999 resultados para Hepatite C Prognóstico
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La prsente thse doctorale propose ltude de lactivit thtrale dveloppe dans les thtres permanents construits en Amrique Portugaise au long du XVIIIe et dans la premire dcennie du XIXe sicle, en mettant laccent sur les idalisateurs des Casas da pera et les moyens de financement utiliss dans ldification et lentretien de celles-ci, le rpertoire mis en scne, les artistes composant les compagnies thtrales, les spectateurs et les possibilits de sociabilit tablies dans lespace thtrale et les modles architectoniques qui ont inspir la construction des btiments thtraux au cours de la priode mentionne. Ces cinq axes principaux soulignent lapproche interdisciplinaire qui a orient nos tudes, dans un souci de contribution une plus complte comprhension de notre sujet de recherche. Mots cls : Thtres, Amrique Portugaise, Comdiens Multres, Thtre phmre, Comdies Portugaises, Architecture thtrale luso-amricaine, Casa da pera de Vila Rica/Ouro Preto.
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Trabalho de projecto apresentada como requisito parcial para obteno do grau de Mestre em Cincia e Sistemas de Informao Geogrfica.
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Resumo O objectivo geral deste trabalho foi contribuir para optimizar a teraputica anti-retroviral e o seu impacto na qualidade de vida do indivduo infectado pelo vrus da imunodeficincia humana. Pretendia-se definir se o anlogo no-nuclesido inibidor da transcriptase reversa do vrus da imunodeficincia humana, efavirenz, cumpria os requisitos para ser monitorizado na prtica clnica, estabelecer as condies para a sua eventual monitorizao e, simultaneamente, investigar outras aces farmacodinmicas do efavirenz em teraputicas prolongadas. Os critrios que fundamentam a indicao da monitorizao das concentraes plasmticas de frmacos, em geral, incluem: correlao entre a concentrao do frmaco e a eficcia/toxicidade; variabilidade inter-individual elevada; variabilidade intra-individual e janela teraputica reduzidas e ainda a elevada probabilidade de interaces medicamentosas. A correlao entre concentrao plasmtica de efavirenz e eficcia/toxicidade era conhecida e o facto de o efavirenz ser substrato, indutor e inibidor do sistema enzimtico citocromo P450 e ser utilizado em teraputicas crnicas e nunca em monoterapia, constituam fortes argumentos para a aplicao da monitorizao teraputica ao efavirenz. O presente trabalho contribuiu para o conhecimento de outros critrios, nomeadamente, a variabilidade nas concentraes plasmticas deste frmaco, entre indivduos e no mesmo indivduo, e permitiu definir diferentes aspectos para a prtica da monitorizao teraputica deste frmaco, entre eles, o volume de plasma necessrio, o parmetro farmacocintico a avaliar e a periodicidade das quantificaes. Para se atingirem os objectivos definidos foi necessrio, em primeiro lugar, proceder instalao e validao de um mtodo de quantificao de concentraes de efavirenz, em plasma de indivduos infectados pelo vrus da imunodeficincia humana: ficou disponvel no Laboratrio de Farmacologia da Faculdade de Cincias Mdicas, um mtodo que permite a monitorizao das concentraes plasmticas de nove frmacos anti-retrovirais (nevirapina, indinavir, amprenavir, atazanavir, ritonavir, efavirenz, lopinavir, saquinavir e nelfinavir). O mtodo desenvolvido est presentemente a ser utilizado na monitorizao teraputica destes frmacos e em estudos Farmacolgicos. Esta quantificao realizada numa nica corrida analtica de cromatografia lquida de elevada eficincia, a partir de 0,4 mL de plasma de cada indivduo e a sua qualidade avaliada, bianualmente, por uma entidade externa. Posteriormente, com o objectivo de as comparar, procurou-se conhecer a variabilidade entre indivduos e intra-individual das concentraes lasmticas do frmaco e concluiu-se que a