Prevención de la transmisión maternoinfantil del virus de la hepatitis B. directrices sobre la profilaxis con antivirales en el embarazo / Prevention of mother-to-child transmission of hepatitis B virus. guidelines on antiviral prophylaxis in pregnancy

Según estimaciones de la Organización Mundial de la Salud (OMS), en el 2015 257 millones de personas en el mundo tenían la infección crónica por el virus de la hepatitis B (VHB) y 900 000 fallecieron a causa de ella, en la mayor parte de los casos de cirrosis o carcinoma hepatocelular. La mayoría de las defunciones asociadas con el VHB en personas adultas obedecen a infecciones contraídas al nacer o en los cinco primeros años de vida. En mayo del 2016, la Asamblea Mundial de la Salud aprobó la Estrategia mundial del sector de la salud contra las hepatitis víricas 2016-2021, en la que se hace un llamado a eliminar las hepatitis virales como amenaza de salud pública ­definida como una reducción de 90% de la incidencia de infecciones y una reducción de 65% de la mortalidad­ para el 2030. La eliminación de la infección por el VHB como amenaza de salud pública conlleva la necesidad de reducir la prevalencia del antígeno de superficie del virus de la hepatitis B (HBsAg) a menos de 0,1% en los niños de 5 años de edad. Esta meta se puede lograr mediante la vacunación de todos los recién nacidos contra la hepatitis B y otras intervenciones orientadas a prevenir la transmisión maternoinfantil del VHB

Reducción en la infección por VHB y VHD en dos poblaciones indígenas de la Amazonia peruana después de la vacunación contra la hepatitis B / Reduction of HBV and HDV infection in two indigenous peoples of Peruvian Amazon after the vaccination against hepatitis B

Resumen: Objetivo: Conocer el resultado de la vacunación contra la hepatitis B en las comunidades hiperendémicas Kandozi y Chapra de la Amazonia Peruana a partir de la prevalencia de infecciones por los virus de la hepatitis B (VHB) y Delta (VHD), ocho años después de iniciada la vacunación. Material y métodos: Se realizó un estudio transversal en 2 944 pobladores de 67 comunidades indígenas Kandozi y Chapra en abril de 2010. El tamizaje serológico para el antígeno de superficie del VHB (HBsAg), anticuerpos anti-HBc IgM e IgG, anticuerpos anti-HBs y anti-VHD se determinaron mediante pruebas de ELISA. Resultados: Las tasas de prevalencia del HBsAg, anti-HBc IgG, anti-HBs ≥10 mlUI/ml y anti-VHD fueron 2.3, 39.13, 50.95 y 2.11%, respectivamente. La prevalencia del HBsAg en niños <11 años fue cero. Entre los portadores del HBsAg, las tasas de prevalencia de sobreinfeccion por el VHD e infección aguda por el VHB fueron 2.11% (todos fueron >14 años) y 11.94%, respectivamente. Conclusiones: Estos hallazgos muestran la eliminación de portadores de VHB en niños <11 años, ocho años después de iniciada la vacunación contra el VHB.

Abstract: Objective: To determine the outcome of the vaccination against hepatitis, we determined the prevalence of hepatitis B virus (HBV) and hepatitis D virus (HDV) infections, eight years after introduction of the vaccination. Materials and methods: A cross-sectional study was performed in 2 944 participants of 67 Kandozi and Chapra indigenous peoples in April 2010. Serological screening for hepatitis B surface antigen (HBsAg), antibody anti-HBc IgM and IgG, antibody anti-HBs and anti-HDV were determined by ELISA tests. Results: The prevalence rates of HBsAg, anti-HBc total, anti-HBs ≥10 mlUI/ml and anti-HDV were 2.3, 39.13, 50.95 and 2.11%, respectively. The prevalence rate of HBsAg in children <11 years was 0%. Among carriers of HBsAg, the prevalence rates of HDV and acute HBV infections were 2.11% (all were >14 years) and 11.94%, respectively. HBsAg and anti-HBc total were associated with individuals ≥10 years (p<0.001). Conclusions: These findings show the elimination of HBV carriers in children <11 years, eight years following introduction of the vaccination against HBV.

