Inflamación sistémica y desregulación inmune: rol en la patogénesis de la coinfección VIH/VHC / Systemic inflammation and immune dysregulation: role in the pathogenesis of HIV / HCV coinfection

La disfunción inmune asociada a la infección por el virus de la inmunodeficiencia humana (VIH) es generada por una estimulación crónica del sistema inmune secundaria a la imposibilidad del organismo de erradicar el virus. La misma se encuentra exacerbada en el contexto de la coinfección por el virus de la hepatitis C (VHC). La inflamación sistémica producto de la coinfección por ambos virus genera un aumento de la morbilidad y mortalidad en los individuos afectados. Son varios los mediadores solubles de activación inmunológica, como IP-10, TNF-α, IL-6, IL-1ß (marcadores de inflamación sistémica); IL-17 (linfocitos T CD4+ Th17); IL-2, IFN-γ (linfocitos T CD4+ Th1); IL-8 (inducción de neutrofilia); CD23s, ICAMs, CD14s, CD163s (marcadores de activación de monocitos/macrófagos), niveles circulantes de lipopolisacárido (LPS) (translocación bacteriana); entre otros. Actualmente se necesitan más estudios para lograr definir cuáles serían los biomarcadores de progresión óptimos para el seguimiento de los individuos coinfectados por VIH/VHC. El objetivo de esta revisión es realizar una reseña sobre los mecanismos inmunopatológicos de la infección por VIH/VHC involucrados en la inflamación, daño hepático y su impacto en la morbimortalidad de los individuos coinfectados

The immune dysfunction associated with Human Immunodeficiency Virus (HIV) infection is generated by a chronic stimulation of the immune system, because of the inability to eradicate the virus from the host. This immune dysfunction is exacerbated in the context of coinfection with Hepatitis C Virus (HCV). Systemic inflammation caused by coinfection with both viruses generates an increase in morbidity and mortality in affected individuals. There are several soluble mediators of immunological activation, such as IP-10, TNF-α, IL-6, IL-1ß (systemic inflammation markers); IL-17 (CD4+ T cells Th17); IL-2, IFN-γ (CD4+ T cells Th1); IL-8 (neutrophilia); CD23s, ICAMs, CD14s, CD163s, lipopolysaccharide (LPS) (monocyte/macrophage activation markers and bacterial translocation); among others. Currently, more studies are needed to define optimal progression biomarkers for the follow-up of HIV/HCV coinfected individuals. In this review, we focus on the immunopathological mechanisms of HIV/HCV infection involved in inflammation, liver damage and its impact on the morbidity and mortality of affected individuals

Characteristics associated with anti-HCV serological markers in prisoners in the state of Paraná, Brazil: a case-control study

ABSTRACT Background: The prison system in Paraná, Brazil, is experiencing serious problems related to the increasing number of prisoners. Control of hepatitis C virus (HCV) has become more intense because the incarcerated population is considered a high-risk group for contagious diseases due to the favorable conditions found in prisons for the spread of these morbidities. The objective of this study was to identify features associated with hepatitis C infection among male prisoners in correctional institutions of Paraná state, Brazil. Methods: This was a case-control study (27 cases and 54 controls) of men incarcerated in 11 penitentiaries in Paraná, Brazil. Information was obtained through a questionnaire in a cross-sectional epidemiological survey on HCV infection during the period from May 2015 to December 2016. Eligible men were recruited after testing positive for anti-HCV antibodies. Cases and controls were selected based on serological results of enzyme-linked immunosorbent assays and were matched by age, location of the penitentiary, and time in prison. Logistic regression analysis was used to identify risk factors for HCV seropositivity. Results: The main significant independent risk factor for the acquisition of HCV infection was the use of injectable drugs (OR = 4.00; 95%CI:1.41-11.35; p < 0.001). Conclusions: This study provides evidence that HCV infection is associated with drug use by this population. This information is pivotal for tailoring prevention programs and guiding specific socioeducational measures that aim to reduce or prevent HCV transmission within the prison setting.

Epidemiological survey of hepatitis C in a region considered to have high prevalence: the state of Minas Gerais, Brazil

Abstract INTRODUCTION: The prevalence of hepatitis C virus (HCV) infection is affected by demographic, virological, clinical, and lifestyle-related factors and varies in different regions in Brazil or worldwide. The present study aimed to clarify the epidemiological patterns of HCV infection in the interior region of Brazil. METHODS: This study was conducted in the Southern Triangle Macro-region of the state of Minas Gerais, Brazil, according to the guidelines of the National Program for the Prevention and Control of Viral Hepatitis. The participants answered a structured questionnaire on social and epidemiological factors. Immunochromatographic rapid tests were used for the qualitative detection of antibodies against HCV in whole blood (Alere HCV® Code 02FK10) in adult subjects by a free-standing method. RESULTS: Of 24,085 tested individuals, 184 (0.76%) were anti-HCV positive. The majority of anti-HCV-positive individuals were born between 1951 and 1980 (n=146 [79.3%]), with 68 women and 116 men. Identified risk factors included syringe and/or needle sharing (p = 0.003), being in prison (p = 0.004), and having tattoos or piercings (p = 0.005) and were significantly associated with the decade of birth. CONCLUSIONS: The study shows the importance of testing populations at risk for HCV infection, including incarcerated individuals, those with tattoos or piercings, those who share or have shared syringes or needles, and those in high-risk birth cohorts (1950s, 1960s, and 1970s) in the Southern Triangle Macro-region.