variabilidade entre indivduos superior intra-individual, o que suporta a monitorizao das suas concentraes. Uma vez encontrada uma variabilidade inter-individual elevada, surgiu um outro objectivo especfico, que consistiu na identificao de possveis factores a justificassem. Na presente dissertao foi mostrado que o sexo, idade, peso e etnia no justificam por si s esta variao, no sendo possvel o ajuste de dose com base nestas variveis. Esta concluso constitui um factor adicional que refora que a toma da dose recomendada de efavirenz poder no ser apropriada para todos os indivduos. A co-infeco pelos vrus da hepatite B e/ou C comum nesta populao e poderia ser um dos factores implicados nesta variabilidade farmacocintica. A realizao do presente trabalho permitiu sugerir que a presena desta co-infeco per se no contribui para o aumento das concentraes plasmticas do frmaco; que, em indivduos co-infectados com funo heptica normal, no h um risco acrescido de toxicidade dependente da concentrao e que as indicaes para a monitorizao teraputica de efavirenz em indivduos co-infectados, com funo heptica normal, so semelhantes aquelas descritas para indivduos mono-infectados pelo vrus da imunodeficincia humana. Um outro objectivo especfico deste trabalho surgiu quando foi descrito que os efeitos dos anlogos no-nuclesidos inibidores da transcriptase reversa no perfil de lpidos e lipoprotenas dos indivduos pareciam diferir dos efeitos descritos para os inibidores de protease, que eram frequentemente associados a deslipidmia. Os anlogos no-nuclesidos inibidores da transcriptase reversa tinham sido associados a aumentos nos nveis de colesterol associado s lipoprotenas de elevada densidade. Esta observao, alm de no ser consensual, podia ser imputada ao decrscimo na carga viral dos indivduos em teraputica e correspondia a estudos observacionais de curta-durao. Estes factos estimularam a realizao de uma anlise prospectiva dos valores da concentrao de lpidos e lipoprotenas em doentes medicados com efavirenz e avaliao da sua eventual relao com a concentrao deste nti-retroviral, a curto e a longo-termo. Pela primeira vez, foi demonstrado que o efeito do efavirenz no colesterol associado s lipoprotenas de elevada densidade permaneceu durante 36 meses, que o aumento dependente do valor basal destas lipoprotenas e da concentrao plasmtica do frmaco. Mostrou-se tambm que, em associao a este aumento quantitativo, o efavirenz estava associado a um aumento qualitativo, com uma melhoria da funo antioxidante destas lipoprotenas, avaliada pela actividade do enzima paraoxonase-1. Em resumo, os diferentes estudos includos na presente dissertao tm como concluso geral que possvel optimizar a resposta teraputica com efavirenz atravs da monitorizao das suas concentraes plasmticas. A realizao deste trabalho contribuiu para o conhecimento cientfico atravs: 1. Da instalao e validao de um mtodo de quantificao de concentraes de anlogos no-nuclesidos inibidores da transcriptase reversa e inibidores da protease em plasma de indivduos infectados pelo vrus da imunodeficincia humana. 2. Do estudo da variabilidade inter e intra-individual nas concentraes plasmticas de efavirenz. A superioridade da variabilidade inter-individual relativamente associada ao mesmo indivduo comprova a importncia de monitorizar as concentraes plasmticas deste frmaco. 3. Da definio de procedimentos operativos para a monitorizao teraputica do efavirenz em geral e numa populao particular: os indivduos co-infectados pelos vrus da hepatite B e/ou C com funo heptica normal. 4. Da descoberta de aces farmacodinmicas do efavirenz, a longo prazo, nomeadamente o efeito benfico (quantitativo e qualitativo) no colesterol associado s lipoprotenas de elevada densidade. Este efeito mantido durante trs anos e dependente da concentrao plasmtica do frmaco, o que salienta a importncia de monitorizar as suas concentraes.
