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1.
Klin Lab Diagn ; 66(1): 59-64, 2021 Feb 10.
Artículo en Inglés | MEDLINE | ID: mdl-33567175

RESUMEN

A method for detecting HBV DNA in peripheral blood at low viral load using real-time PCR was developed and its significance in identifying HBsAg-negative viral hepatitis B was evaluated. When developing the method, blood plasma samples and liver tissue biopsy material were used from 128 patients living in St. Petersburg, in various regions of the Russian Federation, as well as in the Central Asia countries. We also used blood plasma samples from 96 pregnant women and 37 hemodialysis center patients living in Northwestern Federal District, 199 foreign citizens undergoing medical examination to obtain work permits at the Directorate for Migration in the Northwestern Federal District, 397 conditionally healthy people living in the Socialist Republic of Vietnam. HBV was detected by nested PCR. Analytical sensitivity was tested using the stepwise dilution method. According to the method developed by us, at the first stage, the HBV DNA is amplified using at the first stage oligonucleotides flanking the genome region 2932-3182 ... 1-1846 nt., and at the second stage two oligonucleotides pairs to the genome virus regions (gene S and gene X) and corresponding oligonucleotide fluorescently labeled probes complementary to the amplified fragments regions carrying fluorophores at the 5'-end, and non-fluorescent quenchers at the 3'-end. The channel corresponding to the FAM fluorophore detects the HBV DNA S-region amplification product, and the channel corresponding to the ROX fluorophore detects the HBV DNA X-region amplification product. The method sensitivity for DNA extraction from plasma with a 100 µl volume was 10 IU/ml. Obtaining a threshold cycle Ct for only one FAM or ROX fluorophore may indicate the HBV DNA presence in a sample at a load of less than 10 IU / ml, HBV detection in this case is possible with a repeated PCR study of the corresponding sample with HBV DNA extraction from an increased plasma volume (200-1000 µl). The developed method makes it possible to identify various HBV genovariants, both characteristic and rare in the Russian Federation, circulating in other world regions. The method can be used to detect HBV in risk groups, in the population, as well as in screening blood donors in order to ensure the blood transfusions safety.


Asunto(s)
Virus de la Hepatitis B , Hepatitis B , Donantes de Sangre , ADN Viral/genética , Femenino , Hepatitis B/diagnóstico , Hepatitis B/epidemiología , Antígenos de Superficie de la Hepatitis B/genética , Virus de la Hepatitis B/genética , Humanos , Plasma , Embarazo , Reacción en Cadena en Tiempo Real de la Polimerasa , Federación de Rusia , Carga Viral
2.
Medicine (Baltimore) ; 100(3): e23961, 2021 Jan 22.
Artículo en Inglés | MEDLINE | ID: mdl-33545977

RESUMEN

INTRODUCTION: This protocol is for a meta analysis that aims to systematically review the diagnostic value of anti-hepatitis B virus in serum tested by the enzyme linked immunosorbent assay in patients with hepatitis B. METHODS AND ANALYSIS: The following electronic databases will be searched from inception to Mar 2021: PubMed, Web of Science, ScienceDirect, EMBASE, MEDLINE, Springer, China National Knowledge Infrastructure, Chinese Biomedical Literature Database, VIP Chinese Science and Technology Periodical Database, and Wanfang Database. All study about enzyme linked immunosorbent assay reagents have been published at home and abroad to diagnose hepatitis B virus will be included. MetaDisc 1.4 soft will used to calculate pooled effect size in sensitivity, specifi city, likelihood ratio, diagnostic odds ratio and summary receiver operating characteristic curve, and area under the curve as well. ETHICS AND DISSEMINATION: Formal ethical approval is not required, as the data are not individualized. The findings of this systematic review will be disseminated in a peer-reviewed publication and/or presented at relevant conferences. REGISTRATION NUMBER: INPLASY2020100051.


