NVH a été noté contre les dommages causés par le CCl4. Cet effet protecteur s’est traduit par une diminution dose-dépendante et significative des transaminases sériques et une importante diminution des lésions hépatiques. Ceci, associé à la capacité antiinflammatoire in vitro et in vivo. En outre, un composé anti-radicalaire a été isolé de NVH. Par ailleurs, dans le modèle ConA, NVH n’a présenté qu’un faible effet protecteur. Ce qui suggère une efficacité sélective de cet extrait.En conclusion, nous avons démontré dans notre étude, un effet hépatoprotecteur de NV à travers l’extrait aqueux qui a présenté un effet hépatoprotecteur modèle dépendant. Cet effet, semble être médié au moins, par la capacité anti-radicalaire de la plante. Nos résultats présentent ainsi les premiers arguments en faveur de l’utilisation traditionnelle de NV contre les hépatites. Des études plus poussées permettraient de mieux comprendre les mécanismes d’action de cette plante et d’exploiter au mieux son potentiel thérapeutique, sans risque de toxicité. Ainsi, bien que présentant une toxicité, l’extrait éthanolique qui mime la préparation traditionnelle, a révélé un potentiel thérapeutique qui pourrait être très intéressant à très faibles doses. / Hepatitis is a liver inflammation caused by different agents. It remains a public health problem worldwide since current treatment methods are increasingly expensive. Medicinal plants are known as an important source of new molecules. A better knowledge of these natural resources appears interesting to develop alternative treatments. The aim of this study was then to evaluate the hepatoprotective effect of Neoboutonia velutina (NV), a Cameroonian medicinal plant, and decipher underlying mechanisms.NV aqueous (NVH) and ethanol (NVE) extracts have been prepared referring to the traditional use. Phytochemical and toxicological analyses were performed in vitro and in vivo. Similarly, extracts antioxidant and antiinflammatory potential was assessed on cells (or not) and in mice. Acute hepatitis was induced with carbon tetrachloride (CCl4) or Concanavalin A (ConA), in mice receiving or not different extracts doses by gavage. NVH fractionation was done to identify active compounds.NVE was containing sterols and polyterpens. Though it displayed a high radical scavenging capacity compared to NVH, it appeared more toxic. Thus, for assays, priority was given to NVH, containing saponins and glycosides. NVH showed a radical scavenging capacity with a very low toxicity. It remarkably protected mice from CCl4-induced liver injuries. As shown by significant dose dependent transaminases serum level decrease and liver injury important limitation. These, associated with NVH anti-inflammatory capacity. Furthermore, NVH fractionation led to a radical scavenging compound isolation. Otherwise, in ConA model NVH displayed weak effects. These findings suggested a selective NVH efficacy. In summary, we showed that NVH presents a model dependent hepatoprotective effect that may be mediated at least, through its radical scavenging property. Our findings are in line with Neoboutonia velutina traditional use and provide the first scientific arguments in favor of the traditional use of NV against hepatitis. Additional studies are needed to better understand NV mechanisms of action and then ensured its safe use. NVE mimics the traditional preparation. Even though that extract appeared toxic, it exhibited a therapeutic potential that could be interesting at very low doses.