IgG1 and IgG4 antibodies against core and NS3 antigens of hepatitis C virus

Abstract INTRODUCTION: IgG subclasses involved in the immune response to hepatitis C virus (HCV) antigens have been rarely studied. We investigated the immune response mediated by IgG1 and IgG4 antibodies against the recombinant core and NS3 antigens in patients with chronic hepatitis C. METHODS: Sixty patients infected with HCV genotype 1 without antiviral treatment and 60 healthy subjects participated in the study. Serum levels of alanine aminotransferase, HCV viremia, and the presence of cryoglobulinemia and liver fibrosis were determined. We investigated the serum IgG1 and IgG4 antibodies against recombinant HCV core and NS3 non-structural protein antigens using amplified indirect ELISA. RESULTS: Anti-core and anti-NS3 IgG1 antibodies were detected in 33/60 (55%) and 46/60 (77%) patients, respectively, whereas only two healthy control samples reacted with an antigen (NS3). Anti-core IgG4 antibodies were not detected in either group, while 30/60 (50%) patients had anti-NS3 IgG4 antibodies. Even though there were higher levels of anti-NS3 IgG4 antibodies in patients with low viremia (< 8 × 105 IU/mL), IgG1 and IgG4 antibody levels did not correlate with ALT levels, the presence of cryoglobulinemia, or degree of hepatic fibrosis. High production of anti-core and anti-NS3 IgG1 antibodies was observed in chronic hepatitis C patients. In contrast, IgG4 antibodies seemed to only be produced against the NS3 non-structural antigen and appeared to be involved in viremia control. CONCLUSIONS: IgG1 antibodies against structural and non-structural antigens can be detected in chronic hepatitis C, while IgG4 antibodies seem to be selectively stimulated by non-structural HCV proteins, such as the NS3 antigen.

Fluctuations in serological hepatitis C virus levels in HIV patients

Abstract INTRODUCTION: Hepatitis C virus (HCV) and human immunodeficiency virus (HIV) have identical transmission routes, explaining the high prevalence of coinfections. The main aim of this study was to detect fluctuations in serological HCV levels in HIV patients. METHODS: We analyzed samples of 147 patients who attended an outpatient service that supports HIV/AIDS patients in São Paulo city. We also recruited 22 HCV-monoinfected patients who attended the Instituto Adolfo Lutz Laboratory in São Paulo city, to compare the test results. Serological testing of the blood samples was performed for the detection of HCV antibodies. The samples were then analyzed using real-time PCR for RNA viral quantification and sequencing. RESULTS We found that 13.6% of the study population was coinfected with HIV and HCV. In 20% of coinfected patients, fluctuations in serology results were detected in samples collected during the follow-up. No changes in anti-HCV serological markers were observed in HCV-monoinfected patients. An HCV viral load was detected in 9,5% of the samples collected from HIV patients. CONCLUSIONS: Our findings provide important clinical data to public health professionals and highlight the importance of periodic monitoring of HCV/HIV coinfected patients.

High-risk behaviors for hepatitis B and C infections among female sex workers

Abstract INTRODUCTION: The prevalence of hepatitis B and hepatitis C and risk behaviors among 402 female sex workers in Central Brazil were investigated by respondent-driven sampling. METHODS: Blood samples were tested for hepatitis B and C markers by enzyme-linked immunosorbent assay. Two hepatitis B vaccination schedules were performed. RESULTS: The prevalence of hepatitis B and C infections were 9.3% and 0.5%, respectively. Susceptibility to hepatitis B infection was observed in 61.5% of subjects. There was no significant difference in adherence index (p=0.52) between vaccination schedules and all participants had protective antibody titers. CONCLUSIONS: This hard-to-reach population requires hepatitis B and C surveillance.

Viral Outcome in Patients with Occult HBV Infection or HCV-Ab Positivity Treated for Lymphoma