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Nearly 400 hemodialysis patients treated at 5 different hemodialysis units in Rio de Janeiro were tested for one year for the presence of hepatitis C and B markers. During the same period, samples were also obtained from 35 continuous ambulatory peritoneal dialysis (CAPD) patients and from 242 health care workers. Depending on the hemodialysis unit studied, anti-HCV prevalence rates ranging from 47% to 82% (mean 65%) were detected. CAPD patients showed a lower prevalence of 17%. The prevalence of antibodies against hepatitis C virus (anti-HCV) among health care workers was 2.9%. We observed a hepatitis C attack rate of 11.5% per year in the anti-HCV-negative hemodialysis patient population. An average of 9.4% of the hemodialysis patients were chronic carriers of hepatitis B virus (HBV) (range 1.8% - 20.4%), while 48.9% showed markers of previous HBV infection. The HBV attack rate was 4.5% per year (range 0% - 6%). These results indicate an alarming high prevalence of anti-HCV among hemodialysis patients of this studied region.
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The response to interferon treatment in chronic hepatitis NANB/C has usually been classified as complete, partial or absent, according to the behavior of serum alanine aminotransferase (ALT). However, a more detailed observation of the enzymatic activity has shown that the patterns may be more complex. The aim of this study was to describe the long term follow-up and patterns of ALT response in patients with chronic hepatitis NANB/C treated with recombinant interferon-alpha. A follow-up of 6 months or more after interferon-a was achieved in 44 patients. We have classified the serum ALT responses into six patterns and the observed frequencies were as follows: I. Long term response = 9 (20.5%); II. Normalization followed by persistent relapse after IFN = 7 (15.9%); III. Normalization with transient relapse = 5 (11.9%); IV. Temporary normalization and relapse during IFN = 4 (9.1%); V. Partial response (more than 50% of ALT decrease) = 7 (15.9%); VI. No response = 12 (27.3%). In conclusion, ALT patterns vary widely during and after IFN treatment and can be classified in at least 6 types.
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In the present study we report the results of an analysis, based on serotyping, multilocus enzyme electrophoresis (MEE), and ribotyping of N. meningitidis serogroup C strains isolated from patients with meningococcal disease (MD) in Rio Grande do Sul (RS) and Santa Catarina (SC) States, Brazil, as the Center of Epidemiology Control of Ministry of Health detected an increasing of MD cases due to this serogroup in the last two years (1992-1993). We have demonstrated that the MD due to N.meningitidis serogroup C strains in RS and SC States occurring in the last 4 years were caused mainly by one clone of strains (ET 40), with isolates indistinguishable by serogroup, serotype, subtype and even by ribotyping. One small number of cases that were not due to an ET 40 strains, represent closely related clones that probably are new lineages generated from the ET 40 clone referred as ET 11A complex. We have also analyzed N.meningitidis serogroup C strains isolated in the greater So Paulo in 1976 as representative of the first post epidemic year in that region. The ribotyping method, as well as MEE, could provide useful information about the clonal characteristics of those isolates and also of strains isolated in south Brazil. The strains from 1976 have more similarity with the actual endemic than epidemic strains, by the ribotyping, sulfonamide sensitivity, and MEE results. In conclusion, serotyping with monoclonal antibodies (C:2b:P1.3), MEE (ET 11 and ET 11A complex), and ribotyping by using ClaI restriction enzyme (Rb2), were useful to characterize these epidemic strains of N.meningitidis related to the increased incidence of MD in different States of south Brazil. It is mostly probable that these N.meningitidis serogroup C strains have poor or no genetic corelation with 1971-1975 epidemic serogroup C strains. The genetic similarity of members of the ET 11 and ET 11A complex were confirmed by the ribotyping method by using three restriction endonucleases.