Asunto(s)
Protocolos Clínicos , Virus de la Hepatitis B/inmunología , Hepatitis B/enzimología , Ensayo de Inmunoadsorción Enzimática/métodos , Virus de la Hepatitis B/patogenicidad , Humanos , Metaanálisis como Asunto , Revisiones Sistemáticas como Asunto
3.
Medicine (Baltimore) ; 100(4): e24354, 2021 Jan 29.
Artículo en Inglés | MEDLINE | ID: mdl-33530229

RESUMEN

ABSTRACT: Diabetes mellitus (DM) increases the risk of developing hepatocellular carcinoma (HCC), and how DM affects the prognosis of HCC have not been elucidated. The aim of this study was to compare clinicopathological characteristics and survival between hepatitis B virus (HBV)-related HCC patients with and without DM and to determine risk factors for overall survival after hepatectomy.Among 474 patients with HBV-related HCC, 119 patients had DM. Patients were divided into the diabetic group and nondiabetic group. The short-term and long-term outcomes were evaluated by using propensity score matching analysis.After 1:2 propensity score matching, there were 107 patients in diabetic group, 214 patients in nondiabetic group. The proportion of vessels invasion were higher in diabetic group. The overall survival rate in the diabetic group was 44.7% at 3 years, which was lower than that in the nondiabetic group (56.1%, P = .025). The multivariate analysis indicated that fasting blood glucose >7.0, capsular invasion, microvascular invasion and satellite were independent risk factor of poor prognosis in HCC.DM dose affect the recurrence-free survival and overall survival in HBV-related HCC patients after hepatectomy. One of the more significant findings to emerge from this study is that DM induced higher proportion of major vessel invasion in HCC patients implied unfavorable prognosis.


Asunto(s)
Carcinoma Hepatocelular/mortalidad , Diabetes Mellitus Tipo 2/virología , Virus de la Hepatitis B , Hepatitis B/complicaciones , Neoplasias Hepáticas/mortalidad , Glucemia/análisis , Carcinoma Hepatocelular/cirugía , Carcinoma Hepatocelular/virología , Diabetes Mellitus Tipo 2/sangre , Femenino , Hepatectomía/mortalidad , Hepatitis B/virología , Humanos , Neoplasias Hepáticas/cirugía , Neoplasias Hepáticas/virología , Masculino , Persona de Mediana Edad , Análisis Multivariante , Pronóstico , Puntaje de Propensión , Factores de Riesgo , Tasa de Supervivencia , Resultado del Tratamiento
4.
Nat Commun ; 12(1): 589, 2021 01 26.
Artículo en Inglés | MEDLINE | ID: mdl-33500404

RESUMEN

Symmetrical protein complexes are ubiquitous in biology. Many have been re-engineered for chemical and medical applications. Viral capsids and their assembly are frequent platforms for these investigations. A means to create asymmetric capsids may expand applications. Here, starting with homodimeric Hepatitis B Virus capsid protein, we develop a heterodimer, design a hierarchical assembly pathway, and produce asymmetric capsids. In the heterodimer, the two halves have different growth potentials and assemble into hexamers. These preformed hexamers can nucleate co-assembly with other dimers, leading to Janus-like capsids with a small discrete hexamer patch. We can remove the patch specifically and observe asymmetric holey capsids by cryo-EM reconstruction. The resulting hole in the surface can be refilled with fluorescently labeled dimers to regenerate an intact capsid. In this study, we show how an asymmetric subunit can be used to generate an asymmetric particle, creating the potential for a capsid with different surface chemistries.


Asunto(s)
Proteínas de la Cápside/metabolismo , Cápside/ultraestructura , Virus de la Hepatitis B/fisiología , Modelos Moleculares , Ensamble de Virus , Cápside/metabolismo , Proteínas de la Cápside/genética , Proteínas de la Cápside/aislamiento & purificación , Proteínas de la Cápside/ultraestructura , Microscopía por Crioelectrón , Virus de la Hepatitis B/ultraestructura , Multimerización de Proteína/fisiología , Proteínas Recombinantes/genética , Proteínas Recombinantes/aislamiento & purificación , Proteínas Recombinantes/metabolismo , Proteínas Recombinantes/ultraestructura
5.
Nat Commun ; 12(1): 98, 2021 01 04.
Artículo en Inglés | MEDLINE | ID: mdl-33397935

RESUMEN

Glucose metabolism and innate immunity evolved side-by-side. It is unclear if and how the two systems interact with each other during hepatitis B virus (HBV) infections and, if so, which mechanisms are involved. Here, we report that HBV activates glycolysis to impede retinoic acid-inducible gene I (RIG-I)-induced interferon production. We demonstrate that HBV sequesters MAVS from RIG-I by forming a ternary complex including hexokinase (HK). Using a series of pharmacological and genetic approaches, we provide in vitro and in vivo evidence indicating that HBV suppresses RLR signaling via lactate dehydrogenase-A-dependent lactate production. Lactate directly binds MAVS preventing its aggregation and mitochondrial localization during HBV infection. Therefore, we show that HK2 and glycolysis-derived lactate have important functions in the immune escape of HBV and that energy metabolism regulates innate immunity during HBV infection.