ABSTRACT HBV and HCV reactivation has been widely reported in patients undergoing immunosuppressive therapy for oncohaematological diseases. We aimed to evaluate the HBV and HCV reactivation events in patients with non-Hodgkin lymphoma (NHL) or Hodgkin lymphoma (HL) underwent cytotoxic chemotherapy containing or not rituximab. This is a retrospective observational study, including all patients with NHL and HL attending an Italian tertiary referral hospital, the University of Naples "Federico II". A total of 322 patients were enrolled. We evaluated serum HBV and HCV markers. A total of 47 (38%) patients with occult HBV infection were enrolled. Seven/47 were treated with therapeutic cytotoxic schedule containing rituximab. Of them, 6/7 received prophylaxis with lamivudine. HBV reactivation was observed in two patients treated with rituximab. A reactivation was observed in the only patient (HBcAb+/HBsAb+) not receiving lamivudine prophylaxis, and the other one was observed in 1 patient with isolated HBcAb positivity during lamivudine prophylaxis. Moreover, 8 patients with HCV-Ab positivity were enrolled. No viral reactivation was observed in these patients. In conclusion, patients with occult HBV infection receiving chemotherapy containing rituximab for lymphoma without antiviral prophylaxis are at risk of viral reactivation. On the contrary, there is no risk of reactivation in patients undergoing rituximab-free schedule. Our findings suggest that there is also very low risk of HCV reactivation. This preliminary report underlines the concept that HBV reactivation is strongly related to the type of immunosuppressive therapy administered and that antiviral prophylaxis needs to be tailored.

Genotipos circulantes del virus de la hepatitis C en Colombia / Hepatitis C virus genotypes circulating in Colombia

Resumen Introducción: La infección crónica por el virus de la hepatitis C es un problema de salud pública y se estima que hay más de 180 millones de personas infectadas en el mundo. En Colombia no se conoce la epidemiología de la infección ni los genotipos virales más frecuentes. Objetivo. Describir los genotipos y subtipos del virus de la hepatitis C en pacientes colombianos infectados. Materiales y métodos: Se hizo un estudio descriptivo y retrospectivo de pruebas realizadas en dos laboratorios de referencia nacional, entre el 2003 y el 2015, mediante electroforesis en geles de poliacrilamida (Polyacrylamide Gel Electrophoresis, PAGE) o reacción en cadena de la polimerasa en tiempo real (quantitative PCR, qPCR). Resultados. Se estudiaron 1.538 aislamientos del virus de la hepatitis C de 1.527 pacientes con una edad promedio de 53 años, de los cuales 70 % tenía entre 40 y 70 años y 52 % eran mujeres. El 57 % de las pruebas se ordenaron en la ciudad de Bogotá, y el 80 % de los casos provenía de los departamentos de Cundinamarca, Valle y Atlántico. Se encontró el genotipo 1 en 88,6 % de los casos, distribuido así: subtipo 1b, 70 %, subtipo 1a, 13,5 %, y no determinado, 5,1 % de los casos; el genotipo 2 se encontró en el 5,4 % de los casos, el 3, en el 2 %, y el 4, en el 4 %. Se encontraron genotipos mixtos en 0,8 % de la muestra. Conclusión: El genotipo 1 del virus de la hepatitis C es el que circula con mayor frecuencia en el país, con predominio del subtipo 1b.

Abstract Introduction: Chronic hepatitis C virus infection is a worldwide public health problem; it has been estimated that over 180 million people are infected with this virus worldwide. Its precise incidence and prevalence (i.e., epidemiology) and the most frequent circulating genotypes in Colombia are unknown. Objective: To describe the hepatitis C virus (HCV) genotypes and subtypes in infected Colombian patients. Materials and methods: We recovered the data on 1,538 HCV isolates from 1,527 patients in two Colombian reference laboratories typed by PAGE or qPCR. Results: Patients' mean age was 53 years; 70% of them were 40 to 70 years old, and 52%, females; 57% of all tests were ordered in Bogotá and 80% of cases were from Cundinamarca, Valle and Atlántico departments. Genotype 1 was detected in 88.6% of cases, distributed as follows: 70% subtype 1b, 13.5% subtype 1a and 5.1%, undetermined subtypes. Genotype 2 was found in 5.4% of the patients, genotype 3 in 2% and genotype 4 in 4%. Mixed genotypes were found in 0.8% of the samples. Conclusion: Genotype 1 is the most common HCV genotype circulating in Colombia, and subtype 1b the most frequent.

Hepatitis C among blood donors: cascade of care and predictors of loss to follow-up

ABSTRACT OBJECTIVE To investigate the HCV cascade of care and to identify the factors associated with loss or absence to follow-up of patients identified as infected with hepatitis C through blood donation. METHODS Blood donors from 1994 to 2012, identified with positive anti- HCV by enzyme immunoassay and immunoblot tests were invited to participate in the study, through letters or phone calls. Patients who agreed to participate were interviewed and their blood samples were collected for further testing. The following variables were investigated: demographic data, data on comorbidities and history concerning monitoring of hepatitis C. Multiple regression analysis by Poisson regression model was used to investigate the factors associated with non-referral for consultation or loss of follow-up. RESULTS Of the 2,952 HCV-infected blood donors, 22.8% agreed to participate: 394 (58.2%) male, median age 48 years old and 364 (53.8%) Caucasian. Of the 676 participants, 39.7% did not receive proper follow-up or treatment after diagnosis: 45 patients referred not to be aware they were infected, 61 did not seek medical attention and 163 started a follow-up program, but were non-adherent. The main reasons for inadequate follow-up were not understanding the need for medical care (71%) and health care access difficulties (14%). The variables showing a significant association with inadequate follow-up after multiple regression analysis were male gender (PR = 1.40; 95%CI 1.15–1.71), age under or equal to 50 years (PR = 1.36; 95%CI 1.12–1.65) and non-Caucasians (PR = 1.53; 95%CI 1.27–1.84). CONCLUSIONS About 40.0% of patients did not receive appropriate follow-up. These data reinforce the need to establish strong links between primary care and reference centers and the need to improve access to specialists and treatments.

