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  1. Hepatitis B (HBV)

    MedlinePLUS

    ... How Can I Help a Friend Who Cuts? Hepatitis B (HBV) KidsHealth > For Teens > Hepatitis B (HBV) Print A A A Text Size ... Prevented? How Is It Treated? What Is It? Hepatitis (pronounced: hep-uh-TIE-tiss) is a disease ...

  2. Hepatitis B (HBV)

    MedlinePLUS

    ... from Nemours for Parents for Kids for Teens Teens Home Body Mind Sexual Health Food & Fitness Diseases & Conditions Infections Q&A School & Jobs Drugs & Alcohol Staying Safe Recipes En Espaol Making a Change Your Personal ... For Teens > Hepatitis B (HBV) Print A A A Text ...

  3. Strategies to eliminate HBV infection

    PubMed Central

    Kapoor, Rama; Kottilil, Shyam

    2014-01-01

    Chronic HBV infection is a major public health concern affecting over 240 million people worldwide. Although suppression of HBV replication is achieved in the majority of patients with currently available newer antivirals, discontinuation of therapy prior to hepatitis B surface antigen loss or seroconversion is associated with relapse of HBV in the majority of cases. Thus, new therapeutic modalities are needed to achieve eradication of the virus from chronically infected patients in the absence of therapy. The basis of HBV persistence includes viral and host factors. Here, we review novel strategies to achieve sustained cure or elimination of HBV. The novel approaches include targeting the viral and or host factors required for viral persistence, and novel immune-based therapies, including therapeutic vaccines. PMID:25309617

  4. Anti-HBV effect of TAT- HBV targeted ribonuclease

    PubMed Central

    Ding, Jin; Liu, Jun; Xue, Cai-Fang; Gong, Wei-Dong; Li, Ying-Hui; Zhao, Ya

    2003-01-01

    AIM: To prepare and purify TAT-HBV targeted ribonuclease fusion protein, evaluate its transduction activity and investigate its effect on HBV replication in 2.2.15 cells. METHODS: The prokaryotic expression vector pTAT containing TR gene was used in transforming E.coli BL21 (DE3) LysS and TR was expressed with the induction of IPTG. The TAT-TR fusion protein was purified using Ni-NTA-agrose and PD-10 desalting columns, and analyzed by SDS-PAGE. Transduction efficiency of TAT-TR was detected with immunofluorescence assay and the concentration of HBeAg in the supernatant of the 2.2.15 cells was determined via solid-phase radioimmunoassay (spRIA). MTT assay was used to detect the cytotoxicity of TAT-TR. RESULTS: The SDS-PAGE showed that the TAT-TR fusion protein was purified successfully, and the purity of TAT-TR was 90%. The visualization of TAT-TR by immunofluorescence assay indicated its high efficiency in transducing 2.2.15 cells. RIA result suggests that TAT-TR could inhibit the replication of HBV effectively, it didn’t affect cell growth and had no cytotoxicity. CONCLUSION: TAT-TR possesses a significant anti-HBV activity and the preparation of TAT-TR fusion protein has laid the foundation for the use of TR in the therapeutic trial of HBV infection. PMID:12854156

  5. HBV Genotypic Variability in Cuba

    PubMed Central

    Loureiro, Carmen L.; Aguilar, Julio C.; Aguiar, Jorge; Muzio, Verena; Pentn, Eduardo; Garcia, Daymir; Guillen, Gerardo; Pujol, Flor H.

    2015-01-01

    The genetic diversity of HBV in human population is often a reflection of its genetic admixture. The aim of this study was to explore the genotypic diversity of HBV in Cuba. The S genomic region of Cuban HBV isolates was sequenced and for selected isolates the complete genome or precore-core sequence was analyzed. The most frequent genotype was A (167/250, 67%), mainly A2 (149, 60%) but also A1 and one A4. A total of 77 isolates were classified as genotype D (31%), with co-circulation of several subgenotypes (56 D4, 2 D1, 5 D2, 7 D3/6 and 7 D7). Three isolates belonged to genotype E, two to H and one to B3. Complete genome sequence analysis of selected isolates confirmed the phylogenetic analysis performed with the S region. Mutations or polymorphisms in precore region were more common among genotype D compared to genotype A isolates. The HBV genotypic distribution in this Caribbean island correlates with the Y lineage genetic background of the population, where a European and African origin prevails. HBV genotypes E, B3 and H isolates might represent more recent introductions. PMID:25742179

  6. Postexposure Prophylactic Effect of Hepatitis B Virus (HBV)-Active Antiretroviral Therapy against HBV Infection

    PubMed Central

    Watanabe, Tsunamasa; Hamada-Tsutsumi, Susumu; Yokomaku, Yoshiyuki; Imamura, Junji; Sugiura, Wataru

    2014-01-01

    Retrospective study indicates that hepatitis B virus (HBV)-active nucleoside (nucleotide) analogues (NAs) used for antiretroviral therapy reduce the incidence of acute HBV infections in human immunodeficiency virus (HIV)-infected patients. Learning from HIV postexposure prophylaxis (PEP), we explored the possibility of using NAs in PEP following HBV exposure, if preexposure prophylaxis is feasible clinically. Using freshly isolated primary human hepatocytes cultured in vitro, we analyzed the effect of HBV-active tenofovir and lamivudine in primary HBV infection and also the effect of treatment with these NAs after HBV infection. HBV-active NAs applied from 24 h before inoculation could not prevent the secretion of hepatitis B surface antigen into the culture medium, and cessation of the NAs after inoculation allowed the cells to establish an apparent HBV infection. In contrast, hepatitis B immune globulin was able to prevent HBV infection completely. NA treatment before infection, however, can control the spread of HBV infection, as detected by immunohistochemistry. Practically, starting NA treatment within 2 days of primary HBV infection inhibited viral spread effectively, as well as preexposure treatment. We demonstrated that preexposure NA treatment was not able to prevent the acquisition of HBV infection but prevented viral spread by suppressing the production of mature progeny HBV virions. The effect of postexposure treatment within 2 days was similar to the effect of preexposure treatment, suggesting the possibility of HBV PEP using HBV-active NAs in HIV- and HBV-susceptible high-risk groups. PMID:25512419

  7. Peripheral blood dendritic cells are phenotypically and functionally intact in chronic hepatitis B virus (HBV) infection

    PubMed Central

    Tavakoli, S; Mederacke, I; Herzog-Hauff, S; Glebe, D; Grn, S; Strand, D; Urban, S; Gehring, A; Galle, P R; Bcher, W O

    2008-01-01

    Persistence of hepatitis B virus (HBV) infection is associated with reduced anti-viral T cell responses. Impaired dendritic cell (DC) function was suggested as the cause of reduced T cell stimulation in chronic HBV carriers. Thus, we compared myeloid (mDC) and plasmacytoid DC (pDC) from chronic HBV carriers and controls. Frequency and phenotype of isolated DC were analysed by fluorescence activated cell sorter staining, DC function by mixed lymphocyte reaction, cytokine bead array, intracellular cytokine staining, enzyme-linked immunosorbent assay and enzyme-linked immunospot. Expression of HBV DNA and mRNA was studied by polymerase chain reaction (PCR). Circulating total DC, mDC or pDC were not reduced in chronic HBV carriers. Isolated mDC and pDC from chronic HBV carriers exhibited similar expression of co-stimulatory molecules and alloreactive T helper cell stimulation as control DC, whether tested directly ex vivo or after in vitro maturation. Secretion of pro- and anti-inflammatory cytokines by CD40 or Toll-like receptor ligand-stimulated patient DC was intact, as was human leucocyte antigen A2-restricted HBV-specific cytotoxic lymphocyte stimulation. Although both DC populations contained viral DNA, viral mRNA was undetectable by reverse transcriptionPCR, arguing against viral replication in DC. We found no quantitative, phenotypic or functional impairment of mDC or pDC in chronic hepatitis B, whether studied ex vivo or after in vitro maturation. PMID:18031557

  8. General and Abdominal Adiposity and Risk of Death in HBV Versus Non-HBV Carriers

    PubMed Central

    Lin, Wen-Yuan; Peng, Cheng-Yuan; Lin, Cheng-Chieh; Davidson, Lance E.; Pi-Sunyer, F. Xavier; Sung, Pei-Kun; Huang, Kuo-Chin

    2016-01-01

    Abstract Both obesity and hepatitis B virus (HBV) infection increase the risk of death. We investigate the association between general and central obesity and all-cause mortality among adult Taiwanese HBV versus non-HBV carriers. A total of 19,850 HBV carriers and non-hepatitis C virus (HCV) carriers, aged 20 years and older at enrollment in 1998 to 1999 in Taiwan, were matched to 79,400 non-HBV and non-HCV carriers (1:4). Cox proportional-hazards models were used to estimate the relative risks for all-cause mortality during a maximum follow-up period of 10 years. Four obesity-related anthropometric indices—body mass index (BMI), waist circumference, waist-to-hip ratio, and waist-to-height ratio—were the main variables of interest. During the follow-up period, 628 and 2366 participants died among HBV and non-HBV carriers, respectively. Both underweight and general obesity were associated with an increased risk of death. The highest risk of all-cause death in relation to BMI was found in the HBV carriers with underweight (BMI <18.5 kg/m2) and non-HBV carriers with obesity (BMI ≥30 kg/m2). The lowest risks of all-cause death in relation to abdominal adiposity were found at the third quartiles of waist circumference, waist-to-hip ratio, and waist-to-height ratio among HBV carriers, but in the second quartiles among non-HBV carriers. For those with pre-existing liver disease among HBV carriers, patients with underweight have higher risk of death than those with obesity. Hepatitis B virus carriers with underweight have higher risk of death than non-HBV carriers. HBV carriers with mild abdominal obesity have the lowest risk of death, but not in the non-HBV carriers. PMID:26765398

  9. HBV-DNA levels predict overall mortality in HIV/HBV coinfected individuals.

    PubMed

    Nikolopoulos, Georgios K; Paraskevis, Dimitrios; Psichogiou, Mina; Hatzakis, Angelos

    2016-03-01

    The coinfection of Hepatitis B virus (HBV) and human immunodeficiency virus (HIV) has been associated with increased death rates. However, the relevant research has mostly relied on serologic HBV testing [HBV surface antigen (HBsAg)]. The aim of this work was to explore the relationship of HBV viraemia with overall mortality among HIV/HBV coinfected individuals. The analysis included 1,609 HIV seropositives of a previously described cohort (1984-2003) with limited exposure to tenofovir (12%) and a median follow-up of approximately 5 years. Those with persistent expression of HBsAg were further tested for HBV-DNA. The data were analyzed using Poisson regression models. Totally, 101 participants were chronic carriers of HBsAg (6.28%). Of these, 81 were tested for HBV-DNA. The median HBV-DNA levels were 3.81 log (base-10) International Units (IU)/ml. A third (31%) of those tested for HBV-DNA had received tenofovir. Before developing acquired immune deficiency syndrome (AIDS), the adjusted incidence rate ratio (IRR) for all-cause mortality of coinfected patients with HBV viraemia above the median value versus the HIV monoinfected group was 3.44 [95% confidence interval (CI): 1.05-11.27]. Multivariable regressions in the coinfected group only (n?=?81) showed that one log-10 increase in HBV-DNA levels was associated with an elevated risk for death (IRR: 1.24, 95%CI: 1.03-1.49). HBV-DNA levels predict overall mortality in the setting of HIV/HBV coinfection, especially during the period before developing AIDS, and could thus help prioritize needs and determine the frequency of medical monitoring. J. Med. Virol. 88:466-473, 2016. 2015 Wiley Periodicals, Inc. PMID:26288334

  10. Toll-like receptor (TLR)-mediated innate immune responses in the control of hepatitis B virus (HBV) infection.

    PubMed

    Zhang, Ejuan; Lu, Mengji

    2015-02-01

    The role of adaptive immune responses in the control of hepatitis B virus (HBV) infection is well accepted. The contribution of innate immune responses to the viral control is recognized but yet not fully understood. Toll-like receptors (TLRs) sense pathogen-associated molecule patterns and activate antiviral mechanisms including the intracellular antiviral pathways and the production of antiviral effectors like interferons (IFNs) and pro-inflammatory cytokines. Activation of the TLR3 pathway and the production of IFN-β represent one of the major mechanisms leading to the suppression of HBV replication in the liver, as shown in different in vitro and in vivo models. TLR4 signaling and TLR2 signaling result in the activation of intracellular pathways including MAPK and PI-3 K/Akt in hepatocytes and reduce HBV replication in an IFN-independent manner. HBV is able to counteract the actions of TLR3 and TLR2/4 through downregulation of TLR expression and attenuation of the cellular signaling pathways. Thus, TLR ligands are promising candidates as immunomodulators and therapeutics for the treatment of chronic HBV infection. Specific antiviral treatment against HBV could recover the TLR functions in chronic HBV infection and increase the effectiveness of therapeutic approaches based on TLR activation. PMID:25550115

  11. Inhibition of hepatitis B virus (HBV) by LNA-mediated nuclear interference with HBV DNA transcription

    SciTech Connect

    Sun, Zhen; Department of Biochemistry and Molecular Biology, Program in Molecular Cell Biology, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058 ; Xiang, Wenqing; Guo, Yajuan; Chen, Zhi; Liu, Wei; Lu, Daru

    2011-06-10

    Highlights: {yields} LNA-modified oligonucleotides can pass through the plasma membrane of cultured cells even without using transfection machinery. {yields} LNA-modified oligonucleotides passed efficiently across the cell membrane, and lipid-coating facilitated translocation from the cytoplasm to the nucleus. {yields} LNA-oligonucleotide designed to target nuclear HBV DNA efficiently suppresses HBV replication and transcription in cultured hepatic cells. -- Abstract: Silencing target genes with small regulatory RNAs is widely used to investigate gene function and therapeutic drug development. Recently, triplex-based approaches have provided another attractive means to achieve targeted gene regulation and gene manipulation at the molecular and cellular levels. Nuclear entry of oligonucleotides and enhancement of their affinity to the DNA targets are key points of such approaches. In this study, we developed lipid-based transport of a locked-nucleic-acid (LNA)-modified oligonucleotide for hepatitis B virus (HBV) DNA interference in human hepatocytes expressing HBV genomic DNA. In these cells, the LNA-modified oligonucleotides passed efficiently across the cell membrane, and lipid-coating facilitated translocation from the cytoplasm to the nucleus. The oligonucleotide specifically targeting HBV DNA clearly interfered with HBV DNA transcription as shown by a block in pregenomic RNA (pgRNA) production. The HBV DNA-targeted oligonucleotide suppressed HBV DNA replication and HBV protein production more efficiently than small interfering RNAs directed to the pgRNA. These results demonstrate that fusion with lipid can carry LNA-modified oligonucleotides to the nucleus where they regulate gene expression. Interfering with HBV DNA transcription by LNA-modified oligonucleotides has strong potential as a new strategy for HBV inhibition.

  12. HBV: Do I treat my immunotolerant patients?

    PubMed

    Vlachogiannakos, Jiannis; Papatheodoridis, George V

    2016-01-01

    Immunotolerant patients with chronic hepatitis B virus (HBV) infection are characterized by positive HBeAg, high viral replication, persistently normal ALT and no or minimal liver damage. Since the risk of the progression of liver disease and the chance of a sustained response with existing anti-HBV agents are low, current guidelines do not recommend treatment but close monitoring with serial alanine aminotransferase (ALT) and HBV DNA measurements instead. However, not treating all these patients is a concern because advanced histological lesions have been reported in certain cases who are usually older (>30-40years old), and continued high HBV replication could increase the risk of hepatocellular carcinoma (HCC). Thus, the optimal management of immunotolerant patients is often individualised according to age, which is associated with histological severity and patient outcome. In particular, immunotolerant patients <30years old can be monitored for ALT and HBV DNA, while treatment is often recommended in the few patients over 40. A liver biopsy and/or non-invasive assessment of fibrosis may be helpful to determine the therapeutic strategy in patients between 30 and 40years old. Moreover, there are three specific subgroups of immunotolerant patients who often require treatment with oral anti-HBV agents: patients who will receive immunosuppressive treatment or chemotherapy, women with serum HBV DNA >10(6-7) IU/ml during the last trimester of pregnancy and certain healthcare professionals with high viraemia levels. More studies are needed to further clarify the natural history for the optimal timing of treatment in this setting. PMID:26725904

  13. Anti-HBV Drugs: Progress, Unmet Needs, and New Hope

    PubMed Central

    Kang, Lei; Pan, Jiaqian; Wu, Jiaofen; Hu, Jiali; Sun, Qian; Tang, Jing

    2015-01-01

    Approximately 240 million people worldwide are chronically infected with hepatitis B virus (HBV), which represents a significant challenge to public health. The current goal in treating chronic HBV infection is to block progression of HBV-related liver injury and inflammation to end-stage liver diseases, including cirrhosis and hepatocellular carcinoma, because we are unable to eliminate chronic HBV infection. Available therapies for chronic HBV infection mainly include nucleos/tide analogues (NAs), non-NAs, and immunomodulatory agents. However, none of them is able to clear chronic HBV infection. Thus, a new generation of anti-HBV drugs is urgently needed. Progress has been made in the development and testing of new therapeutics against chronic HBV infection. This review aims to summarize the state of the art in new HBV drug research and development and to forecast research and development trends and directions in the near future. PMID:26389937

  14. Anti-HBV Drugs: Progress, Unmet Needs, and New Hope.

    PubMed

    Kang, Lei; Pan, Jiaqian; Wu, Jiaofen; Hu, Jiali; Sun, Qian; Tang, Jing

    2015-09-01

    Approximately 240 million people worldwide are chronically infected with hepatitis B virus (HBV), which represents a significant challenge to public health. The current goal in treating chronic HBV infection is to block progression of HBV-related liver injury and inflammation to end-stage liver diseases, including cirrhosis and hepatocellular carcinoma, because we are unable to eliminate chronic HBV infection. Available therapies for chronic HBV infection mainly include nucleos/tide analogues (NAs), non-NAs, and immunomodulatory agents. However, none of them is able to clear chronic HBV infection. Thus, a new generation of anti-HBV drugs is urgently needed. Progress has been made in the development and testing of new therapeutics against chronic HBV infection. This review aims to summarize the state of the art in new HBV drug research and development and to forecast research and development trends and directions in the near future. PMID:26389937

  15. GP73, a new marker for diagnosing HBV-ACLF in population with chronic HBV infections.

    PubMed

    Wei, Hongshan; Zhang, Jing; Li, Hongmin; Ren, Hui; Hao, Xiaohua; Huang, Yubo

    2014-05-01

    Although Golgi protein 73 (GP73) has been widely evaluated for diagnosing hepatocellular carcinoma (HCC) and other liver diseases in recent decade, its serum profile of patients with hepatitis B virus (HBV)-associated acute-on-chronic liver failure (HBV-ACLF) is still unknown. This study was designed to evaluate the serum levels of GP73 in patients with HBV-ACLF. The participants included 200 apparently healthy controls; 200 patients with chronic hepatitis B (CHB); 200 patients with HCC; 210 patients with HBV-ACLF, in which 29 HBV-ACLF patients were followed up for 3 months. All patients were Hepatitis B virus surface antigen (HBsAg) positive. The concentrations of GP73 in patients with HBV-ACLF (285.3 ± 128.5 ng/mL) were markedly higher than those HCC patients (159.1 ± 105.8 ng/mL), CHB patients (64.65 ± 44.99 ng/mL), and healthy controls (35.37 ± 12.41 ng/mL). When the cut-off value was set at 182.1 ng/mL, the sensitivity and specificity of HBV-ACLF diagnosis were 77.62% (95% confidence interval [CI]: 71.37%-83.07%) and 95.50% (95% CI: 92.27%-98.26%), respectively. If serum GP73 concentration was still above 361.6 ng/mL after 14 days of follow-up, the patient's prognosis may be depressed. Serum GP73 may be used to diagnosis HBV-ACLF in population with chronic HBV infections. PMID:24560809

  16. Global strategies are required to cure and eliminate HBV infection.

    PubMed

    Revill, Peter; Testoni, Barbara; Locarnini, Stephen; Zoulim, Fabien

    2016-04-01

    Chronic HBV infection results in >1 million deaths per year from cirrhosis and liver cancer. No known cure for chronic HBV exists, due in part to the continued presence of transcriptionally active DNA in the nucleus that is not directly targeted by current antiviral therapies. A coordinated approach is urgently needed to advance an HBV cure worldwide, such as those established in the HIV field. We propose the establishment of an International Coalition to Eliminate Hepatitis B Virus (ICE-HBV) to facilitate the formation of international working groups on HBV virology, immunology, innovative tools and clinical trials: to promote awareness and education as well as to drive changes in government policy and ensure funds are channelled to HBV cure research and drug development. With the ICE-HBV in place, it should be possible to enable a HBV cure within the next decade. PMID:26907881

  17. Relationship between HBV viremia level of pregnant women and intrauterine infection: neated PCR for detection of HBV DNA

    PubMed Central

    Zhang, Shu-Lin; Han, Xiao-Bing; Yue, Ya-Fei

    1998-01-01

    AIM: To determine the incidence of hepatitis B virus (HBV) in trauterine infection and to explore the relationship between HBV viremia level of pregnant women and HBV intrauterine infection. METHODS: Sixty-nine pregnant women were divided into three groups. Group A, 41 HBsAg positive patients, 14 of them were HBeAg positive (group A1), and 27 HBeAg negative (group A2); Group B, 12 HBsAg negative patients, but positive for anti-HBs and/or anti-HBe and/or anti-HBc; and Group C, 16 patients negative for all HBV markers. Blood samples of mothers were taken at delivery, samples of their infants were collected within 24 h after birth (before injection of HBIG and HBV vaccine). All the serum samples were stored at - 20 C. HBV serum markers were tested by radioimmunoassay and HBV NDA were detected by nested polymerase chain reaction. RESULTS: In group C, all of 16 newborns were negative for HBsAg and HBV DNA. In group A, 7 infants were HBsAg positive (17.1%), and 17 (41.5%) were HBV DNA positive (P < 0.05). The incidence of intrauterine HBV infection was much higher in group A1 than that in group A2 (HBsAg 42.9% vs 3.7%, HBV DNA 92.9% vs 14.8%, P < 0.05). The incidence of HBV intrauterine infection was significantly different between high and low HBV viremia of mothers (93.3% vs 42.9%, P < 0.05). CONCLUSION: The incidence of HBV intrauterine infection is high when HBV DNA in newborns detected with nested PCR is used as a marker of HBV infection. It is related to HBV viremia level of mothers. PMID:11819234

  18. Distribution of HBV genotypes in Latin America.

    PubMed

    Alvarado-Mora, Mónica V; Pinho, João R Rebello

    2013-01-01

    Approximately 2 billion people worldwide are infected with HBV, and 350 million people are chronic carriers. HBV is classified into nine genotypes (A to I). Genotype F is the most prevalent in the Spanish-speaking countries and in the Amerindian population in South America. HBV genotype F was primarily found in indigenous populations from South America and is divided into four subgenotypes (F1 to F4). Subgenotype F1 is further divided into F1a (found in Costa Rica and El Salvador) and F1b (found in in Alaska, Argentina and Chile). Subgenotypes F2 and F3 cocirculate in the north of South America: F2a is found in Brazil and Venezuela, F2b is described only in Venezuela, F3 is frequent in Colombia, Venezuela and Panama, and F4 is reported from the central and south areas of South America, including Bolivia, Argentina and southern Brazil. HBV genotypes and subgenotypes have distinct geographical distributions. It is currently under discussion whether they are associated with different prognoses, considering the patterns of severity of liver diseases in various populations. Furthermore, global human migrations affect the pattern of genotype distribution, introducing genotypes differing from those found in the original inhabitants. PMID:23792558

  19. Detection of Hepatitis B Virus (HBV) Genomes and HBV Drug Resistant Variants by Deep Sequencing Analysis of HBV Genomes in Immune Cell Subsets of HBV Mono-Infected and/or Human Immunodeficiency Virus Type-1 (HIV-1) and HBV Co-Infected Individuals

    PubMed Central

    Lee, Z.; Nishikawa, S.; Gao, S.; Eksteen, J. B.; Czub, M.; Gill, M. J.; Osiowy, C.; van der Meer, F.; van Marle, G.; Coffin, C. S.

