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2.
Immunology ; 159(2): 178-182, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31613998

RESUMO

Hepatitis B virus (HBV) infection causes a self-limiting disease in most individuals. However, < 10% of infected subjects develop a chronic disease. Genetic host variability of polymorphic genes at the interface of innate and acquired immunity, such as killer immunoglobulin-like receptors (KIR), their human leucocyte antigen (HLA) and IgG allotypes (GM), could explain this different clinical picture. We previously showed a protective role of the KIR2DL3 gene for the development of chronic hepatitis B (CHB), and a detrimental role of the KIR ligand groups, HLA-A-Bw4 and HLA-C2. We have expanded the previous analysis genotyping patients for GM23 and GM3/17 allotypes. The comparison of the patients with CHB with those who resolved HBV infection showed that the presence of GM17 allele virtually eliminated the risk of developing CHB (OR, 0·03; 95% CI, 0·004-0·16; P < 0·0001). In addition, the combination of GM17, KIR2DL3, HLA-A-Bw4 and HLA-C2 was highly sensitive to predict the outcome of HBV infection.


Assuntos
Antígenos HLA-B/genética , Antígenos HLA-C/genética , Hepatite B Crônica/prevenção & controle , Alótipos Gm de Imunoglobulina/genética , Receptores KIR2DL3/genética , Estudos de Casos e Controles , Frequência do Gene , Predisposição Genética para Doença , Antígenos HLA-B/imunologia , Antígenos HLA-C/imunologia , Vírus da Hepatite B/imunologia , Hepatite B Crônica/genética , Hepatite B Crônica/imunologia , Interações Hospedeiro-Patógeno , Humanos , Alótipos Gm de Imunoglobulina/imunologia , Fenótipo , Fatores de Proteção , Receptores KIR2DL3/imunologia , Medição de Risco , Fatores de Risco
3.
Artigo em Inglês | MEDLINE | ID: mdl-31505743

RESUMO

Hepatitis B Virus (HBV) is a significant public health challenge. Around 250 million people live with chronic HBV infection. With a global approach to this issue, we focus on new perspective in diagnosis, management and prevention of HBV chronic infection. Precise diagnosis of HBV status is crucial to guide patient management. Although available drugs reduce the risk of liver disease progression, they are not able to definitely eradicate HBV, and new therapeutic options are urgently needed. Thus, prevention of HBV infection is still the most effective strategy to achieve the control of the disease. Key aspects of prevention programs include surveillance of viral hepatitis, screening programs and immunization strategies. In spite of the high success rate of licensed HBV vaccines, a need for improved vaccine persists, especially in order to provide coverage of current non-responders.


Assuntos
Hepatite B Crônica , Antivirais/uso terapêutico , Vacinas contra Hepatite B/administração & dosagem , Vírus da Hepatite B/imunologia , Hepatite B Crônica/diagnóstico , Hepatite B Crônica/tratamento farmacológico , Hepatite B Crônica/prevenção & controle , Humanos , Imunização , Imunocompetência
5.
BMC Infect Dis ; 19(1): 638, 2019 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-31319805

RESUMO

BACKGROUND: Chronic hepatitis B (CHB) is a major cause of liver-related morbidity and mortality. High HBV prevalence in immigrants and ethnic minorities and numerous barriers to healthcare access are associated with serious health disparities in the United States. Reportedly, self-awareness of HBV infection is low, suggesting a greater need for effective screening and education. Further, low levels of linkage to care (LTC) (completion of a first doctor's visit after the diagnosis of chronic HBV infection) may be responsible for the lack of engagement over the continuum of care and for needed services. METHODS: Demographics and survey data were obtained from 97 Korean American adults chronically infected with HBV, initially identified through a series of community screening events in northern New Jersey between Dec. 2009 and June 2015. Eight year follow-up on these HBV-infected individuals was obtained to determine their access to care, and thus the efficacy of a campaign to improve LTC. The participants' self-awareness of HBV infection and other factors for LTC were also evaluated. RESULTS: Of a total of 97 HBV-infected participants (age range 30 to 79), 74 were aware of their infections at screening. The remaining 23 had been unaware of their infections until screening. Eight years after the campaign, some 66 of these 97 individuals accessed care (LTC rate 68%). Health insurance status, presence or absence of symptoms and level of knowledge of CHB were among the most significant factors in LTC. CONCLUSION: A community-based hepatitis B screening and education campaign can be instrumental in prompting HBV infected individuals to access care, as demonstrated in the cumulative increase in LTC in our cohort. Despite many years of awareness of HBV infection, many are not accessing care owing to a lack of health insurance, suggesting a pressing need for advocacy and health education to improve access to affordable coverage in the Asian American population. Community efforts and strategies similar to the ones employed in the current study may serve as a model to improve the engagement of HBV-infected individuals in high risk immigrant populations.


