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1.
Anticancer Res ; 40(1): 245-252, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31892573

RESUMO

AIM: It has been shown that the integration of hepatitis B virus (HBV) gene into the host genome is a high-risk factor for development of hepatocellular carcinoma (HCC). However, the relationship between HBV S-integrated human extra spindle pole bodies-like 1 (ESPL1) gene and HCC is unknown. This study was designed to detect HBV S-integrated human ESPL1 fusion gene in patients with HCC for potentially using this fusion gene as a biomarker for HCC diagnosis. PATIENTS AND METHODS: Nineteen and 70 patients with chronic hepatitis B (CHB) were recruited to the experimental and control groups, respectively, and both groups underwent an effective nucleoside/nucleotide analog therapy and follow-up for HCC occurrence for up to 11 years. HCC tissues were obtained by surgical resection from the experimental group, while liver tissues were collected by liver biopsy in the control group prior to treatment with nucleoside/nucleotide analogs. Alu polymerase chain reaction was used to assess HBV S gene integration in the liver tissues from both groups. HBV S-integrated human ESPL1 fusion gene was then detected in patients with HBV S gene integration using a gene database. RESULTS: All patients in the experimental group developed HCC, whereas no HCC was diagnosed in the control group. HBV S gene integration was identified in 12 out of 19 HCC tissues in the experimental group, giving a detection rate of 63.2%, which was significantly greater than that of 15.7% (11/70) in the control group (p<0.001). We further showed that HBV S-integrated human ESPL1 fusion gene was detected in eight patients (rate of 66.7%) among the 12 patients with HCC with HBV S gene integration in the experimental group, whereas the fusion gene was not detectable in any of the patients in the control group (p=0.001). CONCLUSION: This research demonstrates a high detection rate of HBV S-integrated human ESPL1 fusion gene in patients with HBV-related HCC and shows that this fusion gene appears to be associated with HCC development in patients with CHB. These findings suggest that HBV S-integrated human ESPL1 fusion gene may potentially serve as a biomarker for early detection of HCC in HBV-infected populations.


Assuntos
Grupo com Ancestrais do Continente Asiático , Vírus da Hepatite B/genética , Neoplasias Hepáticas/genética , Proteínas de Fusão Oncogênica/genética , Separase/genética , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Estudos de Casos e Controles , Feminino , Regulação Neoplásica da Expressão Gênica , Hepatite B Crônica/genética , Humanos , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Proteínas de Fusão Oncogênica/metabolismo , Separase/metabolismo , Proteínas do Envelope Viral/genética , Proteínas do Envelope Viral/metabolismo
2.
Medicine (Baltimore) ; 99(1): e18462, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31895778

RESUMO

Proinflammatory interleukin-26 (IL-26) is involved in chronic inflammation; however, the role of IL-26 in chronic hepatitis B (CHB) remains unknown.In this study, serum IL-26 was quantified in a cohort of CHB patients at baseline and during telbivudine (LdT) treatment.Our results showed that the serum IL-26 level was significantly elevated in CHB patients compared with that in healthy controls and was time-dependently decreased during LdT treatment, accompanying hepatitis B e antigen (HBeAg) seroconversion and reduced serum levels of hepatitis B virus (HBV) DNA, aspartate transaminase, and alanine transaminase across baseline and treatment. In addition, the serum level of IL-26 exhibited a similar declining trend to that of T helper 17 (Th17) cell-secreted IL-17 during LdT treatment in CHB patients. The percentage of IL-26-expressing CD4 cells was significantly higher than that of IL-26-expressing CD4 cells isolated from the peripheral blood mononuclear cells of CHB patients, suggesting that serum IL-26 might be mainly released from CD4 T cells. Furthermore, the baseline mRNA levels of IL-26 and orphan nuclear receptor RORγt-an important transcription factor expressed by Th17 cells-were positively correlated and displayed the same declining trend across the baseline and LdT treatment in CHB patients, suggesting that Th17 cells could be a possible cellular source of the increased serum IL-26 in CHB patients.Taken together, our results suggest that serum IL-26, possibly produced by Th17 CD4 cells, is a novel and potential biomarker for CHB prognosis and treatment.