    2015-01-01

    The hepatitis B virus (HBV) and the human immunodeficiency virus type 1 (HIV-1) can infect cells of the lymphatic system. It is unknown whether HIV-1 co-infection impacts infection of peripheral blood mononuclear cell (PBMC) subsets by the HBV. Aims To compare the detection of HBV genomes and HBV sequences in unsorted PBMCs and subsets (i.e., CD4+ T, CD8+ T, CD14+ monocytes, CD19+ B, CD56+ NK cells) in HBV mono-infected vs. HBV/HIV-1 co-infected individuals. Methods Total PBMC and subsets isolated from 14 HBV mono-infected (4/14 before and after anti-HBV therapy) and 6 HBV/HIV-1 co-infected individuals (5/6 consistently on dual active anti-HBV/HIV therapy) were tested for HBV genomes, including replication indicative HBV covalently closed circular (ccc)-DNA, by nested PCR/nucleic hybridization and/or quantitative PCR. In CD4+, and/or CD56+ subsets from two HBV monoinfected cases, the HBV polymerase/overlapping surface region was analyzed by next generation sequencing. Results All analyzed whole PBMC from HBV monoinfected and HBV/HIV coinfected individuals were HBV genome positive. Similarly, HBV DNA was detected in all target PBMC subsets regardless of antiviral therapy, but was absent from the CD4+ T cell subset from all HBV/HIV-1 positive cases (P<0.04). In the CD4+ and CD56+ subset of 2 HBV monoinfected cases on tenofovir therapy, mutations at residues associated with drug resistance and/or immune escape (i.e., G145R) were detected in a minor percentage of the population. Summary HBV genomes and drug resistant variants were detectable in PBMC subsets from HBV mono-infected individuals. The HBV replicates in PBMC subsets of HBV/HIV-1 patients except the CD4+ T cell subpopulation. PMID:26390290

  20. Spontaneous reactivation of hepatitis B virus (HBV) infection in patients with resolved or occult HBV infection.

    PubMed

    Kamitsukasa, Hiroshi; Iri, Masanobu; Tanaka, Akihisa; Nagashima, Shigeo; Takahashi, Masaharu; Nishizawa, Tsutomu; Okamoto, Hiroaki

    2015-04-01

    Reactivation of a former hepatitis B virus (HBV) infection can be triggered by immunosuppressive therapy, diseases associated with an immunocompromised state, organ transplantation or the withdrawal of antiviral drugs. Despite the absence of such risk factors, a spontaneous reactivation of HBV replication occurred in two elderly patients with resolved or occult HBV infection. A 73-year-old male underwent coronary artery bypass grafting in October 2008, and was negative for HBsAg but positive for anti-HBs. In July 2009, his serum became positive for HBsAg, HBeAg and HBV DNA (6.4 log copies/ml; genotype C), but negative for anti-HBc IgM, with abrupt elevation of the liver enzymes. The entire genomic sequence of HBV recovered from this patient revealed no mutations in the core promoter and precore regions that interfere with HBeAg production. A 76-year-old male with a history of endoscopic mucosal resection for esophageal cancer in 2002 and an initial diagnosis of diabetes mellitus in 2009, at which time he was negative for HBsAg. He was found to be positive for HBsAg in September 2012 during a laboratory examination performed prior to the resection of recurrent esophageal cancer, despite a low HBV load (2.1 log copies/ml). Three months later, without the administration of any anticancer drugs, the HBV DNA (genotype B) level increased to 5.1 log copies/ml. A precore G1896A variant with high quasispecies diversity was recovered from the patient. Aging, surgical stress and complication of disease(s) associated with compromised immunity, such as cancer, arteriosclerosis and diabetes mellitus may trigger spontaneous HBV reactivation. PMID:25612181

  1. The Role of Immune Cells in Chronic HBV Infection

    PubMed Central

    Li, Hai-Jun; Zhai, Nai-Cui; Song, Hong-Xiao; Yang, Yang; Cui, An; Li, Tian-Yang; Tu, Zheng-Kun

    2015-01-01

    Hepatitis B virus (HBV) infection is a major cause of chronic liver diseases that may progress to liver cirrhosis and hepatocellular carcinoma. Host immune responses are important factors that determine whether HBV infection is cleared or persists. After infection, viral replication occurs inside hepatocytes, and the secretion of infectious virions can take place at high rates for decades. Consequently, HBV DNA and viral proteins, like HBV early antigen (HBeAg) and HBV surface antigen (HBsAg), can be easily detected in serum. Chronic infection with HBV is the result of an ineffective antiviral immune response towards the virus. In this review, we discuss the role of immune cells in chronic HBV infection. PMID:26807384

  2. HBV endemicity in Mexico is associated with HBV genotypes H and G

    PubMed Central

    Roman, Sonia; Panduro, Arturo

    2013-01-01

    Hepatitis B virus (HBV) genotypes have distinct genetic and geographic diversity and may be associated with specific clinical characteristics, progression, severity of disease and antiviral response. Herein, we provide an updated overview of the endemicity of HBV genotypes H and G in Mexico. HBV genotype H is predominant among the Mexican population, but not in Central America. Its geographic distribution is related to a typical endemicity among the Mexicans which is characterized by a low hepatitis B surface antigen seroprevalence, apparently due to a rapid resolution of the infection, low viral loads and a high prevalence of occult B infection. During chronic infections, genotype H is detected in mixtures with other HBV genotypes and associated with other co-morbidities, such as obesity, alcoholism and co-infection with hepatitis C virus or human immunodeficiency virus. Hepatocellular carcinoma prevalence is low. Thus, antiviral therapy may differ significantly from the standard guidelines established worldwide. The high prevalence of HBV genotype G in the Americas, especially among the Mexican population, raises new questions regarding its geographic origin that will require further investigation. PMID:24023487

  3. HBV endemicity in Mexico is associated with HBV genotypes H and G.

    PubMed

    Roman, Sonia; Panduro, Arturo

    2013-09-01

    Hepatitis B virus (HBV) genotypes have distinct genetic and geographic diversity and may be associated with specific clinical characteristics, progression, severity of disease and antiviral response. Herein, we provide an updated overview of the endemicity of HBV genotypes H and G in Mexico. HBV genotype H is predominant among the Mexican population, but not in Central America. Its geographic distribution is related to a typical endemicity among the Mexicans which is characterized by a low hepatitis B surface antigen seroprevalence, apparently due to a rapid resolution of the infection, low viral loads and a high prevalence of occult B infection. During chronic infections, genotype H is detected in mixtures with other HBV genotypes and associated with other co-morbidities, such as obesity, alcoholism and co-infection with hepatitis C virus or human immunodeficiency virus. Hepatocellular carcinoma prevalence is low. Thus, antiviral therapy may differ significantly from the standard guidelines established worldwide. The high prevalence of HBV genotype G in the Americas, especially among the Mexican population, raises new questions regarding its geographic origin that will require further investigation. PMID:24023487

  4. The influence of HLA alleles and HBV subgenotyes on the outcomes of HBV infections in Northeast China.

    PubMed

    Li, Xingku; Liu, Wei; Wang, Hongyan; Jin, Xi; Fang, Shaohong; Shi, Yuguang; Liu, Zhen; Zhang, Shuyun; Yang, Shufen

    2012-01-01

    Hepatitis B virus (HBV) infection has a wide variety of clinical outcomes, it could be spontaneouly recovered and also could develop fulminant liver failure or cirrhosis with hepatocellular carcinoma. Human leukocyte antigen (HLA) polymorphism and HBV (sub)genotypes have been speculated to associate with the outcome of HBV infection because the data obtained from various populations who bear different HLA alleles have shown a HLA polymorphism associated outcome of HBV infection. However, as the most important viral and host genetic factors, the impact of HBV (sub)genotypes in combination with HLA polymorphism on the clinical outcomes of HBV infections remains unclear. To demonstrate the association of HLA allele polymorphism in combination with HBV subgenotypes with the outcome of HBV infection in Northeastern Han Chinese population, a total of 230 HBV-infected individuals (Infection group) were compared to 210 random selected controls (Control group) who are negative for HBV infection for their HLA alleles frequency as well as the associations with the virus infection, clearance and persistence in combination with HBV subgenotypes. Of the 230 HBV-infected subjects, 54 were acute self-limited hepatitis (ASH) with HBV subgenotype C2 (ASH-C2), 144 were chronic hepatitis (CH) with HBV subgenotype C2 and B2 (CH-C2 and CH-B2), and 32 were spontaneously recovered (SR) without subgenotype results. When two groups are compared, the results suggest that B*48, B*51 and DRB1*12 carrier may have a high risk for HBV infection, but B*51 is likely association with spontaneous recovery and DRB1*07, 12 may be implied in viral persistence. HLA-B*15, DRB1*11 and 14 associated with viral clearance in the cases of HBV-C2 infection; HLA-B*54 carriers in chronic group are more sensitive to with the infection of HBV subgenotype B2; HLA-B*07 and DRB1*13 may protect subjects from HBV infection. The data presented a link between HLA polymorphism and HBV pathogenesis and suggested potential therapeutic targets for hepatitis B. PMID:22056847

  5. MicroRNAs Associated With HBV Infection And HBV-related HCC

    PubMed Central

    Xie, Kun-Lin; Zhang, Yan-Ge; Liu, Jun; Zeng, Yong; Wu, Hong

    2014-01-01

    Hepatitis B virus (HBV) infection is a global problem and a major risk factor for hepatocellular carcinoma (HCC). microRNAs (miRNAs) comprise a group of small noncoding RNAs regulating gene expression at the posttranslational level, thereby participating in fundamental biological processes, including cell proliferation, differentiation, and apoptosis. In this review, we summarize the roles of miRNAs in HBV infection, the recently identified mechanism underlying dysregulation of miRNAs in HBV-associated HCC, and their association with hepatocarcinogenesis. Moreover, we discuss the recent advances in the use of circulating miRNAs in the early diagnosis of HCC as well as therapies based on these aberrantly expressed miRNAs. PMID:25285167

  6. Emergence of Lamivudine-Resistant HBV during Antiretroviral Therapy Including Lamivudine for Patients Coinfected with HIV and HBV in China

    PubMed Central

    Li, Yijia; Zhu, Ting; Song, Xiaojing; Huang, Ying; Yang, Feifei; Guan, Shuo; Xie, Jing; Gohda, Jin; Hosoya, Noriaki; Kawana-Tachikawa, Ai; Liu, Wenjun; Gao, George Fu; Iwamoto, Aikichi; Li, Taisheng; Ishida, Takaomi

    2015-01-01

    In China, HIV-1-infected patients typically receive antiretroviral therapy (ART) that includes lamivudine (3TC) as a reverse-transcriptase inhibitor (RTI) (ART-3TC). Previous studies from certain developed countries have shown that, in ART-3TC, 3TC-resistant HBV progressively emerges at an annual rate of 1520% in patients coinfected with HIV-1 and HBV. This scenario in China warrants investigation because >10% of all HIV-infected patients in China are HBV carriers. We measured the occurrence of 3TC-resistant HBV during ART-3TC for HIV-HBV coinfection and also tested the effect of tenofovir disoproxil fumarate (TDF) used as an additional RTI (ART-3TC/TDF) in a cohort study in China. We obtained 200 plasma samples collected from 50 Chinese patients coinfected with HIV-1 and HBV (positive for hepatitis B surface antigen) and examined them for the prevalence of 3TC-resistant HBV by directly sequencing PCR products that covered the HBV reverse-transcriptase gene. We divided the patients into ART-3TC and ART-3TC/TDF groups and compared the efficacy of treatment and incidence of drug-resistance mutation between the groups. HIV RNA and HBV DNA loads drastically decreased in both ART-3TC and ART-3TC/TDF groups. In the ART-3TC group, HBV breakthrough or insufficient suppression of HBV DNA loads was observed in 20% (10/50) of the patients after 96-week treatment, and 8 of these patients harbored 3TC-resistant mutants. By contrast, neither HBV breakthrough nor treatment failure was recorded in the ART-3TC/TDF group. All of the 3TC-resistant HBV mutants emerged from the cases in which HBV DNA loads were high at baseline. Our results clearly demonstrated that ART-3TC is associated with the emergence of 3TC-resistant HBV in patients coinfected with HIV-1 and HBV and that ART-3TC/TDF reduces HBV DNA loads to an undetectable level. These findings support the use of TDF-based treatment regimens for patients coinfected with HIV-1 and HBV. PMID:26288093

  7. HBV cccDNA in patients sera as an indicator for HBV reactivation and an early signal of liver damage

    PubMed Central

    Chen, Ying; Sze, Johnny; He, Ming-Liang

    2004-01-01

    AIM: To evaluate the covalently closed circle DNA (cccDNA) level of hepatitis B virus (HBV) in patients liver and sera. METHODS: HBV DNA was isolated from patients liver biopsies and sera. A sensitive real-time PCR method, which is capable of differentiation of HBV viral genomic DNA and cccDNA, was used to quantify the total HBV cccDNA. The total HBV viral DNA was quantitated by real-time PCR using a HBV diagnostic kit (PG Biotech, LTD, Shenzhen, China) described previously. RESULTS: For the first time, we measured the level of HBV DNA and cccDNA isolated from ten HBV patients liver biopsies and sera. In the liver biopsies, cccDNA was detected from all the biopsy samples. The copy number of cccDNA ranged from from 0.03 to 173.1 per cell, the copy number of total HBV DNA ranged from 0.08 to 3 717 per cell. The ratio of total HBV DNA to cccDNA ranged from 1 to 3 406. In the sera, cccDNA was only detected from six samples whereas HBV viral DNA was detected from all ten samples. The ratio of cccDNA to total HBV DNA ranged from 0 to 1.77%. To further investigate the reason why cccDNA could only be detected in some patients sera, we performed longitudinal studies. The cccDNA was detected from the patients sera with HBV reactivation but not from the patients sera without HBV reactivation. The level of cccDNA in the sera was correlated with ALT and viral load in the HBV reactivation patients. CONCLUSION: HBV cccDNA is actively transcribed and replicated in some patients hepatocytes, which is reflected by a high ratio of HBV total DNA vs cccDNA. Detection of cccDNA in the liver biopsy will provide an end-point for the anti-HBV therapy. The occurrence of cccDNA in the sera is an early signal of liver damage, which may be another important clinical parameter. PMID:14695774

  8. Mycophenolic acid, an immunosuppressive agent, inhibits HBV replication in vitro.

    PubMed

    Gong, Z J; De Meyer, S; Clarysse, C; Verslype, C; Neyts, J; De Clercq, E; Yap, S H

    1999-05-01

    Mycophenolate mofetil (MMF), the morpholinoethyl ester of mycophenolic acid (MPA), is currently used as an immunosuppressive agent in kidney transplant recipients. After oral administration, MMF is hydrolysed to MPA, the active compound, which is a potent inhibitor of inosine monophosphate dehydrogenase (IMP-DH). Inhibition of this enzyme results in a depletion of the intracellular GTP and dGTP pools. MPA has been shown to inhibit the replication of a number of viruses, including arena viruses (Junin and Tacaribe), yellow fever virus, reovirus-1, parainfluenza-3 virus, Coxsackie B4 virus, Epstein-Barr virus and human immunodeficiency virus. To examine whether MPA also has an inhibitory effect on HBV replication, experiments were performed using cultures of primary human hepatocytes and HBV-transfected, HepG2 2.2.15 cells. After in vitro infection with HBV in human hepatocytes, HBV covalently-closed-circular (ccc) DNA and HBV mRNAs were detectable in the cells during the 10 days following infection. HBV DNA and hepatitis B surface antigen (HBsAg) were also secreted into the culture medium. In the presence of 10 microg ml-1 MPA (the therapeutic serum level of MPA as an immunosuppressive agent) in culture medium, HBV ccc DNA and HBV mRNAs became undetectable 5 days after treatment was started. The secretion of HBV DNA and HBsAg into the medium was also markedly reduced. No cytotoxic effect of the drug was noted during the experiments. The effect of MPA on HBV replication was abolished by the presence of guanosine (50 microg ml-1). In HepG2 2.2.15 cells (which contain an integrated tandem dimer of the HBV genome), MPA treatment had no significant inhibitory effect on the secretion of HBV DNA and HBsAg into the culture medium. HBV ccc DNA and HBV mRNAs in HepG2 2.2.15 cells were also not affected. The observed effect of MPA on HBV replication in primary human hepatocyte cultures may involve only episomal replication and may have clinical implications, especially before integration of HBV DNA into the host genome. PMID:10607235

  9. Progress and Prospects of Anti-HBV Gene Therapy Development

    PubMed Central

    Maepa, Mohube B.; Roelofse, Ilke; Ely, Abdullah; Arbuthnot, Patrick

    2015-01-01

    Despite the availability of an effective vaccine against hepatitis B virus (HBV), chronic infection with the virus remains a major global health concern. Current drugs against HBV infection are limited by emergence of resistance and rarely achieve complete viral clearance. This has prompted vigorous research on developing better drugs against chronic HBV infection. Advances in understanding the life cycle of HBV and improvements in gene-disabling technologies have been impressive. This has led to development of better HBV infection models and discovery of new drug candidates. Ideally, a regimen against chronic HBV infection should completely eliminate all viral replicative intermediates, especially covalently closed circular DNA (cccDNA). For the past few decades, nucleic acid-based therapy has emerged as an attractive alternative that may result in complete clearance of HBV in infected patients. Several genetic anti-HBV strategies have been developed. The most studied approaches include the use of antisense oligonucleotides, ribozymes, RNA interference effectors and gene editing tools. This review will summarize recent developments and progress made in the use of gene therapy against HBV. PMID:26263978

  10. Neutralization of hepatitis B virus (HBV) by human monoclonal antibody against HBV surface antigen (HBsAg) in chimpanzees.

    PubMed

    Kim, Se-Ho; Shin, Yong Won; Hong, Kwang-Won; Chang, Ki-Hwan; Ryoo, Kyung-Hwan; Paik, Sang-Hoon; Kim, Jin-Man; Brotman, Betsy; Pfahler, Wolfram; Prince, Alfred M

    2008-09-01

    The virus neutralizing efficacy of HB-C7A, a human monoclonal antibody raised against the surface antigen of hepatitis B virus (HBsAg), was proved using hepatitis B virus (HBV)-nave chimpanzees. One control chimpanzee which received 100CID(50) of HBV, subtype adw, without HB-C7A antibody became infected by HBV as evidenced by the appearance of HBV DNA on week 10 and subsequent appearance of HBsAg, anti-HBc and anti-HBs in the serum. Two experimental chimpanzees were inoculated intravenously with same dose of HBV as the control chimpanzee, which was previously incubated with 0.1mg and 10mg of HB-C7A antibody prior to inoculation. HBV infection was not observed in the antibody-treated chimpanzees during 12 months of follow-up, exhibiting neither detectable HBsAg nor anti-HBc antibody. This work demonstrates the neutralization of HBV by HB-C7A monoclonal antibody and shows the possibility of prevention of HBV infection using this antibody in liver transplantation and exposure to HBV. PMID:18479762

  11. Reactivation of hepatitis B virus (HBV) infection in adult T-cell leukemia-lymphoma patients with resolved HBV infection following systemic chemotherapy.

    PubMed

    Totani, Haruhito; Kusumoto, Shigeru; Ishida, Takashi; Masuda, Arisa; Yoshida, Takashi; Ito, Asahi; Ri, Masaki; Komatsu, Hirokazu; Murakami, Shuko; Mizokami, Masashi; Ueda, Ryuzo; Niimi, Akio; Inagaki, Hiroshi; Tanaka, Yasuhito; Iida, Shinsuke

    2015-04-01

    Reactivation of hepatitis B virus (HBV) infection may occur in adult T-cell leukemia-lymphoma (ATL) patients with resolved HBV infection who receive monotherapy with the anti-CC chemokine receptor 4 monoclonal antibody, mogamulizumab. However, there is little evidence regarding the incidence and characteristics of HBV reactivation in ATL patients receiving systemic chemotherapy, including the use of this antibody. We conducted a retrospective study for 24 ATL patients with resolved HBV infection underwent regular HBV DNA monitoring to assess HBV reactivation in Nagoya City University Hospital between January 2005 and June 2013. With median HBV DNA follow-up of 238 days (range 57-1420), HBV reactivation (defined as the detection of HBV DNA) was observed in three (12.5 %) of 24 patients with resolved HBV infection. No hepatitis due to HBV reactivation occurred in those patients who were diagnosed with HBV DNA levels below 2.1 log copies/mL and who received antiviral drugs. Mogamulizumab was administered prior to HBV reactivation in two of three HBV-reactivated patients. In the mogamulizumab era, further well-designed prospective studies are warranted to estimate the incidence of HBV reactivation and to establish regular HBV DNA monitoring-guided preemptive antiviral therapy for such patients. PMID:25633779

  12. Bloodborne Pathogens: HIV and HBV Contagion Risks at Camp.

    ERIC Educational Resources Information Center

    Skaros, Susan

    1996-01-01

    AIDS and hepatitis B are diseases caused by the viruses HIV and HBV, respectively, which are spread in blood and body fluids. HBV is 100 times more contagious than HIV. Diligent implementation of universal precautions, an exposure control plan, use of personal protective equipment, a vaccination program, and ongoing staff and camper education can

  13. Genie Pro

    SciTech Connect

    2004-05-15

    Genie Pro is a general purpose, interactive, adaptive tool for automatically labeling regions and finding objects in large amounts of image data. Genie Pro uses supervised learning techniques to search for spatio-spectral algorithms that are best able to match exaple labels provided by a user during a training session. After Genie Pro has discovered a useful algorithm, this algorith can then be applied to other similar types of image data, to label regions and objects similar to those provided during the training session. Genie Pro was originally developed for analyzing multispectral satellite data, but it works equally well with panchromatic (grayscale) and hyperspectral satellite data, aerial imagery, and various kinds of medical imagery. AS a rough guideline, Genie Pro can work with any imagery where the scene being imaged is all approximately at a constant distance fromt he imaging device, and so the scale of imagery is fixed. Applications for Genie Pro include: Crop and terrain type mapping, Road and river network mapping, Broad area search for vehicles and buildings, and Cancer identification in histological images.

  14. Genie Pro

    Energy Science and Technology Software Center (ESTSC)

    2004-05-15

    Genie Pro is a general purpose, interactive, adaptive tool for automatically labeling regions and finding objects in large amounts of image data. Genie Pro uses supervised learning techniques to search for spatio-spectral algorithms that are best able to match exaple labels provided by a user during a training session. After Genie Pro has discovered a useful algorithm, this algorith can then be applied to other similar types of image data, to label regions and objectsmore » similar to those provided during the training session. Genie Pro was originally developed for analyzing multispectral satellite data, but it works equally well with panchromatic (grayscale) and hyperspectral satellite data, aerial imagery, and various kinds of medical imagery. AS a rough guideline, Genie Pro can work with any imagery where the scene being imaged is all approximately at a constant distance fromt he imaging device, and so the scale of imagery is fixed. Applications for Genie Pro include: Crop and terrain type mapping, Road and river network mapping, Broad area search for vehicles and buildings, and Cancer identification in histological images.« less

  15. Rapamycin Enhances HBV Production by Inducing Cellular Autophagy

    PubMed Central

    Huang, Wenjuan; Zhao, Fengrong; Huang, Ying; Li, Xia; Zhu, Sufei; Hu, Qin; Chen, Weixian

    2014-01-01

    Background: Some reports revealed that rapamycin could reactivate HBV infection. However, the mechanism has not been clearly explained. Objectives: In this report, we studied the mechanism by which rapamycin enhances HBV replication and expression by inducing cellular autophagy. Materials and Methods: HepG2.2.15 cells were treated with rapamycin to induce autophagy. Autophagosomes were observed by fluorescence microscopy and transmission electron microscopy. Autophagy marker protein LC3-?/LC3-?was detected by Western blotting. HBV DNA and mRNA were determined by real time PCR and Southern blotting. HBsAg was evaluated by ELISA. Results: In HepG2.2.15 cells, HBV DNA and HBsAg increased when host cells were treated with rapamycin and the effect was reversed by autophagy inhibitor, 3-methyladenine (3-MA). Conclusions: These results indicated a potential explanation for reactivation of HBV infection when patients with hepatitis receive rapamycin. PMID:25419217

  16. Application of CRISPR/Cas9 Technology to HBV

    PubMed Central

    Lin, Guigao; Zhang, Kuo; Li, Jinming

    2015-01-01

    More than 240 million people around the world are chronically infected with hepatitis B virus (HBV). Nucleos(t)ide analogs and interferon are the only two families of drugs to treat HBV currently. However, none of these anti-virals directly target the stable nuclear covalently closed circular DNA (cccDNA), which acts as a transcription template for viral mRNA and pre-genomic RNA synthesis and secures virus persistence. Thus, the fact that only a small number of patients treated achieve sustained viral response (SVR) or cure, highlights the need for new therapies against HBV. The clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 gene editing system can specifically target the conserved regions of the HBV genome. This results in robust viral suppression and provides a promising tool for eradicating the virus. In this review, we discuss the function and application of the CRISPR/Cas9 system as a novel therapy for HBV. PMID:26540039

  17. Application of CRISPR/Cas9 Technology to HBV.

    PubMed

    Lin, Guigao; Zhang, Kuo; Li, Jinming

    2015-01-01

    More than 240 million people around the world are chronically infected with hepatitis B virus (HBV). Nucleos(t)ide analogs and interferon are the only two families of drugs to treat HBV currently. However, none of these anti-virals directly target the stable nuclear covalently closed circular DNA (cccDNA), which acts as a transcription template for viral mRNA and pre-genomic RNA synthesis and secures virus persistence. Thus, the fact that only a small number of patients treated achieve sustained viral response (SVR) or cure, highlights the need for new therapies against HBV. The clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 gene editing system can specifically target the conserved regions of the HBV genome. This results in robust viral suppression and provides a promising tool for eradicating the virus. In this review, we discuss the function and application of the CRISPR/Cas9 system as a novel therapy for HBV. PMID:26540039

  18. Epigallocatechin-3-gallate opposes HBV-induced incomplete autophagy by enhancing lysosomal acidification, which is unfavorable for HBV replication.

