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1.
Medicine (Baltimore) ; 99(2): e18752, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31914096

RESUMO

The high prevalence of hepatitis B virus (HBV) infection and intracranial atherosclerotic stenosis (ICAS) in Asia raises the question as to whether HBV infection is associated with ICAS. To answer this question, we tested the association between HBV infection and ICAS. Totally, 3072 in-hospital subjects were retrospectively enrolled. All subjects underwent computed tomography angiography (CTA) and serological testing for HBV infection. Based on the results of CTA, all subjects were categorized into 4 groups including ICAS, extracranial atherosclerotic stenosis (ECAS), ICAS/ECAS (both ICAS and ECAS), and normal. HBV infection was divided into 4 patterns including hepatitis B core antibody (anti-HBc) positive/hepatitis B surface antigen (HBsAg) positive, anti-HBc-positive/HBsAg-negative, anti-HBc-negative/HBsAg-positive, and anti-HBc-negative/HBsAg-negative. Risk factors for atherosclerosis were collected based on medical records. Multiple logistic regression models were used to determine the association between infection patterns and ICAS. We found that the anti-HBc-positive / HBsAg-negative pattern was associated with the increased risk of ICAS (OR = 1.462) and not associated with ECAS or ICAS / ECAS. The HBc-positive/HBsAg-positive pattern was not associated with ICAS, ECAS or ICAS/ECAS. In conclusions, the anti-HBc-positive/HBsAg-negative pattern was associated with the increased risk of ICAS. Anti-HBc should be employed to investigate the association between HBV infection and cerebrovascular diseases.


Assuntos
Aterosclerose/epidemiologia , Anticorpos Anti-Hepatite B/sangue , Antígenos de Superfície da Hepatite B/sangue , Hepatite B/epidemiologia , Arteriosclerose Intracraniana/epidemiologia , Idoso , Aterosclerose/diagnóstico por imagem , China/epidemiologia , Angiografia por Tomografia Computadorizada , Constrição Patológica , Feminino , Hepatite B/sangue , Hepatite B/imunologia , Humanos , Arteriosclerose Intracraniana/diagnóstico por imagem , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco
2.
Adv Exp Med Biol ; 1179: 71-107, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31741334

RESUMO

More than 95% of adult infected with HBV show acute self-limited infection and eventually eliminate the virus. In contrast, about 90% of people exposed to HBV in early childhood develop chronic infection. The specificity of the virus and the host's antiviral immune responses together determine the outcome of HBV infection. It is generally believed that viral genome variation, viral titers, and inhibition of viral components against the host immune system are associated with persistent infection and liver damage. The dysfunction of innate immune cells (NK cells, monocyte/macrophages, NKT cells, etc.) and adaptive immune cells (antigen-presenting cells, T cells, B cells) is a key factor leading to virus clearance failure and liver inflammation. In this chapter, we summarize these viral factors and host factors in acute and chronic hepatitis B and update recent understanding of the immune-tolerant phase and pathological mechanisms associated with age and vertical transmission. This will help us to understand more fully the mechanisms of chronic HBV infection and liver injury and to develop combined treatment strategies of direct antiviral drugs for HBV life cycle and immunomodulators.


Assuntos
Vírus da Hepatite B , Hepatite B , Antivirais/uso terapêutico , Hepatite B/tratamento farmacológico , Hepatite B/imunologia , Hepatite B/patologia , Hepatite B/virologia , Vírus da Hepatite B/genética , Vírus da Hepatite B/imunologia , Hepatite B Crônica/imunologia , Hepatite B Crônica/patologia , Hepatite B Crônica/virologia , Humanos , Carga Viral
3.
BMC Infect Dis ; 19(1): 955, 2019 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-31706284

RESUMO

BACKGROUND: Identification and knowledge of settings with high prevalence of hepatitis C virus (HCV) infection is important when aiming for elimination of HCV. The primary aim of this study was to estimate the prevalence of viremic HCV infection among Swedish prisoners. Secondary aims were to estimate the prevalence of hepatitis B surface antigen (HBsAg), human immunodeficiency virus (HIV), and the proportion who have received hepatitis B virus (HBV) vaccination. METHODS: A cross-sectional study of all incarcerated persons (n = 667) at all prisons (n = 9) in Stockholm County was conducted. All prisoners are routinely offered opt-in screening for HCV antibodies (anti-HCV), HCV RNA, HBsAg, anti-HBs, anti-HBc and HIV Ag/Ab at prison in Sweden. Data on the results of these tests and the number of received HBV vaccine doses were collected from the prison medical records. The parameters of HCV RNA, anti-HCV, and occurrence of testing for HCV were analysed in multiple logistic regression models in relation to age, sex and prison security class. RESULTS: The median age was 35 (IQR 26-44) years, and 93.4% were men. Seventy-one percent (n = 471) had been tested for anti-HCV, 70% (n = 465) for HBsAg and 71% (n = 471) for HIV. The prevalence of anti-HCV, HCV RNA, HBsAg and HIV Ag/Ab was 17.0, 11.5, 1.9, and 0.2%, respectively among tested persons. The proportion of prisoners who had received full HBV vaccination was 40.6% (n = 271) among all study subjects. CONCLUSIONS: The prevalence of viremic HCV infection among Swedish prisoners in Stockholm County was 11.5%, which is high in comparison to the general population. Therefore, when aiming for the WHO goal of HCV elimination, prisons could suit as a platform for identification and treatment of HCV infection. There is a need to increase testing for blood-borne viruses and to improve vaccination coverage against HBV in Swedish prisons.