Asunto(s)
Virus de la Hepatitis B/fisiología , Inmunidad Innata , Metaboloma , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Anaerobiosis , Animales , Células Cultivadas , Proteína 58 DEAD Box/metabolismo , Glucosa/metabolismo , Glucólisis , Células Hep G2 , Hepatocitos/metabolismo , Hepatocitos/patología , Hepatocitos/virología , Humanos , Evasión Inmune , Interferones/metabolismo , Ácido Láctico/metabolismo , Ratones Endogámicos C57BL , Modelos Biológicos , Transducción de Señal , Virión/metabolismo
6.
BMC Infect Dis ; 21(1): 41, 2021 Jan 09.
Artículo en Inglés | MEDLINE | ID: mdl-33422017

RESUMEN

BACKGROUND: In order to reduce the burden on organ shortage around the world, using potential infectious donor might be an option. However, scarce evidences have been published on kidney transplantation (KTx) from hepatitis B surface antigen (HBsAg) + donors to HBsAg- recipients [D (HBsAg+)/R(HBsAg-)] without hepatitis B virus (HBV) immunity. Here, we reported the results of D(HBsAg+/HBV DNA- or +)/R(HBsAg-) living KTx recipients with or without HBV immunity. METHODS: We retrospectively identified 83 D(HBsAg+)/R(HBsAg-) living KTx recipients, and 83 hepatitis B core antibody (HBcAb) + living donors to HBcAb- recipients [D(HBcAb+)/R(HBcAb-)] were used as control group by reviewing medical archives and propensity score matching. Treatment failure (defined as any HBV serology conversion, liver injury, graft loss, or recipient death) is the primary endpoint. RESULTS: Twenty-four donors (28.9%) were HBV DNA+, and 20 recipients had no HBV immunity in the D(HBsAg+)/R(HBsAg-) group pre-transplantation. HBV prophylaxis was applied in all D(HBsAg+)/R(HBsAg-) recipients, while none was applied in the D(HBcAb+)/R(HBcAb-) group. We observed a significant higher treatment failure in D(HBsAg+)/R(HBsAg-) than D(HBcAb+)/R(HBcAb-) group (21.7% vs. 10.8%, P < 0.001). Interestingly, no significant difference was found between groups on HBV seroconversion, liver and graft function, rejection, infection, graft loss, or death. However, 2/20 recipients without HBV immunity in the D(HBsAg+)/R(HBsAg-) group developed HBV DNA+ or HBsAg+, while none observed in the D(HBcAb+)/R(HBcAb-) group. HBV DNA+ donor and male recipient were significant risk factors for treatment failure. CONCLUSION: D(HBsAg+)/R(HBsAg-) should be considered for living kidney transplantation, but with extra caution on donors with HBV DNA+ and male candidates.


Asunto(s)
Antígenos de Superficie de la Hepatitis B/genética , Hepatitis B/virología , Trasplante de Riñón/efectos adversos , Complicaciones Posoperatorias/virología , Adulto , Anciano , ADN Viral/genética , Femenino , Hepatitis B/sangre , Hepatitis B/epidemiología , Anticuerpos contra la Hepatitis B/sangre , Antígenos del Núcleo de la Hepatitis B/genética , Antígenos del Núcleo de la Hepatitis B/inmunología , Antígenos de Superficie de la Hepatitis B/inmunología , Virus de la Hepatitis B/genética , Virus de la Hepatitis B/inmunología , Humanos , Riñón/virología , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/sangre , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Estudios Retrospectivos , Factores de Riesgo , Donantes de Tejidos/estadística & datos numéricos , Receptores de Trasplantes/estadística & datos numéricos , Insuficiencia del Tratamiento
7.
Niger J Clin Pract ; 24(1): 38-44, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-33473023