    PubMed

    Zhong, L; Hu, J; Shu, W; Gao, B; Xiong, S

    2015-01-01

    Epigallocatechin-3-gallate (EGCG), a major polyphenol in green tea, exhibits diverse beneficial properties, including antiviral activity. Autophagy is a cellular process that is involved in the degradation of long-lived proteins and damaged organelles. Recent evidence indicates that modulation of autophagy is a potential therapeutic strategy for various viral diseases. In the present study, we investigated the effect of EGCG on hepatitis B virus (HBV) replication and the possible involvement of autophagy in this process. Our results showed that HBV induced autophagosome formation, which was required for replication of itself. However, although EGCG efficiently inhibited HBV replication, it enhanced, but not inhibited, autophagosome formation in hepatoma cells. Further study showed that HBV induced an incomplete autophagy, while EGCG, similar to starvation, was able to induce a complete autophagic process, which appeared to be unfavorable for HBV replication. Furthermore, it was found that HBV induced an incomplete autophagy by impairing lysosomal acidification, while it lost this ability in the presence of EGCG. Taken together, these data demonstrated that EGCG treatment opposed HBV-induced incomplete autophagy via enhancing lysosomal acidification, which was unfavorable for HBV replication. PMID:25996297

  19. Therapeutic vaccines in HBV: lessons from HCV.

    PubMed

    Barnes, Eleanor

    2015-02-01

    Currently, millions of people infected with hepatitis B virus (HBV) are committed to decades of treatment with anti-viral therapy to control viral replication. However, new tools for immunotherapy that include both viral vectors and molecular checkpoint inhibitors are now available. This has led to a resurgence of interest in new strategies to develop immunotherapeutic strategies with the aim of inducing HBeAg seroconversion--an end-point that has been associated with a decrease in the rates of disease progression. Ultimately, a true cure will involve the elimination of covalently closed circular DNA which presents a greater challenge for immunotherapy. In this manuscript, I describe the development of immunotherapeutic strategies for HBV that are approaching or currently in clinical studies, and draw on observations of T cell function in natural infection supported by recent animal studies that may lead to additional rational vaccine strategies using checkpoint inhibitors. I also draw on our recent experience in developing potent vaccines for HCV prophylaxis based on simian adenoviral and MVA vectors used in prime-boost strategies in both healthy volunteers and HCV infected patients. I have shown that the induction of T cell immune responses is markedly attenuated when administered to people with persistent HCV viremia. These studies and recently published animal studies using the woodchuck model suggest that potent vaccines based on DNA or adenoviral vectored vaccination represent a rational way forward. However, combining these with drugs to suppress viral replication, alongside checkpoint inhibitors may be required to induce long-term immune control. PMID:25573348

  20. Targeted screening of SiRNA directed HBV polymerase gene for effective inhibition of HBV expression.

    PubMed

    Yao, Jinjian; Yu, Weiling; Chang, Ying; Ren, Jinghua; Xu, Dong; Han, Siyuan; Lin, Jusheng

    2008-06-01

    In order to screen potential mRNA locations of P gene in which targeting siRNAs can effectively inhibit HBV expression, 5 recombinant plasmids containing 4 targeting-specific siRNA fragments and a control were prepared and transfected into 2.2.15 cells respectively. The expression levels of HBx mRNA, HBs mRNA and HBc mRNA were detected by RT-PCR. The concentrations of the hepatitis B virus antigens, including HBsAg and HBeAg harvested from the culture supernatant of transfected 2.2.15 cells, were measured by ELISA. X protein was tested by Western blot. The results showed that four siRNAs against distinct mRNA locations of HBV polymerase gene had different inhibitory effects on their targeted mRNA. The plasmid-derived psiRNA1 and psiRNA2 could effectively inhibit the transcription and translation of HBs gene, whereas the inhibitory efficiency of psiRNA3, psiRNA4 for HBe gene was much higher than that of psiRNA1 and psiRNA2. In comparison to the rest of psiRNAs in this study, psiRNA4 was the most effective to suppress the transcription and translation of HBx. It is suggested that siRNA can be considered as a powerful therapeutic agent for reducing HBV expression. The siRNAs against HBV polymerase are effective largely depending on the location of targeted sites. To enhance inhibitory efficiency, hunting for high effective target in polymerase gene is necessary and feasible. PMID:18563320

  1. [Risk Management of HBV Reactivation: Construction of Check System].

    PubMed

    Tanaka, Yasuhito

    2015-09-01

    In recent years, reactivation of HBV in patients receiving cancer chemotherapy or immunosuppressive therapy has been a problem. Generally, HBV-DNA levels are elevated prior to HBsAg concentration, and then hepatic dysfunction is observed in the process of hepatitis by HBV reactivation. Therefore, the monitoring of HBV-DNA is useful for the prediction of hepatic dysfunction, and nucleoside/nucleoside analogue (NA) administration is able to prevent this HBV reactivation. According to these facts, "Guidelines for the Prevention of HBV Reactivation in Patients Receiving Immunosuppressive Therapy or Chemotherapy", 2009 (revised as "JSH Guidelines for the Management of Hepatitis B Virus Infection", 2013) is established, and the diagnostic algorithm of HBsAg, anti-HBc, anti-HBs, and HBV-DNA has relevant descriptions. Combination therapy with rituximab and steroid for malignant lymphoma has a high risk of leading to fulminant hepatitis and, consequently, the guidelines are widely followed in such cases. We introduced the improvement of electronic medical recording and ordering systems in collaboration with hepatologists, and such a system has been widely used. Although the monitoring of HBV-DNA levels is required every 1-3 months, the guidelines are not followed strictly in cases such as rheumatoid disease and solid tumors only with chemotherapy or steroid treatment. Since a DNA assay is complicated and expensive, cost-effective, time-saving, and highly sensitive/specific measurements are required as well. Therefore, Lumipulse HBsAg-HQ (CLIA method) with high sensitivity is expected to be used for the monitoring of HBV reactivation. PMID:26731893

  2. Clinical correlation between HBV infection and concomitant bacterial infections

    PubMed Central

    Li, Wei; Jin, Ronghua; Chen, Peng; Zhao, Guoxian; Li, Ning; Wu, Hao

    2015-01-01

    Bacterial infections are common in patients suffering viral hepatitis and critical for prognosis. However, any correlation between HBV and concomitant bacterial infections is not well characterized. A retrospective study was conducted from Jan 2012 to Jan 2014 on 1333 hospitalized patients infected with bacteria. Among them, 491 HBV-infected patients were co-infected with E. coli (268), S. aureus (61), P. aeruginosa (64) or K. pneumoniae (98). A group of 300 complication-free chronically HBV-infected patients were controls. We found that HBV DNA levels were elevated in patients with each of the bacterial infections (all P < 0.05). ALT and HBeAg were strong determinants of high HBV DNA concentration. Patterns of determinants varied in infections by Gram-positive and Gram-negative bacteria. Patients with HBV DNA ≥ 2000 IU/mL had higher rates of all four concomitant bacterial infections (all P < 0.001). All types of strains isolated from HBV-positive patients showed less resistance to tested antimicrobials. The HBV DNA serum concentrations were inversely correlated to the number of ineffective antimicrobials in E. coli, P. aeruginosa and K. pneumoniae infections (P = 0.022, 0.017 and 0.016, respectively), but not S. aureus (P = 0.194). In conclusion, bacterial infections are associated with a high level of HBV replication, which, in turn, has a significant positive impact on bacterial resistance to antimicrobials. These correlations vary between Gram-negative and Gram-positive bacteria. PMID:26634436

  3. HBV DNA vaccine with adjuvant cytokines induced specific immune responses against HBV infection

    PubMed Central

    Du, De-Wei; Jia, Zhan-Sheng; Li, Guang-Yu; Zhou, Yong-Ying

    2003-01-01

    AIM: To seek for an effective method to improve the immune responses induced by DNA vaccine expressing HBV surface antigen (pCR3.1-S) in Balb/c mice (H-2d). METHODS: The pCR3.1-S plasmid and the eukaryotic expression vectors expressing murine IL-2 (pDOR-IL-2) or IL-12 (pWRG3169) were injected into mice subcutaneously. The immune responses to pCR3.1-S and the adjuvant effect of the cytokines plasmid were studied. Meanwhile the effect of pCR3.1-S on anti-translated subcutaneous tumor of P815 mastocytoma cells stably expressing HBsAg (P815-HBV-S) was also studied. Anti-HBs in serum was detected by enzyme-linked immunoadsordent assay (ELISA) and HBsAg specific cytotoxic T lymphocytes (CTLs) activity was measured by 51Cr release assay. After three weeks of DNA immunization, the cells of P815-HBV-S were inoculated into mice subcutaneously and the tumor growth was measured every five days. The survival rate and living periods of mice were also calculated. RESULTS: After 8 wk DNA immunization, the A 450 nm values of sera in mice immunized with pCR3.1, pCR3.1-S and pCR3.1-S codeliveried with IL-2 or IL-12 plasmids were 0.03 0.01, 1.24 0.10, 1.98 0.17 and 1.67 0.12 respectively. Data in mice codeliveried pCR3.1-S with IL-2 or IL-12 plasmids were significantly higher than that of mice injected pCR3.1 or pCR3.1-S only. The HBsAg specific CTL activities in mice coinjected with pCR3.1-S and IL-2 or IL-12 eukaryotic expression vectors were (61.9 7.1)% and (73.3 8.8)%, which were significantly higher than that of mice injected with pCR3.1 (10.1 2.1)% or pCR3.1-S (50.5 6.4)%. The HBsAg specific CTL activities in mice injected with pCR3.1, pCR3.1-S, pCR3.1-S combined with IL-2 or IL-12 eukaryotic expression vectors decreased significantly to (3.2 0.8)%, (10.6 1.4)%, (13.6 1.3)% and (16.9 2.3)% respectively after the spleen cells were treated by anti-CD8+ monoclonal antibody, but presented no significant change to anti-CD4+ monoclonal antibody or unrelated to monoclonal antibody. The HBV-S DNA vaccine (pCR3.1-S) could evidently inhibit the tumor growth, prolong the survival period of mice and improve the survival rate of mice and these effects could be improved by IL-12 gene codeliveried. CONCLUSION: HBV DNA vaccine has a strong antigenicity in humoral and cellular immunities, which can be promoted by plasmid expressing IL-2 or IL-12. CD8+ cells executed the CTL activities. DNA vaccine may be useful for both prophylaxis and treatment of HBV infection. PMID:12508362

  4. Trained immunity in newborn infants of HBV-infected mothers

    PubMed Central

    Hong, Michelle; Sandalova, Elena; Low, Diana; Gehring, Adam J.; Fieni, Stefania; Amadei, Barbara; Urbani, Simonetta; Chong, Yap-Seng; Guccione, Ernesto; Bertoletti, Antonio

    2015-01-01

    The newborn immune system is characterized by an impaired Th1-associated immune response. Hepatitis B virus (HBV) transmitted from infected mothers to newborns is thought to exploit the newborns’ immune system immaturity by inducing a state of immune tolerance that facilitates HBV persistence. Contrary to this hypothesis, we demonstrate here that HBV exposure in utero triggers a state of trained immunity, characterized by innate immune cell maturation and Th1 development, which in turn enhances the ability of cord blood immune cells to respond to bacterial infection in vitro. These training effects are associated with an alteration of the cytokine environment characterized by low IL-10 and, in most cases, high IL-12p40 and IFN-α2. Our data uncover a potentially symbiotic relationship between HBV and its natural host, and highlight the plasticity of the fetal immune system following viral exposure in utero. PMID:25807344

  5. Trained immunity in newborn infants of HBV-infected mothers.

    PubMed

    Hong, Michelle; Sandalova, Elena; Low, Diana; Gehring, Adam J; Fieni, Stefania; Amadei, Barbara; Urbani, Simonetta; Chong, Yap-Seng; Guccione, Ernesto; Bertoletti, Antonio

    2015-01-01

    The newborn immune system is characterized by an impaired Th1-associated immune response. Hepatitis B virus (HBV) transmitted from infected mothers to newborns is thought to exploit the newborns' immune system immaturity by inducing a state of immune tolerance that facilitates HBV persistence. Contrary to this hypothesis, we demonstrate here that HBV exposure in utero triggers a state of trained immunity, characterized by innate immune cell maturation and Th1 development, which in turn enhances the ability of cord blood immune cells to respond to bacterial infection in vitro. These training effects are associated with an alteration of the cytokine environment characterized by low IL-10 and, in most cases, high IL-12p40 and IFN-?2. Our data uncover a potentially symbiotic relationship between HBV and its natural host, and highlight the plasticity of the fetal immune system following viral exposure in utero. PMID:25807344

  6. Preclinical evaluation of two human anti-hepatitis B virus (HBV) monoclonal antibodies in the HBV-trimera mouse model and in HBV chronic carrier chimpanzees.

    PubMed

    Eren, R; Ilan, E; Nussbaum, O; Lubin, I; Terkieltaub, D; Arazi, Y; Ben-Moshe, O; Kitchinzky, A; Berr, S; Gopher, J; Zauberman, A; Galun, E; Shouval, D; Daudi, N; Eid, A; Jurim, O; Magnius, L O; Hammas, B; Reisner, Y; Dagan, S

    2000-09-01

    Two human monoclonal antibodies (mAbs) against hepatitis B surface antigen (HBsAg) generated in the Trimera mouse system are described. Both mAbs 17.1.41 and 19.79.5 are of the IgG1 isotype and have high affinity constants for HBsAg binding in the range of 10(-10) mol/L. Monoclonal antibody 17.1.41 recognizes a conformational epitope on the a determinant of HBsAg whereas mAb 19.79.5 recognizes a linear one. The 2 mAbs bind to a panel of hepatitis B virus (HBV) subtypes with distinct patterns. The neutralizing activity of these antibodies was tested in 2 different animal model systems. Administration of each mAb to HBV-Trimera mice, a system that provides a mouse model for human hepatitis B infection, reduced the viral load and the percentage of HBV-DNA-positive mice in a dose-dependent manner. These 2 mAbs were more effective than a polyclonal antibody preparation (Hepatect; Biotest Pharma, Dreieich, Germany) in both inhibition of HBV liver infection and reduction of viral load. A single administration of a mixture of these mAbs into HBV chronic carrier chimpanzees resulted in immediate reduction in HBsAg levels followed by recurrence to initial levels within few days. Thus, these mAbs may be potential candidates for preventive therapy or in combination with other antiviral agents against HBV. Further studies in humans are needed to assess these mAbs in various clinical indications. PMID:10960454

  7. The prognosis and management of inactive HBV carriers.

    PubMed

    Invernizzi, Federica; Vigan, Mauro; Grossi, Glenda; Lampertico, Pietro

    2016-01-01

    Patients with chronic hepatitis B virus (HBV) infection lacking the serum hepatitis B e antigen (HBeAg) and with antibodies against HBeAg (anti-HBe), are the prevalent subgroup of HBV carriers worldwide. The prognosis of these patients is different from inactive carriers (ICs), who are characterized by persistently normal serum alanine aminotransferase (ALT) and low (<2000IU/ml) serum HBV DNA levels, a serological profile that may also be intermittently observed in patients with HBeAg-negative chronic hepatitis. This is why a confirmed diagnosis of IC requires quarterly ALT and HBV DNA measurements for at least 1year, while a single-point detection of combined HBsAg <1000IU/ml and HBV DNA <2000IU/ml has a robust predictive value for the diagnosis of IC. Characteristically, ICs have minimal or no histological lesions of the liver corresponding to liver stiffness values on Fibroscan of <5kPa. Antiviral treatment is not indicated in ICs since the prognosis for the progression of liver disease is favourable if there are no cofactors of liver damage such as alcohol abuse, excess weight or co-infection with the hepatitis C virus or delta virus. Moreover, spontaneous HBsAg loss frequently occurs (1-1.9% per year) in these patients while the development of hepatocellular carcinoma (HCC) is rare, at least in Caucasian patients. However, an emerging issue reinforcing the need for clinical surveillance of ICs is the risk of HBV reactivation in patients who undergo immunosuppressive therapy without receiving appropriate antiviral prophylaxis. After diagnosis, management of ICs includes monitoring of ALT and HBV DNA every 12months with periodic measurement of serum HBsAg levels to identify viral clearance. PMID:26725905

  8. Reliable timescale inference of HBV genotype A origin and phylodynamics.

    PubMed

    Zehender, Gianguglielmo; Svicher, Valentina; Gabanelli, Elena; Ebranati, Erika; Veo, Carla; Lo Presti, Alessandra; Cella, Eleonora; Giovanetti, Marta; Bussini, Linda; Salpini, Romina; Alteri, Claudia; Lai, Alessia; Tanzi, Elisabetta; Perno, Carlo Federico; Galli, Massimo; Ciccozzi, Massimo

    2015-06-01

    The worldwide distributed Hepatitis B virus (HBV) genotype A is classified into three subgenotypes, and one quasi-subgenotype. The majority of HBV-A subgenotypes are widespread in Africa and in ethnic groups that have relatively recently emigrated from African countries, whereas HBV-A2 is highly prevalent among subjects at high risk for sexual exposure to HBV in north-western Europe and the USA. The aim of this study was to reconstruct the origin and dispersion of HBV-A subgenotypes on a reliable timescale using short-term calibration based on heterochronous sampling for HBV-A2, and long-term calibration based on historical data for the other subgenotypes. To this aim, we analysed 113 newly characterised HBV-A isolates with 247 reference sequences retrieved from a public database. The phylodynamic reconstruction was performed by a Bayesian framework. The common ancestor of the currently circulating A subgenotypes was placed in west-central Africa a mean 1057 years ago. The genotype diverged into two main clades at the beginning of the 13th century: one including all of the west-central African quasi-subgenotypes and the other corresponding to subgenotype A1, originating in east Africa and further segregating into two main subclades: an "African" and a "cosmopolitan" clade. It is likely that the slave trade was the main source the spread of cosmopolitan HBV-A1, which was exported to Asia in the 17th century as a result of Arab or Portuguese trade, and to Latin America in the 18th centuries through the trans-Atlantic slave trade. The origin of the currently circulating A2 strains dates back to the first decades of the 20th century, and the evolutionary demography analysis suggests an exponential growth of infections, between 1970s and the mid-1990s. In conclusion, the very different epidemiological and evolutionary histories of HBV-A subgenotypes justify the use of different calibration approaches to reconstruct their reciprocal phylodynamics. PMID:25784568

  9. General and Abdominal Adiposity and Risk of Death in HBV Versus Non-HBV Carriers: A 10-Year Population-based Cohort Study.

    PubMed

    Lin, Wen-Yuan; Peng, Cheng-Yuan; Lin, Cheng-Chieh; Davidson, Lance E; Pi-Sunyer, F Xavier; Sung, Pei-Kun; Huang, Kuo-Chin

    2016-01-01

    Both obesity and hepatitis B virus (HBV) infection increase the risk of death. We investigate the association between general and central obesity and all-cause mortality among adult Taiwanese HBV versus non-HBV carriers.A total of 19,850 HBV carriers and non-hepatitis C virus (HCV) carriers, aged 20 years and older at enrollment in 1998 to 1999 in Taiwan, were matched to 79,400 non-HBV and non-HCV carriers (1:4). Cox proportional-hazards models were used to estimate the relative risks for all-cause mortality during a maximum follow-up period of 10 years. Four obesity-related anthropometric indices-body mass index (BMI), waist circumference, waist-to-hip ratio, and waist-to-height ratio-were the main variables of interest.During the follow-up period, 628 and 2366 participants died among HBV and non-HBV carriers, respectively. Both underweight and general obesity were associated with an increased risk of death. The highest risk of all-cause death in relation to BMI was found in the HBV carriers with underweight (BMI <18.5?kg/m) and non-HBV carriers with obesity (BMI ?30?kg/m). The lowest risks of all-cause death in relation to abdominal adiposity were found at the third quartiles of waist circumference, waist-to-hip ratio, and waist-to-height ratio among HBV carriers, but in the second quartiles among non-HBV carriers. For those with pre-existing liver disease among HBV carriers, patients with underweight have higher risk of death than those with obesity.Hepatitis B virus carriers with underweight have higher risk of death than non-HBV carriers. HBV carriers with mild abdominal obesity have the lowest risk of death, but not in the non-HBV carriers. PMID:26765398

  10. Suppression of HBV by Tenofovir in HBV/HIV Coinfected Patients: A Systematic Review and Meta-Analysis

    PubMed Central

    Price, Huw; Dunn, David; Pillay, Deenan; Bani-Sadr, Firouze; de Vries-Sluijs, Theodora; Jain, Mamta K.; Kuzushita, Noriyoshi; Mauss, Stefan; Nez, Marina; Nesch, Reto; Peters, Marion; Reiberger, Thomas; Stephan, Christoph; Tan, Lionel; Gilson, Richard

    2013-01-01

    Background Hepatitis B coinfection is common in HIV-positive individuals and as antiretroviral therapy has made death due to AIDS less common, hepatitis has become increasingly important. Several drugs are available to treat hepatitis B. The most potent and the one with the lowest risk of resistance appears to be tenofovir (TDF). However there are several questions that remain unanswered regarding the use of TDF, including the proportion of patients that achieves suppression of HBV viral load and over what time, whether suppression is durable and whether prior treatment with other HBV-active drugs such as lamivudine, compromises the efficacy of TDF due to possible selection of resistant HBV strains. Methods A systematic review and meta-analysis following PRISMA guidelines and using multilevel mixed effects logistic regression, stratified by prior and/or concomitant use of lamivudine and/or emtricitabine. Results Data was available from 23 studies including 550 HBV/HIV coinfected patients treated with TDF. Follow up was for up to seven years but to ensure sufficient power the data analyses were limited to three years. The overall proportion achieving suppression of HBV replication was 57.4%, 79.0% and 85.6% at one, two and three years, respectively. No effect of prior or concomitant 3TC/FTC was shown. Virological rebound on TDF treatment was rare. Interpretation TDF suppresses HBV to undetectable levels in the majority of HBV/HIV coinfected patients with the proportion fully suppressed continuing to increase during continuous treatment. Prior treatment with 3TC/FTC does not compromise efficacy of TDF treatment. The use of combination treatment with 3TC/FTC offers no significant benefit over TDF alone. PMID:23874527

  11. Infected hematopoietic stem cells and with integrated HBV DNA generate defective T cells in chronic HBV infection patients

    PubMed Central

    Shi, Y; Lan, Y; Cao, F; Teng, Y; Li, L; Wang, F; Li, J; Zhou, J; Li, Y

    2014-01-01

    A weak T-cell response plays a key role in the persistence of hepatitis B virus (HBV) infection. We aimed to confirm that T-cell defects in patients with chronic HBV infection are associated with HBV DNA infection of bone marrow (BM) hematopoietic stem cells (HSCs). Using reverse transcription polymerase chain reaction (RT-PCR) and fluorescence in situ hybridization (FISH), we observed the transcription of HBsAg coding genes and confirmed the integration of HBV DNA in CD34+ BM HSCs from chronic HBV infection patients. T cells were generated by coculturing the HSCs with delta-like ligand 1-expressing OP9 (OP9-DL1) cells. The phenotypes of the T cells were then evaluated by flow cytometric (FACS) analysis on days 14 and 25. The results demonstrated that fewer CD3+TCRaβ+ CD3+CD4+ and CD4+CD8+ T cells were generated from the HSCs of the patients than from the healthy controls, (P < 0.01) but the frequency of CD3+D8+ T cells was not significantly different between the two group (P > 0.05). In contrast, CD4+CD25+ T cells were more in the patient group than in healthy controls (P < 0.01) on both days 14 and 25. There were fewer CD3+CD4+/CD3+CD8+ cells in the patient group than in the healthy control group on day 25 (P < 0.05). Less proliferation and lower levels of IL-2 and IFN- γ were also observed in the patient group compared with the control group (P < 0.05).These data suggest that HBV DNA infected and integrated into the BM HSCs from patients with chronic HBV infection and that these BM HSCs generated defective T cells. PMID:24620791

  12. DTPa-HBV-IPV/Hib vaccine (Infanrix hexa).

    PubMed

    Curran, Monique P; Goa, Karen L

    2003-01-01

    Primary vaccination of infants with diphtheria-tetanus-acellular pertussis-hepatitis B recombinant (adsorbed)-inactivated poliomyelitis-adsorbed conjugated Haemophilus influenzae type b vaccine (DTPa-HBV-IPV/Hib; Infanrix hexa)-inactivated poliomyelitis-absorbed conjugated Haemophilus influenzae type b vaccine (DTPa-HBV-IPV/Hib) refers to Infanrix hexa trade mark.) provided high levels of seroprotection against diphtheria toxoid, tetanus toxoid, poliovirus 1, 2 and 3, pertussis antigens (pertussis toxoid, filamentous haemagglutinin and pertactin), hepatitis B virus surface antigen and H. influenzae polyribosyl-ribitol-phosphate (PRP) antigen. Most infants (97%) had anti-PRP levels >/=0.15 micro g/mL after a booster dose at 18 months. Primary vaccination with the DTPa-HBV-IPV/Hib vaccine produced a similar immune response to that with two different pentavalent plus monovalent vaccine combinations. Coadministration of DTPa-HBV-IPV/Hib vaccine and a heptavalent pneumonococcal conjugate vaccine resulted in a high level of seroprotection and was well tolerated. Primary or booster vaccination with DTPa- HBV-IPV/Hib vaccine was well tolerated. Commonly reported local adverse reactions included redness, pain and swelling. Systemic symptoms were usually mild to moderate, and included fussiness, fever, restlessness and sleepiness. PMID:12656646

  13. Virologic and Clinical Outcomes of Hepatitis B Virus Infection in HIV-HBV Coinfected Transplant Recipients

    PubMed Central

    Coffin, C.S.; Stock, P.G.; Dove, L.M.; Berg, C.L.; Nissen, N.N.; Curry, M.P.; Ragni, M.; Regenstein, F.G.; Sherman, K.E.; Roland, M.E.; Terrault, N.A.