Assuntos
Vírus da Hepatite B/imunologia , Hepatite B Crônica/sangue , Hepatite B Crônica/imunologia , Interleucinas/sangue , Adulto , Antivirais/uso terapêutico , Linfócitos T CD4-Positivos/imunologia , Estudos de Casos e Controles , Ensaio de Imunoadsorção Enzimática , Feminino , Hepatite B Crônica/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade , Telbivudina/uso terapêutico , Células Th17/imunologia , Adulto Jovem
3.
Gut ; 69(2): 343-354, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-30926653

RESUMO

OBJECTIVE: This study aimed to develop a novel therapeutic vaccine based on a unique B cell epitope and investigate its therapeutic potential against chronic hepatitis B (CHB) in animal models. METHODS: A series of peptides and carrier proteins were evaluated in HBV-tolerant mice to obtain an optimised therapeutic molecule. The immunogenicity, therapeutic efficacy and mechanism of the candidate were investigated systematically. RESULTS: Among the HBsAg-aa119-125-containing peptides evaluated in this study, HBsAg-aa113-135 (SEQ13) exhibited the most striking therapeutic effects. A novel immunoenhanced virus-like particle carrier (CR-T3) derived from the roundleaf bat HBV core antigen (RBHBcAg) was created and used to display SEQ13, forming candidate molecule CR-T3-SEQ13. Multiple copies of SEQ13 displayed on the surface of this particulate antigen promote the induction of a potent anti-HBs antibody response in mice, rabbits and cynomolgus monkeys. Sera and purified polyclonal IgG from the immunised animals neutralised HBV infection in vitro and mediated efficient HBV/hepatitis B virus surface antigen (HBsAg) clearance in the mice. CR-T3-SEQ13-based vaccination induced long-term suppression of HBsAg and HBV DNA in HBV transgenic mice and eradicated the virus completely in hydrodynamic-based HBV carrier mice. The suppressive effects on HBsAg were strongly correlated with the anti-HBs level after vaccination, suggesting that the main mechanism of CR-T3-SEQ13 vaccination therapy was the induction of a SEQ13-specific antibody response that mediated HBV/HBsAg clearance. CONCLUSIONS: The novel particulate protein CR-T3-SEQ13 suppressed HBsAg effectively through induction of a humoural immune response in HBV-tolerant mice. This B cell epitope-based therapeutic vaccine may provide a novel immunotherapeutic agent against chronic HBV infection in humans.


Assuntos
Epitopos de Linfócito B/imunologia , Antígenos de Superfície da Hepatite B/sangue , Vacinas contra Hepatite B/imunologia , Hepatite B Crônica/imunologia , Adjuvantes Imunológicos , Animais , Antivirais/uso terapêutico , Terapia Combinada , DNA Viral/sangue , Relação Dose-Resposta Imunológica , Feminino , Anticorpos Anti-Hepatite B/biossíntese , Vacinas contra Hepatite B/uso terapêutico , Vírus da Hepatite B/genética , Hepatite B Crônica/terapia , Hepatite B Crônica/virologia , Imunidade Humoral/imunologia , Imunoterapia/métodos , Macaca fascicularis , Masculino , Camundongos Endogâmicos BALB C , Camundongos Transgênicos , Coelhos
5.
Life Sci ; 242: 117206, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31866520

RESUMO

Autophagy is a metabolic process that maintains the homeostasis of the intracellular environment by degrading damaged proteins and organelles in lysosomes. Recently, independent studies have indicated that some hepatitis viruses develop abilities to hijack autophagy for their replication, such as hepatitis B (HBV) and C (HCV); these two viruses are structurally unrelated, but both of them can cause hepatitis, liver cirrhosis, and even hepatocellular carcinoma (HCC). In this review, we will summarize the current knowledge about the mechanism of autophagy induction in HBV- and HCV-infected hepatocytes, discuss how induced autophagy promotes HBV and HCV replication and describe some autophagy-related therapeutic strategies, which may provide perspective with which to cure HBV and HCV infections and their related liver diseases.


Assuntos
Autofagia , Hepatite B/fisiopatologia , Hepatite C/fisiopatologia , Hepacivirus/fisiologia , Vírus da Hepatite B/fisiologia , Humanos
7.
Gastroenterology ; 158(1): 215-225.e6, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31574268