Identification of hepatitis B virus A1762T/G1764A double mutant strain in patients in Southern Brazil

Abstract Infection by hepatitis B virus (HBV) is a worldwide public health problem. Chronic HBV infection with high viral replication may lead to cirrhosis and/or hepatocellular carcinoma. Mutant HBV strains, such as the HBV A1762T/G1764A double mutant, have been associated with poor prognosis and higher risk of the patient for developing cirrhosis and/or hepatocellular carcinoma. This study analyzed the presence of the HBV A1762T/G1764A double mutant in patients with chronic HBV and its association with clinical parameters such as viral load, aminotransferases, and HBV antigens. A total of 49 patients with chronic hepatitis B were included in the study, and the HBV A1762T/G1764A double mutant strain was detected in four samples (8.16%) by polymerase chain reaction followed by restriction fragment length analysis (PCR-RFLP). The viral load was not significantly different between patients with or without the double mutant strain (p = 0.43). On the other hand, carriers of the HBV A1762T/G1764A double mutant had higher levels of ALT (p = 0.0028), while AST levels did not differ between groups (p = 0.051). In this study, 75% of the samples with the HBV A1762T/G1764A double mutation were HBeAg negative and anti-HBe positive, reflecting seroconversion even though they still displayed high viral loads. Our study has shown that the HBV A1762T/G1764A double mutant strain circulates in Brazilian patients, and is associated with elevated levels of ALT and HBeAg seroconversion.

Predictors of HBeAg seroconversion after long-term nucleos(t)ide analogues treatment for chronic hepatitis B: a multicenter study in real clinical setting

ABSTRACT Aims: To evaluate the HBeAg seroconversion rate in real clinical setting and explore its predictors in long-term nucleos(t)ide analogues (NAs) treatment for chronic hepatitis B (CHB). Methods: 251 patients were recruited from January 2001 to September 2009 in four hospitals in Hebei province, China, for this retrospective study. Clinical and laboratory data before and after treatment with lamivudine (LAM, 100 mg daily), adefovir (ADV, 10 mg daily), telbivudine (LDT, 600 mg daily), entecavir (ETV, 0.5 mg daily), and LAM/ADV combination were compared among three groups according to treatment outcomes: synchronous HBeAg loss and HBeAg seroconversion, anti-HBe development after treatment, and no anti-HBe. Adherence was also evaluated. Results: In real clinical setting, cumulative HBeAg seroconversion rates were 14.3%, 32.7%, 43.0%, 46.9%, and 50.5% after 1, 2, 3, 5, and 8 years, respectively. 45 patients (17.9%) were non-adherent. Adherence (p < 0.001, Hazard Ratio (HR) = 2.203), elevated alanine aminotransferase (ALT) levels (p < 0.001, HR = 2.049), and non-vertical transmission (p = 0.006, HR = 1.656) were predictors of HBeAg seroconversion. Conclusion: Adherence, elevated ALT, and non-vertical transmission are predictors of HBeAg seroconversion in CHB patients treated with NAs.

Cost-Effectiveness and Clinical Impact of Antiviral Strategies of HBeAG-Positive and Negative Chronic Hepatitis B

ABSTRACT Introduction. Chronic hepatitis B (CHB) is associated with high burden and healthcare costs. Virologic response achieved with antivirals is associated with progression avoidance. This study aimed to estimate the efficiency and clinical impact of antiviral strategies in CHB patients. Material and methods. A Markov model estimated lifetime complications and direct costs in both, HBeAg-positive and HBeAg-negative cohorts. Strategy 1 (71% of treated population) and strategy 2 (100%), both based on pegylated interferon (peg-IFN) followed by oral tenofovir or entecavir, were compared to no treatment. Progression was based on HBV-DNA levels. Rescue therapy with oral antivirals was applied for peg-IFN failure. Disease costs (€, 2014) and utilities were obtained from literature. Results. Compared to natural history, strategy 1 increased QALY (3.98 in HBeAg-positive, 2.16 in -negative cohort). With strategy 2, survival was up to 5.60 (HBeAg-positive) and 3.05 QALY (in HBeAg-negative). The model predicted avoidance of 128 and 86 carcinomas in HBeAg-positive and -negative patients with strategy 1, and up to 181 and 121 in HBeAg-positive and -negative for strategy 2. Total cost increased up to €102,841 (strategy 1) and €105,408 (strategy 2) in HBeAg-positive, and €85,858 and €93,754 in HBeAg-negative. A€1,581/QALY gained ratio was estimated versus the natural history for both strategies. In conclusion, increasing antiviral coverage would be efficient, reducing complications.

Poor sensitivity of rapid tests for the detection of antibodies to the hepatitis B virus: implications for field studies

Rapid tests (RTs) can be used as an alternative method for the conventional diagnosis of hepatitis B virus (HBV). This study aims to evaluate antibodies to HBsAg (anti-HBs) and antibodies to HBeAg (anti-HBe) RTs under different Brazilian settings. The following three groups were included: GI: viral hepatitis outpatient services; GII: low resource areas; and GIII: crack users and beauticians. Imuno-rápido anti-HBsAg™ and Imuno-rápido anti-HBeAg™ RTs were evaluated and showed specificities greater than 95% in all groups. The sensitivity values to anti-HBs were 50.38%, 51.05% and 46.73% and the sensitivity values to anti-HBe were 76.99%, 10.34% and 11.76% in the GI, GII and GIII groups, respectively. The assays had a low sensitivity and high specificity, which indicated their use for screening in regions endemic for HBV.