    2010-01-01

    Liver transplantation (LT) is the treatment of choice for endstage liver disease, but is controversial in patients with human immunodeficiency virus (HIV) infection. Using a prospective cohort of HIV-HBV coinfected patients transplanted between 20012007; outcomes including survival and HBV clinical recurrence were determined. Twenty-two coinfected patients underwent LT; 45% had detectable HBV DNA pre-LT and 72% were receiving anti-HBV drugs with efficacy against lamivudine-resistant HBV. Post-LT, all patients received hepatitis B immune globulin (HBIG) plus nucleos(t)ide analogues and remained HBsAg negative without clinical evidence of HBV recurrence, with a median follow-up 3.5 years. Low-level HBV viremia (median 108 IU/ml, range 9789) was intermittently detected in 7/13 but not associated with HBsAg detection or ALT elevation. Compared with 20 HBV monoinfected patients on similar HBV prophylaxis and median follow-up of 4.0 years, patient and graft survival were similar: 100% vs. 85% in HBV mono- vs coinfected patients (p=0.08, log rank test). LT is effective for HIV-HBV coinfected patients with complications of cirrhosis, including those who are HBV DNA positive at the time of LT. Combination HBIG and antivirals is effective as prophylaxis with no clinical evidence of HBV recurrence but low level HBV DNA is detectable in ~50% of recipients. PMID:20346065

  14. Association of preS/S Mutations with Occult Hepatitis B Virus (HBV) Infection in South Korea: Transmission Potential of Distinct Occult HBV Variants

    PubMed Central

    Kim, Hong; Kim, Bum-Joon

    2015-01-01

    Occult hepatitis B virus infection (HBV) is characterized by HBV DNA positivity but HBV surface antigen (HBsAg) negativity. Occult HBV infection is associated with a risk of HBV transmission through blood transfusion, hemodialysis, and liver transplantation. Furthermore, occult HBV infection contributes to the development of cirrhosis and hepatocellular carcinoma. We recently reported the characteristic molecular features of mutations in the preS/S regions among Korean individuals with occult infections caused by HBV genotype C2; the variants of preS and S related to severe liver diseases among chronically infected patients were also responsible for the majority of HBV occult infections. We also reported that HBsAg variants from occult-infected Korean individuals exhibit lower HBsAg secretion capacity but not reduced HBV DNA levels. In addition, these variants exhibit increased ROS-inducing capacity compared with the wild-type strain, linking HBV occult infections to liver cell damage. Taken together, our previous reports suggest the transmission potential of distinct HBV occult infection-related variants in South Korea. PMID:26084041

  15. Towards an HBV cure: state-of-the-art and unresolved questions--report of the ANRS workshop on HBV cure.

    PubMed

    Zeisel, Mirjam B; Lucifora, Julie; Mason, William S; Sureau, Camille; Beck, Jrgen; Levrero, Massimo; Kann, Michael; Knolle, Percy A; Benkirane, Monsef; Durantel, David; Michel, Marie-Louise; Autran, Brigitte; Cosset, Franois-Loc; Strick-Marchand, Hlne; Trpo, Christian; Kao, Jia-Horng; Carrat, Fabrice; Lacombe, Karine; Schinazi, Raymond F; Barr-Sinoussi, Franoise; Delfraissy, Jean-Franois; Zoulim, Fabien

    2015-08-01

    HBV infection is a major cause of liver cirrhosis and hepatocellular carcinoma. Although HBV infection can be efficiently prevented by vaccination, and treatments are available, to date there is no reliable cure for the >240 million individuals that are chronically infected worldwide. Current treatments can only achieve viral suppression, and lifelong therapy is needed in the majority of infected persons. In the framework of the French National Agency for Research on AIDS and Viral Hepatitis 'HBV Cure' programme, a scientific workshop was held in Paris in June 2014 to define the state-of-the-art and unanswered questions regarding HBV pathobiology, and to develop a concerted strategy towards an HBV cure. This review summarises our current understanding of HBV host-interactions leading to viral persistence, as well as the roadblocks to be overcome to ultimately address unmet medical needs in the treatment of chronic HBV infection. PMID:25670809

  16. Virologic and Serologic Outcomes of Mono vs. Dual HBV Therapy and Characterization of HIV/HBV Coinfection in a US Cohort

    PubMed Central

    Kang, Minhee; Hollabaugh, Kimberly; Pham, Vinh; Koletar, Susan L.; Wu, Kunling; Smurzynski, Marlene; Aberg, Judith A.

    2014-01-01

    Objectives To characterize HIV/HBV coinfection in the ACTG Longitudinal Linked Randomized Trials (ALLRT) cohort and compare long-term HBV outcomes between regimens with one (MONO) or two (DUAL) anti-HBV agents. Design A retrospective study of coinfected ALLRT subjects who received regimens containing anti-HBV agent(s). Methods Stored samples at baseline and weeks 16, 32, 48, 144, and 240 were tested for HBV DNA, HBeAg, HBeAb, and HDV antibody. Resistance and genotype were tested in samples with HBV DNA >600 IU/ml. MONO vs. DUAL analyses were limited to HBV treatment-nave subjects (Nave-MONO, Nave-DUAL). Results Of 150 study subjects, median age was 40 years, 96% were male; 57% White, 26% Black, 13% Hispanic. Baseline median CD4 was 224 cells/mm3, HIV RNA 4.48 log10 copies/ml, HBV DNA 6.30 log10 IU/ml; 59% HBeAg positive and 65% HBeAb negative; HBV genotypes A=69%, G=18%, D=7%, <2% for A/G, B, C, F, H. Coinfection with HDV was 2%. There were 49 Nave-MONO (lamivudine) and 22 Nave-DUAL (11 lamivudine+tenofovir, 11 emtricitabine+tenofovir) with detectable HBV DNA. In the 240-week follow-up, HBV DNA suppression was not significantly higher in Nave-DUAL (p=0.14); lower baseline HBV DNA (p<0.01) was associated with suppression. Among 32 Nave-MONO subjects with detectable HBV DNA at baseline and results at week 48, 41% suppressed; among such 15 Nave-DUAL subjects, 53% suppressed. HBeAg and HBeAb analyses showed similar trends. Conclusions While consistent trends toward increased HBV DNA suppression, HBeAg loss and HBeAb seroconversion were observed in Nave-DUAL compared to Nave-MONO, they were not statistically significant. Overall, HDV coinfection was low. PMID:24694927

  17. Peripheral T-lymphocyte subpopulations in different clinical stages of chronic HBV infection correlate with HBV load

    PubMed Central

    You, Jing; Zhuang, Lin; Zhang, Yi-Feng; Chen, Hong-Ying; Sriplung, Hutcha; Geater, Alan; Chongsuvivatwong, Virasakdi; Piratvisuth, Teerha; McNeil, Edward; Yu, Lan; Tang, Bao-Zhang; Huang, Jun-Hua

    2009-01-01

    AIM: To characterize the peripheral T-cell subpopulation profiles and their correlation with hepatitis B virus (HBV) replication in different clinical stages of chronic HBV infection. METHODS: A total of 422 patients with chronic HBV infection were enrolled in this study. The patients were divided into three stages: immune-tolerant stage, immune active stage, and immune-inactive carrier stage. Composition of peripheral T-cell subpopulations was determined by flow cytometry. HBV markers were detected by enzyme-linked immunosorbent assay. Serum HBV DNA load was assessed by quantitative real-time polymerase chain reaction. RESULTS: CD8+ T-cells were significantly higher in patients at the immune-tolerant stage than in patients at the immune-active and -inactive carrier stages (36.87 7.58 vs 34.37 9.07, 36.87 7.58 vs 28.09 5.64, P < 0.001). The peripheral blood in patients at the immune-tolerant and immune active stages contained more CD8+ T-cells than CD4+ T-cells (36.87 7.58 vs 30.23 6.35, 34.37 9.07 vs 30.92 7.40, P < 0.01), whereas the peripheral blood in patients at the immune-inactive carrier stage and in normal controls contained less CD8+ T-cells than CD4+ T-cells (28.09 5.64 vs 36.85 6.06, 24.02 4.35 vs 38.94 3.39, P < 0.01). ANOVA linear trend test showed that CD8+ T-cells were significantly increased in patients with a high viral load (39.41 7.36, 33.83 7.50, 31.81 5.95 and 26.89 5.71, P < 0.001), while CD4+ T-cells were significantly increased in patients with a low HBV DNA load (37.45 6.14, 33.33 5.61, 31.58 6.99 and 27.56 5.49, P < 0.001). Multiple regression analysis displayed that log copies of HBV DNA still maintained its highly significant coefficients for T-cell subpopulations, and was the strongest predictors for variations in CD3+, CD4+ and CD8+ cells and CD4+/CD8+ ratio after adjustment for age at HBV-infection, maternal HBV-infection status, presence of hepatitis B e antigen and HBV mutation. CONCLUSION: Differences in peripheral T-cell subpopulation profiles can be found in different clinical stages of chronic HBV infection. T-cell impairment is significantly associated with HBV load. PMID:19610139

  18. IL-6 Plays a Crucial Role in HBV Infection

    PubMed Central

    Lan, Tian; Chang, Lei; Wu, Long; Yuan, Yu-Feng

    2015-01-01

    Interleukin-6 (IL-6), a cytokine mainly produced by activated monocytes, has broad pleiotropic actions that affect the functions of a variety of lymphoid cells. The roles of IL-6 in regulating immunity to infections are currently being defined. Remarkably, IL-6-mediated cellular and humoral immune responses play a crucial role in determining the outcome of viral infection. This article reviews the current knowledge on the critical role of IL-6 in hepatitis B virus (HBV) infection. As a competent intermediary, IL-6 derived from activated monocytes plays an important role in promoting lymphocytes responses that are essential for effective viral control. However, as a mediator of inflammation, IL-6 is also involved in the development of HBV-induced liver cirrhosis and exacerbating liver injury. Overall, the current data point to IL-6 as an immunoregulatory cytokine in HBV infection. Immunotherapeutic strategies aimed at optimizing the beneficial effects of IL-6 in HBV infection may prove to be an ordeal in the future, as they should foster the strengths of IL-6 while circumventing potential drawbacks. PMID:26807383

  19. Role of interleukin-21 in HBV infection: friend or foe?

    PubMed Central

    Li, Yongyin; Tang, Libo; Hou, Jinlin

    2015-01-01

    Interleukin (IL)-21, a cytokine produced by activated CD4+ T cells, has broad pleiotropic actions that affect the functions of a variety of lymphoid cells. The roles of IL-21 in modulating immunity to infections are currently being defined. Notably, IL-21-mediated cellular and humoral immune responses play an important role in determining the outcome of viral infection. This article reviews the current knowledge on the critical role of IL-21 in hepatitis B virus (HBV) infection. As a competent intermediary, IL-21 derived from virus-specific CD4+ T cells plays key roles in sustaining CD8+ T cells and promoting B-cell responses that are essential for effective viral control. However, as a mediator of inflammation, IL-21 is also involved in the development of HBV-induced liver cirrhosis and exacerbating liver injury. Overall, the current data point to IL-21 as an immunomodulatory cytokine in HBV infection. Immunotherapeutic strategies aimed at optimizing the beneficial effects of IL-21 in HBV infection may prove to be a rigorous challenge in the future, as they should foster the strengths of IL-21 while circumventing potential drawbacks. PMID:25363528

  20. Cancer Risk in HBV Patients With Statin and Metformin Use

    PubMed Central

    Chen, Chang-I.; Kuan, Ching-Feng; Fang, Yu-Ann; Liu, Shing-Hwa; Liu, Ju-Chi; Wu, Li-Li; Chang, Chun-Jen; Yang, Hsuan-Chia; Hwang, Jaulang; Miser, James S.; Wu, Szu-Yuan

    2015-01-01

    Abstract Chronic infection with hepatitis B virus (HBV) often causes chronic inflammation of the liver with an increased incidence of hepatocellular carcinoma (HCC). HBV-infected individuals may also have an increased incidence of nonliver cancers. Taking statin or metformin may decrease inflammation and infiltration, which may, as a result, reduce the risk of liver cancer or other major cancers in patients with HBV infection. The purpose of this study was to evaluate the hypothesis that statin and metformin could reduce the incidence of liver cancer (HCC) or nonliver cancers in patients with HBV. Using the Taiwan Longitudinal Health Insurance Database 2000 to 2008, this cohort study comprised patients with a recorded diagnosis of HBV (N?=?71,847) between January 1, 2000 and December 31, 2008. Each patient was followed-up until the end of 2008. The occurrence of HCC or a nonliver cancer was evaluated in patients who either were or were not taking statin or metformin. Cox proportional hazard regressions were used to evaluate the cancer incidence after adjusting for known confounding factors. In total, 71,824 HBV-infected patients comprised the study cohort. Our study showed that either metformin or statin use was associated with a reduction in the incidence of cancer. This was most prominent in patients taking both statin and metformin. The adjusted hazard ratios (HRs) for patients using only statin were 0.52 (95% confidence interval [CI], 0.480.57) for all cancers, 0.28 (95% CI, 0.230.35) for liver cancer, and 0.63 (95% CI, 0.570.70) for nonliver cancers. Patients taking only metformin had risk-adjusted HRs of 0.82 (95% CI, 0.750.90) for all cancers, 0.97 (95% CI, 0.841.14) for liver cancer, and 0.75 (95% CI, 0.670.84) for nonliver cancers. A dose-dependent effect of statin use for chemoprevention was observed for all cancers, including both liver cancer and nonliver cancers. A dose-dependent effect of metformin was also seen in liver cancer and nonliver cancers without stratification into different cumulative daily doses of statin use. This population-based cohort study investigated the protective effect of statin and metformin against cancer events in patients with HBV infection. Our study demonstrated that either statin or metformin served as independent chemopreventive agents with a doseresponse effect in reducing the incidence of cancer with a doseresponse effect of the agents and an additive or synergistic effect of combining statin and metformin use in reducing the incidence of many cancers. PMID:25674734

  1. Construction and Immunological Evaluation of Multivalent Hepatitis B Virus (HBV) Core Virus-Like Particles Carrying HBV and HCV Epitopes▿

    PubMed Central

    Sominskaya, Irina; Skrastina, Dace; Dislers, Andris; Vasiljev, Denis; Mihailova, Marija; Ose, Velta; Dreilina, Dzidra; Pumpens, Paul

    2010-01-01

    A multivalent vaccine candidate against hepatitis B virus (HBV) and hepatitis C virus (HCV) infections was constructed on the basis of HBV core (HBc) virus-like particles (VLPs) as carriers. Chimeric VLPs that carried a virus-neutralizing HBV pre-S1 epitope corresponding to amino acids (aa) 20 to 47 in the major immunodominant region (MIR) and a highly conserved N-terminal HCV core epitope corresponding to aa 1 to 60 at the C terminus of the truncated HBcΔ protein (N-terminal aa 1 to 144 of full-length HBc) were produced in Escherichia coli cells and examined for their antigenicity and immunogenicity. The presence of two different foreign epitopes within the HBc molecule did not interfere with its VLP-forming ability, with the HBV pre-S1 epitope exposed on the surface and the HCV core epitope buried within the VLPs. After immunization of BALB/c mice, specific T-cell activation by both foreign epitopes and a high-titer antibody response against the pre-S1 epitope were found, whereas an antibody response against the HBc carrier was notably suppressed. Both inserted epitopes also induced a specific cytotoxic-T-lymphocyte (CTL) response, as shown by the gamma interferon (IFN-γ) production profile. PMID:20410327

  2. Association of Periodontal Diseases and Liver Fibrosis in Patients With HCV and/or HBV infection

    PubMed Central

    Nagao, Yumiko; Kawahigashi, Yuji; Sata, Michio

    2014-01-01

    Background: Periodontal disease and systemic health are closely associated. However, there is no data supporting the association between periodontal disease and patients with liver diseases associated with hepatitis C virus (HCV) and/or hepatitis B virus (HBV) infection. Objectives: The aim of this study was to evaluate the association between periodontitis and progression of liver diseases in patients with HCV and/or HBV infection. Patients and Methods: In this retrospective study, 351 patients with HCV- and/or HBV-related liver diseases underwent screening for periodontal disease using the Salivaster® salivary occult blood test from February 2010 to June 2014. Furthermore, we examined the prevalence of fimbrillin (fimA) genotype of Porphyromonas gingivalis (P. gingivalis) in 28 HCV-infected patients visited at our hospital between January 2013 and June 2014. P. gingivalis with fimA genotype with types I to V was further detected using a PCR method. Results: Of 351 patients, 76 patients (group 1) had a strong positive result for salivary occult blood test and 275 patients (group 2) had weak positive or negative test results. Significant factors between the groups were obesity, level of AST, ALT, LDH, ALP, Alb, D.Bil, T.cho, AFP, platelets (Plt), IRI, HOMA-IR, current interferon (IFN) treatment and the daily frequency of tooth brushing. Between-groups analysis indicated that total protein (T.pro) level and liver fibrosis were significant factors. According to multivariate analysis, five factors were associated with periodontal disease as Plt count below 80000, brushing teeth only once a day, current IFN treatment, aged 65 years or older and obesity. The adjusted odds ratios for these five factors were 5.80, 3.46, 2.87, 2.50 and 2.33, respectively, and each was statistically significant. Twenty-eight saliva specimens had positive results for P. gingivalis with fimA genotype types I to V. The prevalence of fimA genotype II was higher in 14 patients with liver cirrhosis or a history of hepatocellular carcinoma treatment (group B, 50.00%) than 14 patients with only hepatitis C (group A, 21.43%). Conclusions: Periodontitis might be associated with progression of viral liver disease; hence, controlling oral disease is essential for the prevention and management of liver fibrosis. PMID:25737729

  3. HBV Outreach Programs Significantly Increase Knowledge and Vaccination Rates Among Asian Pacific Islanders.

    PubMed

    Zacharias, Tresa; Wang, Winnie; Dao, Doan; Wojciechowski, Helena; Lee, William M; Do, Son; Singal, Amit G

    2015-08-01

    Hepatitis B virus (HBV) testing and vaccination rates remain low among Asian-American/Pacific Islanders (APIs) despite high rates of HBV infection. The aim of our study was to assess the effectiveness of an outreach campaign to increase HBV knowledge, testing, and vaccination among a cohort of APIs. Vietnamese Americans were invited to participate in a free HBV screening and vaccination outreach program though pubic service announcements. Attendees completed a survey to assess barriers to vaccination and HBV-related knowledge before and after a 30-min education session by a bilingual board-certified gastroenterologist. Among 98 participants, 100% (22/22) of HBV nave patients were provided a HBV vaccination series at no cost and over 75% (14/18) of HBV-infected patients were connected to further medical care. Notable reported barriers to prior testing and/or vaccination were cost of the vaccine, concern about missing work for evaluation, and lack of provider recommendation. Knowledge levels about HBV risk factors, potential consequences, and treatment options were poor at baseline but significantly increased after the education session (49 vs. 64%, p < 0.001). Outreach campaigns linked with education can successfully address several barriers to HBV testing and offer an approach to improve HBV awareness and prevention among difficult-to-reach populations. PMID:25476035

  4. The CRISPR/Cas9 System Facilitates Clearance of the Intrahepatic HBV Templates In Vivo

    PubMed Central

    Lin, Su-Ru; Yang, Hung-Chih; Kuo, Yi-Ting; Liu, Chun-Jen; Yang, Ta-Yu; Sung, Ku-Chun; Lin, You-Yu; Wang, Hurng-Yi; Wang, Chih-Chiang; Shen, Yueh-Chi; Wu, Fang-Yi; Kao, Jia-Horng; Chen, Ding-Shinn; Chen, Pei-Jer

    2014-01-01

    Persistence of hepatitis B virus (HBV) covalently closed circular DNA (cccDNA) under current antiviral therapy is a major barrier to eradication of chronic hepatitis B (CHB). Curing CHB will require novel strategies for specific disruption of cccDNA. The clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 system is a newly developed tool for site-specific cleavage of DNA targets directed by a synthetic guide RNA (gRNA) base-paired to the target DNA sequence. To examine whether this system can cleave HBV genomes, we designed eight gRNAs against HBV of genotype A. With the HBV-specific gRNAs, the CRISPR/Cas9 system significantly reduced the production of HBV core and surface proteins in Huh-7 cells transfected with an HBV-expression vector. Among eight screened gRNAs, two effective ones were identified. Interestingly, one gRNA targeting the conserved HBV sequence acted against different genotypes. Using a hydrodynamics-HBV persistence mouse model, we further demonstrated that this system could cleave the intrahepatic HBV genome-containing plasmid and facilitate its clearance in vivo, resulting in reduction of serum surface antigen levels. These data suggest that the CRISPR/Cas9 system could disrupt the HBV-expressing templates both in vitro and in vivo, indicating its potential in eradicating persistent HBV infection. PMID:25137139

  5. Feedback regulation of IFN-?/? signaling by Axl receptor tyrosine kinase modulates HBV immunity.

    PubMed

    Huang, Miao-Tzu; Liu, Wei-Liang; Lu, Chun-Wei; Huang, Jian-Jhih; Chuang, Hsiao-Li; Huang, Yen-Te; Horng, Jau-Haw; Liu, Peng; Han, Dai-Shu; Chiang, Bor-Luen; Shih, Chiaho; Chen, Pei-Jer; Chen, Ding-Shinn

    2015-06-01

    Hepatitis B virus (HBV) is known to cause age-dependent infection outcomes wherein most infections during young age result in chronicity. The mechanism underlying the differential outcome remains elusive. By using hydrodynamic injection of the replication-competent pAAV-HBV, we established a mouse model in which HBV persistence was generated in 4-5 w/o C57BL/6 young mice, but not in adult mice over 10 w/o. HBV-tolerant young mice expressed higher interferon (IFN)-?/? levels in hepatocytes and intrahepatic plasmacytoid DCs (pDCs) than adult mice after pAAV-HBV injection. Excessive IFN-?/? expression in young mice was associated with induction of the Axl regulatory pathway and expansion of intrahepatic Treg cells. In line with these findings, augmented IFN-? expression increased Axl expression in the liver and HBV persistence in adult mice, whereas IFN-?/? signaling blockage decreased Axl expression and HBV persistence in young mice. Accordingly, Axl overexpression decreased HBV clearance of adult mice whereas Axl silencing enhanced HBV clearance of young mice. In vitro, IFN-? priming of pDCs and Axl-overexpressing macrophages enhanced Treg-cell differentiation. These findings suggest that age-dependent HBV chronicity is attributed to IFN-?-Axl immune regulation, which is selectively induced in young mice by excessive IFN-?/? production at early stage of HBV infection. PMID:25820812

  6. Broad Range of Hepatitis B Virus (HBV) Patterns, Dual Circulation of Quasi-Subgenotype A3 and HBV/E and Heterogeneous HBV Mutations in HIV-Positive Patients in Gabon.