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RESMO: Introduo: A anemia de clulas falciformes doena hereditria, com repercusso multi-orgnica, tem grande variabilidade na sua expresso clnica. Da o interesse do estudo de indicadores de prognóstico. A investigao realizada foi precedida de um resumo histrico incidindo sobre a compreenso de aspectos fundamentais da doena ao longo dos tempos. Na primeira parte do estudo e aps reviso bibliogrfica, foram referidos dados da fisiopatologia como base para os estudos que integram a presente dissertao. Abordou-se o estado da arte relativamente s complicaes, aos indicadores de prognóstico e teraputica utilizada. Objectivos: Constituram objectivos deste estudo realizado numa amostra populacional representativa: identificar as leses a nvel dos sistemas cardio-respiratrio e nervoso central, avaliando-se as respectivas repercusses; avaliar a presena de indicadores de prognóstico entre as variveis seleccionadas; estudar a eficcia e toxicidade da HU nos doentes com as formas graves da ACF. Para a prossecuo destes objectivos foram delineados para alm do estudo global trs estudos especficos: Estudo 1- repercusso no sistema cardio-respiratrio; Estudo 2- repercusso no sistema nervoso central; Estudo 3- teraputica com hidroxiureia. Doentes e mtodos: Procedeu-se a um estudo prospectivo e multi-institucional durante um perodo de trs anos tendo-se seleccionado para a amostra, e de acordo com critrios pr-definidos, 30 doentes com ACF na fase estvel da doena, com idades compreendidas entre os sete e os 18 anos, todos de origem africana excepo de um caucasiano. O diagnstico baseou-se em tcnicas de electroforese e estudo molecular que definiu o genotipo da doena e a presena da deleco da -talassmia assim como os haplotipos da amostra populacional. Foram utilizadas diferentes metodologias para avaliar a existncia de leso pulmonar e cerebral. Atravs do estudo estatstico foram seleccionadas diversas variveis como hipotticos indicadores de prognóstico. Estudo 1. Para determinar a existncia de leso a nvel pulmonar usaram-se duas metodologias diferentes, a avaliao da funo pulmonar com estudo da saturao da Hb em O2 no sangue arterial e a tomografia computadorizada de alta resoluo. Estudou-se tambm a possvel disfuno cardaca como repercusso da leso pulmonar, atravs do ecocardiograma, e os indicadores de prognóstico com significado estatstico para a leso encontrada. Estudo 2. O desenho deste estudo foi sobreponvel ao anterior, mas com metodologia adequada para o SNC. Procedeu-se ao estudo das leses cerebrais por meio de exames imagiolgicos, (RMN-CE e DTC) e de testes psicolgicos. Correlacionaram-se as trs metodologias utilizadas e a importncia de cada uma para a deciso de atitudes teraputicas preventivas. Estudo 3. Consistiu num estudo aberto prospectivo no controlado com nove crianas e adolescentes com formas graves de ACF, com o objectivo de avaliar a eficcia da teraputica com hidroxiureia, durante um perodo de 24 meses. Todos os doentes completaram no mnimo 15 meses de teraputica, com uma dose final mdia de 194 mg/K/dia. Resultados globais: Durante o perodo anterior investigao caracterizou-se a amostra populacional estudada quanto ao fenotipo gentico, clnico e hematolgico de acordo com os critrios utilizados por outros investigadores. Verificou-se: predomnio do haplotipo Bantu na forma homozigtica em 53% dos doentes; nmero total de EVO 3/ano em 87,5% dos doentes; crises de sequestrao em 18,75%; dactilites no primeiro ano de vida em 31,2%; quadro de spsis grave apenas num doente; crises de hiper-hemlise em 50%; e STA em 59,38% dos doentes. Quanto ao fenotipo hematolgico evidenciaram-se como factores de risco reticulocitose (13,1x103/l) e hiperbilirrubinmia (2,5 mg/dl) e como factores de bom prognóstico a presena de deleco de um gene da -talassmia em 46,9% dos doentes e valor mdio de Hb 8,1 g/dl. Resultados dos estudos parcelares: Estudo 1. Deste estudo infere-se que a DPR ligeira foi diagnosticada em 70% dos doentes, uma vez que as alteraes da difuso no foram estatisticamente significativas, o estudo dos gases no sangue no evidenciaram resultados anormais e a TCAR evidenciou alteraes em 43,3% dos doentes. Apenas num doente se verificou doena pulmonar obstrutiva relacionada com maior nmero da STA.O estudo da disfuno cardaca encontrada em 86,7% dos doentes no reflecte a repercusso da DPR a nvel