RESUMEN

Background: Hepatitis B virus (HBV) infection has been recognized globally as a major public health challenge necessitating a global call for increased awareness, patients' identification, and development of activities for prevention and control of the disease. Consequently, massive health education campaigns and screening exercises have been mounted globally to mark the World Hepatitis Day (WHD). Aims: As part of WHD 2016 activities, we undertook a survey and screening of health care workers in order to raise awareness, identify patients and contribute to the Global Health Strategy goal of eliminating HBV infection by the year 2030. Method: This was a cross-sectional analytical study done at the University of Nigeria Teaching Hospital, Ituku-Ozalla, Enugu, Nigeria. Hospital workers voluntarily presented themselves to be screened using a rapid test kit and completing a semi-structured investigator-administered questionnaire. Results: A total of 3123 participants were studied. The mean age of the participants was 39.4 ± 9.6 years. The seroprevalence of HBV infection was 2.3%. Most (97.0%) of the participants had previously heard about HBV infection and over two thirds (68.1%) could correctly identify risk factors and modes of transmission of HBV. Twenty-eight and a half percent of the participants knew their hepatitis B virus status prior to the study. Conclusion: The seroprevalence of HBV among healthcare workers in Enugu, Nigeria is relatively low compared to figures from other African countries. The healthcare workers have considerable knowledge of the disease. However, the observed knowledge gaps in awareness and screening need to be addressed.


Asunto(s)
Virus de la Hepatitis B , Hepatitis B , Adulto , Estudios Transversales , Personal de Salud , Hepatitis B/diagnóstico , Hepatitis B/epidemiología , Antígenos de Superficie de la Hepatitis B , Humanos , Persona de Mediana Edad , Nigeria/epidemiología , Prevalencia , Factores de Riesgo , Estudios Seroepidemiológicos
8.
Viruses ; 13(1)2021 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-33467678

RESUMEN

While treatment options are available for hepatitis B virus (HBV), there is currently no cure. Anti-HBV nucleoside analogs and interferon-alpha 2b rarely clear HBV covalently closed circular DNA (cccDNA), requiring lifelong treatment. Recently, we identified GLP-26, a glyoxamide derivative which modulates HBV capsid assembly. The impact of GLP-26 on viral replication and integrated DNA was assessed in an HBV nude mouse model bearing HBV transfected AD38 xenografts. At day 45 post-infection, GLP-26 reduced HBV titers by 2.3-3 log10 versus infected placebo-treated mice. Combination therapy with GLP-26 and entecavir reduced HBV log10 titers by 4.6-fold versus placebo. Next, we examined the pharmacokinetics (PK) in cynomolgus monkeys administered GLP-26 via IV (1 mg/kg) or PO (5 mg/kg). GLP-26 was found to have 34% oral bioavailability, with a mean input time of 3.17 h. The oral dose produced a mean peak plasma concentration of 380.7 ng/mL, observed 0.67 h after administration (~30-fold > in vitro EC90 corrected for protein binding), with a mean terminal elimination half-life of 2.4 h and a mean area under the plasma concentration versus time curve of 1660 ng·hr/mL. GLP-26 was 86.7% bound in monkey plasma. Lastly, GLP-26 demonstrated a favorable toxicity profile confirmed in primary human cardiomyocytes. Thus, GLP-26 warrants further preclinical development as an add on to treatment for HBV infection.


Asunto(s)
Cápside/efectos de los fármacos , Cápside/metabolismo , Cardiotoxinas/farmacocinética , Virus de la Hepatitis B/efectos de los fármacos , Virus de la Hepatitis B/fisiología , Compuestos de Sulfonilurea/farmacocinética , Ensamble de Virus/efectos de los fármacos , Animales , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Hepatitis B/tratamiento farmacológico , Hepatitis B/virología , Humanos , Macaca fascicularis , Masculino , Ratones , Miocitos Cardíacos/efectos de los fármacos , Compuestos de Sulfonilurea/efectos adversos , Compuestos de Sulfonilurea/química , Carga Viral
9.
BMC Infect Dis ; 21(1): 111, 2021 Jan 23.
Artículo en Inglés | MEDLINE | ID: mdl-33485302