    PubMed

    Bivigou-Mboumba, Berthold; François-Souquière, Sandrine; Deleplancque, Luc; Sica, Jeanne; Mouinga-Ondémé, Augustin; Amougou-Atsama, Marie; Chaix, Marie-Laure; Njouom, Richard; Rouet, François

    2016-01-01

    Integrated data on hepatitis B virus (HBV) patterns, HBV genotypes and mutations are lacking in human immunodeficiency virus type 1 (HIV-1) co-infected patients from Africa. This survey was conducted in 2010-2013 among 762 HIV-1-positive adults from Gabon who were predominantly treated with 3TC-based antiretroviral treatment. HBV patterns were identified using immunoassays detecting total antibody to hepatitis B core antigen (HBcAb), hepatitis B surface antigen (HBsAg), IgM HBcAb, hepatitis B e antigen (HBeAg), antibody to HBsAg (HBsAb) and an in-house real-time PCR test for HBV DNA quantification. Occult hepatitis B (OBI) was defined by the presence of isolated anti-HBc with detectable serum HBV DNA. HBV genotypes and HBV mutations were analyzed by PCR-direct sequencing method. Seventy-one (9.3%) patients tested positive for HBsAg, including one with acute hepatitis B (0.1%; 95% CI, 0.0%-0.2%), nine with HBeAg-positive chronic hepatitis B (CHB) (1.2%; 95% CI, 0.6%-2.2%), 16 with HBeAg-negative CHB (2.1%; 95% CI, 1.2%-3.3%) and 45 inactive HBV carriers (5.9%; 95% CI, 4.4%-7.8%). Sixty-one (8.0%; 95% CI, 6.2%-10.1%) patients showed OBI. Treated patients showed similar HBV DNA levels to those obtained in untreated patients, regardless of HBV patterns. Around 15.0% of OBI patients showed high (>1,000 UI/mL) viremia. The mutation M204V/I conferring resistance to 3TC was more common in HBV/A (47.4%) than in HBV/E isolates (0%) (P = .04). Our findings encouraged clinicians to promote HBV vaccination in patients with no exposure to HBV and to switch 3TC to universal TDF in those with CHB. PMID:26764909

  7. Broad Range of Hepatitis B Virus (HBV) Patterns, Dual Circulation of Quasi-Subgenotype A3 and HBV/E and Heterogeneous HBV Mutations in HIV-Positive Patients in Gabon

    PubMed Central

    Bivigou-Mboumba, Berthold; François-Souquière, Sandrine; Deleplancque, Luc; Sica, Jeanne; Mouinga-Ondémé, Augustin; Amougou-Atsama, Marie; Chaix, Marie-Laure; Njouom, Richard; Rouet, François

    2016-01-01

    Integrated data on hepatitis B virus (HBV) patterns, HBV genotypes and mutations are lacking in human immunodeficiency virus type 1 (HIV-1) co-infected patients from Africa. This survey was conducted in 2010–2013 among 762 HIV-1-positive adults from Gabon who were predominantly treated with 3TC-based antiretroviral treatment. HBV patterns were identified using immunoassays detecting total antibody to hepatitis B core antigen (HBcAb), hepatitis B surface antigen (HBsAg), IgM HBcAb, hepatitis B e antigen (HBeAg), antibody to HBsAg (HBsAb) and an in-house real-time PCR test for HBV DNA quantification. Occult hepatitis B (OBI) was defined by the presence of isolated anti-HBc with detectable serum HBV DNA. HBV genotypes and HBV mutations were analyzed by PCR-direct sequencing method. Seventy-one (9.3%) patients tested positive for HBsAg, including one with acute hepatitis B (0.1%; 95% CI, 0.0%-0.2%), nine with HBeAg-positive chronic hepatitis B (CHB) (1.2%; 95% CI, 0.6%–2.2%), 16 with HBeAg-negative CHB (2.1%; 95% CI, 1.2%–3.3%) and 45 inactive HBV carriers (5.9%; 95% CI, 4.4%–7.8%). Sixty-one (8.0%; 95% CI, 6.2%–10.1%) patients showed OBI. Treated patients showed similar HBV DNA levels to those obtained in untreated patients, regardless of HBV patterns. Around 15.0% of OBI patients showed high (>1,000 UI/mL) viremia. The mutation M204V/I conferring resistance to 3TC was more common in HBV/A (47.4%) than in HBV/E isolates (0%) (P = .04). Our findings encouraged clinicians to promote HBV vaccination in patients with no exposure to HBV and to switch 3TC to universal TDF in those with CHB. PMID:26764909

  8. Molecular epidemiology of HBV infection in chronic hepatitis B virus infected patients in northeast India.

    PubMed

    Saikia, Anjan; Bose, Moumita; Barman, Narendra Nath; Deka, Manab; Thangkhiew, Rangsan Singh; Bose, Sujoy

    2015-09-01

    The present study aimed to evaluate the molecular epidemiology of HBV in chronic HBV infected cases from northeast India (NEI), since scanty data are available from the region which has a predominant ethnically distinct tribal population. A total of 523 clinically diagnosed index chronic HBV infected cases and 172 asymptomatic patients (based on family screening) were enrolled with informed consent. Patients were stratified based on serology, imaging, pathology, and clinical data and grouped as chronic HBV and cirrhotic cohorts. Analysis for serum HBV DNA levels and HBV genotyping was performed, and was statistically co-related with disease severity. Males were more prone to chronic HBV infection. Majority of the patients who had Chronic HBV infection based on family screening were females (59.88%), majorly wives of index patients. Mean viral load in Chronic HBV patients was almost 4.5-folds higher than cirrhosis patients, and was significantly associated with e-antigen positive status(P?HBV genotype D was the most prevalent genotype (62.30%) in NEI. Mixed genotype infection of A?+?D was found from Assam, along with C?+?D cases (1.29%) cumulatively. There is a high prevalence of HBV genotype C (13.96%) in our studied cohort which was found to be associated with higher viral load(P?=?0.018), e-antigen positivity(P?=?0.043), and increased cirrhosis risk compared to Chronic HBV cases [OR?=?1.670]. Family contacts in NEI are prone to infection with HBV and development of Chronic HBV. Higher presence of e-positive cases and genotype C along with the mixed genotypes in NEI is unique and of significance with reference to predisposition to disease severity and even response to antiviral therapy. PMID:25919572

  9. Comparison of the effects of formaldehyde and gaseous ozone on HBV-contaminated hospital quilts

    PubMed Central

    Guo, Dan; Li, Ziqiong; Jia, Bei; Che, Xiaoqiong; Song, Tianshuang; Huang, Wenxiang

    2015-01-01

    Background: Besides being highly infectious, Hepatitis B virus (HBV) is a major cause of liver disease worldwide. In hospital settings, it is easy for the environment and quilts to be contaminated by HBV patient blood and body fluids. Therefore, HBV can be transmitted to other patients via contaminated environmental surfaces or quilts, resulting in an HBV nosocomial infection. Formaldehyde and ozone are commonly used disinfectants that may influence this infectious situation. Objective: To investigate the clinical effectiveness of formaldehyde and gaseous ozone for the terminal cleaning of hospital quilts contaminated by HBV. Methods: Thin cloth and thick cotton soaked with the serum from high HBV copy number patients were prepared and disinfected using formaldehyde fumigation and gaseous ozone at different times. The copy numbers of HBV DNA in the HBV-contaminated cloth and cotton samples were measured quantitatively with fluorescent quantitative polymerase chain reaction (PCR). Results: When gaseous ozone was used to disinfect HBV-contaminated quilts for 23 minutes (min), 36 min, 49 min, and 90 min, the HBV DNA copy number displayed no significant decrease compared with the copy number before disinfection (P > 0.05). In comparison, the copy number of the HBV DNA in the cloth group decreased significantly (P < 0.05) after formaldehyde fumigation disinfection for 1 hour (h), and there was no difference when longer times and increased concentrations were used. In the thick cotton group, there was also a significant decrease (P < 0.05) of the HBV DNA copy numbers, but the decrease was not as dramatic. In addition, in this group, the disinfection effect observed at 4 h was the strongest. Conclusions: The application of ozone to disinfect HBV-contaminated hospital quilts possibly has no effect, whereas, formaldehyde oxide fumigation effectively reduced HBV copy numbers. PMID:26770591

  10. Viral hepatitis: past and future of HBV and HDV.

    PubMed

    Thomas, Emmanuel; Yoneda, Masato; Schiff, Eugene R

    2015-02-01

    Viral hepatitis is a significant disease afflicting hundreds of millions of people. Hepatitis-causing viruses initiate significant morbidity and mortality by establishing both acute and chronic infections, and several of these viruses are specifically associated with the development of hepatocellular carcinoma (HCC). Consequently, intense research efforts are focused on increasing our understanding of virus biology and on improving antiviral therapy. Even though viral hepatitis can be caused by several viruses from a range of virus families, the discovery of components of the hepatitis B virus (HBV) became a catalyst for the development of diagnostic assays that differentiate between these viruses as well as strategies for novel methods of vaccine development. Improvements in both the treatment and prevention of viral hepatitis are advancing rapidly. However, HBV, along with the associated infection by the hepatitis D virus, is still among the most common pathogens afflicting humans. PMID:25646383

  11. Molecular characterization of HBV strains circulating among the treatment-naive HIV/HBV co-infected patients of eastern India.

    PubMed

    Saha, Debraj; Pal, Ananya; Biswas, Avik; Panigrahi, Rajesh; Sarkar, Neelakshi; Das, Dipanwita; Sarkar, Jayeeta; Guha, Subhasish Kamal; Saha, Bibhuti; Chakrabarti, Sekhar; Chakravarty, Runu

    2014-01-01

    Previously we reported that the exposure to hepatitis B virus (HBV) infection serves as a major threat among the treatment naive HIV infected population of eastern India. Hence, molecular characterization of these strains is of utmost importance in order to identify clinically significant HBV mutations. A total of 85 treatment naive HIV/HBV co-infected participants were included of whom the complete basal core promoter/precore region, the core and the whole envelope gene could be successfully sequenced for 59, 57 and 39 isolates respectively. Following phylogenetic analysis, it was found that HBV/D was the predominant genotype with HBV/D2 (38.5%) being the most prevalent subgenotype followed by HBV/A1. The major mutations affecting HBeAg expression includes the A1762T/G1764A (13.6%), G1896A (22%) and G1862T mutation (33.9%) which was predominantly associated with HBV/A1. Moreover, the prevalence of G1896A was considerably high among the HBeAg negative HIV/HBV co-infected subjects compared to HBV mono-infection. The main amino acid substitutions within the MHC class II restricted T-cell epitope of HBcAg includes the T12S (15.8%) and T67N (12.3%) mutation and the V27I (10.5%) mutation in the MHC class I restricted T-cell epitope. PreS1/S2 deletion was detected in 3 isolates with all harboring the BCP double mutation. Furthermore, the frequently occurring mutations in the major hydrophilic loop of the S gene include the T125M, A128V and M133I/L. Therefore, this study is the first from India to report useful information on the molecular heterogeneity of the HBV strains circulating among the treatment naive HIV/HBV co-infected population and is thus clinically relevant. PMID:24587360

  12. HBV influence on Response to Antiretroviral Therapy in Horizontally HIV-HBV Coinfected Patient during Early Childhood

    PubMed Central

    Niculescu, Irina; Cup?a, A.M.; Stoian, Andreea Cristina; Dumitrescu, FLorentina; Giubelan, L.I.; Alexandru, D.O.

    2013-01-01

    Background: There are few studies on pediatric HIV-HBV coinfection, so evidences about relationships between the two viruses are scarce. Objectives: influence of HBV infection on virological and immunological response to antiretroviral therapy (ART) in antiretroviral-nave horizontally HIV-HBV coinfected subjects during early childhood. Material and methods: observational study on 826 HIV+ subjects in evidence of Craiova Regional Centre (CRC); we analyzed the immunological and virological response at 6-12 months after starting first antiretroviral regimens compared in 2 groups: horizontally HIV-HBV coinfected subjects during early childhood (CoS) versus horizontally HIV infected subjects during early childhood without HBV infection (non-CoS). Results: Number of subjects: CoS-66 subjects, non-CoS-132 subjects. Demographic data: CoS-gender ratio F:M=0.886, the majority lived in rural area (57.58%), mean age on diagnosis-9.2884.607 years, non-CoS-gender ratio F:M=0.859, the majority lived in urban area (53.79%), mean age on diagnosis-10.7425.107 years. At baseline, HIV category was: CoS-A-1.52%, B-80.30%, C-18.18%, non-CoS-A-2.27%, B-70.45%, C-27.27% (p Chi2=0.332), the mean CD4+ cell count was: CoS-148.33148.10 cells/ml, non-CoS-163.17155.39 cells/ml (p Student=0.521) and the mean HIV viral load (HIV VL) was: CoS-5.060.80 lgcopies/ml (for 29 subjects), non-CoS-5.040.84 lgcopies/ml (for 61 subjects) (p Student=0.978). At the end of the studied period, the mean increase in CD4+ cell count was: CoS-177.068141.676 cells/ml, non-CoS-176.015191.751 cells/ml (p Student=0.969) and the mean decrease in HIV VL was: CoS-5.040.79 lgcopies/ml, non-COS-4.692.04 lgcopies/ml (p Student=0.911). Conclusions: The presence of HBV coinfection does not influence immunological or virological response to ART. PMID:24778861

  13. Occult HBV Infection: A Faceless Enemy in Liver Cancer Development

    PubMed Central

    Morales-Romero, Jaime; Vargas, Gustavo; García-Román, Rebeca

    2014-01-01

    The hepatitis B virus (HBV) represents a worldwide public health problem; the virus is present in one third of the global population. However, this rate may in fact be higher due to occult hepatitis B virus infection (OBI). This condition is characterized by the presence of the viral genome in the liver of individuals sero-negative for the virus surface antigen (HBsAg). The causes of the absence of HBsAg in serum are unknown, however, mutations have been identified that produce variants not recognized by current immunoassays. Epigenetic and immunological host mechanisms also appear to be involved in HBsAg suppression. Current evidence suggests that OBI maintains its carcinogenic potential, favoring the progression of fibrosis and cirrhosis of the liver. In common with open HBV infection, OBI can contribute to the establishment of hepatocellular carcinoma. Epidemiological data regarding the global prevalence of OBI vary due to the use of detection methods of different sensitivity and specificity. In Latin America, which is considered an area of low prevalence for HBV, diagnostic screening methods using gene amplification tests for confirmation of OBI are not conducted. This prevents determination of the actual prevalence of OBI, highlighting the need for the implementation of cutting edge technology in epidemiological surveillance systems. PMID:24717680

  14. Seroprevalence of HBV and HCV in primary hepatocellular carcinoma patients in Zimbabwe

    PubMed Central

    Chin'ombe, Nyasha; Chavhunduka, Evans; Matarira, Hilda T

    2009-01-01

    Background Primary hepatocellular carcinoma (PHC) is one of the most common cancers in Zimbabwe. Hepatitis B virus (HBV) and hepatitis C virus (HCV) are suspected to play a major role in causing this cancer. The objective of this study was to determine the seroprevalence of HBV and HCV in PHC at Parirenyatwa Referral Hospital in Zimbabwe. We evaluated the serological markers of the two viruses in patients with PHC using commercially available enzyme-linked immunosorbent kits. Results Out of the 60 patients with PHC, 48.3% were seropositive for HBV and 20.0% were seropositive for HCV. Co-infection by HCV and HBV was found in 8% of the patients. Only 13.3% of the health controls (blood donors) were positive for HBV. All the controls were negative for HCV. Conclusion The high seropositivity of HBV and HCV in PHC in Zimbabwe suggested that the two viruses were a major cause of the cancer. PMID:19814789

  15. Preliminary study on the efficacy and safety of lamivudine and interferon alpha therapy in decreasing serum HBV DNA level in HBV positive transgenic mice during pregnancy.

    PubMed

    Li, Duan; Xu, De-Zhong; Choi, Bernard C K; Men, Ke; Zhang, Jing-Xia; Lei, Xiao-Ying; Yan, Yong-Ping

    2005-06-01

    Previous studies reported that the HBV DNA level in maternal serum is an important risk factor for intrauterine infection. Two antiviral drugs, lamivudine (3TC) and interferon alpha (IFNalpha), are used extensively clinically to reduce maternal HBV DNA level, However, because of a lack of evidence on the efficacy and safety of these drugs during pregnancy, they are categorized as grade C which prevents their use during pregnancy. This study provides new data on the efficacy and safety of lamivudine and IFNalpha in HBV positive transgenic pregnant mice. In this study, transgenic mice with high titers of hepatitis B virus (HBV) were employed to study the antiviral effects of 3TC and IFNalpha during different gestation periods. The study also examined changes in several serological HBV markers, the effects of perinatal exposure to antiviral drugs on the mother and offspring, drug efficacy in reducing the level of HBV DNA in maternal blood, and the safety to both the mother and offspring. The main conclusion of the study is that a significant decrease in HBV DNA level can be obtained after treatment with lamivudine but not with IFNalpha. No adverse effects were observed in the maternal mice and the offsprings. This finding may provide a rationale for the potential use of lamivudine for the treatment of pregnant women as a safe and effective measure to reduce the level of maternal viremia. PMID:15834875

  16. The cyclic GMP-AMP synthetase-STING signaling pathway is required for both the innate immune response against HBV and the suppression of HBV assembly.

    PubMed

    Dansako, Hiromichi; Ueda, Youki; Okumura, Nobuaki; Satoh, Shinya; Sugiyama, Masaya; Mizokami, Masashi; Ikeda, Masanori; Kato, Nobuyuki

    2016-01-01

    During viral replication, the innate immune response is induced through the recognition of viral replication intermediates by host factor(s). One of these host factors, cyclic GMP-AMP synthetase (cGAS), was recently reported to be involved in the recognition of viral DNA derived from DNA viruses. However, it is uncertain whether cGAS is involved in the recognition of hepatitis B virus (HBV), which is a hepatotropic DNA virus. In the present study, we demonstrated that HBV genome-derived double-stranded DNA induced the innate immune response through cGAS and its adaptor protein, stimulator of interferon genes (STING), in human hepatoma Li23 cells expressing high levels of cGAS. In addition, we demonstrated that HBV infection induced ISG56 through the cGAS-STING signaling pathway. This signaling pathway also showed an antiviral response towards HBV through the suppression of viral assembly. From these results, we conclude that the cGAS-STING signaling pathway is required for not only the innate immune response against HBV but also the suppression of HBV assembly. The cGAS-STING signaling pathway may thus be a novel target for anti-HBV strategies. PMID:26471009

  17. CRTC2 enhances HBV transcription and replication by inducing PGC1? expression

    PubMed Central

    2014-01-01

    Background Hepatitis B virus (HBV) transcription and replication are essentially restricted to hepatocytes. Based on the HBV enhancer and promoter complex that links hepatic glucose metabolism to its transcription and replication, HBV adopts a regulatory system that is unique to the hepatic gluconeogenic genes. CRTC2, the CREB-regulated transcription coactivator 2, is a critical switch modulating the gluconeogenic program in response to both hormonal and intracellular signals. However, the relationship between CRTC2 and HBV transcription and replication remains unclear. Methods To analyze the influence of CRTC2 on HBV transcription and replication, CRTC2 expression construct or siRNA was cotransfected with plasmids containing enhancer II/core promoter complex-controlled luciferase or 1.3 wtHBV genome in Huh-7 cells. Luciferase activity, HBV core protein expression, HBV transcripts, and DNA replication intermediates were measured by luciferase assays, western blots, real-time polymerase chain reaction (PCR), and Southern blots, respectively. Forskolin (FSK) or phosphorylation-defective CRTC2 mutants were further utilized to elucidate the potential mechanism. siRNA against peroxisome proliferator-activated receptor-? coactivator 1? (PGC1?) was also used to examine the mediator involved in CRTC2-regulated HBV biosynthesis in Huh-7 cells. Results CRTC2 overexpression increased HBV transcription and replication in Huh-7 cells, including levels of core protein expression, mRNA, and DNA replication intermediates. Correspondingly, CRTC2 knock down by siRNA reduced HBV biosynthesis. FSK treatment strongly enhanced the effect of CRTC2 through triggering the dephosphorylation and nuclear entry of CRTC2. The phosphorylation-defective mutant (S171A/S275A) of CRTC2 localized in the nucleus and was constitutively active, which dramatically promoted HBV transcription and replication similar to FSK-treated wild-type CRTC2. Knock down of PGC1?, whose expression was induced by CRTC2, greatly compromised the enhancing effect of CRTC2 on HBV transcription and replication. Conclusions Our results clearly indicate that non-phosphorylated CRTC2 strongly enhances HBV biosynthesis through inducing PGC1? expression. Further study of the mechanisms will elucidate the importance of metabolic signals on HBV transcription and replication, and offer insight into potential targets for developing anti-HBV agents. PMID:24529027

  18. A fusion DNA vaccine encoding middle version of HBV envelope protein fused to interleukin-21 did not enhance HBV-specific immune response in mice.