The current treatment for hepatitis C virus (HCV) infection – combination therapy with pegylated interferon and ribavirin – elicits sustained responses in only ~50% of the patients treated. Greater cumulative exposure to ribavirin increases response to interferon-ribavirin combination therapy. A key limitation, however, is the toxic sideeffect of ribavirin, hemolytic anemia, which often necessitates a reduction of ribavirin dosage and compromises treatment response. Maximizing treatment response thus requires striking a balance between the antiviral and hemolytic activities of ribavirin. Current models of viral kinetics describe the enhancement of treatment response due to ribavirin. Ribavirin-induced anemia, however, remains poorly understood and precludes rational optimization of combination therapy. Here, we develop a new mathematical model of the population dynamics of erythrocytes that quantitatively describes ribavirin-induced anemia in HCV patients. Based on the assumption that ribavirin accumulation decreases erythrocyte lifespan in a dose-dependent manner, model predictions capture several independent experimental observations of the accumulation of ribavirin in erythrocytes and the resulting decline of hemoglobin in HCV patients undergoing combination therapy, estimate the reduced erythrocyte lifespan in patients and describe inter-patient variations in the severity of ribavirin-induced anemia. Further, model predictions estimate the threshold ribavirin exposure beyond which anemia becomes intolerable and suggest guidelines for the usage of growth hormones. A small fraction of the population (~30%) with polymorphisms in the ITPA gene shows protection from ribavirin-induced anemia. The optimum dosage of ribavirin that can be tolerated is then dependent on the ITPA polymorphisms. Coupled with a previous population pharmacokinetic study, our model yields a facile formula for estimating the optimum dosage given a patient’s weight, creatinine clearance, pretreatment hemoglobin levels, and ITPA polymorphism. The reduced lifespan we predict is in agreement with independent measurements from breath tests as well as estimates derived from in vitro studies of ATP depletion. The latter estimates also agree with the extent of ATP depletion due to ribavirin that we predict from a detailed analysis of the nucleoside metabolism in erythrocytes. Our model thus facilitates in conjunction with models of viral kinetics the rational identification of treatment protocols. Our formula for optimum dose presents an avenue for personalizing ribavirin dosage. By keeping anemia tolerable, the predicted optimal dosage may improve adherence, reduce the need for drug monitoring, and increase response rates.

The hepatitis delta virus (HDV), composed of ~1,700nt, is the smallest circular RNA pathogen known to infect humans. Understanding the mode of replication of HDV implies on investigating the host proteins that bind to its genome. The polypyrimidine tract-binding protein-associated splicing factor (PSF), an HDV interacting protein, was found to interact with the carboxy terminal domain (CTD) of RNA polymerase II (RNAPII), and to facilitate the interaction of RNA transcripts with the CTD of RNAPII. Both PSF and RNAPII were found to interact with both polarities of the terminal stem loop domains of HDV RNA, which possess RNA promoter activity in vitro. Furthermore, PSF and RNAPII were found to simultaneously interact with HDV RNA in vitro. Together, the above experiments suggest that PSF acts as a transcription factor during HDV RNA replication by interacting with both the CTD of RNAPII and HDV RNA simultaneously. PSF knockdown experiments were performed to indicate that PSF is required for HDV RNA accumulation. Mutagenesis experiments of PSF revealed that HDV RNA accumulation might require the N terminal domain, and the RNA recognition motifs RRM1 and RRM2. I propose that the RRM1 and RRM2 domains might interact with HDV RNA, while the N-terminal domain might interact with the CTD of RNAPII for HDV RNA accumulation. Together, the above experiments provide a better understanding of how an RNA promoter might be recognized by RNAPII.