cardaco, podendo estar associada s alteraes fisiopatolgicas da prpria anemia crnica. Encontraram-se indicadores de prognóstico hematolgicos e clnicos. Entre os primeiros, valores de Hb 8,5 g/dl e de HbF 13% foram considerados indicadores de bom prognóstico para a leso pulmonar. Em relao aos parmetros clnicos, as STA no foram consideradas indicadoras de prognóstico para a DPR ao contrrio do que se verificou com o nmero de EVO. Pela anlise dos parmetros genticos e socio-econmicos provou-se a ausncia de relao estatisticamente significativa com leso pulmonar. Estudo 2. Pela RMN-CE foram diagnosticados ES em 33,3% com uma localizao preferencial na substncia branca profunda em 26,6% dos doentes. Relativamente aos parmetros hematolgicos seleccionados, o valor mdio da HbF 8,6% constituu um indicador de bom prognóstico para o aparecimento de ES, enquanto o valor mdio de leuccitos 12.39x103/l foi considerado um indicador de mau prognóstico. No estudo do DTC apenas um doente apresentou aumento da velocidade do fluxo cerebral na ACM igual a 196 cm/segundos, associado a vasculopatia grave. Os testes psicolgicos alterados em 80% dos doentes mostraram ser o mtodo mais sensvel para detectar alteraes do neurodesenvolvimento, mas sem correlao com os ES em 10% dos doentes. Reala-se a baixa percentagem de DTC patolgicos encontrados neste estudo em relao ao nmero elevado de ES e de testes psicolgicos alterados, no se verificando concordncia entre os trs exames. Dos indicadores de prognóstico estudados a -talassmia foi considerada um factor de proteco para o coeficiente de inteligncia da escala de Wechsler. Em relao a parmetros clnicos estudados os doentes com maior nmero de EVO, tem em mdia valores inferiores nos testes psicolgicos. Estudo 3. Neste estudo verificou-se que o valor mdio da HbF aumentou significativamente de 7,04% para 13,75,3% (p=0,028) ao fim de 15 meses de teraputica com hidroxiureia. Clinicamente todos os doentes responderam significativamente com uma reduo de 80% no nmero de EVO, 69% no nmero de internamentos, 76% no nmero de dias de hospitalizao e 67% no nmero de transfuses. Deste modo comprovou-se no s a eficcia desta teraputica neste grupo peditrico como tambm a falta de efeitos secundrios significativos. Considera-se a necessidade de estudos mais prolongados e em grande sries, para com segurana se usar a HU antes que a leso orgnica se estabelea, portanto logo nos primeiros anos de vida. Concluso: Na amostra populacional estudada foram evidenciadas leses pulmonares e cerebrais na grande maioria dos doentes que condicionaram a sua qualidade de vida. Foram identificados indicadores de prognóstico que podero eventualmente ditar medidas teraputicas precoces com o objectivo de diminuir a morbilidade e a mortalidade neste grupo etrio. Demonstrou-se que a teraputica com a HU foi eficaz e bem tolerada----------ABSTRACT: Background: Sickle cell anemia (SCA), a hereditary disease characterized by pain and lifetime multi-organic lesion, is a challenge for all that work with carriers of this disease. The clinical expression variability of SCA is a constant reality and a problem to be solved in the current world of investigation, for which the knowledge of prognostic indicators responsible for the different aspects of clinical evolution diversity wiil be an added value. The study is preceded by a historical summary of the most important factors in the evolution of SCA, which are in themselves, an incentive for future research. In the first part of the study, after an extensive bibliographical revision, physiopathology data is referred to in general and specifically regarding the target organs, that constituted the base for the studies presented in the dissertation. The state of the art for the complications to be studied, the choice of prognostic indicators and the therapeutics application, were approached for the renewed interest in the theme. Aims: In regard to the investigation, the objective was to study the lesions in the most affected organs of a chosen pediatric group, to investigate prognostic indicators for lung and cerebral lesions and to evaluate the protective effect of hydroxyurea in children with severe outcomes. Patients and methods: A prospective and multi-institutional study was carried out during a three-year period, February 1998 to March 2001, with children and adolescents followed up at a Immunohematology