Assuntos
Conhecimentos, Atitudes e Prática em Saúde , Acesso aos Serviços de Saúde , Hepatite B/epidemiologia , Adulto , Idoso , Americanos Asiáticos/estatística & dados numéricos , Emigrantes e Imigrantes , Feminino , Seguimentos , Hepatite B Crônica/prevenção & controle , Humanos , Seguro Saúde , Masculino , Programas de Rastreamento/estatística & dados numéricos , Pessoa de Meia-Idade , New Jersey/epidemiologia , Prevalência
7.
Am J Trop Med Hyg ; 101(1): 214-219, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31115298

RESUMO

In 2016, the World Health Assembly endorsed the Global Health Sector Strategy on Viral Hepatitis, which calls for elimination of hepatitis B virus (HBV) by 2030 (definition: ≤ 0.1% hepatitis B surface antigen [HBsAg] prevalence among children aged 5 years). The burden of chronic HBV infection among children in Haiti is unknown. We conducted a nationally representative cross-sectional serological survey among 5- to 7-year-old children based on a two-stage cluster design with two strata: West (includes metropolitan Port-au-Prince) and non-West (all other departments). We collected demographic, socioeconomic, and vaccination history data and tested for HBsAg using a rapid point-of-care test. We estimated HBsAg prevalence and evaluated the association of HBV infection with vaccination history, demographics, and socioeconomic characteristics. Of the 1,152 children, seven (0.5%, 95% CI: 0.2-1.2) were HBsAg positive. The HBsAg prevalence varied by region (West: 0.1%, 95% CI: 0.01-0.9; non-West: 0.7%, 95% CI: 0.2-1.9) (P = 0.1), gender (males: 0.7%, 95% CI: 0.2-2.4; females: 0.2%, 95% CI: 0.05-1.1) (P = 0.3), and caregiver's education level (none: 0.8%, 95% CI: 0.2-3.1; some or completed primary: 0.5%, 95% CI: 0.1-1.8; some secondary: 0.4%, 95% CI: 0.1-1.8; secondary and higher: 0.0%, 95% CI: 0-0), although the differences were not statistically significant. None of the HBsAg-positive children had documented vaccination with hepatitis B vaccine (HepB). Haiti's chronic HBV infection prevalence among children is low; however, it is above the elimination target. To reach elimination, Haiti needs to achieve high coverage with the three HepB doses and introduce a HepB birth dose.


Assuntos
Vacinas contra Hepatite B/imunologia , Hepatite B Crônica/epidemiologia , Adulto , Cuidadores , Criança , Pré-Escolar , Estudos Transversais , Feminino , Haiti/epidemiologia , Antígenos de Superfície da Hepatite B/sangue , Vacinas contra Hepatite B/administração & dosagem , Hepatite B Crônica/prevenção & controle , Humanos , Masculino , Prevalência , Estudos Soroepidemiológicos , Fatores Socioeconômicos , Vacinação
8.
Korean J Gastroenterol ; 73(3): 132-140, 2019 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-31013556

RESUMO

The clinical practice guideline for the management of chronic hepatitis B (CHB) was originally enacted in 2004 by the Korean Association for the Study of the Liver in order to provide medical practitioners with specific medical information regarding CHB to help them facilitate their understanding of the disease and treatment of the infected patients. Other than an update on the treatment of antiviral resistance in 2014, which is a partial revision, the guidelines for the treatment of chronic hepatitis B have been revised entirely three times in 2007, 2011, and 2015. Although several major international liver association have established and revised clinical practice guidelines, since the medical environment in each country is somewhat different depending on race, region, institution, and economic conditions, it is necessary to revise the Korean guidelines to that reflect our medical environment and own research results. In this review, major change and its background will be summarized about 2018 updated clinical practice guidelines for the management of CHB.