Assuntos
Infecções por HIV/epidemiologia , Hepatite B/epidemiologia , Hepatite C/epidemiologia , Vacinação/estatística & dados numéricos , Adulto , Estudos Transversais , Feminino , Infecções por HIV/imunologia , Hepatite B/imunologia , Antígenos de Superfície da Hepatite B/sangue , Hepatite C/imunologia , Anticorpos Anti-Hepatite C/sangue , Humanos , Modelos Logísticos , Masculino , Prevalência , Prisioneiros , RNA Viral/análise , Suécia/epidemiologia
4.
Cancer Immunol Immunother ; 68(12): 2041-2054, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31720814

RESUMO

Hepatitis B virus-associated hepatocellular carcinoma (HBV-HCC) is usually considered an inflammation-related cancer associated with chronic inflammation triggered by exposure to HBV and tumor antigens. T-cell exhaustion is implicated in immunosuppression of chronic infections and tumors. Although immunotherapies that enhance immune responses by targeting programmed cell death-1(PD-1)/PD-L1 are being applied to malignancies, these treatments have shown limited response rates, suggesting that additional inhibitory receptors are also involved in T-cell exhaustion and tumor outcome. Here, we analyzed peripheral blood samples and found that coexpression of PD-1 and T-cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif (ITIM) domain (TIGIT) was significantly upregulated on CD4+ and CD8+ T cells from patients with HBV-HCC compared with those from patients with chronic HBV or HBV-liver cirrhosis. Additionally, PD-1+ TIGIT+ CD8+ T-cell populations were elevated in patients with advanced stage and progressed HBV-HCC. Importantly, PD-1+ TIGIT+ CD8+ T-cell populations were negatively correlated with overall survival rate and progression-free survival rates. Moreover, we showed that PD-1+ TIGIT+ CD8+ T cells exhibit features of exhausted T cells, as manifested by excessive activation, high expression of other inhibitory receptors, high susceptibility to apoptosis, decreased capacity for cytokine secretion, and patterns of transcription factor expression consistent with exhaustion. In conclusion, PD-1+ TIGIT+ CD8+ T-cell populations are associated with accelerated disease progression and poor outcomes in HBV-HCC, which might not only have important clinical implications for prognosis but also provide a rationale for new targets in immunotherapy.


Assuntos
Linfócitos T CD8-Positivos/imunologia , Carcinoma Hepatocelular/imunologia , Vírus da Hepatite B/fisiologia , Hepatite B/imunologia , Neoplasias Hepáticas/imunologia , Adulto , Carcinogênese , Carcinoma Hepatocelular/mortalidade , Senescência Celular/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Hepatite B/mortalidade , Humanos , Neoplasias Hepáticas/mortalidade , Masculino , Pessoa de Meia-Idade , Prognóstico , Receptor de Morte Celular Programada 1/metabolismo , Estudos Prospectivos , Receptores Imunológicos/metabolismo , Análise de Sobrevida
5.
Nature ; 574(7777): 200-205, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31582858

RESUMO

The responses of CD8+ T cells to hepatotropic viruses such as hepatitis B range from dysfunction to differentiation into effector cells, but the mechanisms that underlie these distinct outcomes remain poorly understood. Here we show that priming by Kupffer cells, which are not natural targets of hepatitis B, leads to differentiation of CD8+ T cells into effector cells that form dense, extravascular clusters of immotile cells scattered throughout the liver. By contrast, priming by hepatocytes, which are natural targets of hepatitis B, leads to local activation and proliferation of CD8+ T cells but not to differentiation into effector cells; these cells form loose, intravascular clusters of motile cells that coalesce around portal tracts. Transcriptomic and chromatin accessibility analyses reveal unique features of these dysfunctional CD8+ T cells, with limited overlap with those of exhausted or tolerant T cells; accordingly, CD8+ T cells primed by hepatocytes cannot be rescued by treatment with anti-PD-L1, but instead respond to IL-2. These findings suggest immunotherapeutic strategies against chronic hepatitis B infection.