Hepatitis C Virus (HCV) is one of the most important causes of chronic liver disease, affecting more than 170 million people worldwide. The mechanisms of hepatitis C pathogenesis are unknown. Viral cytotoxicity and immune mediated mechanisms might play an important role in its pathogenesis. HCV infection and alcohol abuse frequently coexist and together lead to more rapid progression of liver disease, increasing the incidence and prevalence of cirrhosis and hepatocellular carcinoma. The cytopathic effect of HCV proteins, especially the core, E1 and E2 structural proteins, which induce liver steatosis, oxidative stress and cell transformation may be amplified by alcohol abuse. The purpose of this study was to characterize the liver damage mechanisms induced by HCV structural proteins and alcohol and to determine the potential molecular mechanism(s) that may promote chronic, progressive liver damage. A transgenic mouse model expressing HCV core, E1 and E2 was used to investigate whether alcohol increased HCV RNA expression. Real-time RT-PCR analysis of genes involved in lipid metabolism and transport confirmed their abnormal expression in the alcohol-fed transgenic mice. In addition, light and electron microscopy analysis were performed on liver tissues of transgenic mice on an alcoholic diet versus those on a normal diet, in order to identify histological changes. The severe hepatopathy in HCV transgenic mice was exacerbated by alcohol. Mitochondria and endoplasmic reticulum had severe abnormalities in the electron microscopy analysis. The second part of this study focused on adaptive immune responses, which may also play an important role in HCV pathogenesis. I focused my analysis on dendritic cells (DC), which have been the main suspects to explain immune impairment in HCV infection. Their powerful antigen-presenting function allows them to stimulate the antiviral response of CD4+ and CD8+ T cells, the effector cells of the immune system. This unique function of the DC makes them possible targets for immune evasion by the Hepatitis C virus. In this study, DCs were generated from mouse bone marrow cells. I investigated their maturation capacity in the presence of structural proteins of HCV. The impact of HCV core/E1/E2 polyprotein on DCs cytokine expression and ability to activate T-cell lymphocytes was also analyzed. A dysfunctional CD4 T cell response was observed after exposure of DCs to core/E1/E2 polyprotein, indicating inefficient CD4 priming, which might lead to chronic HCV infection in humans. The presence of the core/E1/E2 polyprotein reduced the DC maturation capacity and the expression of certain cytokines (IL-12, IFNg, IL-6, MCP-1) important for stimulation and chemotaxis of T cells and other immune cells. My studies contribute to the understanding of HCV pathogenesis and may have implications to the development of better therapies for HCV infection.

Hepatitis C virus (HCV) infection is a leading cause of liver transplantation and hepatocellular carcinoma worldwide. HCV, like all obligate parasites, relies on host pathways to facilitate its pathogenesis. In particular, the virus possesses an intimate link with hepatic lipid metabolism, promoting a lipid-rich cellular environment conducive to HCV propagation. Clinically, these metabolic perturbations manifest as steatosis in over 50% of patients. The majority of research to-date examining how the virus co-opts hepatic lipid pathways has been focused on coding genes and their protein products. MicroRNAs (miRNAs) are post-transcriptional regulators of gene expression, which have been implicated in virtually every cellular process. Through interactions with partially complementary mRNAs, each individual miRNA has the capacity to repress the expression of hundreds of genes and induce significant regulatory effects. Herein, we demonstrate that hepatic miRNAs, including miR-7, miR-27a/b, miR-130b, and miR-185, act as crucial regulatory molecules to the maintenance of hepatic lipid homeostasis. These miRNAs cooperate to regulate fatty acid and cholesterol metabolism. HCV modulates the expression of a subset of these miRNAs (miR-27a/b, miR-130b, and miR-185) to promote hepatocellular lipid accumulation and the HCV life cycle. There appears to be a broad viral requirement for lipids, and the mammalian innate immune response strategically targets host metabolic pathways to restrict virus’ access to key lipid species. We demonstrate that 25-hydroxycholesterol, a broadly anti-viral oxysterol produced as part of the innate anti-viral response, activates miR-185 expression in the liver to deplete virus infected cells of lipids. HCV appears to actively counteract this anti-viral response by suppressing miR-185 expression. Collectively, our results highlight the role of microRNAs in hepatic lipid metabolism and the immunometabolic response to viral infection.