Evolution of hepatitis B serological markers in HIV coinfected patients: a case study

ABSTRACT OBJECTIVE To describe the evolution of serological markers among HIV and hepatitis B coinfected patients, with emphasis on evaluating the reactivation or seroreversion of these markers. METHODS The study population consisted of patients met in an AIDS Outpatient Clinic in São Paulo State, Brazil. We included in the analysis all HIV-infected and who underwent at least two positive hepatitis B surface antigen serological testing during clinical follow up, with tests taken six months apart. Patients were tested with commercial kits available for hepatitis B serological markers by microparticle enzyme immunoassay. Clinical variables were collected: age, sex, CD4+ T-cell count, HIV viral load, alanine aminotransferase level, exposure to antiretroviral drugs including lamivudine and/or tenofovir. RESULTS Among 2,242 HIV positive patients, we identified 105 (4.7%) patients with chronic hepatitis B. Follow up time for these patients varied from six months to 20.5 years. All patients underwent antiretroviral therapy during follow-up. Among patients with chronic hepatitis B, 58% were hepatitis B “e” antigen positive at the first assessment. Clearance of hepatitis B surface antigen occurred in 15% (16/105) of patients with chronic hepatitis B, and 50% (8/16) of these patients presented subsequent reactivation or seroreversion of hepatitis B surface antigen. Among hepatitis B “e” antigen positive patients, 57% (35/61) presented clearance of this serologic marker. During clinical follow up, 28.5% (10/35) of those who initially cleared hepatitis B “e” antigen presented seroreversion or reactivation of this marker. CONCLUSIONS Among HIV coinfected patients under antiretroviral therapy, changes of HBV serological markers were frequently observed. These results suggest that frequent monitoring of these serum markers should be recommended.

TeleCondutas: hepatite B / TeleGuides: Hepatitis B

As hepatite virais apresentam forma clínicas diversas, desde infecções assintomáticas até quadros de hepatopatia avançada, como cirrose e hepatocarcinoma. A equipe da atenção primária deve investigar pessoas com sinais e sintomas comuns da infecção, bem como assintomáticos que fazem parte do grupo de risco. Esta guia apresenta informação que orienta a conduta para casos de hepatite B no contexto da Atenção Primária à Saúde, incluindo: forma de transmissão, quadro clínico, suspeita ou diagnóstico de cirrose, diagnóstico de hepatite b, avaliação sorológica da hepatite b, avaliação de paciente com hepatite b aguda, avaliação de paciente com hepatite b crônica, rastreamento, vacina para hepatite b, encaminhamento para serviço especializado.

Efficacy of entecavir and tenofovir in chronic hepatitis B under treatment in the public health system in southern Brazil

There are about 350 million hepatitis B virus (HBV) carriers worldwide and chronic HBV is considered a major public health problem. The objective of the present study was to assess the effectiveness of the nucleos(t)ide analogues tenofovir (TDF) and entecavir (ETV) in the treatment of chronic HBV. A cross-sectional study was carried out from March-December 2013, including all patients with chronic HBV, over 18 years of age, undergoing therapy through the public health system in southern Brazil. Only the data relating to the first treatments performed with TDF or ETV were considered. Retreatment, co-infection, transplanted or immunosuppressed patients were excluded. Six hundred and forty patients were evaluated, of which 336 (52.5%) received TDF and 165 (25.8%) ETV. The other 139 (21.7%) used various combinations of nucleos(t)ide analogues and were excluded. The negativation of viral load was observed in 87.3% and 78.8% and the negativation of hepatitis B e antigen was achieved in 79% and 72% of those treated with ETV or TDF, respectively. Negativation of hepatitis B surface antigen was not observed. There was no occurrence of adverse effects. This is a real-life study demonstrating that long-term treatment with ETV and TDF is both safe and effective.

Characteristics of an outpatient chronic hepatitis B virus infection cohort / Caracterização de uma coorte ambulatorial de pacientes com infecção por vírus da hepatite B crônica

ABSTRACT Objective: To characterize a chronic hepatitis B cohort based on initial and follow-up clinical evaluations. Methods: A retrospective and descriptive analysis of clinical and laboratory data from chronic HBsAg adult carriers, without HIV, unexposed to treatment, with at least two outpatient visits, between February 2006 and November 2012. Fisher´s exact test, χ², Wilcoxon, Spearman, multiple comparisons and Kappa tests were applied, the level of significance adopted was 5%, with a 95% confidence interval. Results: 175 patients with mean age of 42.95±12.53 years were included: 93 (53.1%) were men, 152 (86.9%) were negative for hepatitis B e-antigen (HBeAg), 3 (1.7%) had hepatitis C coinfection, 15 (8.6%) had cirrhosis, and 2 (1.1%) had hepatocellular carcinoma. Genotype A predominated. Sixty-six patients (37.7%) had active hepatitis, 6 (3.4%) presented immune tolerance, and 38 (21.7%) were inactive carriers. Exacerbations and/or viral breakthrough were detected in 16 patients (9.1%). In 32 patients (18.3%), hepatitis B virus DNA remained persistently elevated and alanine aminotransferase levels were normal, whereas in 17 (9.7%), there was low hepatitis B virus DNA and alterated alanine aminotransferase. If only initial alanine aminotransferase and hepatitis B virus DNA values were considered, 15 cases of active hepatitis would not have been detected. Advanced fibrosis was more common in HBeAg-positive patients, and it was significantly associated with transaminases, hepatitis B virus DNA, and age. Conclusion: Many patients had active hepatitis, but almost 25%, who were HBeAg non-reactive, were only identified because of combined analyses of the hepatitis B virus DNA and transaminases levels, sometimes associated with histological data, after clinical follow-up. .