Outpatient Clinic of Dona Estefnia's Hospital, Lisbon. Based in predefined criteria, 30 children with SCA were selected in a stable phase of the disease, aged from seven to 18 years old, all of whom were of African origin with exception of one who was Caucasian. The diagnosis was based on electrophoresis techniques and molecular study that allowed to define the genotype, the presence of deletional alpha-thalassemia as well as haplotypes in the population. Different methodologies were used to evaluate the existence of lung and cerebral lesion. Statistical study of the different variables selected the prognostic indicators. In Study 1, to determine the existence of lung lesion two different methodologies were used: pulmonar function study with arterial blood gases determination; and high resolution computerized tomography. Heart dysfunction as a repercussion of lung lesion was also studied through echocardiography, and prognostic indicators were statistically significant for lesions found. The design of Study 2 was similar to Study 1, but with the appropriate methodology for CNS. After neurological examination, which was normal in all patients (control group), cerebral lesions were studied with imagiologic exams (MRN-CE and TCD) and psychological tests. These three methodologies were correlated and the importance of each one in the decision of the therapeutic profilactic attitudes. Study 3 consisted of a controlled prospective open study in children with severe forms of SCA, with the aim of the evaluating therapeutic effectiveness of hydroxyurea, during a period of 24 months. Results: In the global overall study preceding the Studies 1,2 and 3, there were a prevalence of haplotype Bantu (53%) and other risk factors, namely the number of VOC (87,5%), sequestration crisis (18,75%), dactilytis in first year of life(31,2%), hyperhemolysis crisis (50%) and ATC in more than half of the patients (59,38%). This group of bad prognostic indicators, associated with the population of the lower class according to the Graffar scale, demonstrates the importance of primary health care services, information provided to the children and their relatives, as well as the interest in prophylactic therapeutics, specific screening and prenatal diagnosis. Study 1. It was evident from this study that slight RPD was diagnosed in 70% of the patients, because alterations of the diffusion had no statistical significance and arterial blood gases determinations were normal. Only one patient had restrictive lung disease related with numerous ACS. However ACS was not considered a prognostic indicator for RPD, contrary to the number of EVO. HRTC revealed discreet fibrotic lines that could be related with slight RPD, but the lack of correlation of these two exams (33%) supports the value of lung function tests for precocious diagnosis of RPD. Heart dysfunction was found in 86,7% of patients, does not reflect the repercussion of RPD, but with the physiopathology of chronic anemia. Hematologic and clinical prognostic indicators were found. Good prognostic indicators for the non-evolution of RPD with average Hb values of 8,5 g/dl and average HbF values of 13%, respectively. The genetic and social-economic factors had no statistical significance; nevertheless, they were more prevalent among Bantu haplotype (53,3%) in patients with RPD. Study 2. RMN-CE detected SI in 33,3% of the patients, with preferential location in deep white substance in 26,6% and in front lobe in 20%. This distribution can be related to structural aspects of the brain and with the high sensibility of this organ to hypoxia. From the hematological parameters selected, average HbF value 8,6% and average leucocyte count 12.39x103/l were prognostic indicators with different meaning to SI. The increase in the total bilirubin related to hyperhemolysis clinically explains the genesis of SI In the TCD study, only one patient had increased cerebral flow speed >196 cm/sec in CMA, which corresponded to serious vasculopathy in AngioMR. This patient never present previously neurological symptoms and had several hyperhemolysis crisis and VOC as risk factors. Low percentage of pathological TCD in this study, in relation to the high number of SI and altered tests, although without correlation among the three exams, is probably attributed to factors related to the methodology, aspects of cerebral