    PubMed

    Zhang, Ye; Su, Wen-Jing; Wang, Jue; Bai, Xue-Fan; Huang, Chang-Xing; Lian, Jian-Qi

    2014-11-01

    DNA vaccination can generate both humoral and cellular immunity, resulting in potential prophylactic and therapeutic vaccines in variety of conditions, including hepatitis B virus (HBV) infection. Fusion of cytokine gene is one of the ways to increase the immunogenicity of DNA vaccine. Interleukin (IL)-21 has been demonstrated to play an immunomodulatory role in HBV infection. Thus, we aimed to investigate the ability of IL-21 in the regulation of middle version of HBV envelop protein (MS) DNA vaccine. Fusion plasmid encoding IL-21 linked with MS was constructed. Normal and HBV transgenic mice were immunized by plasmid. pcDNA-IL-21/S2S induced a comparable level of anti-HBs antibody and HBsAg-specific CD8+ T-cell response with pcDNA-S2S. Furthermore, the level of circulating HBsAg was decreased by induction of anti-HBs antibody and HBsAg-specific CD8+ T-cell response to both pcDNA-IL-21/S2S and pcDNA-S2S vaccination in HBV transgenic mice. Thus, immunization with DNA vaccine encoding HBV MS protein induced both T- and B-cell response by targeting the specific antigen. Furthermore, it was also revealed that MS DNA vaccination could break immune tolerance in HBV transgenic mice. But IL-21 did not strengthen immune response induced by HBV DNA immunization. Our study suggested that MS-expressing plasmid may be useful for both preventive and therapeutic methods in HBV infection. However, IL-21 does not improve the immunogenicity and efficacy of MS DNA vaccination, and thus may not be used as a therapeutic marker for chronic hepatitis B. PMID:25211639

  19. A Fusion DNA Vaccine Encoding Middle Version of HBV Envelope Protein Fused to Interleukin-21 Did Not Enhance HBV-Specific Immune Response in Mice

    PubMed Central

    Zhang, Ye; Su, Wen-Jing; Wang, Jue; Bai, Xue-Fan

    2014-01-01

    Abstract DNA vaccination can generate both humoral and cellular immunity, resulting in potential prophylactic and therapeutic vaccines in variety of conditions, including hepatitis B virus (HBV) infection. Fusion of cytokine gene is one of the ways to increase the immunogenicity of DNA vaccine. Interleukin (IL)-21 has been demonstrated to play an immunomodulatory role in HBV infection. Thus, we aimed to investigate the ability of IL-21 in the regulation of middle version of HBV envelop protein (MS) DNA vaccine. Fusion plasmid encoding IL-21 linked with MS was constructed. Normal and HBV transgenic mice were immunized by plasmid. pcDNA-IL-21/S2S induced a comparable level of anti-HBs antibody and HBsAg-specific CD8+ T-cell response with pcDNA-S2S. Furthermore, the level of circulating HBsAg was decreased by induction of anti-HBs antibody and HBsAg-specific CD8+ T-cell response to both pcDNA-IL-21/S2S and pcDNA-S2S vaccination in HBV transgenic mice. Thus, immunization with DNA vaccine encoding HBV MS protein induced both T- and B-cell response by targeting the specific antigen. Furthermore, it was also revealed that MS DNA vaccination could break immune tolerance in HBV transgenic mice. But IL-21 did not strengthen immune response induced by HBV DNA immunization. Our study suggested that MS-expressing plasmid may be useful for both preventive and therapeutic methods in HBV infection. However, IL-21 does not improve the immunogenicity and efficacy of MS DNA vaccination, and thus may not be used as a therapeutic marker for chronic hepatitis B. PMID:25211639

  20. HBV carriage in children born from HIV-seropositive mothers in Senegal: The need of birth-dose HBV vaccination.

    PubMed

    Gueye, Sokhna Bousso; Diop-Ndiaye, Halimatou; Lo, Gora; Mintsa, Sandrine; Guindo, Ibrahima; Dia, Aminata; Sow-Sall, Amina; Gaye-Diallo, Aissatou; Mboup, Souleymane; Touré-Kane, Coumba

    2016-05-01

    Hepatitis B is a major public health problem in Senegal, a country with high prevalence and a transmission occurring mainly during infancy. Only, one 6-8 weeks vaccination campaign was initiated in 2005 and it was part of the expanded program of immunization. The aim of this study was to determine the prevalence of HBsAg in children born from HIV-seropositive mothers by using dried blood specimens. Specimens were collected between July 2007 and November 2012 from children aged 2-48 weeks in Dakar and decentralized sites working on HIV mother-to-child transmission prevention. HBsAg detection was performed using Architect HBsAg Qualitative II kit (Abbott Diagnostics, Ireland) and for all reactive samples confirmation was done using Architect HBsAg Qualitative II Confirmatory kit (Abbott Diagnostics, Ireland). Nine hundred thirty samples were collected throughout the country with 66% out of Dakar, the capital city. The median age was 20 weeks and 88% of children were less than 1 year of age with a sex ratio of 1.27 in favor of boys. HBsAg was detected in 28 cases giving a global prevalence of 3%. According to age, HBsAg prevalences were 5.1% for children less than 6 weeks, 4.1% and 4.6%, respectively, for those aged 12-18 weeks and 18-24 weeks of age. The HIV prevalence was 2.6% with no HIV/HBV co-infection. This study showed a high rate of HBV infection in children under 24 months, highlighting the need to promote birth-dose HBV vaccination as recommended by WHO. J. Med. Virol. 88:815-819, 2016. © 2015 Wiley Periodicals, Inc. PMID:26488892

  1. Chronic HBV: which pregnant women should be treated?

    PubMed

    He, Tianyu; Jia, Jidong

    2016-01-01

    Universal HBV vaccination in infants has led to a dramatic decline of HBsAg prevalence in many parts of the world, but the positive rate of HBsAg in women of childbearing age is still high in endemic areas. Antiviral therapy during pregnancy may be indicated to control the liver disease of the mother or to prevent the MTCT. The decision on initiation, switching, continuation or stopage of the antiviral therapy should be made after careful consideration of the benefit and risk to both mothers and foetuses. For prepregnant women of childbearing age, a finite course of interferon is preferred if a pregnancy in the distant future is planned, whereas safer NAs could be started if a pregnancy in the near future is desired. For those who already started therapy with interferon or NAs before pregnancy, the switch to safer NAs is preferred. For women with newly diagnosed or with flare of CHB during pregnancy, category B NAs may be taken to treat their liver disease. For pregnant women with serum HBV DNA >10(6-7) IU/ml, safer NAs could be started in the third trimester to further the reduce MTCT rate. PMID:26725906

  2. IL-35 inhibits HBV antigen-specific IFN-?-producing CTLs invitro.

    PubMed

    Li, Xuefen; Tian, Li; Dong, Yuejiao; Zhu, Qiaoyun; Wang, Yiyin; Han, Wenzheng; Liu, Xia; Ni, Qin; Chen, Yu; Li, Lanjuan

    2015-09-01

    Interleukin (IL)-35 is an inhibitory cytokine consisting of IL-12A and Epstein-Barr virus-induced gene 3 (Ebi3) and is required by regulatory T-cells (Tregs) for maximal activity. During chronic hepatitis B virus (HBV) infection, Tregs have immunosuppressive effects on HBV-specific T helper (Th) cells, yet little is known about the complex regulation of Tregs and their contribution to the inadequate immune system response to the virus. In the present study, we investigated whether IL-35 is involved in HBV-related cellular immune responses. Cluster of differentiation (CD)4(+) T-cells from peripheral blood were derived from healthy volunteers, resolved HBV individuals and chronic active hepatitis B patients and stimulated with CD3/28-conjugated beads. We analysed mRNA and protein levels of IL-35 and assessed the inhibitory effect of IL-35 on HBV core antigen-specific cytotoxic T lymphocytes (CTLs), dendritic cells (DCs) and effector T-cells (Teffs). Correlation analyses between liver inflammation and HBV DNA load were conducted. Results show that chronic HBV patients harbour significantly higher levels of Ebi3 mRNA and protein in CD4(+) T-cells compared with healthy volunteers and resolved HBV individuals. IL-35 suppressed the proliferation of HBV antigen-specific CTLs and interferon (IFN)-? production invitro. Ex vivo, IL-35 decreased the proliferation of CD4(+)CD45RA(+) nave T-cells, especially in CD4(+)CD25(-)CD45RA(+) nave Teffs. IL-35 inhibited the expansion of CD11c(+) DCs. Our data indicate that IL-35 is highly expressed in chronic HBV CD4(+) T-cells and plays an important role in the inhibition of the cellular immune response in chronic HBV. PMID:25869609

  3. Integration of tumour and viral genomic characterisations in HBV-related hepatocellular carcinomas

    PubMed Central

    Amaddeo, Giuliana; Cao, Qian; Ladeiro, Yannick; Imbeaud, Sandrine; Nault, Jean-Charles; Jaoui, Daphne; Gaston Mathe, Yann; Laurent, Christophe; Laurent, Alexis; Bioulac-Sage, Paulette; Calderaro, Julien; Zucman-Rossi, Jessica

    2015-01-01

    Background and aim Hepatocellular carcinoma (HCC) is the most common liver cancer. We characterised HCC associated with infection compared with non-HBV-related HCC to understand interactions between viral and hepatocyte genomic alterations and their relationships with clinical features. Methods Frozen HBV (n=86) or non-HBV-related (n=90) HCC were collected in two French surgical departments. Viral characterisation was performed by sequencing HBS and HBX genes and quantifying HBV DNA and cccDNA. Nine genes were screened for somatic mutations and expression profiling of 37 genes involved in hepatocarcinogenesis was studied. Results HBX revealed frequent non-sense, frameshift and deletions in tumours, suggesting an HBX inactivation selected in HCC. The number of viral copies was frequently lower in tumour than in non-tumour tissues (p=0.0005) and patients with low HBV copies in the non-tumour liver tissues presented additional risk factor (HCV, alcohol or non-alcoholic steato-hepatitis, p=0.006). P53 was the most frequently altered pathway in HBV-related HCC (47%, p=0.001). Furthermore, TP53 mutations were associated with shorter survival only in HBV-related HCC (p=0.02) whereas R249S mutations were identified exclusively in migrants. Compared with other aetiologies, HBV-HCC were more frequently classified in tumours subgroups with upregulation of genes involved in cell-cycle regulation and a progenitor phenotype. Finally, in HBV-related HCC, transcriptomic profiles were associated with specific gene mutations (HBX, TP53, IRF2, AXIN1 and CTNNB1). Conclusions Integrated genomic characterisation of HBV and non-HBV-related HCC emphasised the immense molecular diversity of HCC closely related to aetiologies that could impact clinical care of HCC patients. PMID:25021421

  4. RPB5-Mediating Protein Suppresses Hepatitis B Virus (HBV) Transcription and Replication by Counteracting the Transcriptional Activation of Hepatitis B virus X Protein in HBV Replication Mouse Model

    PubMed Central

    Zhou, Qiaoling; Huang, Feijun; Chen, Lanlan; Chen, Enqiang; Bai, Lang; Cheng, Xing; He, Min; Tang, Hong

    2015-01-01

    Background: RPB5-Mediating protein (RMP) is associated with the RNA polymerase II subunit RPB5. This protein functionally counteracts the transcriptional activation of Hepatitis B Virus X protein (HBx) by competitively binding to the RPB5; however, the effects of RMP on Hepatitis B virus (HBV) transcription and replication remain unknown. Objectives: The purpose of this study was to investigate the effect of RMP on viral transcription and replication in vivo by using the hydrodynamic-based HBV replication mouse model. Materials and Methods: Male balb/c mice were transfected with wild type (1.2 wt) or the HBx minus HBV plasmids (1.2x (-)) with or without HBx and RMP, to establish an HBV replication mouse model by hydrodynamic injection through the tail vein. The HBV RNA and HBV DNA replication intermediates (RI) were analyzed in the liver. Results: RPB5-Mediating protein could inhibit HBV transcription and replication in groups transfected with the 1.2 wt and HBx. The inhibitory effect disappeared in the 1.2x (-) groups, yet it reappeared in the groups co-transfected with 1.2x (-) and HBx. An inhibitory effect was indicated at a low dose of RMP (0.3 ug, 0.5 ug and 0.7 ug) compared to the control group and groups that had received high doses of RMP. Conclusions: Our study demonstrated that a low dose of RMP could inhibit HBV transcription and replication, which is dependent on the appearance of HBx in vivo. PMID:26495109

  5. Molecular characterization of hepatitis B virus (HBV) strains circulating in the northern coast of the Persian Gulf and its comparison with worldwide distribution of HBV subgenotype D1.

    PubMed

    Pourkarim, Mahmoud Reza; Vergote, Valentijn; Amini-Bavil-Olyaee, Samad; Sharifi, Zohre; Sijmons, Steven; Lemey, Philippe; Maes, Piet; Alavian, Seyed Moayed; Van Ranst, Marc

    2014-05-01

    Iran is a large country that covers the northern coast of the Persian Gulf. Iranian residents of this coastal region interact closely with people from neighboring countries because of historical and cultural relationships, as well as economic activities. In addition, the inhabitants of this border region have experienced several wars, which have affected public health infrastructures. This study characterized for the first time, the evolution of the full-length genome of HBV strains in asymptomatic carrier patients living in this particular region. In addition, this study was compared and complemented by a comprehensive evolutionary analysis of the worldwide geographical distribution of HBV subgenotype D1. Evolutionary analysis demonstrates that patients living in the northern coast of the Persian Gulf are mainly infected with HBV subgenotype D1, subtype ayw2. Specific mutations related to advanced liver disease were found more frequently in these strains compared to other strains isolated from asymptomatic carriers from other regions of Iran. This global comprehensive analysis showed that HBV subgenotype D1 strains have a worldwide distribution and that human mobility and immigration had a large impact on dispersal of HBV subgenotype D1, subtype ayw2 in Middle Eastern countries such as Iran, Syria, and Turkey. In addition to association of subtype ayw2 with subgenotype D1, it was demonstrated that other HBV subtypes like adw2, ayw1, and ayw3 are associated with HBV subgenotype D1 in different regions of the world. This study also revealed a remarkable distribution of subgenotype D1, subtype ayw4 although this particular subtype is associated with subgenotype D4 of HBV in European countries. PMID:24532489

  6. Genomic responses to hepatitis B virus (HBV) infection in primary human hepatocytes

    PubMed Central

    Ancey, Pierre-Benoit; Testoni, Barbara; Gruffaz, Marion; Cros, Marie-Pierre; Durand, Geoffroy; Le Calvez-Kelm, Florence; Durantel, David; Herceg, Zdenko; Hernandez-Vargas, Hector

    2015-01-01

    Viral infections are able to modify the host's cellular programs, with DNA methylation being a biological intermediate in this process. The extent to which viral infections deregulate gene expression and DNA methylation is not fully understood. In the case of Hepatitis B virus (HBV), there is evidence for an interaction between viral proteins and the host DNA methylation machinery. We studied the ability of HBV to modify the host transcriptome and methylome, using naturally infected primary human hepatocytes to better mimic the clinical setting. Gene expression was especially sensitive to culture conditions, independently of HBV infection. However, we identified non-random changes in gene expression and DNA methylation occurring specifically upon HBV infection. There was little correlation between expression and methylation changes, with transcriptome being a more sensitive marker of time-dependent changes induced by HBV. In contrast, a set of differentially methylated sites appeared early and were stable across the time course experiment. Finally, HBV-induced DNA methylation changes were defined by a specific chromatin context characterized by CpG-poor regions outside of gene promoters. These data support the ability of HBV to modulate host cell expression and methylation programs. In addition, it may serve as a reference for studies addressing the genome-wide consequences of HBV infection in human hepatocytes. PMID:26565721

  7. Reactive oxygen species promote heat shock protein 90-mediated HBV capsid assembly.

    PubMed

    Kim, Yoon Sik; Seo, Hyun Wook; Jung, Guhung

    2015-02-13

    Hepatitis B virus (HBV) infection induces reactive oxygen species (ROS) production and has been associated with the development of hepatocellular carcinoma (HCC). ROS are also an important factor in HCC because the accumulated ROS leads to abnormal cell proliferation and chromosome mutation. In oxidative stress, heat shock protein 90 (Hsp90) and glutathione (GSH) function as part of the defense mechanism. Hsp90 prevents cellular component from oxidative stress, and GSH acts as antioxidants scavenging ROS in the cell. However, it is not known whether molecules regulated by oxidative stress are involved in HBV capsid assembly. Based on the previous study that Hsp90 facilitates HBV capsid assembly, which is an important step for the packing of viral particles, here, we show that ROS enrich Hsp90-driven HBV capsid formation. In cell-free system, HBV capsid assembly was facilitated by ROS with Hsp90, whereas it was decreased without Hsp90. In addition, GSH inhibited the function of Hsp90 to decrease HBV capsid assembly. Consistent with the result of cell-free system, ROS and buthionine sulfoximine (BS), an inhibitor of GSH synthesis, increased HBV capsid formation in HepG2.2.15 cells. Thus, our study uncovers the interplay between ROS and Hsp90 during HBV capsid assembly. PMID:25576869

  8. Viral hepatitis. HBV cure--can we pin our hopes on immunotherapy?

    PubMed

    Yang, Hung-Chih; Kao, Jia-Horng

    2015-03-01

    Therapeutic vaccines are considered to be able to reverse the dysfunctional immune state of chronic hepatitis B and thus hold the promise for HBV cure. Martin et al. developed a novel adenovirus-based therapeutic vaccine TG1050 and demonstrated its induction of long-lasting antiviral CD8+ T-cell immunity in mouse models of HBV persistence. PMID:25623202

  9. Spotlight on DTPa-HBV-IPV/Hib Vaccine (Infanrix hexa).

    PubMed

    Dhillon, Sohita

    2010-10-01

    Infanrix hexa, administered intramuscularly, is a diphtheria, tetanus, acellular pertussis, hepatitis B (HBV), inactivated poliomyelitis and Haemophilus influenzae type b (Hib) conjugate vaccine, indicated for primary and booster vaccination of infants. Infanrix hexa should be administered as a two- or three-dose primary vaccination course in infants aged < or =6 months, followed by booster vaccination between 11 and 18 months of age, with an interval of at least 6 months between the last dose of primary vaccination and the booster dose. This spotlight reviews the immunogenicity and protective effectiveness, as well as the reactogenicity and safety of Infanrix hexa. Infanrix hexa as primary and booster vaccination was safe and highly immunogenic for all its component toxoids/antigens in infants aged <2 years, regardless of vaccination schedules. Its immunogenicity and safety profiles were generally similar to those of currently available vaccines, the diphtheria, tetanus and acellular pertussis-based pentavalent vaccines plus monovalent HBV or Hib vaccines. In large clinical studies, Infanrix hexa elicited a strong immune response against vaccine toxoids/antigens, as indicated by high seroprotection/seropositivity/vaccine response rates and geometric mean titers. Moreover, antibodies against vaccine toxoids/antigens persisted for up to a mean of approximately 6 years after booster vaccination, and the vaccine induced long-term immune memory against hepatitis B surface antigen and Hib antigen. A strong immune response against Infanrix hexa toxoids/antigens after primary vaccination was also induced in infants who had received a dose of HBV vaccine at birth and in pre-term infants, although the response in the latter group was somewhat lower than that in full-term infants. In addition, when coadministered with other childhood vaccines, the immunogenicity of Infanrix hexa or that of the concomitantly administered vaccine was generally not altered. Hexavalent vaccines, including Infanrix hexa, were protective against invasive Hib disease; Infanrix hexa is also expected to be protective against pertussis. Most solicited local and general symptoms with Infanrix hexa were mild to moderate in intensity and the vaccine was associated with few unsolicited adverse events. Available clinical data from more than 10 years' experience with the vaccine suggest that Infanrix hexa as primary and booster vaccination is a safe and useful option for providing protection against the common childhood diseases of diphtheria, tetanus, poliomyelitis, pertussis, hepatitis B and invasive Hib disease. PMID:20795752

  10. Dynamics of an HBV Model with Drug Resistance Under Intermittent Antiviral Therapy

    NASA Astrophysics Data System (ADS)

    Zhang, Ben-Gong; Tanaka, Gouhei; Aihara, Kazuyuki; Honda, Masao; Kaneko, Shuichi; Chen, Luonan

    2015-06-01

    This paper studies the dynamics of the hepatitis B virus (HBV) model and the therapy regimens of HBV disease. First, we propose a new mathematical model of HBV with drug resistance, and then analyze its qualitative and dynamical properties. Combining the clinical data and theoretical analysis, we demonstrate that our model is biologically plausible and also computationally viable. Second, we demonstrate that the intermittent antiviral therapy regimen is one of the possible strategies to treat this kind of complex disease. There are two main advantages of this regimen, i.e. it not only may delay the development of drug resistance, but also may reduce the duration of on-treatment time compared with the long-term continuous medication. Moreover, such an intermittent antiviral therapy can reduce the adverse side effects. Our theoretical model and computational results provide qualitative insight into the progression of HBV, and also a possible new therapy for HBV disease.

  11. Proteomics Based Identification of Cell Migration Related Proteins in HBV Expressing HepG2 Cells

    PubMed Central

    Feng, Huixing; Li, Xi; Chan, Vincent; Chen, Wei Ning

    2014-01-01

    Proteomics study was performed to investigate the specific protein expression profiles of HepG2 cells transfected with mutant HBV compared with wildtype HBV genome, aiming to identify the specific functions of SH3 binding domain (proline rich region) located in HBx. In addition to the cell movement and kinetics changes due to the expression of HBV genome we have observed previously, here we further targeted to explore the specific changes of cellular proteins and potential intracellular protein interactions, which might provide more information of the potential cellular mechanism of the differentiated cell movements. Specific changes of a number of proteins were shown in global protein profiling in HepG2 cells expressing wildtype HBV, including cell migration related proteins, and interestingly the changes were found recovered by SH3 binding domain mutated HBV. The distinctive expressions of proteins were validated by Western blot analysis. PMID:24763314

  12. Both HCV and HBV are major causes of liver cancer in Southeast Asians.

    PubMed

    Lin, Hillary; Ha, Nghiem B; Ahmed, Aijaz; Ayoub, Walid; Daugherty, Tami J; Lutchman, Glen A; Garcia, Gabriel; Nguyen, Mindie H

    2013-12-01

    The incidence of hepatocellular carcinoma (HCC) is higher in Asian Americans than in other ethnicities. While hepatitis B virus (HBV) is common, hepatitis C virus (HCV) is more prevalent in some subgroups. Our goal was to determine the etiology of liver disease associated with HCC in subgroups of Asian Americans. This was an analysis of 510 Asian HCC patients at a US medical center. Patients were identified using ICD9 diagnosis. Multivariate logistic regression was used to study predictors of HCV as the cause of HCC. Patients were Southeast Asian, Chinese, and Korean, with similar gender, age, and foreign-born status. Southeast Asians had a similar proportion of HBV- and HCV-related HCC, while Chinese and Korean patients had a higher proportion of HBV-related HCC. HCC was usually associated with HBV in Chinese and Korean patients, but both HCV and HBV were important associations in Southeast Asians. PMID:23864445

  13. The transcription factor c-JUN/AP-1 promotes HBV-related liver tumorigenesis in mice.

    PubMed

    Trierweiler, C; Hockenjos, B; Zatloukal, K; Thimme, R; Blum, H E; Wagner, E F; Hasselblatt, P

    2016-04-01

    Hepatocellular carcinoma (HCC) develops as a consequence of chronic inflammatory liver diseases such as chronic hepatitis B virus (HBV) infection. The transcription factor c-Jun/activator protein 1 (AP-1) is strongly expressed in response to inflammatory stimuli, promotes hepatocyte survival during acute hepatitis and acts as an oncogene during chemically induced liver carcinogenesis in mice. Here, we therefore aimed to characterize the functions of c-Jun during HBV-related liver tumorigenesis. To this end, transgenic mice expressing all HBV envelope proteins (HBV(+)), an established model of HBV-related HCC, were crossed with knockout mice lacking c-Jun specifically in hepatocytes and tumorigenesis was analyzed. Hepatic expression of c-Jun was strongly induced at several time points during tumorigenesis in HBV(+) mice, whereas expression of other AP-1 components remained unchanged. Importantly, formation of premalignant foci and tumors was strongly reduced in HBV(+) mice lacking c-Jun. This phenotype correlated with impaired hepatocyte proliferation and increased expression of the cell cycle inhibitor p21, whereas hepatocyte survival was not affected. Progression and prognosis of HBV-related HCC correlates with the expression of the cytokine osteopontin (Opn), an established AP-1 target gene. Opn expression was strongly reduced in HBV(+) livers and primary mouse hepatocytes lacking c-Jun, demonstrating that c-Jun regulates hepatic Opn expression in a cell-autonomous manner. These findings indicate that c-Jun has important functions during HBV-associated tumorigenesis by promoting hepatocyte proliferation as well as progression of dysplasia. Therefore, targeting c-Jun may be a useful strategy to prevent hepatitis-associated tumorigenesis. PMID:26470729

  14. Hepatitis B Surface Antigen Concentrations in Patients with HIV/HBV Co-Infection

    PubMed Central

    Jaroszewicz, Jerzy; Reiberger, Thomas; Meyer-Olson, Dirk; Mauss, Stefan; Vogel, Martin; Ingiliz, Patrick; Payer, Berit Anna; Stoll, Matthias; Manns, Michael P.; Schmidt, Reinhold E.; Flisiak, Robert; Wedemeyer, Heiner; Peck-Radosavljevic, Markus; Rockstroh, Jürgen; Cornberg, Markus

    2012-01-01

    HBsAg clearance is associated with clinical cure of chronic hepatitis B virus (HBV) infection. Quantification of HBsAg may help to predict HBsAg clearance during the natural course of HBV infection and during antiviral therapy. Most studies investigating quantitative HBsAg were performed in HBV mono-infected patients. However, the immune status is considered to be important for HBsAg decline and subsequent HBsAg loss. HIV co-infection unfavorably influences the course of chronic hepatitis B. In this cross-sectional study we investigated quantitative HBsAg in 173 HBV/HIV co-infected patients from 6 centers and evaluated the importance of immunodeficiency and antiretroviral therapy. We also compared 46 untreated HIV/HBV infected patients with 46 well-matched HBV mono-infected patients. HBsAg levels correlated with CD4 T-cell count and were higher in patients with more advanced HIV CDC stage. Patients on combination antiretroviral therapy (cART) including nucleos(t)ide analogues active against HBV demonstrated significant lower HBsAg levels compared to untreated patients. Importantly, HBsAg levels were significantly lower in patients who had a stronger increase between nadir CD4 and current CD4 T-cell count during cART. Untreated HIV/HBV patients demonstrated higher HBsAg levels than HBV mono-infected patients despite similar HBV DNA levels. In conclusion, HBsAg decline is dependent on an effective immune status. Restoration of CD4 T-cells during treatment with cART including nucleos(t)ide analogues seems to be important for HBsAg decrease and subsequent HBsAg loss. PMID:22905219

  15. Identification of occult hepatitis B virus (HBV) infection and viral antigens in healthcare workers who presented low to moderate levels of anti-HBs after HBV vaccination

    PubMed Central

    Borzooy, Zohreh; Jazayeri, Seyed Mohammad; Mirshafiey, Abbass; Khamseh, Azam; Mahmoudie, Masoud Karkhaneh; Azimzadeh, Pedram; Geravand, Babak; Boroumand, Mohammad Ali; Afshar, Mina; Poortahmasebi, Vahdat; Hosseini, Mostafa; Streinu-Cercel, Adrian

    2015-01-01

    Background Worldwide, healthcare workers (HCWs) show different levels of response to hepatitis B virus (HBV) vaccine. One of the factors associated with vaccine unresponsiveness may be the existence of current or past HBV infection. Regardless of the presence of HBsAg (overt infection), occult HBV infection (OBI, defined as presence of HBV DNA in the absence of HBsAg) might also account for some non- or hypo-response cases. Methods Sera from 120 HBsAg-negative HCWs with low and moderate levels of anti-HBs, <10 IU/mL (group I) and <100 IU/mL (group II) respectively, were selected and were examined for OBI by sensitive real-time PCR regardless of HBV serological profiles. Direct sequencing on surface genes was carried out in OBI-positive cases. Results Four (3.3%) were positive for OBI. All were negative for anti-HBc. Two of the positive cases had moderate levels of anti-HBs (>10 to <100 IU/mL). No significant differences were found between the two groups in terms of risk factors or serological data. No mutations were found in surface proteins of OBI cases. Conclusion OBI in these subjects might be due to other factors rather than presence of a determinant mutations. Healthcare workers with inadequate to moderate levels of anti-HBs (<100 IU/mL) following vaccination, regardless of their serological profile for HBV, should be tested for the presence of HBV DNA by sensitive molecular tests. Anti-HBc is not a reliable marker for suspicion of OBI, especially in high-risk group individuals. PMID:26716102

  16. Hepatitis B virus (HBV) receptors: Deficiency in tumor results in scant HBV infection and overexpression in peritumor leads to higher recurrence risk.