RESUMO Objetivo: Caracterizar uma coorte de pacientes com hepatite B crônica, segundo parâmetros iniciais e evolutivos. Métodos: Análise retrospectiva e descritiva dos dados clínicos e laboratoriais de portadores crônicos adultos do HBsAg, sem HIV, virgens de tratamento, com ao menos duas consultas ambulatoriais entre fevereiro de 2006 a novembro de 2012. Empregaram-se os testes exato de Fisher, χ², Wilcoxon, Spearman, Kappa e comparações múltiplas, o nível de significância estatística adotado foi de 5% e intervalo de confiança de 95%. Resultados: Foram incluídos 175 pacientes com média de idade de 42,95±12,53 anos, 93 (53,1%) do sexo masculino, 152 (86,9%) não reagentes para o antígeno e (HBeAg), 3 (1,7%) coinfectados com hepatite C, 15 (8,6%) cirróticos e 2 (1,1%) com carcinoma hepatocelular. Predominou o genótipo A. Constataram-se hepatite ativa em 66 pacientes (37,7%), imunotolerância em 6 (3,4%), estado de portador inativo em 38 (21,7%), exacerbações e/ou escapes virais em 16 (9,1%). Em 32 (18,3%), havia DNA viral persistentemente elevado e alanina aminotransferase normal; em 17 (9,7%), carga viral constantemente baixa e alanina aminotransferase alterada. Se fossem considerados apenas transaminases e DNA viral iniciais, 15 casos de hepatite ativa não teriam sido evidenciados. Fibrose avançada foi mais prevalente em HBeAg reagentes e associou-se direta e significativamente ao DNA do vírus da hepatite, idade e transaminases. Conclusão: Grande parte dos pacientes apresentou hepatite ativa. Porém, aproximadamente um quarto (todos pertencentes ao grupo HBeAg não reagente) foram identificados somente em função da análise conjunta das mensurações sequenciais de DNA do vírus da hepatite e transaminases, por vezes aliada a dados histológicos, após seguimento. .

Os genótipos do vírus da hepatite B na África e no Brasil: evolução, disseminação e associação com a rota de escravos / The genotypes of hepatitis B virus in Africa and in Brazil: evolution, spread and association with the route of slaves

A infecção pelo vírus da hepatite B (HBV) representa um grave problema de saúde públicamundial, apesar da existência de uma vacina eficiente. Estima-se que cerca de 350 milhõesde indivíduos no mundo estejam cronicamente infectados, dos quais a maior parte seencontra em países em desenvolvimento. A heterogeneidade das sequências dos isoladosdo HBV permite a sua classificação em oito genótipos, A a H, baseada na divergência do genoma completo de mais de 7,5 por cento. A presente tese é composta principalmente de três manuscritos, sendo um trabalho publicado e dois outros em submissão, além de cinco trabalhos como colaboradora. Esses estudos se propuseram a investigar a evolução dos genótipos do HBV entre África e Brasil e associar a dispersão dos genótipos no Brasil com a rota de escravos. No primeiro trabalho, entitulado Analysis of Complete NucleotideSequences of Angolan Hepatitis B Virus Isolates Reveals the Existence of a SeparateLineage within Genotype E, realizamos a caracterização filogenética viral dos isolados circulantes em Angola e sua associação com os perfis sorológicos e moleculares existentes naquela população. Através dessas análises, identificamos a separação das amostrasangolanas como pertencentes a uma nova linhagem, composta por Angola, Namibia eRepublica Democratica do Congo, provisoriamente denominada pela nossa equipe, SWL(Southwest African Lineage). No segundo trabalho, entitulado HBV subgenotype A1:Relationships between Brazilian, African and Asian isolates, fomos em busca das históriaevolutiva do HBV/A1, e suas suas rotas de dispersão entre África e Brasil durante o período do tráfico negreiro. Surpreendentemente, observamos que todas as amostras brasileiras estão geneticamente relacionadas às amostras da Ásia, ao invés da África. Esse fato sugere quer que o HBV/A1 possa ter sido introduzino no Brasil a partir dos portos de Moçambique,no sudeste africano, ou diretamente atravpés da Índia por navegantes portugueses...