Assuntos
Linfócitos T CD8-Positivos/imunologia , Apresentação Cruzada/imunologia , Vírus da Hepatite B/imunologia , Hepatócitos/imunologia , Hepatócitos/virologia , Animais , Antígeno B7-H1/antagonistas & inibidores , Linfócitos T CD8-Positivos/citologia , Linfócitos T CD8-Positivos/metabolismo , Diferenciação Celular , Cromatina/metabolismo , Feminino , Hepatite B/tratamento farmacológico , Hepatite B/imunologia , Hepatite B/virologia , Humanos , Tolerância Imunológica , Interleucina-2/imunologia , Interleucina-2/uso terapêutico , Macrófagos do Fígado/imunologia , Ativação Linfocitária , Masculino , Camundongos , Transcriptoma/genética
6.
J Med Microbiol ; 68(11): 1686-1693, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31592765

RESUMO

Introduction. Tunisia is an intermediate hepatitis B virus (HBV) endemic country. The vaccination against hepatitis B was introduced in 1995 including four doses with a first dose administrated at birth. Decreasing the level of antibodies against hepatitis B surface antigen (anti-HBs) over time can be alarming. This study was conducted to explore the anti-HBV immune response among children under 6 years old, vaccinated according to the national vaccination schedule, by evaluating the immunological response to primary vaccination and by exploring the anamnestic immune response to a booster dose.Methods. We conducted a cross-sectional prospective study from June 2016 to June 2017 (n=180), based on voluntary participation. Children were recruited from the public pediatric ward sectors in Sahloul University Hospital of Sousse in Central Tunisia. An anti-HB titre was determined based on electro-chemiluminescence micro-particle immunoassay (ECLIA), using Elecsys Anti-HBs II kit, Roche.Results. Mean age at the time of enrollment in the study was 33±14.8 months. The seroprotection rate was 77.2 %. The anti-HB titre differed significantly between the different age groups (P=0.002). The predicting variable for having no seroprotective antibody level was older age. Children with anti-HB levels <10 IU l- 1 were offered an additional dose of HBV vaccine. Anamnestic response 1 month after the challenge dose was observed in 100 % of subjects. The probability of developing a high antibody response, following the booster dose increased in conjunction with an increased pre-booster antibody level.Conclusion. The response to a booster dose suggests the persistence of immune memory in almost all vaccinated individuals. Although a booster dose increases substantially anti-HB titre, the clinical relevance of such an increase remains unknown.


Assuntos
Anticorpos Anti-Hepatite B/imunologia , Vacinas contra Hepatite B/administração & dosagem , Vírus da Hepatite B/imunologia , Hepatite B/imunologia , Criança , Pré-Escolar , Estudos Transversais , Feminino , Hepatite B/virologia , Antígenos de Superfície da Hepatite B/administração & dosagem , Antígenos de Superfície da Hepatite B/imunologia , Vacinas contra Hepatite B/imunologia , Humanos , Memória Imunológica , Lactente , Masculino , Estudos Prospectivos , Tunísia , Vacinação
7.
Isr Med Assoc J ; 21(7): 480-486, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31507125

RESUMO

BACKGROUND: Serum rheumatoid factors are autoantibodies of different isotypes directed against the Fc fraction of immunoglobulin G (IgG) and represent paradigmatic autoantibodies that have been largely used in clinical practice for decades. Traditionally IgG has been associated with rheumatoid arthritis and more recently included also in the classification criteria for SjÓ§gren's syndrome. Researchers have established that rheumatoid factors are positive in a variety of infectious, autoimmune, and neoplastic disorders, thus requiring a comprehensive evaluation of seropositive patients. Of note, hepatitis B and C viruses represent a crossroad that includes the high rheumatoid factor seroprevalence and chronic inflammatory disease, as well as progression to non-Hodgkin's lymphomas. Chronic antigen stimulation is the likely common ground of these processes and rheumatoid factors may represent mere bystanders or drivers of pathology. Mixed cryoglobulinemia and lymphoproliferative disease are prime examples of the deleterious effects of rheumatoid factor-B cell activity, possibly associated with hepatitis B and C. More importantly, they show a clear association in a physiological host response to infection, chronic inflammation, and the slide toward autoimmunity and malignancy. The association between hepatitis B and C infections and the appearance of serum rheumatoid factors is further supported by prevalence data, which support a coexistence of these markers in a significant proportion of cases, with viral infections being frequent causes of rheumatoid factors in patients without a rheumatic condition. We provide a comprehensive overview of the known connections between hepatitis B and C infections and rheumatoid factors.