Assuntos
Antivirais/uso terapêutico , Hepatite B Crônica/tratamento farmacológico , DNA Viral/sangue , Farmacorresistência Viral , Antígenos de Superfície da Hepatite B/sangue , Vírus da Hepatite B/genética , Vírus da Hepatite B/isolamento & purificação , Hepatite B Crônica/imunologia , Hepatite B Crônica/prevenção & controle , Humanos , Imunossupressores/uso terapêutico , Neoplasias Hepáticas/complicações , Neoplasias Hepáticas/diagnóstico , Guias de Prática Clínica como Assunto
9.
Zhonghua Gan Zang Bing Za Zhi ; 27(2): 85-87, 2019 Feb 20.
Artigo em Chinês | MEDLINE | ID: mdl-30818909

RESUMO

The main transmission route of chronic hepatitis B virus infection is mother-to-child transmission of hepatitis B virus and the main cause of combined immune prophylaxis failure in neonates at the end of pregnancy is high viral load. Moreover, oral administration of nucleos(t)ide analogues (NAs) during the second and third trimesters of pregnancy can significantly reduce or even completely block mother-to-child transmission of HBV. This article focuses on the necessity and feasibility of oral NAs antiviral therapy for HBV carrier pregnant woman with high viral load, and the issues commences at the time of medication and viral load thresholds.


Assuntos
Antivirais/uso terapêutico , Vírus da Hepatite B/efeitos dos fármacos , Hepatite B Crônica/tratamento farmacológico , Hepatite B Crônica/transmissão , Transmissão Vertical de Doença Infecciosa/prevenção & controle , Antivirais/administração & dosagem , DNA Viral , Feminino , Hepatite B Crônica/prevenção & controle , Humanos , Recém-Nascido , Nucleosídeos/uso terapêutico , Nucleotídeos/uso terapêutico , Gravidez , Complicações Infecciosas na Gravidez/virologia , Carga Viral
10.
Zhonghua Gan Zang Bing Za Zhi ; 27(1): 3-5, 2019 Jan 20.
Artigo em Chinês | MEDLINE | ID: mdl-30685915

RESUMO

Since the 40th anniversary of China's reform and opening-up, earth-shattering development has taken place in all walks of life across the country. Research field on the prevention and treatment of chronic hepatitis B has been rewarding after 40 years of trials and tribulations. Additionally, hepatitis B vaccination program and effective antiviral therapy has amazingly reduced the prevalence of hepatitis B virus infection. Coupled with the literary evidence, a consensus has gradually emerged in the field of anti-HBV treatment that "high potency, low incidence of drug resistance and immunomodulation coexists". We believe that in the near future, according to the principle of "prevention first, prevention with treatment", universal vaccination program for infants, vaccination of high-risk groups, active treatment of HBV carriers and chronic hepatitis B patients, and the realization of "early screening, diagnosis and treatment" of hepatocellular carcinoma will eradicate HBV infection.


Assuntos
Carcinoma Hepatocelular/prevenção & controle , Vacinas contra Hepatite B/administração & dosagem , Vírus da Hepatite B/efeitos dos fármacos , Hepatite B Crônica/prevenção & controle , Neoplasias Hepáticas/prevenção & controle , Antivirais/uso terapêutico , Carcinoma Hepatocelular/virologia , China/epidemiologia , Hepatite B/tratamento farmacológico , Hepatite B/epidemiologia , Hepatite B/prevenção & controle , Vacinas contra Hepatite B/imunologia , Hepatite B Crônica/tratamento farmacológico , Hepatite B Crônica/epidemiologia , Humanos , Neoplasias Hepáticas/virologia , Prevalência , Vacinação
11.
J Virol ; 93(5)2019 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-30541859