RESUMEN

BACKGROUND: T cells play an important role in the prognosis of hepatitis B virus (HBV) infection, and are involved in the seroconversion of a patient from HBsAb negative to positive. To compare the T-cell receptor ß-chain variable region (TcRBV) complementarity-determining region 3 (CDR3) in subjects with or without hepatitis B surface antigen (HBsAg) convert to hepatitis B surface antibody (HBsAb), the TcRBV was determined using high throughput sequencing (HTS). METHODS: The clonotype and diversity of CDR3 in peripheral blood mononuclear cells of subjects with resolved acute hepatitis B (AHB, HBsAb+, HBsAg-) (n = 5), chronic hepatitis B (CHB, HBsAb-, HBsAg+) (n = 5), and healthy controls (HC, HBsAb-, HBsAg-) (n = 3) were determined and analyzed using HTS (MiSeq). RESULTS: The overlapping rate of CDR3 clones of any two samples in AHB group was 2.00% (1.74% ~ 2.30%), CHB group was 1.77% (1.43% ~ 2.61%), and HC group was 1.82% (1.62% ~ 2.12%), and there was no significant difference among the three groups by Kruskal-Wallis H test. However, among the top 10 cumulative frequencies of clonotypes, only the frequency of clonotype (TcRBV20-1/BD1/BJ1-2) in AHB group was lower than that of HC group (P < 0.001). Moreover, exclude the 10 top clonotypes, there are 57 markedly different frequency of clones between AHB and CHB groups (18 clones up, 39 clones down), 179 (180-1) different clones between AHB and HC groups, and 134 different clones between CHB and HC groups. With regard to BV and BJ genotypes, there was no significant different frequency among the groups. Furthermore, there was no significant difference in the diversity of TcRBV CDR3 among the three groups (P > 0.05). CONCLUSIONS: Thus, there are 57 TcRBV clonotypes that may be related to HBsAg seroconversion of AHB subjects, but the diversity of TcRBV CDR3 is not significantly related to the HBsAb positive status.


Asunto(s)
Regiones Determinantes de Complementariedad/genética , Hepatitis B/inmunología , Receptores de Antígenos de Linfocitos T alfa-beta/genética , Linfocitos T/inmunología , Adulto , Femenino , Hepatitis B/sangre , Anticuerpos contra la Hepatitis B/sangre , Antígenos de Superficie de la Hepatitis B/sangre , Virus de la Hepatitis B/inmunología , Hepatitis B Crónica/genética , Hepatitis B Crónica/inmunología , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Leucocitos Mononucleares/inmunología , Masculino , Persona de Mediana Edad , Seroconversión , Adulto Joven
10.
West Afr J Med ; 38(1): 19-23, 2021 01.
Artículo en Inglés | MEDLINE | ID: mdl-33463702

RESUMEN

BACKGROUND: The Hepatitis B surface Antigen (HBsAg) is the most utilized indicator marker of hepatitis B infection. This study assesses the accuracy of the two most common screening assays used to detect HBsAg among blood donors. MATERIALS AND METHODS: A total of 350 eligible blood donors were screened for HBsAg using both Bio-Check HBsAg Rapid screening kit (BioCheck Inc, South San Francisco, USA) and a fourth-generation Enzyme-Linked Immunoassays (ELISA) kit, MonolisaTM HBs Ag Ultra (Bio-Rad Laboratories, Marnes-la-Coquette-France). Questionnaires were used to inquire about risk factors for HBV infection among blood donors. The calculation of sensitivity, specificity, negative predictive and positive predictive values were carried out by comparing the performance of the rapid kit with ELISA test as the reference standard. RESULTS: The prevalence of HBV infection using Rapid Diagnostic Test (RDT) was 5.7% but was 14.6% by ELISA. Using ELISA as a reference, the sensitivity and specificity of RDT were 31.4% and 98.7% respectively. The positive predictive value and negative predictive value for RDT were 80.0% and 89.4% respectively. Overall non-compliance with transfusion-transmitted infection (TTI) risk-related deferral criteria was 38%. CONCLUSION: The low sensitivity of RDT kits precludes its continuous use in high HBV endemic regions where many donors fail to disclose full and truthful information about their risk for TTI. It is suggested that blood banks should complement the use of RDT with a more sensitive assay such as ELISA.