Assuntos
Hepatite B/imunologia , Hepatite C/imunologia , Fator Reumatoide/imunologia , Autoanticorpos/imunologia , Doenças Autoimunes/imunologia , Autoimunidade/imunologia , Crioglobulinemia/imunologia , Humanos , Transtornos Linfoproliferativos/imunologia , Neoplasias/imunologia , Fator Reumatoide/sangue
8.
Arch Virol ; 164(11): 2645-2658, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31399876

RESUMO

Anti-HBs antibodies develop after natural infection with hepatitis B virus (HBV) or vaccination against this virus, as a result of activation of the human immune system by the HBV surface antigen (HBsAg). Anti-HBs-positive individuals are immunologically competent against HBV infection. This immunity is determined by the antibody levels in the bloodstream after resolution of natural infection or after vaccination. Anti-HBs antibody levels have been observed to decrease to below the protective level years after natural infection or vaccination, and there is reason to doubt that protective immunity to HBV is maintained after that. Factors that affect the maintenance of the anti-HBs antibody level in the bloodstream have been reported. Maintenance of immunity to HBV has been reported in anti-HBs negative individuals and those with detectable but low levels after natural infection or after vaccination. On the other hand, detection of anti-HBs antibodies without protective activity has also been observed. The presence or absence of anti-HBs antibodies in the context of HBV immunity has been the subject of extensive discussion and clinical, laboratory and epidemiological interest. These three scenarios of the anti-HBs response are discussed in this review article.


Assuntos
Anticorpos Anti-Hepatite B/sangue , Antígenos de Superfície da Hepatite B/imunologia , Vacinas contra Hepatite B/imunologia , Vírus da Hepatite B/imunologia , Hepatite B/imunologia , Anticorpos Anti-Hepatite B/imunologia , Humanos , Vacinação
9.
Medicine (Baltimore) ; 98(32): e16401, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31393348

RESUMO

Viral hepatitis is caused by different etiological agents with distinct epidemiological, clinical, and laboratory characteristics accounting for significant worldwide morbidity and mortality. Since 1996, the Brazilian Department of Sexually Transmitted Infections (STIs), Acquired Immune Deficiency Syndrome (AIDS) and Viral Hepatitis (DIAHV) in collaboration with the Ministry of Defense has been conducting periodic serosurveys of conscripts enlisted for the Brazilian army to assess STI prevalence and obtain data on knowledge and risk factors pertaining to STIs. This article aims to present the hepatitis B (hepatitis B surface antigen - HBsAg) and C (anti-HCV) seroprevalence estimates and risk factors as per the 8th edition of the Conscript Survey performed in 2016.This cross-sectional study was conducted among conscripts across Brazil aged 17 to 22 years from August to December 2016. It included a self-reported questionnaire and blood testing for syphilis, human immunodeficiency virus (HIV), and hepatitis B and C.In total 38,247 conscripts were enrolled; after applying exclusion criteria, 37,282 conscripts were included. The estimated HBsAg and anti-HCV prevalence rates were 0.22% and 0.28%, respectively. Higher HBsAg and anti-HCV prevalence rates were observed in the North Region (0.49%) and in the Central-west Region (0.65%), respectively. Regarding hepatitis B vaccination, 23.5% (n = 8412) of the individuals reported being unvaccinated and 47.4% (n = 16,970) did not know if they had been vaccinated. Among the anti-HCV positive conscripts, 53% (n = 51, 0.56%, P = .049) reported that they had never had sexual intercourse. Regarding self-reported STI status, most of the positive anti-HCV (n = 100, 0.29%, P < .01) and positive HBsAg (n = 76, 0.22%, P = .205) conscripts reported not having a STI. From those who tested positive for HBsAg, 89% (n = 42, 0.28%, P = .005) reported not making consistent use of condoms with steady partners.Our data suggest a low prevalence of hepatitis B virus (HBV) and hepatitis C virus (HCV) infections among Brazilian young men, and relatively low rates of self-reported HBV immunization. History of STIs, higher number of partners, inconsistent use of condoms, and lack of awareness of routes of transmission were significantly associated with HBV and HCV infections. To achieve the World Health Organization's goal of viral hepatitis elimination, access to hepatitis information, testing, and surveillance need to be improved.


Assuntos
Hepatite B/epidemiologia , Hepatite C/epidemiologia , Adolescente , Fatores Etários , Brasil/epidemiologia , Preservativos/estatística & dados numéricos , Estudos Transversais , Escolaridade , Conhecimentos, Atitudes e Prática em Saúde , Hepatite B/imunologia , Hepatite B/prevenção & controle , Antígenos de Superfície da Hepatite B/sangue , Vacinas contra Hepatite B/administração & dosagem , Hepatite C/imunologia , Anticorpos Anti-Hepatite C/sangue , Humanos , Masculino , Militares/estatística & dados numéricos , Prevalência , Fatores de Risco , Estudos Soroepidemiológicos , Doenças Sexualmente Transmissíveis/epidemiologia , Adulto Jovem
10.
World J Gastroenterol ; 25(26): 3299-3312, 2019 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-31341357