Hepatitis C virus (HCV) is remarkably capable of efficiently hijacking host cell pathways including lipid metabolism in the liver in order to create pro-viral environments for pathogenesis. It is becoming increasingly clear that identifying small molecule inhibitors that target host factors exploited by the virus will expand available HCV treatment options. As such, a thorough understanding of host-virus interactions is critical to the development of alternative therapeutic strategies. Hepatic lipid droplets (LDs) are recruited by HCV to play essential roles in the viral lifecycle. The intracellular location of LDs is modified upon interacting with viral structural core protein. This enables formation of platforms that support viral particle assembly. Because these interactions are non-static, capturing its dynamic processes in order to better understand viral assembly can be achieved with label-free molecular imaging enhanced with live-cell capabilities. Chemical biology approaches that includes CARS microscopy employed in a multi-modal imaging system was used to probe interactions between HCV and host LDs. By successfully tracking LD trajectories, we identified core protein’s ability to alter LD speed and control for LD directionality. Using protein expression model systems that allowed for simultaneous tracking of core protein and LDs, our data revealed that mutations in the core protein region that vary in hydrophobicity and LD binding strengths, are factors that control for differential modulation of LD kinetics. Furthermore, we measured bidirectional LD travels runs and velocities, and observed critical properties by which core protein induces LD migration towards regions of viral particle assembly. Given that many steps in the HCV lifecycle are directly linked to host lipid metabolism, it is not surprising that disrupting lipid biosynthetic pathways would negatively affect viral replication. From this outlook, we explored small molecule inhibitors that targeted several lipid metabolic pathways to study its antiviral properties. Using fluorescent probes covalently labeled to viral RNA, we captured the visualization of disrupted replication complexes upon antagonizing nuclear hormone receptors that are linked to regulating lipid homeostasis. Correspondingly, biochemistry and molecular imaging techniques were also employed to identify novel antiviral mechanisms of small molecule inhibitors that target additional HCV-dependent lipid metabolic pathways.

Hepatitis C virus (HCV) infects an estimated 170 million people worldwide and is a major cause of chronic hepatitis and hepatocellular carcinoma. As there are limited treatment options, the elucidation of novel host-viral interactions during HCV pathogenesis will be critical for the development of new therapeutics. My thesis work has identified cell death-inducing DFF45-like effector B (CIDEB) as a host factor that is disregulated during HCV infection, and has delineated the relevance of CIDEB’s dual roles in apoptosis and lipid metabolism in the context of the HCV lifecycle. Moreover, additional host factors necessary for the HCV lifecycle were investigated using unnatural amino acid (UAA) technology. With this technique, the photo-cross-linking UAA p-azido-phenlyalanine (AZF) and 3’-azibutyl-N-carbamoyl-lysine (Abk) were incorporated into viral proteins by expanding the genetic code of the host organism. This conferred diverse physicochemical and biological properties to these proteins that were exploited to investigate protein structure and function in vitro and in vivo. In summary, gaining insight into the numerous host-viral interactions that take place during HCV infection will both advance our understanding of HCV pathogenesis and uncover potential therapeutic targets.