RESUMO

Therapeutic vaccines may be an important component of a treatment regimen for curing chronic hepatitis B virus (HBV) infection. We previously demonstrated that recombinant wild-type vesicular stomatitis virus (VSV) expressing the HBV middle surface glycoprotein (MHBs) elicits functional immune responses in mouse models of HBV replication. However, VSV has some undesirable pathogenic properties, and the use of this platform in humans requires further viral attenuation. We therefore generated a highly attenuated VSV that expresses MHBs and contains two attenuating mutations. This vector was evaluated for immunogenicity, pathogenesis, and anti-HBV function in mice. Compared to wild-type VSV, the highly attenuated virus displayed markedly reduced pathogenesis but induced similar MHBs-specific CD8+ T cell and antibody responses. The CD8+ T cell responses elicited by this vector in naive mice prevented HBV replication in animals that were later challenged by hydrodynamic injection or transduction with adeno-associated virus encoding the HBV genome (AAV-HBV). In mice in which persistent HBV replication was first established by AAV-HBV transduction, subsequent immunization with the attenuated VSV induced MHBs-specific CD8+ T cell responses that corresponded with reductions in serum and liver HBV antigens and nucleic acids. HBV control was associated with an increase in the frequency of intrahepatic HBV-specific CD8+ T cells and a transient elevation in serum alanine aminotransferase activity. The ability of VSV to induce a robust multispecific T cell response that controls HBV replication combined with the improved safety profile of the highly attenuated vector suggests that this platform offers a new approach for HBV therapeutic vaccination.IMPORTANCE A curative treatment for chronic hepatitis B must eliminate the virus from the liver, but current antiviral therapies typically fail to do so. Immune-mediated resolution of infection occurs in a small fraction of chronic HBV patients, which suggests the potential efficacy of therapeutic strategies that boost the patient's own immune response to the virus. We modified a safe form of VSV to express an immunogenic HBV protein and evaluated the efficacy of this vector in the prevention and treatment of HBV infection in mouse models. Our results show that this vector elicits HBV-specific immune responses that prevent the establishment of HBV infection and reduce viral proteins in the serum and viral DNA/RNA in the liver of mice with persistent HBV replication. These findings suggest that highly attenuated and safe virus-based vaccine platforms have the potential to be utilized for the development of an effective therapeutic vaccine against chronic HBV infection.


Assuntos
Vacinas contra Hepatite B/imunologia , Vírus da Hepatite B/imunologia , Hepatite B Crônica/prevenção & controle , Hepatite B Crônica/terapia , Vacinas Atenuadas/imunologia , Vírus da Estomatite Vesicular Indiana/imunologia , Alanina Transaminase/sangue , Animais , Linfócitos T CD8-Positivos/imunologia , Hepatite B Crônica/imunologia , Imunoterapia/métodos , Glicoproteínas de Membrana/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Vacinas Virais/imunologia , Replicação Viral/imunologia
13.
Zhonghua Gan Zang Bing Za Zhi ; 27(12): 938-961, 2019 Dec 20.
Artigo em Chinês | MEDLINE | ID: mdl-31941257

RESUMO

Based on the progression of clinical and basic research in hepatitis B virus (HBV), we updated the previous HBV guidelines from 2015. The guidelines included the prevention, diagnosis, and antiviral therapy of chronic hepatitis B, which accelerates ro achieve the goal of "the elimination of viral hepatitis as a public health threat by 2030" proposed by the World Health Organization.


Assuntos
Antivirais/uso terapêutico , Vírus da Hepatite B/efeitos dos fármacos , Hepatite B Crônica/tratamento farmacológico , Hepatite B Crônica/prevenção & controle , Guias de Prática Clínica como Assunto , Vírus da Hepatite B/isolamento & purificação , Hepatite B Crônica/diagnóstico , Hepatite B Crônica/virologia , Humanos , Saúde Pública , Organização Mundial da Saúde
14.
Zhonghua Liu Xing Bing Xue Za Zhi ; 40(12): 1650-1653, 2019 Dec 10.
Artigo em Chinês | MEDLINE | ID: mdl-32062932

RESUMO

There have been 6-10 million reported patients with chronic hepatitis B virus (HBV) infection worldwide, and the United Nations (UN) called for a "90% reduction by 2030" strategy. Since the wide practice of HBV vaccination, the numbers of HBV cases have been reduced by 85% and the incidence of hepatocellular carcinoma has also decreased by 50%. As formulated by the UN in 2015, the sustainable development agenda for the eradication of hepatitis B included the success rate of preventing mother-to-child viral transmission by 95%, together with the reduction of new hepatitis B infections by 90% in 2030. In order to achieve the agenda, we proposed a strategy to achieve the "three 96%" goals derived from the Shanghai experience. In brief, hepatitis B vaccine should cover for 96% newborns within 24 h, and the vaccination boosting rate should reach 96% for both one and six months after birth. If cutting off the mother-to-child viral transmission strategy can be successfully achieved, the future of hepatitis B prevention will be promising, and the task of eliminating hepatitis B and controlling hepatocellular carcinoma can be completed ahead of 2030, time proposed by the UN.