RESUMO

Reactivation of hepatitis B virus (HBV) replication is characterized by increased HBV-DNA serum values of about 1 log or by HBV DNA turning positive if previously undetectable in serum, possibly associated with liver damage and seldom life-threatening. Due to HBV reactivation, hepatitis B surface antigen (HBsAg)-negative/anti-HBc-positive subjects may revert to HBsAg-positive. In patients with hemo-lymphoproliferative disease, the frequency of HBV reactivation depends on the type of lymphoproliferative disorder, the individual's HBV serological status and the potency and duration of immunosuppression. In particular, it occurs in 10%-50% of the HBsAg-positive and in 2%-25% of the HBsAg- negative/anti-HBc-positive, the highest incidences being registered in patients receiving rituximab-based therapy. HBV reactivation can be prevented by accurate screening of patients at risk and by a pharmacological prophylaxis with anti-HBV nucleo(t)sides starting 2-3 wk before the beginning of immunosuppressive treatment and covering the entire period of administration of immunosuppressive drugs and a long subsequent period, the duration of which depends substantially on the degree of immunodepression achieved. Patients with significant HBV replication before immunosuppressive therapy should receive anti-HBV nucleo(t)sides as a long-term (may be life-long) treatment. This review article is mainly directed to doctors engaged every day in the treatment of patients with onco-lymphoproliferative diseases, so that they can broaden their knowledge on HBV infection and on its reactivation induced by the drugs with high immunosuppressive potential that they use in the care of their patients.


Assuntos
Antibioticoprofilaxia/métodos , Antivirais/uso terapêutico , Vírus da Hepatite B/isolamento & purificação , Hepatite B/prevenção & controle , Imunossupressores/efeitos adversos , Transtornos Linfoproliferativos/tratamento farmacológico , DNA Viral/sangue , Hepatite B/imunologia , Hepatite B/virologia , Anticorpos Anti-Hepatite B/sangue , Anticorpos Anti-Hepatite B/imunologia , Antígenos de Superfície da Hepatite B/sangue , Antígenos de Superfície da Hepatite B/imunologia , Vírus da Hepatite B/genética , Vírus da Hepatite B/imunologia , Humanos , Transtornos Linfoproliferativos/imunologia , Fatores de Tempo , Ativação Viral/efeitos dos fármacos , Ativação Viral/imunologia
11.
Biomed Res Int ; 2019: 3453105, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31317025

RESUMO

Background: This study assesses the prevalence of Vietnamese children receiving the hepatitis B (HepB) vaccine birth dose and explores its associated socioeconomic factors. Methods: We used the data of the Multiple Indicator Cluster Survey, 2014. We estimated the overall percentage of HepB birth dose vaccination among 0-23-month-old children and its percentages according to selected characteristics. Multiple logistic regression was applied. Results: 62.8% of children received the HepB vaccine birth dose. The prevalence rates by selected factors ranged from 35.3% to 76.7%. The categories with the lowest prevalence rates were children who had low birth weight (41.6%), had a mother aged less than 20 years (35.3%), had a mother with primary or less education (42.7%), belonged to ethnic minorities (30.3%), resided in rural areas (59.9%), and were in the 1st quintile of mother's socioeconomic status (38.6%). Receiving HepB vaccine birth dose was associated with child's birth weight, mother's age, mother's education, socioeconomic status, and ethnicity. Conclusions: This study identified vulnerable groups, upon which policy-makers should focus their efforts to equitably and sustainably tackle birth dose HepB vaccine coverage as well as the full vaccination coverage, thereby promoting long-lasting herd immunity in this country.


Assuntos
Vacinas contra Hepatite B/uso terapêutico , Hepatite B/prevenção & controle , Programas de Imunização , Adulto , Relação Dose-Resposta a Droga , Feminino , Hepatite B/epidemiologia , Hepatite B/imunologia , Hepatite B/virologia , Vacinas contra Hepatite B/imunologia , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Mães , Parto/imunologia , Gravidez , Classe Social , Vacinação , Vietnã/epidemiologia
12.
Clin Lab ; 65(7)2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-31307178

RESUMO

BACKGROUND: Generally, HBV infection serum markers have been globally measured, and the analysis of entire an-tibody details include the affinity, total protein content and antibody activity are rarely measured between two different ethnic groups. We detected and determined the entire characteristics of anti-HBs (antibody to HBs anti-gen) among Sudanese and Chinese HBV resolved patient's using a terminal antibody (TA) method. METHOD: Serum samples of Sudanese and Chinese resolved HBV infection positive anti-HBs were collected. All se-rum samples were diluted in serial dilutions (20, 40, 80, and 160 dilutions). Anti-HB markers were measured with enzyme-linked immunosorbent assay (ELISA), antibody affinity, total protein content, and total antibody activity to anti-HBs were calculated according to the results obtained for each dilution. RESULTS: The antibody affinity to HBV statistically showed higher significance among Sudanese than Chinese (p < 0.05). The total antibody activity to HBV among Sudanese was higher statistically than Chinese patients (p < 0.05). Statistically, there was a high correlation between age and antibody affinity to HBV among Sudanese compared to the Chinese group (p < 0.05). CONCLUSIONS: The measurement of the antibody affinity, total antibody activity, and protein content of anti-HBs among Sudanese and Chinese, two different ethnic groups, may predict HBV infection status among African race and Asian race, and in addition, may play an important role in a high or a low incidence of the disease between different ethnicities.