    PubMed

    Jing, Ying-Ying; Liu, Wen-Ting; Guo, Shi-Wei; Ye, Fei; Fan, Qing-Min; Yu, Guo-Feng; Yu, Dan-Dan; Gao, Lu; Sun, Kai; Han, Zhi-Peng; Li, Rong; Yang, Yang; Zhao, Qiu-Dong; Wu, Meng-Chao; Wang, Hong-Yang; Wei, Li-Xin

    2015-12-15

    Hepatitis B virus (HBV) infection is a risk factor for hepatocarcinogenesis and recurrence. Here, we sought to characterize intratumoral and peritumoral expression of HBsAg and its specific receptors in HBsAg-positive hepatocellular carcinoma (HCC) patients and further examined their correlation with the recurrence-free survival (RFS). HCC tissue and adjacent normal tissue specimens were acquired from HBsAg-positive patients. The presence of HBsAg and receptors, as well as hepatic progenitor cells (HPCs) were detected by tissue microassay and immunohistochemistry. Necroinflammatory activity was evaluated by HE staining. The mean IOD of HBsAg and HBV DNA in the intratumoral tissues was markedly lower than that in the peritumoral tissues (P < 0.001). Pearson correlation analysis further showed a significant correlation between the expression of HBsAg and NTCP (r = 0.461, P < 0.001) or ASGPR (r = 0.506, P < 0.001) in peritumoral tissues. And the peritumoral HBsAg and receptors presented a positive association with necroinflammatory activity (P < 0.05). Inflammation induced by HBV infection presented a positive association with HPCs activation (P < 0.05). Additionally, due to lack of HBV receptors, HPCs was not preferentially infected with HBV, but activated HPCs had a significant correlation with HBsAg expression in peritumoral tissues, and the peritumoral HPCs activation was associated with RFS of HCC patients, therefore, the overexpression of HBsAg and receptors in peritumor were also with higher recurrence risk (P < 0.05). In conclusion, lack of HBV receptors resulted in scant HBV infection in tumor cells, and overexpression of HBsAg and receptors in peritumor was strongly associated with higher recurrence risk in HCC patients. PMID:26515593

  17. Clearance of HBV DNA in immunized children born to HBsAg-positive mothers, years after being diagnosed with occult HBV infection.

    PubMed

    Sadeghi, A; Yahyapour, Y; Poortahmasebi, V; Shahmoradi, S; Roggendorf, M; Karimzadeh, H; Alavian, S M; Jazayeri, S M

    2016-04-01

    In a previous study, we observed immunoprophylaxis failure due to occult hepatitis B virus (HBV) infection (OBI) despite the presence of adequate levels of anti-HBs in 21 (28%) of 75 children born to HBsAg-positive mothers. The aim of the study was to explore the maintenance of this cryptic condition in this population. Of 21 OBI-positive children, 17 were enrolled. HBV serological profiles were determined by enzyme-linked immunosorbent assay. Highly sensitive real-time and standard PCR followed by direct sequencing were applied in positive cases. The mean age (±SD) of studied patients was 6.57 ± 2.75 years. All children still were negative for HBsAg. All but one (94%) were negative for HBV DNA. Only two children were positive for anti-HBc. The results of the most recent anti-HBs titration showed that 4 (23.5%) and 13 (76.5%) had low (<10 IU/mL) and adequate (>10 IU/mL) levels of anti-HBs, respectively. The only still OBI-positive patient had an HBV DNA level of 50 copy/mL, carried the G145R mutation when tested in 2009 and again in 2013 in the 'a' determinant region of the surface protein. Further follow-up showed that after 18 months, he was negative for HBV DNA. In high-risk children, the initial HBV DNA positivity early in the life (vertical infection) does not necessarily indicate a prolonged persistence of HBV DNA (occult infection). Adequate levels of anti-HBs after vaccine and hepatitis B immune globulin immunoprophylaxis following birth could eventually clear the virus as time goes by. Periodic monitoring of these children at certain time intervals is highly recommended. PMID:26598112

  18. Hepatitis B virus (HBV) receptors: Deficiency in tumor results in scant HBV infection and overexpression in peritumor leads to higher recurrence risk

    PubMed Central

    Ye, Fei; Fan, Qing-Min; Yu, Guo-Feng; Yu, Dan-Dan; Gao, Lu; Sun, Kai; Han, Zhi-Peng; Li, Rong; Yang, Yang; Zhao, Qiu-Dong; Wu, Meng-Chao; Wang, Hong-Yang; Wei, Li-Xin

    2015-01-01

    Hepatitis B virus (HBV) infection is a risk factor for hepatocarcinogenesis and recurrence. Here, we sought to characterize intratumoral and peritumoral expression of HBsAg and its specific receptors in HBsAg-positive hepatocellular carcinoma (HCC) patients and further examined their correlation with the recurrence-free survival (RFS). HCC tissue and adjacent normal tissue specimens were acquired from HBsAg-positive patients. The presence of HBsAg and receptors, as well as hepatic progenitor cells (HPCs) were detected by tissue microassay and immunohistochemistry. Necroinflammatory activity was evaluated by HE staining. The mean IOD of HBsAg and HBV DNA in the intratumoral tissues was markedly lower than that in the peritumoral tissues (P < 0.001). Pearson correlation analysis further showed a significant correlation between the expression of HBsAg and NTCP (r = 0.461, P < 0.001) or ASGPR (r = 0.506, P < 0.001) in peritumoral tissues. And the peritumoral HBsAg and receptors presented a positive association with necroinflammatory activity (P < 0.05). Inflammation induced by HBV infection presented a positive association with HPCs activation (P < 0.05). Additionally, due to lack of HBV receptors, HPCs was not preferentially infected with HBV, but activated HPCs had a significant correlation with HBsAg expression in peritumoral tissues, and the peritumoral HPCs activation was associated with RFS of HCC patients, therefore, the overexpression of HBsAg and receptors in peritumor were also with higher recurrence risk (P < 0.05). In conclusion, lack of HBV receptors resulted in scant HBV infection in tumor cells, and overexpression of HBsAg and receptors in peritumor was strongly associated with higher recurrence risk in HCC patients. PMID:26515593

  19. Extended HBV vaccination in liver transplant recipients for HBV-related cirrhosis: report of two successful cases.

    PubMed

    Di Paolo, D; Lenci, I; Trinito, M O; Tisone, G; Angelico, M

    2005-10-01

    The effectiveness of hepatitis B virus vaccination in liver transplant recipients for hepatitis B virus-related end-stage liver disease is controversial. We report two successful cases, who developed sustained protection after long-term vaccination. Case 1. A 58-year-old male, transplanted 9 years earlier, received three intramuscular monthly doses of 40 microg of recombinant S vaccine and developed an anti-hepatitis B surface titre of 154 IU/L. After an additional 40 microg dose, he reached an anti-hepatitis B surface peak of 687 IU/L and then maintained a "protective" titre (>100 IU/L) without further vaccinations for the next 40 months. At this time, revaccination with three monthly doses of 40 microg resulted in an anti-hepatitis B surface titre greater than 25,000 IU/L, sustained over time. Case 2. A 56-year-old woman, transplanted 8 years earlier, first received three intramuscular monthly doses of 40 microg of S vaccine without developing any detectable anti-HBs. She was then given multiple intradermal vaccine doses which resulted in a titre of 37 IU/L. Next, after readministration of three 40 microg intramuscular monthly doses, she developed an anti-HBs titre of 280 IU/L. In the following 4 years, the anti-HBs titre dropped below 100 IU/L four times (at month 20, 30, 38 and 44) and readministration of single 40 microg doses of vaccine was always sufficient to restore a protective titre. Conclusion. Extended HBV vaccination may afford valid protection against HBV recurrence in selected liver transplant recipients. PMID:16024302

  20. Molecular dissection of HBV evasion from restriction factor tetherin: A new perspective for antiviral cell therapy

    PubMed Central

    Miyakawa, Kei; Matsunaga, Satoko; Watashi, Koichi; Sugiyama, Masaya; Kimura, Hirokazu; Yamamoto, Naoki; Mizokami, Masashi; Wakita, Takaji; Ryo, Akihide

    2015-01-01

    Viruses have evolved various strategies to escape from the innate cellular mechanisms inhibiting viral replication and spread. Extensive evidence has highlighted the ineffectiveness of interferon (IFN) therapy against chronic hepatitis B virus (HBV) infection, implying the existence of mechanisms by which HBV evades IFN-induced antiviral responses. In our current study, we demonstrate that HBV surface protein (HBs) plays a crucial role in counteracting the IFN-induced antiviral response mediated by tetherin (also known as BST-2). The type I IFN treatment of HBV-producing cells marginally but significantly inhibited the release of HBsAg and viral DNA, but this release was recovered by the knockdown of tetherin. HBs can interact with tetherin via its fourth transmembrane domain thereby inhibiting its dimerization and antiviral activity. The expression of a tetherin mutant devoid of the HBs-binding domain promoted a prominent restriction of HBV particle production that eventually resulted in the alleviation of caspase-1-mediated cytotoxicity and interleukin-1? secretion in induced pluripotent stem cell (iPSC)-derived hepatocytes. Our current results thus reveal a previously undescribed molecular link between HBV and tetherin during the course of an IFN-induced antiviral response. In addition, strategies to augment the antiviral activity of tetherin by impeding tetherin-HBs interactions may be viable as a therapeutic intervention against HBV. PMID:26334101

  1. Molecular dissection of HBV evasion from restriction factor tetherin: A new perspective for antiviral cell therapy.

    PubMed

    Miyakawa, Kei; Matsunaga, Satoko; Watashi, Koichi; Sugiyama, Masaya; Kimura, Hirokazu; Yamamoto, Naoki; Mizokami, Masashi; Wakita, Takaji; Ryo, Akihide

    2015-09-01

    Viruses have evolved various strategies to escape from the innate cellular mechanisms inhibiting viral replication and spread. Extensive evidence has highlighted the ineffectiveness of interferon (IFN) therapy against chronic hepatitis B virus (HBV) infection, implying the existence of mechanisms by which HBV evades IFN-induced antiviral responses. In our current study, we demonstrate that HBV surface protein (HBs) plays a crucial role in counteracting the IFN-induced antiviral response mediated by tetherin (also known as BST-2). The type I IFN treatment of HBV-producing cells marginally but significantly inhibited the release of HBsAg and viral DNA, but this release was recovered by the knockdown of tetherin. HBs can interact with tetherin via its fourth transmembrane domain thereby inhibiting its dimerization and antiviral activity. The expression of a tetherin mutant devoid of the HBs-binding domain promoted a prominent restriction of HBV particle production that eventually resulted in the alleviation of caspase-1-mediated cytotoxicity and interleukin-1β secretion in induced pluripotent stem cell (iPSC)-derived hepatocytes. Our current results thus reveal a previously undescribed molecular link between HBV and tetherin during the course of an IFN-induced antiviral response. In addition, strategies to augment the antiviral activity of tetherin by impeding tetherin-HBs interactions may be viable as a therapeutic intervention against HBV. PMID:26334101

  2. Association of an HLA-G 14-bp Insertion/Deletion polymorphism with high HBV replication in chronic hepatitis.

    PubMed

    Laaribi, A B; Zidi, I; Hannachi, N; Ben Yahia, H; Chaouch, H; Bortolotti, D; Zidi, N; Letaief, A; Yacoub, S; Boudabous, A; Rizzo, R; Boukadida, J

    2015-10-01

    Identification of an HLA-G 14-bp Insertion/Deletion (Ins/Del) polymorphism at the 3' untranslated region of HLA-G revealed its importance in HLA-G mRNA stability and HLA-G protein level variation. We evaluated the association between the HLA-G 14-bp Ins/Del polymorphism in patients with chronic Hepatitis B virus (HBV) infection in a case-control study. Genomic DNA was extracted from 263 patients with chronic HBV hepatitis and 246 control subjects and was examined for the HLA-G 14-bp Ins/Del polymorphism by PCR. The polymorphic variants were genotyped in chronic HBV seropositive cases stratified according to HBV DNA levels, fibrosis stages and in a control population. There was no statistical significant association between the 14-bp Ins/Del polymorphism and increased susceptibility to HBV infection neither for alleles (P = 0.09) nor for genotypes (P = 0.18). The stratification of HBV patients based on HBV DNA levels revealed an association between the 14-bp Ins/Del polymorphism and an enhanced HBV activity with high HBV DNA levels. In particular, the Ins allele was significantly associated with high HBV DNA levels (P = 0.0024, OR = 1.71, 95% CI 1.2-2.4). The genotype Ins/Ins was associated with a 2.5-fold (95% CI, 1.29-4.88) increased risk of susceptibility to high HBV replication compared with the Del/Del and Ins/Del genotypes. This susceptibility is linked to the presence of two Ins alleles. No association was observed between the 14-bp Ins/Del polymorphism and fibrosis stage of HBV infection. We observed an association between the 14-bp Ins/Del polymorphism and high HBV replication characterized by high HBV DNA levels in chronic HBV patients. These results suggest a potential prognostic value for disease outcome evaluation. PMID:25619305

  3. Correlation Between Hepatitis B Surface Antigen Titers and HBV DNA Levels

    PubMed Central

    Alghamdi, Amal; Aref, Nagwa; El-Hazmi, Malak; Al-Hamoudi, Waleed; Alswat, Khalid; Helmy, Ahmed; Sanai, Faisal M.; Abdo, Ayman A.

    2013-01-01

    Background/Aim: To assess the correlation between serum HBsAg titers and hepatitis B virus (HBV) DNA levels in patients with hepatitis B envelop antigen-negative (HBeAg −ve) HBV genotype-D (HBV/D) infection. Patients and Methods: A total of 106 treatment- naïve, HBeAg −ve HBV/D patients were included; 78 in the inactive carrier (IC) state and 28 in the active hepatitis (AH) stage. HBV DNA load and HBsAg titers were tested using TaqMan real-time polymerase chain reaction (PCR) and automated chemiluminescent microparticle immunoassay, respectively. Results: The median (range) log10 HBsAg titer was significantly lower in the IC group compared with AH group, 3.09 (−1 to –4.4) versus 3.68 (−0.77 to 5.09) IU/mL, respectively; P < 0.001. The suggested cutoff value of HBsAg titer to differentiate between the two groups was 3.79 log10 IU/mL. In addition, there was a significant positive correlation between HBsAg and HBV DNA levels in the whole cohort, AH, and IC groups (r = 0.6, P < 0.0001; r = 0.591, P = 0.001; and r = 0.243, P = 0.032, respectively). Conclusion: Serum HBsAg titers may correlate with HBV DNA in treatment-naïve HBeAg –ve HBV/D patients, and supports the use of HBsAg levels in clinical practice as a predictor of serum HBV DNA levels. PMID:24195978

  4. Occult hepatitis B demonstrated by anti-HBc and HBV DNA in HIV-positive patients

    PubMed Central

    Honarmand, Arezoo; Pourahmad, Morteza; Solhjoo, Kavous; Kohan, Mahmoud; Davami, Mohamad Hassan; Mostafavi Zadeh, Seyed Kamyar

    2014-01-01

    Background: In patients who are hepatitis B virus (HBV) DNA-positive, but HBV surface antigen (HBsAg) -negative, the infection is referred to as occult hepatitis B infection (OBI). Occult HBV infection is harmful when other liver diseases are present, and can aggravate liver damage in in patients with chronic liver diseases. In human immunodeficiency virus (HIV) infection the suppression of viral replication by the immune system might be inactivated, and classical HBV infection in OBI patients may occur. Health care professionals should be aware of OBI in HIV patients. The routine test for HBV infection in Iran is the enzyme-linked immunosorbent assay for the HBV surface antigen (ELISA HBsAg); therefore, the aim of this study was to evaluate the prevalence of OBI in Iranian HIV patients. Methods: This cross-sectional study was conducted in 2012 on sera from all the known and accessible HIV patients in Jahrom and Fassa, two cities in southern Iran. All samples were tested for the HBsAg, HBV core antibody (HBcAb). All the results were analyzed using SPSS. Results: Of the 91 patients, seven (7.7%) were HBsAg-positive and forty-five (49.5%) were HBcAb-positive. In patients with negative HBsAg (84 patients), 39 (46.4%) were HBcAb positive and 53 (63%) were positive for HBV DNA. Conclusion: The prevalence of HBV infection is relatively high in HIV patients, and more accurate tests than those presently in use should be used for diagnosis.

  5. Hospital Cluster of HBV Infection: Molecular Evidence of Patient-to-Patient Transmission through Lancing Device

    PubMed Central

    Lanini, Simone; Garbuglia, Anna Rosa; Puro, Vincenzo; Solmone, Mariacarmela; Martini, Lorena; Arcese, William; Nanni Costa, Alessandro; Borgia, Piero; Piselli, Pierluca; Capobionchi, Maria Rosaria; Ippolito, Giuseppe

    2012-01-01

    Introduction In western countries the transmission of hepatitis B virus (HBV) transmission through multi-patients lancing devices has been inferred since early ‘90s, however no study has ever provided biological evidence which directly link these device with HBV cross-infection. Here we present results of an outbreak investigation which could associate, by molecular techniques, the use of lancing device on multiple patients with HBV transmission in an Italian oncohematology unit. Methods The outbreak investigation was designed as a retrospective cohort study to identify all potential cases. All cases identified were eventually confirmed through molecular epidemiology techniques. Audit of personnel including extensive review of infection control measures and reviewing personnel's tests for HBV was done identify transmission route. Results Between 4 May 2006 and 21 February 2007, six incident cases of HBV infection were reported among 162 patients admitted in the oncohematology. The subsequent molecular instigation proved that 3 out 6 incident cases and one prevalent cases (already infected with HBV at the admission) represented a monophyletic cluster of infection. The eventual environmental investigation found that an identical HBV viral strain was present on a multi-patients lancing device in use in the unit and the inferential analysis showed a statistically significant association between undergoing lancing procedures and the infection. Discussion This investigation provide molecular evidence to link a HBV infection cluster to multi-patients lancing device and highlights that patients undergoing capillary blood sampling by non-disposable lancing device may face an unacceptable increased risk of HBV infection. Therefore we believe that multi-patients lancing devices should be banned from healthcare settings and replace with disposable safety lancets that permanently retract to prevent the use of the same device on multiple patients. The use of non-disposable lancing devices should be restricted to individual use at patients' home. PMID:22412991

  6. Predominance of genotype A HBV in an HBV-HIV-1 dually positive population compared with an HIV-1-negative counterpart in Japan.

    PubMed

    Koibuchi, T; Hitani, A; Nakamura, T; Nojiri, N; Nakajima, K; Jyuji, T; Iwamoto, A

    2001-08-01

    Hepatitis B virus (HBV) has seven genotypes, A to G. Previous studies have shown that genotype C is the most prevalent strain in chronic HBV carriers in East Asia. This study was undertaken to investigate the epidemiology of HBV genotypes among Japanese patients who are coinfected with human immunodeficiency virus type 1 (HIV-1). The sequences of the complete hepatitis B surface antifen (HBsAg) genes were obtained from 18 coinfected Japanese patients. Among the 18 patients, 12 of 13 men who had sex with men (MSM) had genotype A (92%), whereas only one of five heterosexual or hemophiliac patients had genotype A. The predominance of genotype A HBV in MSM showed a striking contrast to the current genotype prevalence in the Japanese population. Owing to the recent decrease in the rate of vertical transmission in Japan, the role of sexual behavior in the transmission of HBV cannot be overestimated. Thus, the relative proportion of genotype A may gradually increase in Japan. PMID:11468727

  7. Hepatitis B virus and primary hepatocellular carcinoma: treatment of HBV carriers with Phyllanthus amarus.

    PubMed

    Blumberg, B S; Millman, I; Venkateswaran, P S; Thyagarajan, S P

    1990-03-01

    A viricide capable of eliminating hepatitis B virus (HBV) from chronic carriers should, theoretically, decrease the risk of primary hepatocellular carcinoma. Extracts of Phyllanthus amarus have been shown to inhibit the DNA polymerase of HBV and woodchuck hepatitis virus (WHV) in vitro. Three of four recently infected WHV carriers treated i.p. with P. amarus extract lost WHV, animals infected for greater than or equal to 3 months showed a decrease in virus levels. Preliminary results in human carriers treated orally with P. amarus for 1 month indicated that approximately 60% of the carriers lost HBV during the observation period. PMID:2158192

  8. Hepatitis B virus and hepatocellular carcinoma--treatment of HBV carriers with Phyllanthus amarus.

    PubMed

    Blumberg, B S; Millman, I; Venkateswaran, P S; Thyagarajan, S P

    1989-01-01

    Extracts of Phyllanthus amarus inhibit the DNA polymerase of HBV and related viruses. Woodchuck carriers of woodchuck hepatitis virus (WHV) were treated intraperitoneally with P. amarus extract. Three of four animals which had been recently infected lost the virus. Animals infected for about 3 months or more had a decrease in virus levels. Human carriers of HBV were treated orally for 1 month. About 60% of the carriers lost HBV, which did not return during the observation period. Fractions containing active principles are now being isolated and characterized. PMID:2559794

  9. Combinatorial RNA Interference Therapy Prevents Selection of Pre-existing HBV Variants in Human Liver Chimeric Mice

    PubMed Central

    Shih, Yao-Ming; Sun, Cheng-Pu; Chou, Hui-Hsien; Wu, Tzu-Hui; Chen, Chun-Chi; Wu, Ping-Yi; Enya Chen, Yu-Chen; Bissig, Karl-Dimiter; Tao, Mi-Hua

    2015-01-01

    Selection of escape mutants with mutations within the target sequence could abolish the antiviral RNA interference activity. Here, we investigated the impact of a pre-existing shRNA-resistant HBV variant on the efficacy of shRNA therapy. We previously identified a highly potent shRNA, S1, which, when delivered by an adeno-associated viral vector, effectively inhibits HBV replication in HBV transgenic mice. We applied the “PICKY” software to systemically screen the HBV genome, then used hydrodynamic transfection and HBV transgenic mice to identify additional six highly potent shRNAs. Human liver chimeric mice were infected with a mixture of wild-type and T472C HBV, a S1-resistant HBV variant, and then treated with a single or combined shRNAs. The presence of T472C mutant compromised the therapeutic efficacy of S1 and resulted in replacement of serum wild-type HBV by T472C HBV. In contrast, combinatorial therapy using S1 and P28, one of six potent shRNAs, markedly reduced titers for both wild-type and T472C HBV. Interestingly, treatment with P28 alone led to the emergence of escape mutants with mutations in the P28 target region. Our results demonstrate that combinatorial RNAi therapy can minimize the escape of resistant viral mutants in chronic HBV patients. PMID:26482836

  10. Genomic and transcriptome profiling identified both human and HBV genetic variations and their interactions in Chinese hepatocellular carcinoma.