RESUMO

BACKGROUND & AIMS: There have been conflicting results from studies comparing the risk of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B virus (HBV) infection treated with tenofovir disoproxil fumarate (TDF) vs those treated with entecavir. We compared the effects of TDF vs entecavir on HCC risk in a large cohort of patients with chronic HBV infection in China. METHODS: We performed a retrospective study of consecutive adults with chronic HBV infection who initially received treatment with entecavir or TDF, for at least 6 months, from January 2008 through June 2018. Patients who had cancers or liver transplantation before or within the first 6 months of treatment were excluded. Propensity score weighting and 1:5 matching were used to balance the clinical characteristics between the 2 groups. Fine-Gray model was used to adjust for competing risk of death and liver transplantation. RESULTS: We analyzed data from 29,350 patients (mean age, 52.9 ± 13.2 years; 18,685 men [63.7%]); 1309 were first treated with TDF (4.5%) and 28,041 were first treated with entecavir (95.5%). TDF-treated patients were younger (mean age, 43.2 years vs 53.4 years) and a lower proportion had cirrhosis (38 patients [2.9%] vs 3822 patients treated with entecavir [13.6%]). At a median follow-up time of 3.6 years after treatment began (interquartile range, 1.7-5.0 years), 8 TDF-treated patients (0.6%) and 1386 entecavir-treated patients (4.9%) developed HCC. Patients' clinical characteristics were comparable after propensity score weighting. TDF treatment was associated with a lower risk of HCC than entecavir treatment after propensity score weighting (weighted subdistribution hazard ratio, 0.36; 95% confidence interval 0.16-0.80; P = .013) and 1:5 matching (weighted subdistribution hazard ratio, 0.39; 95% confidence interval 0.18-0.84; P = .016). CONCLUSIONS: In a retrospective analysis of 29,350 patients with chronic HBV infection in China, treatment with TDF was associated with a lower risk of HCC than treatment with entecavir, over a median follow-up time of 3.6 years.


Assuntos
Antivirais/administração & dosagem , Carcinoma Hepatocelular/prevenção & controle , Guanina/análogos & derivados , Hepatite B Crônica/tratamento farmacológico , Neoplasias Hepáticas/prevenção & controle , Tenofovir/administração & dosagem , Adulto , Assistência ao Convalescente , Carcinoma Hepatocelular/epidemiologia , Carcinoma Hepatocelular/virologia , China/epidemiologia , Progressão da Doença , Feminino , Guanina/administração & dosagem , Vírus da Hepatite B/isolamento & purificação , Hepatite B Crônica/patologia , Hepatite B Crônica/virologia , Humanos , Incidência , Fígado/efeitos dos fármacos , Fígado/patologia , Fígado/virologia , Cirrose Hepática/epidemiologia , Cirrose Hepática/prevenção & controle , Cirrose Hepática/virologia , Neoplasias Hepáticas/epidemiologia , Neoplasias Hepáticas/virologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento
8.
Adv Exp Med Biol ; 1179: 1-16, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31741331

RESUMO

Hepatitis B virus (HBV) is a DNA virus, belonging to the Hepadnaviridae family. It is a partially double-stranded DNA virus with a small viral genome (3.2 kb). Chronic HBV infection remains a global public health problem. If left untreated, chronic HBV infection can progress to end-stage liver disease, such as liver cirrhosis and hepatocellular carcinoma (HCC). In recent years, tremendous advances in the field of HBV basic and clinical research have been achieved, ranging from the HBV biological characteristics, immunopathogenesis, and animal models to the development of new therapeutic strategies and new drugs against HBV. In this overview, we begin with a brief history of HBV discovery and treatment milestones. We then briefly summarize the HBV research advances, which will be detailed in the following chapters.


Assuntos
Carcinoma Hepatocelular , Vírus da Hepatite B , Hepatite B Crônica , Cirrose Hepática , Neoplasias Hepáticas , Animais , Carcinoma Hepatocelular/etiologia , Hepatite B/complicações , Vírus da Hepatite B/fisiologia , Hepatite B Crônica/complicações , Cirrose Hepática/etiologia , Neoplasias Hepáticas/etiologia , Pesquisa/tendências
9.
Adv Exp Med Biol ; 1179: 17-37, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31741332

RESUMO

Chronic hepatitis B virus (HBV) infection remains to be a serious threat to public health and is associated with many liver diseases including chronic hepatitis B (CHB), liver cirrhosis, and hepatocellular carcinoma. Although nucleos(t)ide analogues (NA) and pegylated interferon-α (Peg-IFNα) have been confirmed to be efficient in inhibiting HBV replication, it is difficult to eradicate HBV and achieve the clinical cure of CHB. Therefore, long-term therapy has been recommended to CHB treatment under the current antiviral therapy. In this context, the new antiviral therapy targeting one or multiple critical steps of viral life cycle may be an alternative approach in future. In the last decade, the functional receptor [sodium-taurocholate cotransporting polypeptide (NTCP)] of HBV entry into hepatocytes has been discovered, and the immature nucleocapsids containing the non- or partially reverse-transcribed pregenomic RNA, the nucleocapsids containing double-strand linear DNA (dslDNA), and the empty particles devoid of any HBV nucleic acid have been found to be released into circulation, which have supplemented the life cycle of HBV. The understanding of HBV life cycle may offer a new instruction for searching the potential antiviral targets, and the new viral markers used to monitor the efficacy of antiviral therapy for CHB patients in the future.