Asunto(s)
Donantes de Sangre , Ensayo de Inmunoadsorción Enzimática , Antígenos de Superficie de la Hepatitis B , Hepatitis B , ADN Viral , Hepatitis B/diagnóstico , Hepatitis B/epidemiología , Virus de la Hepatitis B , Humanos
11.
BMC Infect Dis ; 21(1): 56, 2021 Jan 12.
Artículo en Inglés | MEDLINE | ID: mdl-33435880

RESUMEN

BACKGROUND: Hepatitis B virus (HBV) infection is a high-risk factor of hepatocellular carcinoma (HCC). Cellular immune responses are essential for HCC development, and the CD4+ and CD8+ T subtypes are identified as the primary anti-tumor immune cells. In the study, we investigated the effect and mechanism of amygdalin in the cellular immune response in HBV-related HCC and HCC progression. METHODS: The cell proliferation was examined by MTT analysis. Cells metastasis ability was detected by Invasion and migration assays. Quantification of apoptotic cells was performed with Flow cytometer assay. The protein levels of p-STAT3, STAT3, p-JAK2, JAK2, caspase-3, cleaved caspase-3 were detected by performing immunoblotting assays. RESULTS: We demonstrate that amygdalin treatment could rescue the HBV-T cell viability and IFN-γ and TNF-αproduction. In HBV-T cells, the MFI levels of CD8+ are lower than that in NC-T cells. Moreover, the phosphorylation levels of STAT3 and JAK2 are higher in HBV-T cells, compared to those in NC-T cells, and then reduced by amygdalin treatment. Co-culture with HBV-T cells could reduce IFN-γ and TNF-α, production while increase IL-6 and IL-10 production in HepG2.2.15 cells; these alterations could be partially reversed by amygdalin pretreatment. Finally, co-culture with HBV-T cells significantly promoted the cell viability, inhibited the apoptosis, and promoted the migration of HepG2.2.15 cells, and these alterations could be partially reversed by amygdalin treatment. CONCLUSION: Our findings provide a rationale for further studies on the functions and mechanism of amygdalin inhibiting HBV-related HCC cell proliferation, invasion, and migration via T cell-mediated tumor immunity.


Asunto(s)
Amigdalina/farmacología , Carcinoma Hepatocelular/sangre , Carcinoma Hepatocelular/virología , Progresión de la Enfermedad , Hepatitis B/complicaciones , Janus Quinasa 2/metabolismo , Neoplasias Hepáticas/sangre , Neoplasias Hepáticas/virología , Factor de Transcripción STAT3/metabolismo , Transducción de Señal/efectos de los fármacos , Linfocitos T/efectos de los fármacos , Anciano , Amigdalina/metabolismo , Apoptosis/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Técnicas de Cocultivo , Citocinas/metabolismo , Femenino , Células Hep G2 , Hepatitis B/virología , Virus de la Hepatitis B/fisiología , Humanos , Masculino , Persona de Mediana Edad , Linfocitos T/metabolismo , Linfocitos T/virología
12.
BMC Infect Dis ; 21(1): 83, 2021 Jan 19.
Artículo en Inglés | MEDLINE | ID: mdl-33468062

RESUMEN

BACKGROUND: Hepatitis B virus (HBV) infection is a major concern for blood safety in high-prevalence HBV countries such as China. In Shenzhen, dual hepatitis B surface antigen (HBsAg) enzyme-linked immunosorbent assays (ELISAs) have been adopted in parallel with nucleic acid testing (NAT) for donors for over a decade. A small proportion of blood donors test reactive (R) for HBsAg but negative through routine NAT, which can lead to HBV infection with an extremely low viral load. OBJECTIVES: We aimed to investigate and analyze the molecular characteristics of HBV among blood donors that tested HBsAg R in a single ELISA test. METHODS: Blood donations were evaluated in this study if confirmed HBsAg R through one of two ELISA kits. Samples with non-reactive (NR) results by NAT were collected and tested for HBsAg by chemiluminescent microparticle immunoassay (CLIA) with a neutralization test. The level of HBsAg was further assessed by electrochemiluminescence immunoassay (ECLIA). The viral basic core promoter (BCP) and pre-core (PC) and S regions were amplified by nested PCR. Quantitative real-time PCR (qPCR) for viral load determination and individual donation (ID)-NAT were adopted simultaneously. HBsAg was confirmed with CLIA, ECLIA, nested PCR, qPCR, and ID-NAT. RESULTS: Of the 100,252 donations, 38 and 41 were identified as HBsAg R with Wantai and DiaSorin ELISA kits, respectively. Seventy-nine (0.077%, 79/100,252) blood samples with ELISA R-NR and NAT NR results were enrolled in the study. Of these, 17 (21.5%,17/79) were confirmed as HBsAg-positive. Of the 14 genotyped cases, 78.6% (11/14) were genotype B, and C and D were observed in two and one sample, respectively. Mutations were found in the S gene, including Y100C, Y103I, G145R, and L175S, which can affect the detection of HBsAg. A high-frequency mutation, T1719G (93.3%), was detected in the BCP/PC region, which reduced the viral replication. CONCLUSION: A small number of blood samples with HBsAg ELISA R-NR and NAT NR results were confirmed as HBV infection, viral nucleic acids were found in most of the samples through routine NAT methods. It is necessary to employ more sensitive and specific assays for the detection of HBV infection among blood donors.