physiopathology or perhaps a sign of good prognostic if the duration of study had not been so short. TCD should be used as a screening method in the age groups with higher risk of AVC and should never be considered separately in prophylactic therapeutics indication. Psychological tests were the most sensitive method to detect neurodevelopment impairment; in 80% of patients the neuropsychologics tests were altered, but without correlation with SI (10%). Since SI can become evident during the first two years of life and develop with time, the first psychological tests should be carried out between 3 and 5 years of age to timely be referred to special education and stimulation programs. Prognostic indicators to psychological tests were also found: alpha-thalassemia was found to be a protection factor of the IQ, just as other hematologic factors (hematocrit, MGCV and erythrocytes count). In relation to clinical parameters, although without statistical significance, patients with larger number of VOC had average lower scores versus the average in tests, except in TP. Results from different studies were conclusive as to the type of lesion found and the importance of prognostic indicators. Study 3. All the patients completed a minimum of 15 months therapeutic treatment with the final average daily dose of 194 mg/kg/day. The average value of the fetal hemoglobin increased significantly from 7,03,9% to 13,75,3% (p=0.028). The HbF average values increased from 6% to 15% after 15 months of therapeutic treatment. Clinically there was a reduction of 80% in the number of VOE , 69% in the number of hospitalization, 76% in the number of days of hospitalization and 67% in the number of transfusions. Once again the effectiveness of this treatment in this pediatric group, as well as the lack of any significant secondary effects, was evident. The study confirms the need for further detailed research in order to safely effect the appropriate treatment prior to the development of organic lesions, which ideally should be in the first year of life. Conclusions: These results allow us to clarify the importance of either pulmonary lesions or either nervous central system impairment among patients, children and adolescents, with sickle cell anemia. These lesions were demonstrated in most of the patients studied compromising their quality of life and the mortality. The treatment with HU is proved to be effective and having low toxicity.
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Hepatitis G virus/ GB virus C is a novel flavivirus recently detected in hepatitis non A-E cases. In this study, the presence of this virus in chronic non-B, non-C hepatitis patients was evaluated using GBV-C specific PCR and this virus was detected in one out of thirteen patients. This patient has presented a severe liver failure, has lived for a long time in the Western Amazon basin and no other cause for this clinical picture was reported. The impact of the discovery of this new agent is still under evaluation throughout the world. The study of the prevalence of this virus among chronic hepatitis patients and healthy individuals (as blood donors) will furnish subside to evaluate its real pathogenicity.
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The identification of the major agents causing human hepatitis (Hepatitis A, B, C, D and E Viruses) was achieved during the last 30 years. These viruses are responsible for the vast majority of human viral hepatitis cases, but there are still some cases epidemiologically related to infectious agents without any evidence of infection with known virus, designated as hepatitis non A - E. Those cases are considered to be associated with at least three different viruses: 1 - Hepatitis B Virus mutants expressing its surface antigen (HBsAg) with altered epitopes or in low quantities; 2 - Another virus probably associated with enteral transmitted non A-E hepatitis, called Hepatitis F Virus. Still more studies are necessary to better characterize this agent; 3 - Hepatitis G Virus or GB virus C, recently identified throughout the world (including Brazil) as a Flavivirus responsible for about 10% of parenteral transmitted hepatitis non A-E. Probably still other unknown viruses are responsible for human hepatitis cases without evidence of infection by any of these viruses, that could be called as non A-G hepatitis.