Assuntos
Antivirais , Vírus da Hepatite B , Hepatite B Crônica , Antivirais/farmacologia , Vírus da Hepatite B/efeitos dos fármacos , Vírus da Hepatite B/genética , Vírus da Hepatite B/crescimento & desenvolvimento , Hepatite B Crônica/virologia , Hepatócitos/virologia , Humanos , Interferon-alfa/farmacologia , Internalização do Vírus/efeitos dos fármacos , Replicação Viral/efeitos dos fármacos
10.
Adv Exp Med Biol ; 1179: 39-69, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31741333

RESUMO

Hepatitis B virus (HBV) is a major human pathogen lacking a reliable curative therapy. Current therapeutics target the viral reverse transcriptase/DNA polymerase to inhibit viral replication but generally fail to resolve chronic HBV infections. Due to the limited coding potential of the HBV genome, alternative approaches for the treatment of chronic infections are desperately needed. An alternative approach to the development of antiviral therapeutics is to target cellular gene products that are critical to the viral life cycle. As transcription of the viral genome is an essential step in the viral life cycle, the selective inhibition of viral RNA synthesis is a possible approach for the development of additional therapeutic modalities that might be used in combination with currently available therapies. To address this possibility, a molecular understanding of the relationship between viral transcription and replication is required. The first step is to identify the transcription factors that are the most critical in controlling the levels of HBV RNA synthesis and to determine their in vivo role in viral biosynthesis. Mapping studies in cell culture utilizing reporter gene constructs permitted the identification of both ubiquitous and liver-enriched transcription factors capable of modulating transcription from the four HBV promoters. However, it was challenging to determine their relative importance for viral biosynthesis in the available human hepatoma replication systems. This technical limitation was addressed, in part, by the development of non-hepatoma HBV replication systems where viral biosynthesis was dependent on complementation with exogenously expressed transcription factors. These systems revealed the importance of specific nuclear receptors and hepatocyte nuclear factor 3 (HNF3)/forkhead box A (FoxA) transcription factors for HBV biosynthesis. Furthermore, using the HBV transgenic mouse model of chronic viral infection, the importance of various nuclear receptors and FoxA isoforms could be established in vivo. The availability of this combination of systems now permits a rational approach toward the development of selective host transcription factor inhibitors. This might permit the development of a new class of therapeutics to aid in the treatment and resolution of chronic HBV infections, which currently affects approximately 1 in 30 individuals worldwide and kills up to a million people annually.


Assuntos
Vírus da Hepatite B , Transcrição Genética , Replicação Viral , Animais , DNA Viral/química , Vírus da Hepatite B/genética , Vírus da Hepatite B/fisiologia , Humanos , Camundongos , Transcrição Genética/genética , Replicação Viral/genética
11.
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
12.
Adv Exp Med Biol ; 1179: 109-135, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31741335

RESUMO

Highly representative and relevant cell and mouse models are required for HBV study, including uncovering its lifecycle, investigation of the viral-host interaction, and development and evaluation of the novel antiviral therapy. During the past 40 years, both HBV cell culture models and animal models have evolved over several generations, each with significant improvement for specific purposes. In one aspect, HBV cell culture models experienced the original noninfection model including HBV plasmid DNA transfection and HBV genome integrated stable cells such as HepG2.2.15 which constitutively produces HBV virus and HepAD38 cells and its derivatives which drug-regulated HBV production. As for HBV infection models, HepaRG cells once dominated the HBV infection field for over a decade, but its complicated and labor-extensive cell differentiation procedures discouraged primary researchers from stepping in the field. The identification of human NTCP as HBV receptor evoked great enthusiasm of the whole HBV field, and its readily adaptive characteristic makes it popular in many HBV laboratories. Recombinant cccDNA (rc-cccDNA) emerged recently aiming to tackle the very basic question of how to eventually eradicate cccDNA without HBV real virus infection. In the other aspect, HBV transgenic mouse was firstly generated in the 1990s, which was helpful to decipher HBV production in vivo. However, the HBV transgenic mice were naturally immune tolerant to HBV viral products. Subsequently, a series of nonintegrated HBV mouse models were generated through plasmid hydrodynamic tail vein injection and viral vector-mediated delivery approaches, and HBV full life cycle was incomplete as cccDNA was not formed from HBV relaxed circular DNA (rcDNA). Human NTCP transgenic mouse still could not support productive HBV infection, and humanized mouse liver with human hepatocytes which supported whole HBV life cycle still dominates HBV infection in vivo, a value but expensive model until now. Other methods to empower mouse to carry HBV cccDNA were also exploited. In this chapter, we summarized the advantages and disadvantages of each model historically and provided protocols for HBV infection in HepG2-NTCP cells, HBV rc-cccDNA transfection in HepG2 cells, and HBV infection in NRG-Fah-/- liver humanized mouse.