Assuntos
Afinidade de Anticorpos/imunologia , Anticorpos Anti-Hepatite B/imunologia , Antígenos de Superfície da Hepatite B/imunologia , Vírus da Hepatite B/imunologia , Hepatite B/imunologia , Proteínas Virais/imunologia , Adulto , Grupo com Ancestrais do Continente Africano/estatística & dados numéricos , Grupo com Ancestrais do Continente Asiático/estatística & dados numéricos , Biomarcadores/sangue , China , Ensaio de Imunoadsorção Enzimática , Hepatite B/etnologia , Hepatite B/virologia , Anticorpos Anti-Hepatite B/sangue , Antígenos de Superfície da Hepatite B/sangue , Antígenos de Superfície da Hepatite B/metabolismo , Vírus da Hepatite B/fisiologia , Humanos , Pessoa de Meia-Idade , Sudão , Proteínas Virais/metabolismo
13.
Biomed Res Int ; 2019: 2103943, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31275965

RESUMO

Although current diagnosis and treatment of hepatitis B virus (HBV) infection can maintain viral suppression, new therapies need to be invented to sustain off-treatment virologic suppression and reduce side effects. Exosomes act as intercellular communicators to facilitate direct transfer of proteins, lipids, and nucleic acids between cells in vitro and in vivo. Pioneering work has demonstrated that exosomal cargos changed markedly during HBV infection. An improved understanding of the functions of exosomes during HBV infection could lead to a powerful new strategy for preventing and treating HBV. In this review, we point out the role of exosomes in HBV infection: (1) exosomes could directly participate in HBV replication; (2) exosomes modulate immune response during HBV infections; (3) exosomal RNAs and proteins might be selected as novel biomarkers for the diagnosis of HBV infections; and (4) exosomes can also be designed as vaccines.


Assuntos
Exossomos/metabolismo , Vírus da Hepatite B/fisiologia , Hepatite B/imunologia , Hepatite B/virologia , Interações Hospedeiro-Patógeno/imunologia , Replicação Viral/fisiologia , Biomarcadores/metabolismo , Hepatite B/diagnóstico , Hepatite B/terapia , Humanos
14.
Zhonghua Gan Zang Bing Za Zhi ; 27(6): 468-472, 2019 Jun 20.
Artigo em Chinês | MEDLINE | ID: mdl-31357767

RESUMO

Hepatitis B virus (HBV)/hepatitis C virus (HCV) co-infection shares the same transmission routes, and thereby it is not rare in regions where the prevalence of HBV and HCV is high. However, the co-infection rates of HBV/HCV reported in different regions of the world are relatively dissimilar, and the co-infection rates of HBV/HCV in the population are unidentified due to the presence of silent HBV infection. Thus, the phenomenon of underestimation exists. HCV may have an inhibitory effect on HBV replication when HBV/HCV is co-infected, and the effect of HBV on HCV replication remains to be certain by more studies. Furthermore, the mechanism of interaction may include the direct effect of viral proteins and the indirect effect of immune mediated host response. HBV/HCV co-infection can cause more serious chronic liver diseases and cirrhosis, and can increase the risk of liver cancer. The efficacy of peginterferon plus ribavirin in patients with HBV/HCV co-infection is same as HCV monotherapy. There are few studies on the efficacy of direct-acting antiviral drugs. Patients with HBV/HCV co-infection have the risk of HBV reactivation regardless of anti-HCV treatment with peginterferon plus ribavirin or direct-acting antiviral drugs, but the probability of HBV reactivation and how to assess and prevent it needs more studies to interpret.


Assuntos
Coinfecção , Hepatite B , Hepatite C Crônica , Antivirais , Hepatite B/complicações , Hepatite B/imunologia , Vírus da Hepatite B , Hepatite C , Hepatite C Crônica/complicações , Hepatite C Crônica/imunologia , Humanos , Pesquisa/tendências
15.
Nat Immunol ; 20(9): 1129-1137, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31358998

RESUMO

Natural killer (NK) cells can recognize virus-infected and stressed cells1 using activating and inhibitory receptors, many of which interact with HLA class I. Although early studies also suggested a functional impact of HLA class II on NK cell activity2,3, the NK cell receptors that specifically recognize HLA class II molecules have never been identified. We investigated whether two major families of NK cell receptors, killer-cell immunoglobulin-like receptors (KIRs) and natural cytotoxicity receptors (NCRs), contained receptors that bound to HLA class II, and identified a direct interaction between the NK cell receptor NKp44 and a subset of HLA-DP molecules, including HLA-DP401, one of the most frequent class II allotypes in white populations4. Using NKp44ζ+ reporter cells and primary human NKp44+ NK cells, we demonstrated that interactions between NKp44 and HLA-DP401 trigger functional NK cell responses. This interaction between a subset of HLA-DP molecules and NKp44 implicates HLA class II as a component of the innate immune response, much like HLA class I. It also provides a potential mechanism for the described associations between HLA-DP subtypes and several disease outcomes, including hepatitis B virus infection5-7, graft-versus-host disease8 and inflammatory bowel disease9,10.