Assuntos
Carcinoma Hepatocelular , Vacinas contra Hepatite B , Hepatite B Crônica , Hepatite B , Transmissão Vertical de Doença Infecciosa , Neoplasias Hepáticas , Criança , China/epidemiologia , Feminino , Hepatite B/complicações , Hepatite B/prevenção & controle , Hepatite B/transmissão , Vacinas contra Hepatite B/uso terapêutico , Vírus da Hepatite B , Hepatite B Crônica/epidemiologia , Hepatite B Crônica/prevenção & controle , Hepatite B Crônica/transmissão , Humanos , Incidência , Recém-Nascido , Transmissão Vertical de Doença Infecciosa/prevenção & controle , Neoplasias Hepáticas/epidemiologia , Neoplasias Hepáticas/etiologia , Neoplasias Hepáticas/prevenção & controle , Gravidez
16.
Pol Merkur Lekarski ; 45(269): 192-194, 2018 Nov 28.
Artigo em Polonês | MEDLINE | ID: mdl-30531668

RESUMO

The patient was diagnosed with chronic hepatitis B at 19 years old. Biochemical, serological and histopathological diagnostic processes were followed by pegylated interferon treatment. After 24 weeks of therapy treatment was discontinued due to pathological thyroid hormones values. The patient was diagnosed with Hashimoto's thyroiditis and levothyroxine therapy initiated. Over the following two years, the patient was not under hepatology specialist care. She was admitted to the Clinic due to a high aminotransferase level and concomitant pruritus in the 32nd week of her first pregnancy. In the end the patient was diagnosed as having an exacerbation of chronic hepatitis B. After recognition of high HBV (hepatitis B virus) viremia, treatment with tenofovir was initiated. In the course of treatment the following were observed: HBeAg/anti-Hbe (antigen HBe/anti-HBe antibodies) seroconversion, decrease in viral load, biochemical normalization; and an improvement in clinical status of the patient was obtained. An elective caesarean section was performed in week 40; the new-born received 10 points on the Apgar scale. During the first hours of life, the passive-active immunoprophylaxis: immunoglobulin and the first dose of anti-HBV vaccine, were given to the new-born. Over long-term observation it was found that there was no vertical transmission of the hepatitis B virus to the child.


Assuntos
Cesárea , Hepatite B Crônica/prevenção & controle , Transmissão Vertical de Doença Infecciosa/prevenção & controle , Feminino , Humanos , Recém-Nascido , Gravidez
17.
Lancet ; 392(10162): 2398-2412, 2018 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-30473364

RESUMO

This report presents further evidence on the escalating alcohol consumption in the UK and the burden of liver disease associated with this major risk factor, as well as the effects on hospital and primary care. We reiterate the need for fiscal regulation by the UK Government if overall alcohol consumption is to be reduced sufficiently to improve health outcomes. We also draw attention to the effects of drastic cuts in public services for alcohol treatment, the repeated failures of voluntary agreements with the drinks industry, and the influence of the industry through its lobbying activities. We continue to press for reintroduction of the alcohol duty escalator, which was highly effective during the 5 years it was in place, and the introduction of minimum unit pricing in England, targeted at the heaviest drinkers. Results from the introduction of minimum unit pricing in Scotland, with results from Wales to follow, are likely to seriously expose the weakness of England's position. The increasing prevalence of obesity-related liver disease, the rising number of people diagnosed with type 2 diabetes and its complications, and increasing number of cases of end-stage liver disease and primary liver cancers from non-alcoholic fatty liver disease make apparent the need for an obesity strategy for adults. We also discuss the important effects of obesity and alcohol on disease progression, and the increased risk of the ten most common cancers (including breast and colon cancers). A new in-depth analysis of the UK National Health Service (NHS) and total societal costs shows the extraordinarily large expenditures that could be saved or redeployed elsewhere in the NHS. Excellent results have been reported for new antiviral drugs for hepatitis C virus infection, making elimination of chronic infection a real possibility ahead of the WHO 2030 target. However, the extent of unidentified cases remains a problem, and will also apply when new curative drugs for hepatitis B virus become available. We also describe efforts to improve standards of hospital care for liver disease with better understanding of current service deficiencies and a new accreditation process for hospitals providing liver services. New commissioning arrangements for primary and community care represent progress, in terms of effective screening of high-risk subjects and the early detection of liver disease.