Assuntos
Vírus da Hepatite B , Animais , Linhagem Celular , DNA Viral , Modelos Animais de Doenças , Vírus da Hepatite B/fisiologia , Hepatócitos/virologia , Humanos , Replicação Viral
13.
Adv Exp Med Biol ; 1179: 137-186, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31741336

RESUMO

Chronic hepatitis B (CHB) remains the leading cause of liver-related morbidity and mortality across the world. If left untreated, approximately one-third of these patients will progress to severe end-stage liver diseases including liver failure, cirrhosis, and hepatocellular carcinoma (HCC). High level of serum HBV DNA is strongly associated with the development of liver failure, cirrhosis, and HCC. Therefore, antiviral therapy is crucial for the clinical management of CHB. Current antiviral drugs including nucleoside/nucleotide analogues (NAs) and interferon-α (IFN-α) can suppress HBV replication and reduce the progression of liver disease, thus improving the long-term outcomes of CHB patients. This chapter will discuss the standard and optimization antiviral therapies in treatment-naïve and treatment-experienced patients, as well as in the special populations. The up-to-date advances in the development of new anti-HBV agents will be also discussed. With the combination of the current antiviral drugs and the newly developed antiviral agents targeting the different steps of the viral life cycle or the newly developed agents modulating the host immune responses, the ultimate eradication of HBV will be achieved in the future.


Assuntos
Antivirais , Hepatite B Crônica , Antivirais/farmacologia , Antivirais/uso terapêutico , Vírus da Hepatite B/efeitos dos fármacos , Hepatite B Crônica/tratamento farmacológico , Humanos
14.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 27(6): 1856-1861, 2019 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-31839050

RESUMO

OBJECTIVE: To investigate the conversion rate from negative to positive (positive rate) of HBsAb in lymphoma patients inoculated with different dose of hepatitis B vaccine, to evaluate the immune efficacy of different dose of hepatitis B vaccine, and to analyze the influencing factors. METHODS: Two hundred thirty six patients with lymphoma were selected, whose 5 indexes of hepatitis B (HBsAg, HBsAb, HBeAg, HBeAb and HBcAb) were all negative confirmed by ELISA. The hepatitis B vaccine was inoculated according to 0, 1 and 6 months immune procedures at 1-2 weeks before chemotherapy. The HBsAb level was detected at 1 month after the immunization, the differences in each indexes between HBeAb+ and HBeAb- patients were compared. RESULTS: The positive rate of HBsAb was 75% in all patients with lymphoma.The positive rate of high dose (20 µg) group was 81.4%, which was significantly higher than that of the low dose (10µg) group with 68.6% (χ2=5.09, P<0.05). The positive conversion rate of HBsAb significantly higher in the patients of young, female, B-cell (except DLBCL subtype), early Ann Arbor stage, and the treatment regimens without glucocorticoid and rituximab. There were no statistical significances in systemic symptoms or no and treatment regimens with or without lenalidomide. Two doses of hepatitis B vaccine not displayed obvious adverse reactions. CONCLUSION: The high dose of hepatitis B vaccine can achieve better immune efficacy than that of the low dose in the patients with lymphoma.


Assuntos
Vacinas contra Hepatite B , Hepatite B , Linfoma/terapia , Feminino , Anticorpos Anti-Hepatite B , Antígenos de Superfície da Hepatite B , Vírus da Hepatite B , Humanos
15.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 27(6): 1998-2002, 2019 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-31839073

RESUMO

OBJECTIVE: To understand the infection of hepatitis B virus(HBV) in blood donors, and to evaluate the effectiveness and necessity of TMA technology for HBV-DNA screening in blood donors. METHODS: Using the ELISA/NAT model, routine serology test and NAT were performed in the 169 160 donors,including voluntary blood donors and some of donors returned to donor team. For some donors with test positive NAT, nucleic acid identification test was performed. And the HBsAg neutralized and confirmed assay would conduct in blood donors with unilateral HBsAg positive and HBV-DNA negative result. RESULTS: Among 169 160 donation cases-times, the donors of bilateral positive of HBsAg detection was 803, accounted for 0.476%; donors of unilateral positive was 243, accounted for 0.144%. For 40 specimens with HBV-DNA negative, unilateral HBsAg positive, the neutralization and confirmed assay was performed.In result, only 4 specimens were confirmed to be HBsAg positive, the confirmed positive rate was 10%. Among detected 1003 specimens with HBV-DNA positive specimens, both HBsAg and HBV-DNA positive were 739, the consistency rate between 2 kinds of detection was 73.7%. The comparision of positive rate detected by using 3 kinds of reagents showed that there were statistical differences (P<0.05); moreover, there were statistical difference in positive rate detected by using Murex reagent and In Tec reagent (P<0.0125). The comparison of detected rate of HBsAg+ and HBV-DNA+ during March 2016-February 2017 showed no statistical difference (P>0.05). Among 60 blood donors with HBsAg- and HBV-DNA+ who has retured to the donor team, 1 donor presented the transformation of HBsAg from negative to positive, suggesting the HBV infection of window period, HBsAg of the other 59 was negative. The detection of HBV-DNA showed that the HBV-DNA in 28 donors was negative, and the HBV-DNA in 31 donors was positive, 1 donor showed HBV-DNA was uncertain. CONCLUSION: The routine TMA technology combined with ELISA HBsAg can effectively shorten the window period for detection of HBV infection, effectively detect the occult HBV infection, and reduce the potential risk of hepatitis B spread due to blood transfusion.