Assuntos
Antígenos HLA-DP/imunologia , Imunidade Inata/imunologia , Células Matadoras Naturais/imunologia , Receptor 2 Desencadeador da Citotoxicidade Natural/imunologia , Linhagem Celular , Doença Enxerto-Hospedeiro/imunologia , Hepatite B/imunologia , Humanos , Doenças Inflamatórias Intestinais/imunologia , Células Jurkat
16.
Int J Mol Sci ; 20(11)2019 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-31195619

RESUMO

Chronic hepatitis B virus (HBV) infection represents a worldwide public health concern with approximately 250 million people chronically infected and at risk of developing liver cirrhosis and hepatocellular carcinoma. Nucleos(t)ide analogues (NUC) are the most widely used therapies for HBV infection, but they often require long-lasting administration to avoid the risk of HBV reactivation at withdrawal. Therefore, there is an urgent need to develop novel treatments to shorten the duration of NUC therapy by accelerating virus control, and to complement the effect of available anti-viral therapies. In chronic HBV infection, virus-specific T cells are functionally defective, and this exhaustion state is a key determinant of virus persistence. Reconstitution of an efficient anti-viral T cell response may thus represent a rational strategy to treat chronic HBV patients. In this perspective, the enhancement of adaptive immune responses by a checkpoint inhibitor blockade, specific T cell vaccines, lymphocyte metabolism targeting, and autologous T cell engineering, including chimeric antigen receptor (CAR) and TCR-redirected T cells, constitutes a promising immune modulatory approach for a therapeutic restoration of protective immunity. The advances of the emerging immune-based therapies in the setting of the HBV research field will be outlined.


Assuntos
Vírus da Hepatite B/imunologia , Hepatite B/imunologia , Hepatite B/terapia , Imunoterapia , Engenharia Genética , Hepatite B/genética , Humanos , Linfócitos T/metabolismo , Vacinação
17.
Eur J Pharm Sci ; 136: 104939, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31195071

RESUMO

The liver is a well-known immunotolerogenic environment, which provides the adequate setting for liver infectious pathogens persistence such as the hepatitis B virus (HBV). Consequently, HBV infection can derive in the development of chronic disease in a proportion of the patients. If this situation persists in time, chronic hepatitis B (CHB) would end in cirrhosis, hepatocellular carcinoma and eventually, the death of the patient. It is thought that this immunotolerogenic environment is the result of complex interactions between different elements of the immune system and the viral biology. Therefore, the purpose of this work is to unravel the mechanisms implied in the development of CHB and to design a tool able to help in the study of adequate therapies. Firstly, a conceptual framework with the main components of the immune system and viral dynamics was constructed providing an overall insight on the pathways and interactions implied in this disease. Secondly, a review of the literature was performed in a modular fashion: (i) viral dynamics, (ii) innate immune response, (iii) humoral and (iv) cellular adaptive immune responses and (v) tolerogenic aspects. Finally, the information collected was integrated into a single topological representation that could serve as the plan for the systems pharmacology model architecture. This representation can be considered as the previous unavoidable step to the construction of a quantitative model that could assist in biomarker and target identification, drug design and development, dosing optimization and disease progression analysis.


Assuntos
Vírus da Hepatite B/imunologia , Hepatite B Crônica/imunologia , Hepatite B/imunologia , Imunidade/imunologia , Antígenos de Superfície da Hepatite B/imunologia , Humanos , Fígado/imunologia , Fígado/virologia
18.
PLoS One ; 14(5): e0217415, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31150445

RESUMO

INTRODUCTION AND METHODS: Hepatitis B is a vaccine preventable disease and is notifiable in South Africa. Hepatitis B vaccination was incorporated into the Expanded Programme on Immunisation in South Africa in 1995. We used a convenience sample from community-based febrile rash surveillance in 2013 to estimate hepatitis B sero-prevalence. Of samples serologically negative for acute measles infection, 450 samples spanning nine provinces of South Africa were tested for hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (anti-HBs) and hepatitis B core antibody (anti-HBc). RESULTS: Two children (2/450; 0.4%) tested positive for HBsAg. Three hundred and three children (67.3%) had evidence of vaccine induced immunity. Vaccine induced immunity was present in 80.2% of 1-5 year olds, but only 60.3% of 10-14 year olds. Natural immunity, indicating exposure to circulating hepatitis B, was present in 13/450 (2.9%) children. CONCLUSION: Chronic hepatitis B in South African has decreased in prevalence from highly endemic levels prior to vaccine introduction to approximately 0.4% in this sample, demonstrating impact of a successful vaccination programme 18 years after introduction. Decreased vaccine-induced immunity with increasing age may reflect waning antibody titres over time.