Orientadores: Fernando Lopes Gonçales Junior, Neiva Sellan Lopes Gonçales / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas / Made available in DSpace on 2018-08-07T22:44:35Z (GMT). No. of bitstreams: 1 Tonetto_PriscilaAparecida_M.pdf: 2027435 bytes, checksum: ec4453a66ae541917395dc0f14142ed8 (MD5) Previous issue date: 2006 / Resumo: O vírus da hepatite B (VHB) pode ser classificado em oito principais genótipos (A-H), e essa classificação tem uma distribuição geográfica determinada. Os genótipos do VHB podem influenciar na progressão de doença. O objetivo foi determinar os genótipos e os subtipos do VHB e correlacioná-los com as variáveis clínicas epidemiológicas, laboratoriais e histológicas. Foram determinados os genótipos de 139 amostras de soro de pacientes infectados pelo VHB, coletadas em Campinas, no estado de São Paulo, Brasil. O método para genotipagem utilizado foi o seqüenciamento parcial do gene S do VHB. Os primers utilizados foram desenhados a partir de seqüências do gene S, com genótipo determinado, depositadas no GenBank. Todas as seqüências obtidas foram comparadas com as seqüências depositadas no GenBank para determinação dos genótipos. O genótipo A (55%) do VHB foi o mais predominante na população, seguido pelos genótipos C (3%), D (38%) e F (4%). Entre os pacientes infectados pelos genótipos A e D, observou-se uma provável descendência africana de 18% (14/76) e 11% (6/53), respectivamente. Entre os quatro pacientes infectados pelo genótipo C, dois possuíam descendência asiática e dois eram caucasianos. Todos os pacientes infectados pelo genótipo F eram caucasianos sem ascendência indígena relatada. Aproximadamente 30% dos pacientes eram HBeAg positivo e 70% eram HBeAg negativo. A carga viral do DNA-VHB foi aproximadamente cinco vezes mais alta entre os HBeAg positivo quando comparada aos HBeAg negativo. Os genótipos A e D são os mais prevalentes entre os pacientes, aparentemente em virtude da imigração européia em nossa região / Abstract: Hepatitis B virus (HBV) can be classified into eight major genotypes (A-H) that have mainly a geographic distribution. The HBV genotype may influence disease progression. Our objective was to determine the genotypes and the subtypes of HBV and to correlate them with the with variables clinical epidemiologies, laboratories and histological. Hepatitis B virus genotypes were determined in 139 plasma samples collected in Campinas, in the state of São Paulo, Brazil from HBV-infected patients. A method for genotyping hepatitis B virus by partial HBsAg gene sequencing with primers common to all known genotypes was developed. The results of sequencing corresponded to those found in HBV isolates obtained from GenBank, including all of the known HBV genotypes. HBV genotype A was predominant in our sample, appearing in 76 patients (55%), while genotypes C, D and F was found in 4 (3%), 53 (38%) and 6 (4%) of the patients, respectively. Among the patients infected by genotypes A and D, were observed a probably African descendents of the 18.3% (14/76) and 11.3% (6/53), respectively. Among the genotype C infected patients, 2 (50%) were of Asian descendents and 2 were Caucasians. The genotype F infected patients were all Caucasians without told indigenous origin. About 30% of the patients were HBeAg positive and 70% were HBeAg negative. The viral load of HBV-DNA was about 5 times higher among HBeAg positive than in HBeAg-negative patients. Genotypes A and D were the most prevalent among our HBV-infected patients, apparently a consequence of the types of immigration to our region / Mestrado / Ciencias Basicas / Mestre em Ciências Médicas

Orientadores: Gabriel Hessel, Sandra Cecilia Botelho Costa / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas / Made available in DSpace on 2018-08-07T22:25:30Z (GMT). No. of bitstreams: 1 Brandao_MariaAngelaBellomo_D.pdf: 1559118 bytes, checksum: 46a37bd9b6548c781556e1780d459ae7 (MD5) Previous issue date: 2006 / Resumo: A colestase neonatal pode ser a manifestação inicial de um grupo muito heterogêneo de doenças. O citomegalovírus (CMV) está entre as possíveis etiologias e os critérios para o diagnóstico não estão ainda definidos. A freqüência do CMV como causa de colestase intra-hepática (CIH) varia em função do método utilizado para o diagnóstico. O objetivo do presente estudo foi estabelecer a freqüência do CMV na colestase neonatal intra-hepática por meio dos seguintes métodos: sorologia para CMV (IgM-ELISA), N-PCR e imunohistoquímica no fragmento da biópsia hepática parafinada, e indicadores de histologia (célula de inclusão citomegálica e