Asunto(s)
Donantes de Sangre , Antígenos de Superficie de la Hepatitis B/sangre , Virus de la Hepatitis B/genética , Hepatitis B , China , ADN Viral/genética , Ensayo de Inmunoadsorción Enzimática , Humanos , Técnicas de Amplificación de Ácido Nucleico , Filogenia , Reacción en Cadena de la Polimerasa/métodos
13.
Sheng Wu Gong Cheng Xue Bao ; 37(1): 301-311, 2021 Jan 25.
Artículo en Chino | MEDLINE | ID: mdl-33501810

RESUMEN

Chronic hepatitis B (CHB) is a global epidemic disease caused by hepatitis B virus that can lead to hepatic failure, even liver cirrhosis and hepatocellular carcinoma. The occurrence and development of CHB are closely related to the changes in the gut microbiota communities. To explore the relationship between the structure of gut microbiota and liver biochemical indicators, 14 CHB patients (the CHB group) and 11 healthy people (the CN group) were randomly enrolled in this study. Our results demonstrate that CHB caused changes in the gut microbiota communities and biochemical indicators, such as alanine transaminase, total bilirubin and gamma glutamyl transferase. Furthermore, CHB induced imbalance of the gut microbiota. Prevotella, Blautia, Ruminococcus, Eubacterium eligens group, Bacteroides uniformis and Ruminococcus sp. 5_1_39BFAA were associated with the critical biochemical indicators and liver injury, suggesting a new approach to CHB treatment.


Asunto(s)
Microbioma Gastrointestinal , Hepatitis B Crónica , Neoplasias Hepáticas , Bacteroides , Eubacterium , Virus de la Hepatitis B , Humanos , Cirrosis Hepática
14.
Zhonghua Liu Xing Bing Xue Za Zhi ; 42(1): 15-21, 2021 Jan 10.
Artículo en Chino | MEDLINE | ID: mdl-33503694

RESUMEN

Hepatocellular carcinoma (HCC) caused by hepatitis B virus (HBV) is the first cause of cancer-caused death in China. This study, from the perspective of HBV genomic epidemiology, systematically investigated the evolution of HBV and their interaction with host genetic factors in each stage of HBV carcinogenesis and comprehensively analyzed the role of apolipoprotein B mRNA editing enzyme catalytic polypeptides (APOBEC) family in the inflammation-to-cancer transformation. Based on our findings and related studies, we proposed "cancer evolution and development" (Cancer Evo-Dev) theoretical system suitable for most cancer types. Cancer Evo-Dev lays a theoretical foundation for understanding the mechanism of inflammation to promote the development of cancer, which is of great significance for the specific prevention, prediction, early diagnosis, and targeted therapy of malignant diseases.


Asunto(s)
Carcinoma Hepatocelular , Hepatitis B , Neoplasias Hepáticas , Carcinoma Hepatocelular/genética , China , Hepatitis B/complicaciones , Hepatitis B/genética , Virus de la Hepatitis B/genética , Humanos , Neoplasias Hepáticas/genética , Mutación
15.
Recent Results Cancer Res ; 217: 47-70, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33200361

RESUMEN

Hepatitis B virus (HBV) is a major cause of hepatocellular carcinoma (HCC). There are approximately 250 million people in the world that are chronically infected by this virus, resulting in nearly 1 million deaths every year. Many of these patients die from severe liver diseases, including HCC. HBV may induce HCC through the induction of chronic liver inflammation, which can cause oxidative stress and DNA damage. However, many studies also indicated that HBV could induce HCC via the alteration of hepatocellular physiology that may involve genetic and epigenetic changes of the host DNA, the alteration of cellular signaling pathways, and the inhibition of DNA repair mechanisms. This alteration of cellular physiology can lead to the accumulation of DNA damages and the promotion of cell cycles and predispose hepatocytes to oncogenic transformation.