Association of genotypes with viral load and biochemical markers in HCV-infected Sindhi patients

Abstract The presented study had two objectives. The first was to examine distributions of Hepatitis C Virus (HCV) genotypes in Sindh, Pakistan, where HCV is prevalent. The other was to explore clinically relevant relationships between the genotypes, viral load (measured by real-time polymerase chain reaction assays) and biochemical markers. For this, 1471 HCV-infected patients in six cities in Sindh were recruited and sampled. HCV genotype distributions varied among the cities, but genotype 3a was most prevalent, followed by 3b, 1a and 1b (detected in 51.5, 22.7. 9.25 and 3.2% of the cases, respectively). No type-specific sequences were detected in serum samples from 189 (12.8%) of the 1471 patients. Frequencies of low (<200,000 IU/mL serum), intermediate (200,000-600,000 IU/mL serum) and high (>600,000 IU/mL serum) viral loads were respectively 45.4, 16.5 and 38.1% for patients infected with genotype 3, and 16.9, 36.9 and 46.2%, respectively, for patients with other genotypes. Infection with genotype 1a was associated with significantly higher (p < 0.005) alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase titers than infection with genotype 3a. The results will help in the formulation of treatment strategies.

Descripción de hallazgos virológicos inusuales en hepatitis C aguda / Unusual virologic findings in acute hepatitis C

La hepatitis C aguda es asintomática o inespecífica en un 80 % de los casos, por lo que su diagnóstico suele pasar inadvertido, con escasas descripciones de evolución y manejo en la literatura. El clearance es-pontáneo se produce sólo en el 20 %, ocurriendo en general, dentro de las 12 semanas desde la infección. Las guías clínicas recomiendan un mínimo de seguimiento de 12-16 semanas antes de considerar tra-tamiento antiviral. Se describen dos casos de nuestra consulta donde se logró detectar la recaída virológica, al extender el tiempo de segui-miento

Acute hepatitis C is a diagnostic challenge because it is asymptomatic or non specific in more than 80% of cases. There is limited data on the literature, because of its low incidence. Spontaneous clearance is observed only in 20% of cases, generally within the first 12 weeks. Clinical guidelines, recommend to wait at least 12-16 weeks before considering antiviral treatment. In the following cases at our consultation, we managed to diagnose the viral breakthrough by extending the follow-up period.

Sequence similarity between thyroid self-protein and hepatitis c virus polyprotein: possible triggering mechanism of autoimmune thyroiditis / Similaridade de sequências entre auto-proteínas da tireoide e poliproteínas do vírus da hepatite C: possível mecanismo de desencadeamento da tireoidite auto-imune

ABSTRACT Background - Exposure to viral antigens that share amino acid sequence similar with self- antigens might trigger autoimmune diseases in genetically predisposed individuals, and the molecular mimicry theory suggests that epitope mimicry between the virus and human proteins can activate autoimmune disease. Objective - The purpose of this study is to explore the possible sequence similarity between the amino acid sequences of thyroid self-protein and hepatitis C virus proteins, using databanks of proteins and immunogenic peptides, to explain autoimmune thyroid disease. Methods - Were performed the comparisons between the amino acid sequence of the hepatitis C virus polyprotein and thyroid self-protein human, available in the database of National Center for Biotechnology Information on Basic Local Alignment Search Tool. Results - The sequence similarity was related each hepatitis C virus genotype to each thyroid antigen. The similarities between the thyroid and the viral peptides ranged from 21.0 % (31 identical residues out of 147 amino acid in the sequence) to 71.0% (5 identical residues out of 7 amino acid in the sequence). Conclusion - Bioinformatics data, suggest a possible pathogenic link between hepatitis C virus and autoimmune thyroid disease. Through of molecular mimicry is observed that sequences similarities between viral polyproteins and self-proteins thyroid could be a mechanism of induction of crossover immune response to self-antigens, with a breakdown of self-tolerance, resulting in autoimmune thyroid disease.