Assuntos
Política de Saúde , Hepatopatias/epidemiologia , Hepatopatias/prevenção & controle , Consumo de Bebidas Alcoólicas/epidemiologia , Consumo de Bebidas Alcoólicas/prevenção & controle , Bebidas Alcoólicas/economia , Comorbidade , Custos e Análise de Custo , Erradicação de Doenças , Progressão da Doença , Feminino , Indústria Alimentícia , Hepatite B Crônica/epidemiologia , Hepatite B Crônica/prevenção & controle , Hepatite C Crônica/epidemiologia , Hepatite C Crônica/prevenção & controle , Mortalidade Hospitalar , Humanos , Hepatopatias/mortalidade , Hepatopatias Alcoólicas/epidemiologia , Hepatopatias Alcoólicas/prevenção & controle , Manobras Políticas , Masculino , Neoplasias/epidemiologia , Obesidade/epidemiologia , Obesidade/prevenção & controle , Prevalência , Reino Unido/epidemiologia
18.
Ann Transplant ; 23: 789-801, 2018 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-30420590

RESUMO

BACKGROUND Long-term real-world data are relatively sparse regarding recurrence of chronic hepatitis B virus (HBV) infection after liver transplantation using hepatitis B immunoglobulin (HBIg) and nucleos(t)ide analogue (NUC) prophylaxis. MATERIAL AND METHODS Data from 371 adults transplanted for HBV-related disease at 20 European centers and given HBIg for ³12 months ± NUC therapy were analyzed retrospectively. RESULTS HBIg comprised Hepatect® (iv HBIgB; n=299), subcutaneous Zutectra® (sc HBIg, n=236), and other HBIg preparations (n=130); 93.5% received NUC therapy. Mean follow-up was 6.8±3.5 years. The primary efficacy variable, freedom from HBV recurrence, occurred in 95.7% of patients (95% CI [93.1%, 97.5%]). The observed incidence of recurrence was 16/371 (4.3%) (annual rate 0.65%); 5/16 patients with recurrence had discontinued HBIg and 7/16 had anti-HBs <100 IU/l. Excluding these 7 patients, the HBV recurrence rate was 2.4%. The recurrence rate while on HBIg therapy was 1 per 2069 months. In patients who discontinued HBIg, risk of HBV recurrence versus sc HBIg users was increased by 5.2-fold (1 per 1 603 versus 1 per 8379 treatment months). The annual rate of HBV-related hepatocellular carcinoma (HCC) recurrence was 1.7%. CONCLUSIONS These results support the long-term use of HBIg with NUC therapy as an effective management strategy to minimize risk of HBV recurrence and virus-related complications after liver transplantation.


Assuntos
Antivirais/uso terapêutico , Hepatite B Crônica/prevenção & controle , Imunoglobulinas/uso terapêutico , Transplante de Fígado , Nucleosídeos/uso terapêutico , Prevenção Secundária/métodos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Quimioterapia Combinada , Feminino , Seguimentos , Hepatite B Crônica/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
19.
Mol Immunol ; 103: 243-250, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30321734