Assuntos
Exantema/virologia , Vacinas contra Hepatite B/imunologia , Hepatite B/epidemiologia , Hepatite B/imunologia , Adolescente , Criança , Pré-Escolar , Feminino , Anticorpos Anti-Hepatite B/imunologia , Antígenos do Núcleo do Vírus da Hepatite B/imunologia , Antígenos de Superfície da Hepatite B/imunologia , Humanos , Programas de Imunização/métodos , Lactente , Recém-Nascido , Masculino , Sarampo/virologia , Prevalência , África do Sul/epidemiologia , Vacinação/métodos
19.
BMC Infect Dis ; 19(1): 482, 2019 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-31146699

RESUMO

BACKGROUND: To assess the immune persistence conferred by a Chinese hamster ovary (CHO)-derived hepatitis B vaccine (HepB) 17 to 20 years after primary immunization during early life. METHODS: Participants born between 1997 and 1999 who received a full course of primary vaccination with HepB (CHO) and who had no experience with booster vaccination were enrolled. Blood samples were required from each participant for measurement of hepatitis B surface antibody (anti-HBs), surface antigen and core antibody levels. For those who possessed an anti-HBs antibody < 10 mIU/mL, a single dose of HepB was administered, and 30 days later, serum specimens were collected to assess the booster effects. RESULTS: A total of 1352 participants were included in this study. Of these, 1007 (74.5%) participants could retain an anti-HBs antibody ≥10 mIU/mL, with a geometric mean concentration (GMC) of 57.4 mIU/mL. HBsAg was detected in six participants, resulting in a HBsAg carrier rate of 0.4% (6/1352). Of those participants with anti-HBs antibodies < 10 mIU/mL, after a challenge dose, 231 (93.1%) presented an anti-HBs antibody ≥10 mIU/mL, with a GMC of 368.7 mIU/mL. A significant increase in the anti-HBs positive rate (≥ 10 mIU/mL) after challenge was observed in participants with anti-HBs antibodies between 2.5 and 10 mIU/mL and participants boosted with HepB (CHO), rather than those with anti-HBs antibodies < 2.5 mIU/mL and those boosted with HepB (SC). CONCLUSION: Since satisfactory immune protection against HBV infection conferred by primary vaccination administered 17-20 years ago was demonstrated, there is currently no urgent need for booster immunization.


Assuntos
Anticorpos Anti-Hepatite B/sangue , Vacinas contra Hepatite B/administração & dosagem , Hepatite B/prevenção & controle , Imunização Secundária , Prevenção Primária , Vacinas Sintéticas/imunologia , Vacinas Sintéticas/uso terapêutico , Adolescente , Adulto , Animais , Células CHO , Cricetinae , Cricetulus , Feminino , Seguimentos , Hepatite B/imunologia , Antígenos de Superfície da Hepatite B/imunologia , Vacinas contra Hepatite B/imunologia , Humanos , Recém-Nascido , Masculino , Prevenção Primária/métodos , Estudos Retrospectivos , Fatores de Tempo , Adulto Jovem
20.
Future Microbiol ; 14: 41-44, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31187633

RESUMO

Medical residents (MRs) are healthcare workers (HCWs) who are likely to be exposed to blood-borne pathogens such as hepatitis B virus (HBV). A total of 220 (100%) MRs from Catania University Hospital (Italy) were enrolled for a seroprevalence study in the framework of occupational surveillance in order to evaluate HBV vaccination coverage. For each MR, Hepatitis B surface antigen (HbsAg), Hepatitis B surface antibody (HBsAb), Hepatitis B core antiboy (HbcAb), Hepatitis C antibody (HCV-Ab) and HIV antibody (HIV-Ab) were assessed. No one was found to be positive for: HbsAg, HbcAb, HCV-Ab or HIV-Ab. HBV vaccination coverage was found in 80% of those tested. A total of 45 MRs showed a nonprotective antibody titer; in eight, complete vaccination had never been carried out; in 37, the vaccination had been carried out, but the antibody titer was not protective. This research showed high adherence to HBV vaccination; however, the vaccine coverage of HCWs is still suboptimal. Vaccinations for HCWs should be made mandatory.


Assuntos
Vacinas contra Hepatite B , Hepatite B/epidemiologia , Internato e Residência/estatística & dados numéricos , Cobertura Vacinal/estatística & dados numéricos , Adulto , Feminino , Hepatite B/imunologia , Vacinas contra Hepatite B/administração & dosagem , Hospitais Universitários/estatística & dados numéricos , Humanos , Itália/epidemiologia , Masculino , Estudos Soroepidemiológicos
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