microabscesso) e verificar a concordância entre os métodos diagnósticos citados. Participaram do estudo 101 pacientes com o diagnóstico de CIH e que realizaram biópsia hepática . A idade dos pacientes na 1ª consulta variou de 13 dias a 7 meses, com mediana de 1 mês e 21 dias. Para determinar a freqüência da infecção por citomegalovírus foram calculados os valores de sensibilidade, especificidade, valor preditivo positivo, valor preditivo negativo e acurácia, considerando o método de N-PCR como referência. Para verificar a concordância entre os métodos, foi calculado o coeficiente kappa. A freqüência de positividade para o CMV por meio da sorologia foi de 8% (5/62), por PCR foi também de 8% (6/77), por imunohistoquímica foi de 2% (1/44). Pela avaliação histológica, nenhum em 84 pacientes apresentava células de inclusão citomegálica e 17/84 (20%) apresentavam microabscesso. A sensibilidade da sorologia em relação à N-PCR foi nula, a especificidade de 88,89%, o valor preditivo positivo nulo, o valor preditivo negativo de 90,91% e a acurácia foi de 81,63. Na pesquisa de microabscessos a sensibilidade foi de 50% em relação à N-PCR, a especificidade de 77,05%, o valor preditivo positivo de 17,65%, o valor preditivo negativo de 94% e a acurácia de 74,63%. Não houve concordância para a pesquisa de CMV entre os métodos de sorologia (ELISA-IgM) e N-PCR e fraca concordância entre os demais métodos isolados ou agrupados. Conclusões: 1. A freqüência de positividade para o citomegalovírus variou de 2% a 20% dependendo do método diagnóstico empregado, 2. Não houve concordância entre os métodos, 3. Não foram encontradas células de inclusão citomegálica e a imunohistoquímica foi positiva em apenas 1/44 casos, 4. A sorologia (ELISA-IgM) e a presença de microabscessos não foram sensíveis em relação à N-PCR para a determinação do diagnóstico de CMV na CIH, mas foram úteis, quando negativos, para predizer resultado negativo da N-PCR. Palavras chaves: lactente, hepatite / Abstract: A heterogeneous group of diseases may present initially as neonatal cholestasis, a syndrome made up of jaundice, coluria and fecal hypo or acolia. Cytomegalovirus (CMV) is one of the most common causes of neonatal intrahepatic cholestasis (IHC), but the CMV best diagnostic criteria is not yet established since the positivity of different diagnostic tests varies considerably. The aim of this study was to determine the CMV frequency in neonatal intrahepatic cholestasis and to compare results of different diagnostic tests: IgM by ELISA test, IHQ and PCR in paraffin-embedded hepatic biopsy sample and a review of liver histological features (liver microabscess and cytomegalic inclusion cells). The study has included 101 patients neonatal IHC patients who had been submitted to a liver biopsy during investigation. Median age at the first medical visit was 1 month and 21 days (13 days to 7 months). Sensibility, specificity, negative predictive value, positive predictive value and accuracy were calculated of each test in relation to N-PCR. To analyze concordance among laboratorial methods Kappa (?) coefficient was calculated. Frequency of CMV positive tests: CMV ELISA - IgM was positive in 5/62 (8%), N-PCR in 6/77 (8%), and IHQ in 1/44 (2%). Liver histological features showed 0/84 cytomegalic inclusion cells and 17/84 (20%) liver microabscess. Sensibility of serology was null, specificity was 88,98%, negative predictive value was 90,91%, positive predictive value was null, and accuracy was 81,63%. Sensibility of searching for microabscess was 50%, specificity was 77,05%, negative predictive value was 17,65%, positive predictive value was null94%, and accuracy was 74,63%.There was no concordance between ELISA-IgM and N-PCR (Value of ? =-0, 1) and weak concordance between other methods when considered as a group or individually. Conclusions: 1. Frequency of CMV varied of 2% to 20%, according the diagnostic test. 2. There was no concordance among tests. 3. Searching for inclusion cells was null and IHQ was 2%( 1/44). 4. ELISA-IgM and microabscess sensitivity were poor in relation to N-PCR, but if these methods are negative, probably N-PCR will be negative too. Key words: hepatitis, infant / Doutorado / Pediatria / Doutor em Saude da Criança e do Adolescente