Hepatitis B virus (HBV) infection is one of the major global human health problems, despitethe existence of an effective vaccine. It is estimated that around 350 million people worldwideare chronically infected; most of them is in developing countries. The sequenceheterogeneity of HBV isolates has led to the classification of HBV into eight genotypes, A toH, based on full-length genomic divergence of more than 7.5 percent. This thesis is composedmainly of three manuscripts: One of them is already published and two others are insubmission. Five other manuscripts are listed as complementary production. These studieshave set out to understand the evolution of HBV genotypes between Africa and Brazil andassociate its dispersion with slave routes. In the first study, entitled Analysis of CompleteNucleotide Sequences of Hepatitis B Virus Isolates Angolan Reveals the Existence of aSeparate Lineage Within Genotype E , performed the phylogenetic characterization of viralisolates circulating in Angola and its association with serological and molecular profiles.Through these analyzes, we characterized a separated lineage composed by Angolan,Namibia and Democratic Republic of Congo, provisionally named by our team as SWL(Southwest African Lineage). In the second paper, entitled Hepatitis B virus subgenotypeA1: Relationships between Brazilian, African and Asian isolates we aimed investigate theevolutionary history and migration patterns of HBV/A1 from Africa to Brazil during the slavetrade. Surprisingly, was observed that all Brazilian samples are genetically related to Asianisolates, rather than the African ones. These finds suggest that Asia was the source ofHBV/A1 infection in Brazil, probably through Mozambique in southeastern Africa, or directlythrough India by Portuguese sailors...

Economic evaluation of treatments for chronic hepatitis B

The aim of this study was to conduct a cost-utility study of adefovir, entecavir, interferon alpha, pegylated interferon alpha, lamivudine and tenofovir for chronic hepatitis B in the context of Brazilian Public Health Care System. A systematic review was carried out for efficacy and safety. Another review was performed to collect utility data and transition probabilities between health states. A Markov model was developed in a time horizon of 40 years with annual cycles for three groups of: HBeAg positive, HBeAg negative, and all patients. These strategies were compared to a fourth group that received no treatment. Discount rates of 5% were applied and sensitivity analyses were performed. Tenofovir offered the best cost-utility ratio for the three evaluated models: U$397, U$385 and U$384 (per QALY, respectively, for HBeAg positive, negative, and all patients). All other strategies were completely dominated because they showed higher costs and lower effectiveness than tenofovir. The sequence of cost-utility in the three models was: tenofovir, entecavir, lamivudine, adefovir, telbivudine, pegylated interferon alpha, and interferon alpha. In the sensitivity analysis, adefovir showed lower cost-utility than telbivudine in some situations. The study has some limitations, primarily related to the creation of scenarios and modeling. In this study, tenofovir presented the best cost-utility ratio. The results obtained in this study will be valuable in decision-making and in the review of the clinical protocol, mainly involving the allocation of available resources for health care.

Relevamiento de la carga viral en áreas geográficas de Argentina con alta prevalencia del virus de hepatitis B / [Viral load survey from geographical areas within Argentina with high hepatitis B virus prevalence].

Several studies have demonstrated that viral load is a key factor to determine the development of HBV infection and to assess treatment options for the disease. There is a lack of studies analyzing viral load levels in chronic hepatitis B patients in Argentina and the epidemiologic information is limited. The aim of this study was to determine viral load levels and its distribution in patients diagnosed with chronic hepatitis B from geographical areas with high prevalence for HBV in Argentina. Fifty-one per cent of the study population had HBV DNA levels > or = 10(4) copies/ml and a median viral load of 11,910 copies/ml. The viral load was significantly higher in HBeAg seropositive patients compared with those seronegative for HBeAg (P < 0.05). Salta and Entre Ríos provinces showed low viral loads, while Chaco, Misiones and Formosa provinces had a median viral load ranging between 10(4) and 10(5) copies/ ml. This is the first study providing detailed information on viral load in chronic hepatitis B patients from Argentina. Availability of viral load levels in chronic hepatitis B enables evaluation of implementation of actions to analyze follow-up and/or treatment options for preventing disease complications, improving health care and diminishing the potential burden on the health care system.