RESUMO

Reversal of T cell dysfunction is a novel and promising approach for the treatment of chronic diseases. PGE2, one of most studied Prostaglandins, exhibits strong and versatile immunoregulation activity on different immune cells including T cells, and has become a promising therapeutic target. Here we found that compared to healthy donors, patients with chronic Hepatitis B virus (HBV) infection had significantly elevated serum PGE2 level. Importantly, serum PGE2 concentration correlated with viral load and liver damage in Chronic hepatitis B(CHB)patients. In AAV-HBV1.2 mouse model, administration of PGE2 analogue promoted HBV replication, while antagonists for EP2 and EP4, two important receptors for PGE2, inhibited virus replication. However, PGE2 analogue had no significant effect on the growth and virus replication in cultured HBV-harboring hepatocyte cell line. Further analysis showed that high PGE2 level in CHB patients correlated with high Tim-3 expression and low level of perforin and granzme B in CD8 + T cells. In parallel, blockade of PGE2 signaling restored the function of CD8 + T cells and controls HBV infection. Depletion of CD8 + T cells almost abrogated the effects of PGE2 on HBV replication. These findings identify PGE2 as a negative regulator for CD8 + T cells contributing to HBV persistence and the intervention of PGE2 signaling might be of potentially translational significance.


Assuntos
Linfócitos T CD8-Positivos/imunologia , Dinoprostona/imunologia , Vírus da Hepatite B/imunologia , Hepatite B Crônica/imunologia , Linfócitos T Citotóxicos/imunologia , Replicação Viral/imunologia , Animais , Linfócitos T CD8-Positivos/efeitos dos fármacos , Linfócitos T CD8-Positivos/virologia , Dinoprostona/metabolismo , Dinoprostona/farmacologia , Células Hep G2 , Vírus da Hepatite B/fisiologia , Hepatite B Crônica/prevenção & controle , Hepatite B Crônica/virologia , Interações Hospedeiro-Patógeno/efeitos dos fármacos , Interações Hospedeiro-Patógeno/imunologia , Humanos , Camundongos Endogâmicos C57BL , Perforina/imunologia , Perforina/metabolismo , Antagonistas de Prostaglandina/farmacologia , Linfócitos T Citotóxicos/efeitos dos fármacos , Linfócitos T Citotóxicos/virologia , Carga Viral/efeitos dos fármacos , Carga Viral/imunologia , Replicação Viral/efeitos dos fármacos , Xantonas/farmacologia
20.
Sci Rep ; 8(1): 15514, 2018 10 19.
Artigo em Inglês | MEDLINE | ID: mdl-30341345

RESUMO

Mother-to-child transmission is the major cause of chronic hepatitis B virus (HBV) infection. This double-blind trial tested the effect of tenofovir disoproxil fumarate (TDF) in preventing vertical transmission. Pregnant women who were HBsAg/HBeAg-positive with a HBV DNA titer ≥ 2×106 IU/mL were randomly assigned to the control (n = 60) and TDF-treated (n = 60) groups. TDF treatment (oral dose 300 mg/day) was initiated at 24 weeks of gestation and continued to 4 weeks after delivery. The subjects were followed up to 28 weeks postpartum. The effects of TDF on vertical transmission, outcomes of the mothers and infants and virological changes were monitored. TDF dynamically reduced the serum HBV DNA level of the mothers, particularly during the first 4 weeks of treatment. The lower viral loads were maintained in the pregnancies until delivery. Approximately 90% and 33.9% of the TDF-treated mothers had viral loads ≤2000 IU/mL after delivery and at 28 weeks postpartum, respectively. No cervical transmission or adverse effects were observed in the TDF-treated individuals, whereas 13.5% of the infants were infected with HBV in the control group. We conclude that TDF treatment initiated at 24 weeks of gestation in high-viremia, HBsAg/HBeAg-positive mothers efficiently prevents mother-to-child HBV transmission without adverse events in mothers and infants.


Assuntos
Vírus da Hepatite B/fisiologia , Hepatite B Crônica/tratamento farmacológico , Hepatite B Crônica/transmissão , Transmissão Vertical de Doença Infecciosa , Tenofovir/uso terapêutico , Carga Viral/fisiologia , Adulto , Estudos de Casos e Controles , DNA Viral/sangue , Feminino , Vírus da Hepatite B/efeitos dos fármacos , Hepatite B Crônica/prevenção & controle , Hepatite B Crônica/virologia , Humanos , Recém-Nascido , Período Pós-Parto/sangue , Gravidez , Tenofovir/farmacologia , Resultado do Tratamento , Carga Viral/efeitos dos fármacos
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