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Dissertao apresentada na Faculdade de Cincias e Tecnologia da Universidade Nova de Lisboa para obteno do grau de Mestre em BioOrgnica
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The determination of aminotranferases levels is very useful in the diagnosis of hepatopathies. In recent years, an elevated serum ALT level in blood donors has been associated with an increased risk of post-transfusion hepatitis (PTH). The purpose of the study was to research the factors associated with elevated ALT levels in a cohort of voluntary blood donors and to evaluate the relationship between increased ALT levels and the development of hepatitis C (HCV) infection. 166 volunteer blood donors with elevated ALT at the time of their first donation were studied. All of the donors were questioned about previous hepatopathies, exposure to hepatitis, exposure to chemicals, use of medication or drugs, sexual behaviour, contact with blood or secretions and their intake of alcohol. Every three months, the serum levels of AST, ALT, alkaline phosphatase, gamma glutamyl transpeptidase, cholesterol, triglyceride and glycemia are assessed over a two year follow-up. The serum thyroid hormone levels as well as the presence of auto-antibodies were also measured. Abdominal ultrasound was performed in all patients with persistently elevated ALT or AST levels. A needle biopsy of liver was performed in 9 donors without definite diagnostic after medical investigation. The presence of anti-HCV antibodies in 116 donors were assayed again the first clinical evaluation. At the end of follow-up period (2 years later) 71 donors were tested again for the presence of anti-HCV antibodies. None of donors resulted positive for hepatitis B or hepatitis C markers during the follow-up. Of the 116 donors, 101 (87%) had persistently elevated ALT serum levels during the follow-up. Obesity and alcoholism were the principal conditions related to elevated ALT serum levels in 91/101 (90.1%) donors. Hypertriglyceridemia, hypercholesterolemia, hypothyroidism and diabetes mellitus also were associated with increased ALT levels. Only 1/101 (0.9%) had mild chronic active non A-G viral hepatitis and 3/101 (2.9%) had liver biopsy with non-specific reactive hepatitis. The determination of ALT levels was not useful to detect donors infected with HCV at donation in Brazil, including the initial seronegative anti-HCV phase.
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We assessed the frequency of serological markers of hepatitis B virus (HBV) and hepatitis C virus (HCV) infections in 365 alcoholics by determining, by ELISA, the presence of HBsAg, anti-HBc, anti-HBs and anti-HCV. Fifty patients were cirrhotics and 315 had no evidence of hepatic cirrhosis; of the latter HBsAg was assessed in all, anti-HBc and anti-HBs in 130, and anti-HCV in 210. Among the alcoholics the frequencies of HBsAg (1.9%), anti-HBc (28.3%) and anti-HCV (3.8%) were higher (p<0.001) than among the controls (N=17,059), 0.4%, 4.0% and 0.4% respectively. The frequency of positive HBsAg was higher (p<0.001) in the cirrhotic patients (8.0%) than in alcoholics without cirrhosis (0.95%) and in controls (0.4%), and similar between the latter; of anti-HBc in alcoholics without cirrhosis (28.5%) was similar in cirrhotics patients (28.0%) and higher (p<0.001) than in the controls (4.0%); of anti-HBs in alcoholics without cirrhosis (20.8%) was similar to that of the cirrhotic patients (10.0%), and the anti-HCV was similar between alcoholics with (6.0%) and without cirrhosis (3.3%) and higher (p<0.001) than in controls (0.4%). We concluded that: a) alcoholics with or without cirrhosis have similar frequencies of infection with HBV and HCV between them, and higher than in nonalcoholics; b) alcoholics without cirrhosis had a frequency of HBV active infection (HBsAg+) which was similar to the controls, whereas among those who progressed to cirrhosis this frequency was significantly higher, what suggests that HBV may be implicated in the pathogenesis of cirrhosis in a few alcoholic individuals.