Orientador: Helaine Maria Besteti Pires Mayer Milanez / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas / Made available in DSpace on 2018-08-24T05:11:32Z (GMT). No. of bitstreams: 1 Candido_ElaineCristina_M.pdf: 1043425 bytes, checksum: 4797b5103af38ecbe53b5dd29b496856 (MD5) Previous issue date: 2013 / Resumo: Objetivos: avaliar a transmissão vertical (TV) em gestantes portadoras de hepatite B crônica, em um serviço universitário. Sujeitos e Método: foram analisadas as sorologias para hepatite B de todas as gestantes atendidas no serviço entre 2000 e 2005, identificando-se as HbsAg +; nessas foi realizado levantamento de prontuários, avaliando a presença do marcador de replicação viral (HbeAg positivo), imunoprofilaxia neonatal e taxa de TV. Análise de dados: foi avaliada a proporção de casos com HbsAg+ e nessas a presença do HbeAg. Para as portadoras de hepatite B, analisaram-se características clínicas e epidemiológicas através de frequências simples e a presença de TV. Resultados: entre 2000 e 2005 foram rastreadas para hepatite B no CAISM 5638 mulheres; dessas 28 (0,5%) apresentavam HbsAg+, definindo-se como portadoras crônicas. Não se encontrou nenhuma com replicação viral (HbeAg+). A idade média foi de 25 anos, com escolaridade média de sete anos, sendo 57% de brancas. O número de gestações médio foi de dois, sendo 52% de nulíparas. A categoria de exposição foi ignorada em 20; em quatro a via foi a sexual, em duas por TV e em duas por uso de drogas. A média de Idade gestacional ao parto foi de 38 semanas, com uma taxa de cesárea de 42%. O peso médio ao nascimento foi de 3094g e todos os recém-nascidos apresentaram boas condições de vitalidade e receberam imunoprofilaxia neonatal (vacina e imunoglobulina específica) nas primeiras horas de vida. Não houve TV. Conclusões: Nas gestantes atendidas no período, a prevalência de hepatite B crônica foi de 0,5%. Todas as crianças receberam imunoprofilaxia neonatal nas primeiras horas de vida e não ocorreu nenhum caso de TV, reforçando que para as gestantes sem replicação viral, as medidas de imunoprofilaxia neonatal protegeram a totalidade de seus recém-nascidos / Abstract: The purpose of this paper is to evaluate mother-to-child transmission of chronic hepatitis B in a university hospital. Subjects and methods: Hepatitis B serologic studies were pooled from all pregnant women referred to this prenatal service from 2000 to 2005. HBsAg positive patients were selected and, for those, clinical, laboratory and epidemiologic data were analyzed, including presence of HBeAg marker, immunoprophylactic procedures for the newborn and mother-to-child transmission rates. Data analysis: HBsAg carriers were characterized for clinical and epidemiologic factors associated with mother-to-child transmission. Results: Between 2000 and 2005, 5638 pregnant women were referred to high-risk prenatal care at our facility; of these, 28 women (0,5%) were HbsAg+ ¿ defined as chronic Hepatitis B virus (HBV) carriers. None of these were seropositive for HBeAg. Mean age was 25 years with a mean of 7 years of formal education and 57% were white; 52% were nulliparous. Exposure to hepatitis B virus was ignored in 20 women, sexual in 4, from mother-to-child transmission in 2 and associated with drug use in 2. Mean gestational age at delivery was 38 weeks with cesarean delivery in 42% of women. Mean weight at birth was 3094g and all newborns presented with good vitality and received immunoprophylactic procedures. There were no cases of mother-to-child transmission. Conclusion: Among all pregnant women seen at this tertiary high risk prenatal care facility between 2000 and 2005, chronic HBV infection was detected in 0,5% of patients. All newborns received immunoprophylaxis during the first hours after delivery and no case of mother-to-child transmission was detected. Our findings support that, among pregnant chronic HBV carriers without serologic evidence of active viral replication, immunoprophylactic measures are effective in preventing mother-to-child transmission in all instances / Mestrado / Saúde Materna e Perinatal / Mestra em Ciências da Saúde