RESUMO Contexto - A exposição a antígenos virais que compartilham sequência de aminoácidos semelhantes a auto-antígenos pode provocar doenças auto-imunes em indivíduos predispostos geneticamente, e a teoria do mimetismo molecular sugere que o mimetismo entre epítopos de vírus e proteínas humanas pode ativar doenças auto-imunes. Objetivo - O objetivo deste estudo foi explorar a possível semelhança entre as sequências de aminoácidos de auto-proteinas da tireóide e proteínas do vírus da hepatite C, utilizando bancos de dados de proteínas e peptídeos imunogênicos, para explicar a doença auto-imune da tireóide. Métodos - Foram realizadas comparações entre as sequências de aminoácidos de poliproteínas do vírus da hepatite C e auto-proteinas da tireóide humana, disponível na base de dados do National Center for Biotechnology Information no Basic Local Alignment Search Tool. Resultados - A semelhança de sequências foi relacionada para cada genótipo de vírus da hepatite C e proteínas da tireóide. As semelhanças entre proteínas da tireóide e os peptídeos virais variaram de 21,0% (31 resíduos idênticos da sequência de 147 aminoácidos) a 71,0% (cinco resíduos idênticos da sequência de 7 aminoácidos). Conclusão - Dados de bioinformática sugerem uma possível ligação entre vírus da hepatite C e doença auto-imune da tireóide. Através de mimetismo molecular observa-se que as semelhanças entre as sequências de poliproteínas virais e auto-proteínas da tireóide pode ser um mecanismo de indução de resposta imune resultando em doença auto-imune da tireóide.

CROSS SECTIONAL STUDY OF PREVALENCE AND RISK FACTORS OF HEPATITIS B AND HEPATITIS C INFECTION IN A RURAL VILLAGE OF INDIA

Background - Hepatitis B virus and hepatitis C virus are among the principal causes of severe liver disease. There is limited data of epidemiology of Hepatitis B in community, more so in rural population. Objective - To find the prevalence of hepatitis B and C infection in community and study the risk factors for their transmission. Methods - This was a community based cross sectional study. A total of 1833 randomly selected subjects from a rural area were interviewed for risk factors for transmission and tested for markers of hepatitis B and hepatitis C infection. All the positive card tests were confirmed by ELISA. Results - Out of 2400 subjects, rate for participation was 76.38%. None of the subjects was positive for anti hepatitis C virus antibody. Point prevalence for HBsAg positivity was 0.92. Being healthcare worker and having tattoo were significantly associated with HBsAg positive results. Nose and ear piercing was reported by almost. History of blood or blood product transfusion, I/V drug abuse, multiple sexual partners, unsafe Injections, hemodialysis and any h/o surgery was not associated with HBsAg positivity. Conclusion - Health care workers are at high risk for transmission of hepatitis B. Educating common people regarding mode of transmission of Hepatitis B and C will help to reduce their transmission.

Contexto - O vírus da hepatite B e o vírus da hepatite C estão entre as principais causas de doença grave do fígado. Há dados limitados de epidemiologia da hepatite B na comunidade observada, mais ainda na população rural. Objetivo - Encontrar a prevalência de infecção de hepatite B e C em uma comunidade da India e pesquisar os fatores de risco para sua transmissão. Métodos - Feito estudo de corte transversal em uma comunidade. Um total de 1833 sujeitos selecionados aleatoriamente em uma área rural foram entrevistados para fatores de risco para transmissão e testados para marcadores da infecção por hepatite B e C. Todos os testes positivos de cartão foram confirmados por ELISA. Resultados - Dos 2400 pacientes objetivados houve uma taxa de participação de 76.38%. Nenhum dos indivíduos foi positivo para anticorpo anti vírus da hepatite C. A prevalência pontual para a positividade do HBsAg foi de 0,92. Ser trabalhador na área de saúde e ter tatuagem foram significativamente associados com resultados positivos de HBsAg. "Piercing" em nariz e orelha foram relatados por quase todos. História de transfusão de sangue ou uso de hemoderivados, abuso de drogas via endovenosa, múltiplos parceiros sexuais, injeções inseguras, hemodiálise e história prévia de cirurgia, não estiveram associadas à positividade do HBsAg. Conclusão - Os trabalhadores de saúde estão em alto risco para a transmissão de hepatite B. Educar pessoas comuns sobre o modo de transmissão de hepatite B e C ajudará a reduzir a sua transmissão.

Early predictive efficacy of core antigen on antiviral outcomes in genotype 1 hepatitis C virus infected patients

Response-guided therapy is of limited use in developing countries because hepatitis C virus RNA detection by sensitive molecular methods is time- and labor-consuming and expen- sive. We evaluated early predictive efficacy of serum hepatitis C virus core antigen kinetics on sustained virologic response in patients with genotype 1 hepatitis C virus during pegylated interferon plus ribavirin treatment. For 478 patients recruited, hepatitis C virus RNAs were detected at baseline, and at weeks 4, 12, 24, 48, and 72 using Cobas TaqMan. Architect hepatitis C virus core antigen was performed at baseline, and weeks 4 and 12. Predictive values of hepatitis C virus core antigen on sustained virologic response were compared to hepatitis C virus RNA. In the first 12 weeks after treatment initiation the dynamic patterns of serum hepatitis C virus core antigen and hepatitis C virus RNA levels were similar in sustained virologic response, relapse, and null response patients groups. Although areas under the receiver operating characteristics curves of hepatitis C virus core antigen were lower than those of hepatitis C virus RNA at the same time points, modeling analysis showed that undetectable hepatitis C virus core antigen (rapid virological response based on hepatitis C virus core antigen) had similar positive predictive value on sustained virologic response to hepatitis C virus RNA at week 4 (90.4% vs 93.3%), and hepatitis C virus core antigen decrease greater than 1 log10 IU/mL (early virological response based on hepatitis C virus core antigen) had similar negative predictive value to hepatitis C virus RNA at week 12 (94.1% vs 95.Z%). Analysis on the validation group demonstrated a positive predictivevalue of 97.5% in rapid virological response based on hepatitis C virus core antigen and a negative predictive value of 100% in early virological response based on hepatitis C virus core antigen. In conclusion, hepatitis C virus core antigen is comparable to hepatitis C virus RNA in predicting sustained virologic response of chronic genotype 1 hepatitis C virus infected patients, and can be used to guide anti-hepatitis C virus treatment, especially in resource-limited areas.