Asunto(s)
Carcinoma Hepatocelular , Virus de la Hepatitis B , Hepatitis B , Neoplasias Hepáticas , Carcinoma Hepatocelular/virología , Reparación del ADN , Hepatitis B/complicaciones , Hepatitis B/genética , Virus de la Hepatitis B/genética , Virus de la Hepatitis B/patogenicidad , Humanos , Neoplasias Hepáticas/virología , Oncogenes
16.
Recent Results Cancer Res ; 217: 71-90, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33200362

RESUMEN

Hepatocellular carcinoma (HCC) is one of the five leading causes of cancer death in human. Hepatitis B virus (HBV) is the most common etiologic agent of HCC in the world. Prevention is the best way to control cancer. There are three levels of liver cancer prevention, i.e., primary prevention by HBV vaccination targeting the general population starting from birth dose, secondary prevention by antiviral agent for high-risk subjects with chronic HBV infection, and tertiary prevention by antiviral agent to prevent recurrence for patients who have been successfully treated for liver cancer. Primary prevention by hepatitis B vaccination is most cost effective, the cancer preventive efficacy support it as the first successful example of cancer preventive vaccine in human. Addition of hepatitis B immunoglobulin immediately after birth and antiviral agent during the third trimester of pregnancy to block mother-to-infant transmission of HBV are existing or possible emerging strategies to enhance the prevention efficacy of HBV infection and its related liver cancer. Secondary prevention with current antiviral agents may reduce the risk or delay the onset of HCC development, but could not eradicate HBV infection and HCC. Better antiviral therapeutic agents are needed for better secondary prevention.


Asunto(s)
Antivirales , Carcinoma Hepatocelular , Virus de la Hepatitis B , Hepatitis B , Neoplasias Hepáticas , Antivirales/uso terapéutico , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/prevención & control , Carcinoma Hepatocelular/virología , Femenino , Hepatitis B/tratamiento farmacológico , Hepatitis B/prevención & control , Vacunas contra Hepatitis B , Virus de la Hepatitis B/inmunología , Virus de la Hepatitis B/patogenicidad , Humanos , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/prevención & control , Neoplasias Hepáticas/virología , Embarazo
19.
Adv Exp Med Biol ; 1287: 69-80, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33034027

RESUMEN

Interactions between liver cells are closely regulated by Notch signaling. Notch signaling has been reported clinically related to bile duct hypogenesis in Alagille syndrome, which is caused by mutations in the Jagged1 gene. Notch activation and hepatocarcinogenesis are closely associated since cancer signaling is affected by the development of liver cells and cancer stem cells. Gene expression and genomic analysis using a microarray revealed that abnormalities in Notch-related genes were associated with the aggressiveness of liver cancer. This pattern was also accompanied with α-fetoprotein- and EpCAM-expressing phenotypes in vitro, in vivo, and in clinical tissues. Hepatitis B or C virus chronic infection or alcohol- or steatosis-related liver fibrosis induces liver cancer. Previous reports demonstrated that HBx, a hepatitis B virus protein, was associated with Jagged1 expression. We found that the Jagged1 and Notch1 signaling pathways were closely associated with the transcription of covalently closed circular hepatitis B virus DNA, which regulated cAMP response element-binding protein, thereby affecting Notch1 regulation by the E3 ubiquitin ligase ITCH. This viral pathogenesis in hepatocytes induces liver cancer. In conclusion, Notch signaling exerts various actions and is a clinical signature associated with hepatocarcinogenesis and liver context-related developmental function.


Asunto(s)
Neoplasias Hepáticas , Receptores Notch/metabolismo , Transducción de Señal , Hepatitis/metabolismo , Hepatitis/virología , Virus de la Hepatitis B/patogenicidad , Humanos , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/virología , Proteínas Represoras/metabolismo , Ubiquitina-Proteína Ligasas/metabolismo
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