Assuntos
Vírus da Hepatite B/genética , Hepatite B , Doadores de Sangue , DNA Viral , Antígenos de Superfície da Hepatite B , Humanos
16.
Georgian Med News ; (295): 109-114, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31804210

RESUMO

Georgia is a country with high prevalence of hepatitis B. Based on a 2015 population serosurvey, the prevalence of hepatitis B surface antigen (HBsAg) is 2.9% and prevalence of anti-HBc is 25.5% in general population. Hepatitis B vaccine has been included in the national immunization schedule of Georgia only since 2002. Thus, most reproductive aged women were not vaccinated during young childhood. Cross-sectional study was conducted in the capital of Georgia, Tbilisi. Reproductive aged women were randomly selected and then recruited from three maternity care centers during prenatal care. The self-administered questionnaire included questions on socio-demographic information, hepatitis B vaccination status and awareness of HBV infection status. A total of 2185 reproductive aged women were enrolled in the study. The mean age was 28.5 (age range 17-46) years. Most (76.4%) had a bachelor and/or master's degree. 20.0% of respondents never heard about HBV. Very few (3.3%) knew they were infected with HBV. We could not determine if women were chronically infected or were exposed and developed antibodies. HBV knowledge was limited: 57.5% were not aware of available HBV treatment; 51.6% didn't know HBV infection could be prevented (35.8% named HBV vaccination, 29.3% named condom use). Only 10% of study participants reported being vaccinated for HBV. Awareness of HBV infection was higher among women over age 25 (72.1%) compared to women aged 25 years or less (27.9%) (P<0.0001). Among women who reported having an HBV infection, 40.6% did not name vaccine as a prevention method and 38.2% did not have information about availability of HBV treatment (P<0.05). Based on our study results, knowledge about HBV infection and vaccination is very low among reproductive aged women in Georgia. Women's health centers can be a good place to reach reproductive aged women for counseling on HBV infection and promote vaccination against hepatitis B.


Assuntos
Conhecimentos, Atitudes e Prática em Saúde , Vacinas contra Hepatite B , Hepatite B , Vacinação , Adolescente , Adulto , Estudos Transversais , Feminino , República da Geórgia , Hepatite B/prevenção & controle , Anticorpos Anti-Hepatite B , Antígenos de Superfície da Hepatite B , Vírus da Hepatite B , Humanos , Pessoa de Meia-Idade , Gravidez , Prevalência , Adulto Jovem
17.
Pol J Microbiol ; 68(3): 317-322, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31880877

RESUMO

Mutations associated with the pol and the S gene can emerge as a consequence of the high replication capacity and proofreading deficiencies of hepatitis B virus during replication. The current study was constructed to evaluate primary, partial, compensatory and the escape mutations in chronic hepatitis B patients in Northern Cyprus. The samples of HBsAg positive treatment naïve 100 patients were involved in this study. HBV pol gene region was sequenced, amplified and HBV pol/S gene mutations were determined. The samples of thirty-two patients were excluded because of their low viral load (HBV < 1000 iu/ml). Among the sequenced 68 samples, there was a partial mutation (1.5%) and 36.7% displayed a resistance profile to lamivudine, adevofir, and telbivudine. Immune response escape, vaccine escape, HBIg and diagnosis escape mutations were determined in 24%, 10%, 6%, and 4% samples of the patients, respectively. Additionally, there were six different combined mutations. These data underscored that there is no concern for primary mutations in Northern Cyprus, however, we have identified a compensatory mutation (rtV173M) that may have primary mutation characteristics by combining with other mutation patterns. Additionally, HBsAg escape mutants demonstrated that detection of the S gene together with the pol gene mutations might be beneficial and important to monitor the surveillance of S variants.Mutations associated with the pol and the S gene can emerge as a consequence of the high replication capacity and proofreading deficiencies of hepatitis B virus during replication. The current study was constructed to evaluate primary, partial, compensatory and the escape mutations in chronic hepatitis B patients in Northern Cyprus. The samples of HBsAg positive treatment naïve 100 patients were involved in this study. HBV pol gene region was sequenced, amplified and HBV pol/S gene mutations were determined. The samples of thirty-two patients were excluded because of their low viral load (HBV < 1000 iu/ml). Among the sequenced 68 samples, there was a partial mutation (1.5%) and 36.7% displayed a resistance profile to lamivudine, adevofir, and telbivudine. Immune response escape, vaccine escape, HBIg and diagnosis escape mutations were determined in 24%, 10%, 6%, and 4% samples of the patients, respectively. Additionally, there were six different combined mutations. These data underscored that there is no concern for primary mutations in Northern Cyprus, however, we have identified a compensatory mutation (rtV173M) that may have primary mutation characteristics by combining with other mutation patterns. Additionally, HBsAg escape mutants demonstrated that detection of the S gene together with the pol gene mutations might be beneficial and important to monitor the surveillance of S variants.