Prevalence of hepatitis B and C virus infections among military personnel

Background: Data regarding Hepatitis B and C viruses (HBV and HCV) prevalence among military personnel in Brazil are lacking, but the work-related risk of exposure can be high. The objective of this study was to estimate the seroprevalence of HBV and HCV and the risk factors associated to HBV exposure among Brazilian military personnel. Methods: A cross-sectional study was conducted and included 433 male military adults aged 18-25 years old working in Rio de Janeiro during October 2013. All individuals completed a questionnaire to assess their risk of exposure and provided a blood sample to HBV and HCV testing. Results: None of the participants presented HBsAg or anti-HBc IgM, 18 (4.1%) were positive for total anti-HBc, 247 (57.0%) were positive for anti-HBs, and 3 (0.7%) were anti-HCV reactive. The majority of military personnel with past HBV infection (anti-HBc reactive) and HBV immunity (anti-HBs reactive) had a history of prior dental procedures (88.9% and 77.3%), consumption of alcohol at least once a week (50% and 55.9%), and practiced oral sex (61.1% and 58.3%, respectively). In addition, anti-HBc positivity was common among individuals with a history of surgery (44.4%) and practice of anal sex (50%). At univariate analysis, age group was associated to anti-HBc and anti-HBs positivity. Conclusions: Low rates of HBV and HCV infection were observed among Brazilian military personnel in comparison to the general Brazilian population. HBV immunity rates were relatively low indicating the need for vaccination campaigns in this group. .

Recombinant hepatitis C virus-envelope protein 2 interactions with low-density lipoprotein/CD81 receptors

Hepatitis C virus (HCV) envelope protein 2 (E2) is involved in viral binding to host cells. The aim of this work was to produce recombinant E2B and E2Y HCV proteins in Escherichia coli and Pichia pastoris, respectively, and to study their interactions with low-density lipoprotein receptor (LDLr) and CD81 in human umbilical vein endothelial cells (HUVEC) and the ECV304 bladder carcinoma cell line. To investigate the effects of human LDL and differences in protein structure (glycosylated or not) on binding efficiency, the recombinant proteins were either associated or not associated with lipoproteins before being assayed. The immunoreactivity of the recombinant proteins was analysed using pooled serum samples that were either positive or negative for hepatitis C. The cells were immunophenotyped by LDLr and CD81 using flow cytometry. Binding and binding inhibition assays were performed in the presence of LDL, foetal bovine serum (FCS) and specific antibodies. The results revealed that binding was reduced in the absence of FCS, but that the addition of human LDL rescued and increased binding capacity. In HUVEC cells, the use of antibodies to block LDLr led to a significant reduction in the binding of E2B and E2Y. CD81 antibodies did not affect E2B and E2Y binding. In ECV304 cells, blocking LDLr and CD81 produced similar effects, but they were not as marked as those that were observed in HUVEC cells. In conclusion, recombinant HCV E2 is dependent on LDL for its ability to bind to LDLr in HUVEC and ECV304 cells. These findings are relevant because E2 acts to anchor HCV to host cells; therefore, high blood levels of LDL could enhance viral infectivity in chronic hepatitis C patients.

Generation and characterisation of HCV genotype 1 viruses most recent common ancestor

Background: Hepatitis C virus [HCV] causes acute and chronic liver diseases in humans. Its two envelope glycoproteins, E1 and E2, interact with host cell receptors and provide a target for neutralising antibodies. Past vaccine studies using unmodified E2 proteins have failed to convincingly generate broadly neutralising antibody responses

Objectives: This study sought to generate and evaluate an immune-focused, vaccine candidate for HCV

Methodology: A synthetic construct based on most recent common ancestral sequence [MRCA] of HCV genotype 1 viruses was generated using sequences available from the Los Alamos HCV database [720 sequences [360 subtype 1a and 360 subtype 1b sequences]], after exclusion of epidemiologically-related sequences. Soluble E2 [sE2] proteins were generated by stably transfected S2 cells and purified using Strep- tag purification and size exclusion chromatography. The MRCA construct was subsequently interrogated using a linear [AP33] and conformational [1: 7] monoclonal antibodies directed at E2. A full length E1E2 construct was used for production of HCV pseudoparticles [HCVpp]. The infectivity of the HCVpp was measured in the presence of monoclonal antibodies; AP33 1: 7 and AR3A