Hepatitis B virus infection in children, adolescents, and their relatives: genotype distribution and precore and core gene mutations / Infecção pelo vírus da hepatite B em crianças, adolescentes e seus familiares: distribuição dos genótipos e mutações no gene pré-core e core

INTRODUCTION:The objectives of this study were evaluate hepatitis B virus (HBV) serological markers in children and adolescents followed up at the Child Institute of the Hospital das Clínicas, Faculdade de Medicina de São Paulo, Universidade de São Paulo; identify chronic HBV carriers and susceptible individuals in the intrafamilial environment; characterize HBV genotypes; and identify mutations in the patients and household contacts. METHODS: Ninety-five hepatitis B surface antigen-positive children aged <19 years and 118 household contacts were enrolled in this study. Commercial kits were used for the detection of serological markers, and PCR was used for genotyping. RESULTS: Hepatitis B e antigen (HBeAg) was detected in 66.3% (63/95) of cases. Three of the 30 HBeAg-negative and anti-HBeAg-positive patients presented with precore mutations and 11 presented with mutations in the basal core promoter (BCP). Genotype A was identified in 39 (43.8%) patients, genotype D in 45 (50.6%), and genotype C in 5 (5.6%). Of the 118 relatives, 40 were chronic HBV carriers, 52 presented with the anti-HBc marker, 19 were vaccinated, and 7 were susceptible. Among the relatives, genotypes A, D, and C were the most frequent. One parent presented with a precore mutation and 4 presented with BCP mutations. CONCLUSIONS: Genotypes A and D were the most frequent among children, adolescents, and their relatives. The high prevalence of HBV in the families showed the possibility of its intrafamilial transmission.

INTRODUÇÃO: Os objetivos deste estudo foram: avaliar os marcadores sorológicos nas crianças e adolescentes acompanhadas no Instituto da Criança do Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo (HC-FMUSP); identificar portadores crônicos do VHB e indivíduos suscetíveis no ambiente intrafamiliar; caracterizar o genótipo do VHB; observar a presença de cepas mutantes entre os pacientes e familiares estudados. MÉTODOS: Noventa e cinco crianças e adolescentes positivas para o antígeno de superfície do vírus da Hepatite B (AgHBs), menores de 19 anos, e 118 familiares foram envolvidos neste estudo. Foram utilizados kits comerciais para a pesquisa dos marcadores sorológicos e a PCR foi utilizada para genotipagem. RESULTADOS: O antígeno e do vírus da hepatite B (AgHBe) foi detectado em 66,3% (63/95) dos casos. Três dos 30 pacientes AgHBe negativo e anti-HBe positivo apresentaram mutação na região pré-core e 11 na região BCP. Em 39 (43,8%) pacientes, foi identificado o genótipo A, 45 (50,6%)o genótipo D e cinco (5,6%) o genótipo C. Dos 118 familiares estudados, 40 eram portadores crônicos do VHB, 52 tinham marcador sorológico de contato prévio e sete eram suscetíveis. Dentre os familiares AgHBs positivos, os genótipos A, D e C foram os mais frequentes. Um familiar apresentou mutação na região pré-core e quatro apresentaram mutação na região do BCP. CONCLUSÕES: Os genótipos A e D foram os mais frequentes dentre as crianças adolescentes e seus familiares. Alta frequência do VHB nos familiares mostrou a possibilidade de transmissão intrafamiliar.

Clinical, demographic and epidemiological characteristics of patients with hepatitis B followed at a university hospital in southeastern Brazil: predominance of HBeAg negative cases / Características clínicas, demográficas e epidemiológicas dos pacientes com hepatite B em seguimento em hospital universitário no sudeste do Brasil: predominância de casos HBeAg negativos

INTRODUCTION: Hepatitis B is common in Brazil, although there are regional differences regarding the degree of endemicity, the most frequent forms of transmission and the presence of different evolutive stages of chronic disease. The present study aimed to determine the clinical, demographic and epidemiological characteristics of patients chronically infected with hepatitis B virus (HBV) residing in the Ribeirão Preto region, southeastern Brazil. METHODS: A total of 529 medical records of individuals with HBV monoinfection were reviewed. RESULTS: More than 60 percent of the subjects were males, with a mean age of 38 years-old. The HBeAg-negative serological pattern was verified in 84.4 percent of the patients, among whom the risk of vertical/intrafamily transmission was 43.2 percent (p = 0.02). The consumption of alcohol in amounts exceeding 20g a day was observed in 21.3 percent of the subjects and was more frequent among men (33 percent) (p < 0.001). Among patients with cirrhosis, 54.1 percent were alcohol abusers (p = 0.04), all of them males. The presence of cirrhosis was more frequent in the HBeAg-positive group (24.4 percent) than in the HBeAg-negative group (10.2 percent) (p < 0.001). CONCLUSIONS: High proportions of HBV-infected subjects with an HBeAg-negative pattern were observed, with a higher risk of vertical/intrafamily transmission. Alcohol abuse was associated with male subjects and with cirrhosis of the liver in this group. A tendency toward an increase in the number of HBeAg-negative cases was observed over time.