Assuntos
Evolução Molecular , Produtos do Gene pol/genética , Antígenos de Superfície da Hepatite B/genética , Vírus da Hepatite B/genética , Hepatite B Crônica/virologia , Adulto , Idoso , Antivirais/farmacologia , Chipre , Farmacorresistência Viral , Feminino , Vírus da Hepatite B/classificação , Vírus da Hepatite B/efeitos dos fármacos , Vírus da Hepatite B/isolamento & purificação , Hepatite B Crônica/tratamento farmacológico , Humanos , Lamivudina/farmacologia , Masculino , Pessoa de Meia-Idade , Mutação , Adulto Jovem
18.
Medicine (Baltimore) ; 98(50): e18319, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31852119

RESUMO

Gamma-glutamyl transpeptidase-to-platelet ratio (GPR) and fibrosis-4 (FIB-4) index have been reported to be useful predictors in predicting hepatocellular carcinoma (HCC) development in chronic hepatitis B (CHB) patients. However, their predictive performances on HCC development have not been validated in elderly patients. Thus, the aim of this study was to evaluate the predictive values of the GPR and FIB-4 index on HCC in elderly CHB patients with in China.Between January 2007 and December 2016, 1011 CHB patients older than 60 years were enrolled in the study, and their data were retrospectively analyzed. Receiver-operating characteristic (ROC) curve analysis was used to determine the optimal cutoff points of GPR and the FIB-4 index. Cumulative HCC incidence rates were calculated by the Kaplan-Meier method and compared by the log-rank test. Univariate and multivariate analyses were performed to detect risk factors for HCC development. The prediction performances of GPR and FIB-4 index were compared based on time-dependent ROC analyses.After a median follow-up of 6.8 (interquartile range 3.9-8.4) years, 39 (3.9%) patients developed HCC. The ROC analysis of GPR and the FIB-4 index at the 5-year time point revealed that the optimal cutoff point was 0.23 for GPR and 4.15 for the FIB-4 index. When stratified by low and high GPR values and FIB-4 indices, the patients' subgroups showed significantly different cumulative incidences of HCC. The multivariate analysis revealed that high GPR (hazard ratio [HR] 4.224; 95% confidence interval [CI] 1.891-9.434, P < .001) was an independent risk factor for HCC development, whereas a high FIB-4 index was not (HR 0.470; 95% CI 0.212-1.043; P = .063). In the time-dependent ROC analysis, GPR showed higher area under curve (AUC) values than the FIB-4 index did at all time points and reached statistical significance at the 5-, 7-, and 10-year time points (GPR vs FIB-4 index, AUC 0.725 vs 0.549 at 5 years, P = .005; GPR vs FIB-4 index, AUC 0.733 vs 0.578 at 7 years, P = .001; GPR vs FIB-4 index, AUC 0.837 vs 0.475 at 10 years, P < .001).In conclusion, our study suggests GPR is superior to the FIB-4 index in predicting HCC development in elderly CHB patients in China.


Assuntos
Carcinoma Hepatocelular/sangue , Vírus da Hepatite B , Hepatite B Crônica/complicações , Cirrose Hepática/sangue , Cirrose Hepática/complicações , Neoplasias Hepáticas/sangue , gama-Glutamiltransferase/sangue , Idoso , Biomarcadores Tumorais , Plaquetas/patologia , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/etiologia , China/epidemiologia , Feminino , Seguimentos , Hepatite B Crônica/sangue , Hepatite B Crônica/virologia , Humanos , Incidência , Cirrose Hepática/diagnóstico , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/etiologia , Masculino , Pessoa de Meia-Idade , Contagem de Plaquetas , Curva ROC , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo
19.
Rev Chilena Infectol ; 36(5): 576-584, 2019 Oct.
Artigo em Espanhol | MEDLINE | ID: mdl-31859798