Results: Monomeric proteins of the MRCA generated using a Drosophila expression system were conformationally intact when examined by the monoclonal antibody 1: 7 that targets the conformational epitope on E2 responsible for interaction with the CD81 receptors. The full length MRCA E1E2 construct showed functionality in the HCV pseudo-particle [HCVpp] system. The MRCA HCVpp construct was susceptible to neutralisation by AP33, 1: 7 and AR3A, in dose- dependant manner

Conclusion: This study demonstrates the generation of a functional construct that could be used as a vaccine candidate in a potential vaccine approach to minimise the problem of genetic diversity between the vaccine construct and contemporary viruses

Prevalence of hepatitis C virus in Brazil's inmate population: a systematic review / Prevalência do vírus da hepatite C na população carcerária do Brasil: revisão sistemática

OBJECTIVE To estimate the prevalence of hepatitis C virus infection in Brazil's inmate population.METHODS Systematic review on hepatitis C virus infection in the inmate population. Brazilian studies published from January 1, 1989 to February 20, 2014 were evaluated. The methodological quality of the studies was assessed using a scale of 0 to 8 points.RESULTS Eleven eligible studies were analyzed and provided data on hepatitis C virus infection among 4,375 inmates from seven states of Brazil, with a mean quality classification of 7.4. The overall hepatitis C virus prevalence among Brazilian inmates was 13.6% (ranging from 1.0% to 41.0%, depending on the study). The chances of inmates being seropositive for hepatitis C virus in the states of Minas Gerais (MG), Sergipe (SE), Mato Grosso do Sul (MS), Rio Grande do Sul (RS), Goiás (GO) and Espirito Santo (ES) were 84.0% (95%CI 0.06;0.45), 92.0% (95%CI 0.04;0.13), 88.0% (95%CI 0.09;0.18), 74.0% (95%CI 0.16;0.42), 84.0% (95%CI 0.08;0.31) and 89.0% (95%CI 0.01;0.05) respectively, lower than that observed in the Sao Paulo state (seroprevalence of 29.3%). The four studies conducted in the city of Sao Paulo revealed a lower prevalence in more recent studies compared to older ones.CONCLUSIONS The highest prevalence of hepatitis C virus infection in Brazil's inmate population was found in Sao Paulo, which may reflect the urban diversity of the country. Despite Brazilian studies having good methodological quality to evaluate the prevalence of the hepatitis C virus, they are scarce and lack data on risk factors associated with this infection, which could support decisions on prevention and implementation of public health policies for Brazilian prisons.

RESUMOOBJETIVO Estimar prevalência de infecção pelo vírus da hepatite C entre a população carcerária no Brasil.MÉTODOS Revisão sistemática sobre infecção pelo vírus da hepatite C em populações carcerárias. Foram avaliados estudos brasileiros publicados a partir de 1 de janeiro de 1989 até 20 de fevereiro de 2014. A qualidade metodológica dos estudos foi avaliada utilizando-se escala de zero a oito pontos.RESULTADOS Onze estudos elegíveis foram analisados, os quais forneceram dados sobre a infecção pelo vírus da hepatite C de 4.375 detentos de sete estados do Brasil, com classificação em média de qualidade de 7,4. A prevalência de infecção pelo vírus da hepatite C na população carcerária brasileira foi 13,6%, (variando de 1,0% a 41,0%, dependendo do estudo). As chances de os indivíduos serem soropositivos para o vírus da hepatite C nos estados de Minas Gerais, Sergipe, Mato Grosso do Sul, Rio Grande do Sul, Goiás e Espírito Santo foram 84,0% (IC95% 0,06;0,45), 92,0% (IC95% 0,04;0,13), 88,0% (IC95% 0,09;0,18), 74% (IC95% 0,16;0,42), 84,0% (IC95% 0,08;0,31) e 89,0% (IC95% 0,01;0,05), respectivamente, inferiores àquela observada no estado de São Paulo (soroprevalência de 29,3%). Os quatro estudos realizados na cidade de São Paulo mostraram menor prevalência em estudos mais recentes em comparação aos mais antigos.CONCLUSÕES A maior prevalência de infecção pelo vírus da hepatite C em população carcerária do Brasil foi encontrada em São Paulo, o que pode refletir a diversidade urbana do País. Apesar de os estudos brasileiros apresentarem boa qualidade metodológica para avaliação da prevalência do vírus da hepatite C, são escassos e faltam dados sobre fatores de risco associados a esta infecção, dados esses que poderiam auxiliar nas decisões de prevenção e implementação de políticas em saúde pública para as prisões brasileiras.

Instituição de longa permanência para idosos: um lugar de cuidado para quem não tem opção? / Long-stay institutions for the elderly: a place of care for those who have no choice? / Institución de larga estadía para las personas mayores: ¿un lugar de atención para aquellos que no tienen otra opción?