INTRODUÇÃO: No Brasil, a hepatite B é comum. No entanto, há diferenças regionais no que diz respeito ao grau de endemicidade, as formas de transmissão mais encontradas e a presença dos diferentes estágios evolutivos da doença crônica. O objetivo deste trabalho foi o de conhecer características clínicas, demográficas e epidemiológicas de pacientes cronicamente infectados pelo vírus da hepatite B (HBV), residentes na região de Ribeirão Preto, no sudeste do Brasil. MÉTODOS: Foi realizada a análise retrospectiva de 529 prontuários de indivíduos com monoinfecção pelo HBV. RESULTADOS: Mais de 60 por cento eram masculinos, a média de idade foi de 38 anos. O padrão sorológico HBeAg negativo foi encontrado em 84,4 por cento dos pacientes, entre os quais o risco para transmissão vertical/intrafamiliar foi de 43,2 por cento (p = 0,02). Verificou-se uso de álcool em quantidades maiores que 20g ao dia em 21,3 por cento dos indivíduos, sendo mais frequente entre os homens (33 por cento) (p < 0,001). Entre os pacientes com cirrose, 54,1 por cento faziam uso abusivo de bebidas alcoólicas (p = 0,04), sendo todos estes do gênero masculino. A presença de cirrose foi maior no grupo HBeAg positivo (24,4 por cento) que no grupo HBeAg negativo (10,2 por cento) (p < 0,001). CONCLUSÕES: Observaram-se elevadas proporções de indivíduos com infecção pelo HBV com padrão sorológico HBeAg negativo, entre os quais houve maior risco para a transmissão vertical/intrafamiliar. O uso abusivo de álcool esteve associado a indivíduos do sexo masculino e, neste grupo, à cirrose hepática. Observou-se tendência ao aumento no número de casos HBeAg negativo ao longo do tempo.

Epidemiology and molecular characterization of hepatitis B virus in Luanda, Angola

An estimated 360 million people are infected with hepatitis B virus (HBV) worldwide. Among these, 65 million live in Africa. Despite the high levels of hepatitis B in Africa, HBV epidemiology is still poorly documented in most African countries. In this work, the epidemiological and molecular characteristics of HBV infection were evaluated among the staff, visitors and adult patients (n = 508) of a public hospital in Luanda, Angola. The overall prevalence of hepatitis B core antibody (anti-HBc) and hepatitis B surface antigen was 79.7 percent and 15.1 percent, respectively. HBV infection was higher in males and was more prevalent in individuals younger than 50 years old. HBV-DNA was detected in 100 percent of HBV "e" antigen-positive serum samples and in 49 percent of anti-hepatitis Be antibody-positive samples. Thirty-five out of the 40 HBV genotypes belonged to genotype E. Circulation of genotypes A (4 samples) and D (1 sample) was also observed. The present study demonstrates that HBV infection is endemic in Luanda, which has a predominance of genotype E. This genotype is only sporadically found outside of Africa and is thought to have emerged in Africa at a time when the trans-Atlantic slave trade had stopped.

Response predictors to treatment with pegylated interferon in chronic hepatitis B

The clinical and epidemiological importance of chronic B hepatitis is currently unquestionable as a cause of end-stage liver disease and hepatocellular carcinoma. Recently, predictors of treatment response of this disease have been studied, both before and during the course of medication. Therapy stopping rules have been proposed, which may be useful in patients presenting poor treatment tolerance. This review discusses the treatment response predictors usefulness, with emphasis on ALT, quantitative HBsAg and HBeAg, quantitative HBV-DNA and HBV genotype.

Simultaneous quantitation of serum HBV DNA and HBeAg can distinguish between slow and fast viral responses to antiviral therapy in patients with chronic hepatitis B / A quantificação simultânea do DNA VHB e do AgHBe séricos podem distinguir entre resposta viral lenta e rápida à terapêutica anti-viral em pacientes com hepatite crônica B

BACKGROUND: The quantitation of serum HBeAg is not commonly used to monitor viral response to therapy in chronic hepatitis B. METHODS: In this study, 21 patients receiving varying therapies were followed and their viral response monitored by concomitant viral load and HBeAg quantitation in order to study the meaning and the kinetics of both parameters. RESULTS: It was possible to distinguish between three different patterns of viral response. The first was characterized by a simultaneous decrease in serum HBV DNA and HBeAg. The second pattern was characterized by a decrease in serum HBeAg but persistent detection of HBV DNA. The third pattern was characterized by undetectable HBV DNA with persistent HBeAg positivity, which points to a non-response (Pattern III-B) except when HBeAg levels showed a slow but steady drop, characterizing a "slow responder" patient (Pattern III-A). CONCLUSIONS: The first pattern is compatible with a viral response. A long-term HBeAg seropositivity with a slow and persistent decrease (Pattern III-A) is also compatible with a viral response and calls for a prolongation of anti-viral treatment.