RESUMO

BACKGROUND: Chile is a low-endemic HBV country, but countries with the highest migratory flow to Chile have an intermediate-high endemicity. In order to avoid vertical transmission of HBV, immunoprophylaxis (IP) in the newborn (NB) is a key factor. AIM: To identify HBsAg prevalence in pregnant immigrants and Chilean pregnant women with risk behaviors (RB) and to asses IP use in the NB. MATERIAL AND METHODS: Prospective HBsAg screening cohort of immigrant and Chilean pregnant women with RB, between July 1, 2017 and June 30, 2018 in CABL. IP of all NB of reactive HBsAg mothers was assessed. RESULTS: 1,415 HBsAg samples, 1,265 immigrants and 150 Chileans with RB. 37 reactive HBsAg. Two false positive. HBsAg prevalence in immigrant pregnant women was 2.7% and 0.66% in Chileans with RB (p < 0.05). 91.1% came from Haiti, with a prevalence of 3.5% in our region. All NB (36) received IP with a median of administration of 3:02 h. CONCLUSIONS: The prevalence in immigrant pregnant women was higher than that reported in the general population and in Chilean women with RB. We proposed the need for universal screening in pregnancy, especially in pregnant women from countries with intermediate-high endemicity.


Assuntos
Emigrantes e Imigrantes , Antígenos de Superfície da Hepatite B/análise , Hepatite B/epidemiologia , Hepatite B/transmissão , Transmissão Vertical de Doença Infecciosa/prevenção & controle , Programas de Rastreamento/métodos , Complicações Infecciosas na Gravidez/epidemiologia , Adulto , Chile/epidemiologia , Feminino , Vírus da Hepatite B/isolamento & purificação , Humanos , Recém-Nascido , Masculino , Gravidez , Complicações Infecciosas na Gravidez/virologia , Estudos Prospectivos , Fatores de Risco , Assunção de Riscos , Estudos Soroepidemiológicos , Fatores de Tempo , Vacinação/métodos , Adulto Jovem
20.
BMC Med Genet ; 20(1): 201, 2019 12 21.
Artigo em Inglês | MEDLINE | ID: mdl-31864292

RESUMO

BACKGROUND: Vitamin D derivatives and their receptor (VDR) are potent modulators of immune responses in various diseases including malignancies as well as in metabolic and infectious disorders. The impact of vitamin D receptor polymorphisms on clinical outcomes of hepatitis B virus (HBV) infection is not well understood. This study aims to investigate the potential role of VDR polymorphisms (TaqI, FokI, ApaI, and BsmI) in Vietnamese HBV infected patients and to correlate these polymorphisms with the progression of HBV-related liver disease. METHODS: Four hundred forty-three HBV infected patients of the three clinically well-defined subgroups chronic hepatitis B (CHB, n = 183), liver cirrhosis (LC, n = 89) and hepatocellular carcinoma (HCC, n = 171) and 238 healthy individuals (HC) were enrolled. VDR polymorphisms were genotyped by DNA sequencing and in-house validated ARMS assays. Logistic regression models were applied in order to determine the association of VDR polymorphisms with manifest HBV infection as well as with progression of related liver diseases mulin different genetic models. RESULTS: The VDR ApaI CA genotype was less frequent in HCC than in CHB patients in different genetic models (codominant model, OR = 0.5, 95%CI = 0.3-0.84, P = 0.004; dominant model, OR = 0.46, 95%CI = 0.27-0.76, P = 0.0023). In the recessive model, the genotype ApaI AA was found more frequently among HCC compared to CHB patients (OR = 2.56, 95%CI = 1.01-6.48, P = 0.04). Similarly, the ApaI CA genotype was less frequent in HCC than in non-HCC group codominant model, OR = 0.6, 95%CI = 0.4-0.98, dominant model, P = 0.04 and OR = 0.6, 95%CI = 0.38-0.90, P = 0.017). The ApaI genotypes CA and AA was significantly associated with higher levels of liver enzymes, bilirubin, and HBV DNA (P < 0.05). No association between TaqI, FokI and BsmI polymorphisms and any clinical outcome as well as liver disease progression was found. CONCLUSIONS: Among the four investigated VDR polymorphisms, ApaI is associated with clinical outcome and liver disease progression in Vietnamese HBV infected patients.


Assuntos
Carcinoma Hepatocelular/genética , Desoxirribonucleases de Sítio Específico do Tipo II/metabolismo , Vírus da Hepatite B/isolamento & purificação , Neoplasias Hepáticas/genética , Polimorfismo de Nucleotídeo Único , Receptores de Calcitriol/genética , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/virologia , Estudos de Casos e Controles , Progressão da Doença , Genótipo , Humanos , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/virologia , Vietnã
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