Pesquisa descritiva, qualitativa, com abordagem compreensiva, que teve por objetivo compreender o significado da instituição de longa permanência para idosos institucionalizados. Os dados foram coletados com 13 idosos institucionalizados, no período de 5 de abril a 25 de maio de 2013 por meio da entrevista narrativa, e submetidos a análise de conteúdo, na modalidade de análise temática. Os resultados indicam que ser idoso institucionalizado significa ter suas necessidades de cuidado atendidas, no que concerne a suas necessidades básicas; ao acesso a serviços e recursos de saúde, e a ter um lugar onde possam envelhecer e morrer. O estudo permitiu concluir que a instituição aparece como um lugar ambíguo para os idosos, pois ao mesmo tempo em que os acolhe, abriga e atende suas necessidades, é um ambiente que inviabiliza a vida independente e autônoma.

This is a descriptive, qualitative research, with comprehensive approach, which aimed to understand the meaning that the longterm institution has to institutionalized elderly. Data were collected with 13 institutionalized elderly in the period from April 5 to May 25, 2013, through narrative interview, and subjected to content analysis, in the form of thematic analysis. The results indicated that being elderly institutionalized means having their care needs met, with respect to their basic needs; access to health services and resources, and to have a place where they can grow old and die. The study concluded that the institution appears as an ambiguous place for the elderly because, even embracing and housing them and meeting their needs, is an environment that prevents the independent and autonomous life.

Investigación descriptiva, cualitativa con enfoque comprehensivo, que tuve como objetivo comprender el significado de la institución a largo plazo tiene para ancianos institucionalizados. Los datos fueron recolectados con 13 ancianos institucionalizados en el periodo comprendido entre el 5 abril-25 mayo de 2013, a través de entrevista narrativa, y tratados mediante análisis de contenido, en la modalidad de análisis temático. Los resultados indican que estar en edad avanzada y estar institucionalizado significa tener sus atendidas sus necesidades básicas; el acceso a los servicios de salud y los recursos, y tener un lugar donde pueden envejecer y morir. El estudio llegó a la conclusión de que la institución se presenta como un lugar ambiguo para las personas mayores, ya que si bien les acoja, albergue y atiendan sus necesidades, es un ambiente que impide la vida independiente y autónoma.

Notícias do Levantamento de Recursos e Necessidades de Enfermagem na Revista Brasileira de Enfermagem (1955-1958) / News of the Inquiry about Nursing Needs and Resources in the Brazilian Journal of Nursing (1955-1958) / Noticias del Levantamiento de Necesidades y Recursos de Enfermería en la Revista Brasileña de Enfermería (1955-1958)

Estudo Histórico Social que tem como objeto notícias sobre o Levantamento de Recursos e Necessidades de Enfermagem no Brasil, publicadas na Revista Brasileira de Enfermagem entre 1955 e 1958. A fonte primária foi constituída pelos exemplares da Revista Brasileira de Enfermagem, publicados dentro do recorte temporal do estudo. As fontes secundárias foram constituídas por livros, artigos, dissertações e teses relativas à história da Enfermagem. A análise dos dados teve apoio das fontes secundárias e do pensamento do sociólogo Pierre Bourdieu. Os dados evidenciaram que a Revista Brasileira de Enfermagem, além de oportunizar a divulgação de notícias acerca do Levantamento, proporcionou visibilidade ao mesmo mediante a veiculação dessas notícias e, por fim, teve o efeito simbólico de conferir poder e prestígio à Enfermagem Brasileira.

Social historical study that has as object news related to the Assessment of the Resources and Needs of Nursing in Brazil published in the Revista Brasileira de Enfermagem between 1955 and 1958. The primary source is constituted of copies of Revista Brasileira de Enfermagem published within the selected period of the study. The secondary sources are constituted of books, papers, dissertations and thesis related to the Nursing history. The data analysis was supported by the secondary sources and the thought of the sociologist Pierre Bourdieu. The results evidenced that Revista Brasileira de Enfermagem, in addition to making possible the dissemination of news about the Assessment provided visibility to it and, at last, had the symbolic effect of giving power and prestige to the Brazilian Nursing.

Estudio Histórico Social que tiene como objeto noticias referentes al Levantamiento de Recursos y Necesidades de Enfermería en Brasil publicadas en la Revista Brasileira de Enfermagem entre 1955 y 1958. La fuente primaria se constituye de los ejemplares de la Revista Brasileira de Enfermagem publicados dentro del recorte temporal do estudio. Las fuentes secundarias están constituidas de libros, artículos disertaciones y tesis relativas a la historia de la Enfermería. El análisis de los datos tuvo apoyo de las fuentes secundarias y del pensamiento del Sociólogo Pierre Bourdieu. Los resultados evidencian que la Revista Brasileira de Enfermagem, además de posibilitar la divulgación de noticias acerca del Levantamiento proporcionó visibilidad al mismo mediante la divulgación de esas noticias y, por fin, tuve el efecto simbólico de conferir poder y prestigio a la Enfermería Brasileña.