INTRODUÇÃO: A quantificação do AgHBe sérico não é habitualmente utilizada para monitorizar a resposta viral ao tratamento da hepatite crônica B. MÉTODOS: Neste estudo, 21 pacientes sob tratamento com diferentes terapias foram acompanhados e a resposta viral monitorizada pela quantificação concomitante da carga viral e do AgHBe a fim de investigar o significado e a cinética de ambos os parâmetros. RESULTADOS: Distinguiram-se três diferentes padrões de resposta viral. O primeiro caracterizou-se pela redução simultânea do HBV DNA e AgHBe séricos. O segundo padrão caracterizou-se por uma redução do AgHBe porém com detecção persistente do HBV DNA. O terceiro padrão caracterizou-se por HBV DNA indetectável com positividade persistente do AgHBe, sugerindo ausência de resposta (Padrão III-B), exceto quando os níveis de AgHBe mostraram uma queda lenta porém persistente, caracterizando um "respondedor lento" (Padrão III-A). CONCLUSÕES: O primeiro padrão é compatível com resposta viral. Uma seropositividade prolongada do AgHBe porém com uma redução lenta e persistente (Padrão III-A) é também compatível com resposta viral, sugerindo o prolongamento do tratamento anti-viral.

Characterization of HBeAg-negative chronic hepatitis B in western Brazilian Amazonia

The present study was conducted with 55 patients native from western Brazilian Amazonia, who were HBV-DNA positive after seroconversion of HBeAg. It is a descriptive case study, with the patients separated into two groups: with hepatitis and without hepatitis on histological examination. The aim of the present study was to describe the clinical and molecular characteristics of patients who are chronic carriers of HBsAg. The prevalence of hepatitis was 63.64 percent, with a predominance of males (41.82 percent) and a mean age of 42.5 years, occurring mostly in natives of the southeast sub-region (32.73 percent). Time was a variable proportional to the course of the disease and the most frequent symptoms were: dyspepsia, asthenia and loss of libido with the majority of the patients having history of prior contact with HBV or positive family history. Splenomegalia was the most frequent sign (40 percent). Among the tests, platelet count, serum albumin and prothrombin activity were significant in the diagnosis of hepatitis. Alpha-fetoprotein was greater in patients with hepatitis, and hepatocellular carcinoma was detected in 3.63 percent of the patients with hepatic cirrhosis. Three types of HBV genotypes were diagnosed: A, D and F in the samples amplified for gene S. Genotype A (AA) was observed in 54.54 percent of the cases with hepatitis, in contrast to other studies showing the predominance of genotype F in this region. We observed mutations in 36.36 percent, with a predominance of the mutations in the core promoter region (31.81 percent), due to the greater prevalence of genotype A in this study.

Perfil epidemiológico dos portadores crônicos de hepatite viral B atendidos em hospital do Distrito Federal / Epidemiological profile of chronic hepatopathic virus B in a Federal District's hospital, Brazil

Introdução. Apesar dos avanços recentes em relação a diagnóstico, tratamento e profilaxia da hepatite viral B, esta se mantém como importante problema de saúde pública nos dias atuais. O estudo da sua distribuição em diferentes populações humanas é relevante, visto que existem variações acentuadas na presença de marcadores segundo áreas e grupamentos distintos. Objetivo. Identificar o perfil epidemiológico de portadores de hepatite viral B crônica, atendidos em hospital do Distrito Federal. Métodos. Estudo epidemiológico, predominantemente descritivo, quantitativo, retrospectivo, de base populacional, que analisa a magnitude e o perfil dos pacientes com hepatite viral B crônica, atendidos no Hospital Regional de Taguatinga no ano de 2007. Resultados. Percebeu-se que a maioria é do sexo masculino, com faixa etária média de 35 anos, brancos, procedentes do DF, com tempo de acompanhamento no ambulatório menor que um ano. São indivíduos, em seu maior percentual, HBeAg negativos, com valores de aminotransferases dentro da normalidade, modo de transmissão indeterminado e quantificação de carga viral baixa. Conclusão. É de grande importância que estudos epidemiológicos sobre esta virose sejam realizados para observar o padrão de acometimento na sociedade e buscar propostas para prevenção e melhor acompanhamento dos pacientes com doença manifesta.

Introduction. Despite recent advances in diagnosis, treatment and prophylaxis of hepatitis B, this condition remains a major public health problem. The study of its distribution in different human populations is relevant, since there are wide variations in markers related to different groups. Objective. Identify the epidemiological profile of chronic virus B hepatopathy in a Brazilian hospital in Distrito Federal. Methods. An epidemiological study, predominantly descriptive, quantitative, retrospective, population-based was performed, which examines the magnitude and profile of patients with chronic hepatitis B in Taguatinga Hospital in 2007. Results. It was noticed that the majority are male, with average age of 35 years, white, from Distrito Federal,with follow-up time shorter than one year. They are predominantly negative HBeAg patients, with undefined mode of transmission undefined and low quantification of viral load. Conclusion. It is important that epidemiological studies are conducted to observe the pattern of involvement in society and seek proposals for prevention and better monitoring of the patients with manifestations of disease.