    PubMed

    Dong, Hua; Qian, Ziliang; Zhang, Lan; Chen, Yunqin; Ren, Zhenggang; Ji, Qunsheng

    2015-12-01

    Interaction between HBV and host genome integrations in hepatocellular carcinoma (HCC) development is a complex process and the mechanism is still unclear. Here we described in details the quality controls and data mining of aCGH and transcriptome sequencing data on 50 HCC samples from the Chinese patients, published by Dong et al. (2015) (GEO#: GSE65486). In additional to the HBV-MLL4 integration discovered, we also investigated the genetic aberrations of HBV and host genes as well as their genetic interactions. We reported human genome copy number changes and frequent transcriptome variations (e.g. TP53, CTNNB1 mutation, especially MLL family mutations) in this cohort of the patients. For HBV genotype C, we identified a novel linkage disequilibrium region covering HBV replication regulatory elements, including basal core promoter, DR1, epsilon and poly-A regions, which is associated with HBV core antigen over-expression and almost exclusive to HBV-MLL4 integration. PMID:26697315

  11. Genomic and transcriptome profiling identified both human and HBV genetic variations and their interactions in Chinese hepatocellular carcinoma

    PubMed Central

    Dong, Hua; Qian, Ziliang; Zhang, Lan; Chen, Yunqin; Ren, Zhenggang; Ji, Qunsheng

    2015-01-01

    Interaction between HBV and host genome integrations in hepatocellular carcinoma (HCC) development is a complex process and the mechanism is still unclear. Here we described in details the quality controls and data mining of aCGH and transcriptome sequencing data on 50 HCC samples from the Chinese patients, published by Dong et al. (2015) (GEO#: GSE65486). In additional to the HBV-MLL4 integration discovered, we also investigated the genetic aberrations of HBV and host genes as well as their genetic interactions. We reported human genome copy number changes and frequent transcriptome variations (e.g. TP53, CTNNB1 mutation, especially MLL family mutations) in this cohort of the patients. For HBV genotype C, we identified a novel linkage disequilibrium region covering HBV replication regulatory elements, including basal core promoter, DR1, epsilon and poly-A regions, which is associated with HBV core antigen over-expression and almost exclusive to HBV-MLL4 integration. PMID:26697315

  12. TGF-? triggers HBV cccDNA degradation through AID-dependent deamination.

    PubMed

    Qiao, Ying; Han, Xiaoxu; Guan, Gefei; Wu, Na; Sun, Jianbo; Pak, Vladimir; Liang, Guoxin

    2016-02-01

    The covalently closed circular DNA (cccDNA) of hepatitis B virus (HBV) is a viral center molecule for HBV infection and persistence. However, the cellular restriction factors of HBV cccDNA are not well understood. Here, we show that TGF-? can induce nuclear viral cccDNA degradation and hypermutation via activation-induced cytidine deaminase (AID) deamination activity in hepatocytes. This suppression by TGF-? is abrogated when AID or the activity of uracil-DNA glycosylase (UNG) is absent, which indicates that AID deamination and the UNG-mediated excision of uracil act in concert to degrade viral cccDNA. Moreover, the HBV core protein promotes the interaction between AID and viral cccDNA. Overall, our results indicate a novel molecular mechanism that allows cytokine TGF-? to restrict viral nuclear cccDNA in innate immunity, thereby suggesting a novel method for potentially eliminating cccDNA. PMID:26867650

  13. Neutrophil-to-Lymphocyte Ratio Predicts Early Mortality in Patients with HBV-Related Decompensated Cirrhosis

    PubMed Central

    Zhang, Honggang; Sun, Qinqin; Mao, Weilin; Fan, Jian; Ye, Bo

    2016-01-01

    Background. The neutrophil-to-lymphocyte ratio (NLR) is an inflammation index that has been shown to independently predict poor clinical outcomes. We aimed to evaluate the clinical value of NLR in the prediction of 30-day mortality in patients with HBV-related decompensated cirrhosis (HBV-DeCi). Methods. This was a retrospective cohort study that included 148 patients with HBV-DeCi. Results. An elevated NLR was associated with increased severity of liver disease and mortality within 30 days. Multivariate analysis suggested that NLR, similar to the model for end-stage liver disease (MELD) score, is an additional independent predictor of 30-day mortality (P < 0.01). Conclusion. Our results suggest that a high NLR can be considered a new independent biomarker for predicting 30-day mortality in patients with HBV-DeCi.

  14. Chronic hepatitis B infection and HBV DNA-containing capsids: Modeling and analysis

    NASA Astrophysics Data System (ADS)

    Manna, Kalyan; Chakrabarty, Siddhartha P.

    2015-05-01

    We analyze the dynamics of chronic HBV infection taking into account both uninfected and infected hepatocytes along with the intracellular HBV DNA-containing capsids and the virions. While previous HBV models have included either the uninfected hepatocytes or the intracellular HBV DNA-containing capsids, our model accounts for both these two populations. We prove the conditions for local and global stability of both the uninfected and infected steady states in terms of the basic reproduction number. Further, we incorporate a time lag in the model to encompass the intracellular delay in the production of the infected hepatocytes and find that this delay does not affect the overall dynamics of the system. The results for the model and the delay model are finally numerically illustrated.

  15. Sorafenib Combined With Transarterial Chemoembolization in Treating HBV-infected Patients With Intermediate Hepatocellular Carcinoma

    ClinicalTrials.gov

    2012-04-24

    PHENYTOIN/SORAFENIB [VA Drug Interaction]; Liver Neoplasms; Carcinoma, Hepatocellular; Digestive System Neoplasms; Neoplasms by Site; Liver Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; DOXORUBICIN/TRASTUZUMAB [VA Drug Interaction]; HBV

  16. HBx truncation mutants differentially modulate SREBP-1a and -1c transcription and HBV replication.

    PubMed

    Wu, Qi; Liu, Qiang

    2015-12-01

    As master transcription factors for lipogenesis, sterol regulatory element-binding protein-1 (SREBP-1) has two isoforms, SREBP-1a and SREBP-1c. Hepatitis B virus X (HBx) can up-regulate the transcription of both SREBP-1a and SREBP-1c. HBx is a small protein consisting of 154 amino acids. Truncated forms of HBx, often found in the tissues after HBV infection, may have a role in the pathogenesis associated with HBV infection. In this study, we examined the effects of two HBx truncation mutants, HBx aa. 1-127 and HBx aa. 43-154, on the transcription of SREBP-1a and SREBP-1c. HBx 1-127 can up-regulate SREBP-1c, but not SREBP-1a transcription, whereas HBx 43-154 can activate SREBP-1a, but not SREBP-1c transcription. We further determined the activities of two HBV enhancers after the expression of the truncated HBx proteins. HBx 1-127 and HBx 43-154 can only up-regulate HBV enhancer I or HBV enhancer II, respectively. Knocking down SREBP-1 abrogates enhancer activation by HBx proteins, suggesting a role of SREBP-1. In addition, using HBV enhancer mutants, we found that the binding sequence for AP-1 on enhancer I is essential for its activation by HBx 1-127, whereas C/EBP and Sp1 sites are required for enhancer II activation by HBx 43-154. Finally, we showed that both HBx 1-127 and HBx 43-154 can increase HBV transcription and HBV replication dependent upon SREBP-1 because knocking down SREBP-1 abrogates the up-regulation. Furthermore, upon ectopic expression of either SREBP-1a or SREBP-1c, we showed that SREBP-1a is involved in HBV transcription and replication up-regulation by HBx 43-154, whereas SREBP-1c is involved in HBV transcription and replication up-regulation by HBx 1-127. Our results should help understand the interactions between HBV and the SREBP-1-mediated lipogenic pathway. PMID:26191620

  17. The Dual Role of an ESCRT-0 Component HGS in HBV Transcription and Naked Capsid Secretion.

    PubMed

    Chou, Shu-Fan; Tsai, Ming-Lin; Huang, Jyun-Yuan; Chang, Ya-Shu; Shih, Chiaho

    2015-10-01

    The Endosomal Sorting Complex Required for Transport (ESCRT) is an important cellular machinery for the sorting and trafficking of ubiquitinated cargos. It is also known that ESCRT is required for the egress of a number of viruses. To investigate the relationship between ESCRT and hepatitis B virus (HBV), we conducted an siRNA screening of ESCRT components for their potential effect on HBV replication and virion release. We identified a number of ESCRT factors required for HBV replication, and focused our study here on HGS (HRS, hepatocyte growth factor-regulated tyrosine kinase substrate) in the ESCRT-0 complex. Aberrant levels of HGS suppressed HBV transcription, replication and virion secretion. Hydrodynamic delivery of HGS in a mouse model significantly suppressed viral replication in the liver and virion secretion in the serum. Surprisingly, overexpression of HGS stimulated the release of HBV naked capsids, irrespective of their viral RNA, DNA, or empty contents. Mutant core protein (HBc 1-147) containing no arginine-rich domain (ARD) failed to secrete empty virions with or without HGS. In contrast, empty naked capsids of HBc 1-147 could still be promoted for secretion by HGS. HGS exerted a strong positive effect on the secretion of naked capsids, at the expense of a reduced level of virions. The association between HGS and HBc appears to be ubiquitin-independent. Furthermore, HBc is preferentially co-localized with HGS near the cell periphery, instead of near the punctate endosomes in the cytoplasm. In summary, our work demonstrated the importance of an optimum level of HGS in HBV propagation. In addition to an effect on HBV transcription, HGS can diminish the pool size of intracellular nucleocapsids with ongoing genome maturation, probably in part by promoting the secretion of naked capsids. The secretion routes of HBV virions and naked capsids can be clearly distinguished based on the pleiotropic effect of HGS involved in the ESCRT-0 complex. PMID:26431433

  18. Osteopontin promotes dendritic cell maturation and function in response to HBV antigens

    PubMed Central

    Cui, Guangying; Chen, Jianing; He, Jianqin; Lu, Chong; Wei, Yingfeng; Wang, Lin; Xu, Xuejun; Li, Lanjuan; Uede, Toshimitsu; Diao, Hongyan

    2015-01-01

    Purpose Dendritic cells (DCs) play critical roles in promoting innate and adaptive immunity in microbial infection. Functional impairment of DCs may mediate the suppression of viral-specific T-cell immune response in chronic hepatitis B (CHB) patients. Osteopontin (OPN) is involved in several liver diseases and infectious diseases. However, whether OPN affects DC function in hepatitis B virus (HBV) infection is unknown. Methods Twenty CHB patients and 20 healthy volunteers were recruited. OPN secreted by DCs was compared. Peripheral blood mononuclear cells cultured with OPN antibody were examined to study the costimulatory molecular expression and interleukin (IL)-12 production of DCs after HBV antigenic stimulation. OPN-deficient mice were used to investigate the influence of OPN on DC maturation and function after HBV antigenic stimulation in vitro and in vivo. Exogenous OPN was administrated to further verify the functioning of DCs from CHB patients upon HBV antigenic stimulation. Results We found that OPN production of DCs from CHB patients was significantly lower than those from healthy volunteers. The absence of OPN impaired IL-12 production and costimulatory molecular expression of DCs upon stimulation with HBV antigens. Defective DC function led to reduced activation of Th1 response to HBV antigens. In addition, OPN deficiency in DCs reduced the HBV antigen-induced inflammatory response in the liver of mice. Importantly, OPN administration significantly promoted the maturation of DCs from CHB patients in vitro. Conclusion These findings suggested that OPN could improve the maturation and functioning of DCs in the immune response to HBV antigens, which might be useful to further improve the effect of DC vaccine. PMID:26109844

  19. The incidence of HBV and HCV infection in Australian travelers to Asia.

    PubMed

    Johnson, Douglas F; Ratnam, Irani; Matchett, Elizabeth; Earnest-Silveria, Linda; Christiansen, Dale; Leder, Karin; Grayson, Michael L; Torresi, Joseph

    2013-01-01

    We analyzed paired pre- and post-travel sera in a cohort of Australian travelers to Asia and demonstrated the acquisition of hepatitis C virus (HCV) and hepatitis B virus (HBV) infection. The incidence density in nonimmune travelers for HCV infection was calculated as 1.8 infections per 10,000 traveler-days and for HBV infection 2.19 per 10,000 traveler-days. PMID:23577867

  20. The Dual Role of an ESCRT-0 Component HGS in HBV Transcription and Naked Capsid Secretion

    PubMed Central

    Chou, Shu-Fan; Tsai, Ming-Lin; Huang, Jyun-Yuan; Chang, Ya-Shu; Shih, Chiaho

    2015-01-01

    The Endosomal Sorting Complex Required for Transport (ESCRT) is an important cellular machinery for the sorting and trafficking of ubiquitinated cargos. It is also known that ESCRT is required for the egress of a number of viruses. To investigate the relationship between ESCRT and hepatitis B virus (HBV), we conducted an siRNA screening of ESCRT components for their potential effect on HBV replication and virion release. We identified a number of ESCRT factors required for HBV replication, and focused our study here on HGS (HRS, hepatocyte growth factor-regulated tyrosine kinase substrate) in the ESCRT-0 complex. Aberrant levels of HGS suppressed HBV transcription, replication and virion secretion. Hydrodynamic delivery of HGS in a mouse model significantly suppressed viral replication in the liver and virion secretion in the serum. Surprisingly, overexpression of HGS stimulated the release of HBV naked capsids, irrespective of their viral RNA, DNA, or empty contents. Mutant core protein (HBc 1–147) containing no arginine-rich domain (ARD) failed to secrete empty virions with or without HGS. In contrast, empty naked capsids of HBc 1–147 could still be promoted for secretion by HGS. HGS exerted a strong positive effect on the secretion of naked capsids, at the expense of a reduced level of virions. The association between HGS and HBc appears to be ubiquitin-independent. Furthermore, HBc is preferentially co-localized with HGS near the cell periphery, instead of near the punctate endosomes in the cytoplasm. In summary, our work demonstrated the importance of an optimum level of HGS in HBV propagation. In addition to an effect on HBV transcription, HGS can diminish the pool size of intracellular nucleocapsids with ongoing genome maturation, probably in part by promoting the secretion of naked capsids. The secretion routes of HBV virions and naked capsids can be clearly distinguished based on the pleiotropic effect of HGS involved in the ESCRT-0 complex. PMID:26431433

  1. IFN-? inhibits liver progenitor cell proliferation in HBV-infected patients and in 3,5-diethoxycarbonyl-1,4-dihydrocollidine diet-fed mice

    PubMed Central

    Weng, Hong-lei; Feng, De-chun; Radaeva, Svetlana; Kong, Xiao-ni; Wang, Lei; Liu, Yan; Li, Qi; Shen, Hong; Gao, Yun-peng; Mllenbach, Roman; Munker, Stefan; Huang, Tong; Chen, Jia-lin; Zimmer, Vincent; Lammert, Frank; Mertens, Peter R; Cai, Wei-min; Dooley, Steven; Gao, Bin

    2013-01-01

    Background & Aims Proliferation of liver progenitor cells (LPCs) is associated with inflammation and fibrosis in chronic liver diseases. However, how inflammation and fibrosis affect LPCs remains obscure. Methods We examined the role of interferon (IFN)-?, an important pro-inflammatory and anti-fibrotic cytokine, in LPC expansion in HBV-infected patients and in mice challenged with 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC)- or choline-deficient, ethionine-supplemented (CDE) diet as well as in primary LPCs and LPC cell line. Results The CK19 staining scores correlated with inflammation and fibrosis grades in the livers from 110 HBV-infected patients. Nine-month IFN-? treatment decreased LPC numbers, inflammation, and fibrosis in these HBV-infected patients. Similarly, a two-week IFN-? treatment also decreased LPC activation in DDC-treated mice. Disruption of IFN-? or its signaling components (eg. IFNGR, STAT1, and IRF-1) increased LPC proliferation and liver fibrosis in DDC-fed mice. In contrast, deletion of IFN-? did not increase but rather slightly reduced LPC proliferation in CDE-fed mice. In vitro, IFN-? attenuated proliferation of the LPC cell line BMOL cells and of primary LPCs from wild-type mice, but not STAT1?/? or IRF-1?/? mice. Furthermore, co-culture assays suggest that IFN-? can indirectly promote LPC proliferation via the activation of macrophages but attenuate it via the inhibition of hepatic stellate cells. Conclusion IFN-? inhibits LPC expansion via the direct inhibition of LPC proliferation and indirect attenuation of liver fibrosis in the DDC model but it may also enhance LPC expansion via the promotion of inflammation in the CDE model; thereby playing dual roles in regulating LPC proliferation in vivo. PMID:23747755

  2. The epidemiology and natural history of HIV/HBV and HIV/HCV co-infections.

    PubMed

    Mathews, Gail; Bhagani, Sanjay

    2003-11-01

    Both hepatitis B virus (HBV) and hepatitis C virus (HCV) are more common in HIV-infected individuals than in the general population as a result of shared risk factors for viral acquisition. Populations of injecting drug users are at particularly high risk for HIV/HCV co-infection. Co-infection with HIV results in greater likelihood of chronicity and enhanced viral replication in the setting of both HBV and HCV infections. Current evidence suggests that HIV infection may have a negative impact on HBV-related liver disease progression, although the mechanisms for this are unclear. HBV seems to have little impact on the progression of HIV disease. HIV co-infection hastens HCV-related liver disease with faster progression to cirrhosis, end-stage liver disease and occurrence of hepatocellular carcinoma. There is still conflicting evidence on the impact of HCV on HIV progression with inconsistent results from cohort studies. Long-term follow-up of highly active antiretroviral therapy (HAART)-treated patients will help elucidate this further. Antiretroviral agents have little long-term impact on HCV viraemia, although some have significant anti-HBV activity. Morbidity and mortality from end-stage liver disease in HIV-infected individuals is increasing and every effort should be made to identify, educate and treat as appropriate those with HBV or HCV co-infection. PMID:14671504

  3. CRISPR/Cas9-based tools for targeted genome editing and replication control of HBV.

    PubMed

    Peng, Cheng; Lu, Mengji; Yang, Dongliang

    2015-10-01

    Hepatitis B virus (HBV) infection remains a major global health problem because current therapies rarely eliminate HBV infections to achieve a complete cure. A different treatment paradigm to effectively clear HBV infection and eradicate latent viral reservoirs is urgently required. In recent years, the development of a new RNA-guided gene-editing tool, the CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats/CRISPR-associated nuclease 9) system, has greatly facilitated site-specific mutagenesis and represents a very promising potential therapeutic tool for diseases, including for eradication of invasive pathogens such as HBV. Here, we review recent advances in the use of CRISPR/Cas9, which is designed to target HBV specific DNA sequences to inhibit HBV replication and to induce viral genome mutation, in cell lines or animal models. Advantages, limitations and possible solutions, and proposed directions for future research are discussed to highlight the opportunities and challenges of CRISPR/Cas9 as a new, potentially curative therapy for chronic hepatitis B infection. PMID:26511989

  4. Cortical signature of patients with HBV-related cirrhosis without overt hepatic encephalopathy: a morphometric analysis

    PubMed Central

    Wu, Xiu; Lv, Xiao-Fei; Zhang, Yu-Ling; Wu, Hua-Wang; Cai, Pei-Qiang; Qiu, Ying-Wei; Zhang, Xue-Lin; Jiang, Gui-Hua

    2015-01-01

    Previous studies have shown that patients with hepatitis B virus-related cirrhosis (HBV-RC) without overt hepatic encephalopathy (OHE) are associated with a varying degree of cognitive dysfunction. Several resting-state functional magnetic resonance imaging (fMRI) studies have been conducted to explore the neural correlates of such cognitive deficits, whereas little effort has been made to investigate the cortical integrity in cirrhotic patients without OHE. Here, using cortical thickness, surface area and local gyrification index (lGI), this study performed a comprehensive analysis on the cortical morphometry of patients with HBV-RC without OHE (HBV-RC-NOHE) vs. matched healthy controls. Compared with healthy controls, we found significantly increased cortical thickness in the bilateral lingual and parahippocampal gyrus, right posterior cingulate cortex, precuneus, peri-calcarine sulcus and fusiform gyrus in patient with HBV-RC-NOHE, which may closely relate to be the low-grade brain edema. Cortical gyrification analysis showed significantly increased lGI in the left superior and inferior parietal cortex as well as lateral occipital cortex, which was speculated to be associated with disruptions in white matter connectivity and sub-optimal intra-cortical organization. In addition, the mean cortical thickness/lGI of the regions with structural abnormalities was shown to be negatively correlated with psychometric hepatic encephalopathy score (PHES) of the patients with HBV-RC-NOHE. These morphological changes may serve as potential markers for the preclinical diagnosis and progression of HBV-RC-NOHE. PMID:26106307

  5. Pediatric HIV-HBV Coinfection in Lusaka, Zambia: Prevalence and Short-Term Treatment Outcomes.

    PubMed

    Peebles, Kathryn; Nchimba, Lweendo; Chilengi, Roma; Bolton Moore, Carolyn; Mubiana-Mbewe, Mwangelwa; Vinikoor, Michael J

    2015-12-01

    Hepatitis B virus (HBV) is endemic in Africa, where it may occur as an HIV coinfection. Data remain limited on HIV-HBV epidemiology in Africa, particularly in children. Using programmatic data from pediatric HIV clinics in Lusaka, Zambia during 2011-2014, we analyzed the prevalence of chronic HBV coinfection (defined as a single positive hepatitis B surface antigen [HBsAg] test) and its impact on immune recovery and liver enzyme elevation (LEE) during the first year of antiretroviral therapy. Among 411 children and adolescents, 10.4% (95% confidence interval, 7.6-14.1) had HIV-HBV. Coinfected patients were more likely to have World Health Organization stage 3/4, LEE and CD4 <14% at care entry (all p?HBV vaccine introduction. These findings support screening pediatric HIV patients in Africa for HBV coinfection. Dedicated cohorts are needed to assess long-term outcomes of coinfection. PMID:26338421

  6. Expression and significance of HBV genes and their antigens in human primary intrahepatic cholangiocarcinoma

    PubMed Central

    Wang, Wen-Liang; Gu, Guang-Yu; Hu, Min

    1998-01-01

    AIM: To explore the etiology and pathogenesis of human primary intrahepatic cholangiocarcinoma, the expression of HBV genes and HBV-antigens was detected in the cancerous tissue and its surrounding hepatic tissues. METHODS: HBV-antigens were detected by immunohistochemical technique and HBV genes were examined with in situ hybridization. RESULTS: In 20 cases of cholangiocarcinoma, the positive detection rate of HBxAg, pre-S1, pre-S2, HBsAg and HBcAg was 75%, 40%, 40%, 10% and 0%, respectively, and in the surrounding hepatic tissues of 19 cases the positive rates were 84.2%, 47.9%, 47.9%, 31.6% and 31.6%. Among 40 cases of cholangiocarcinoma, the positive rate of HBVDNA, x-gene, pre-s gene, s gene and s gene fell on 77.5%, 70.0%, 47.5%, 40% and 42.5%, respectively, and of the surrounding hepatic tissues in 33 cases, 87.9%, 84.8%, 63.6%, 69.7% and 66.7%. CONCLUSION: The development of human primary intrahepatic cholangiocarcinoma bears a close relationship with chronic persistent HBV infection. Particularly, the x gene of HBV and its protein (HBxAg) might play an important role in pathogenesis of hepatic carcinoma. PMID:11819329

  7. Discovering novel direct acting antiviral agents for HBV using in silico screening.

    PubMed

    Murakami, Yoshiki; Hayakawa, Michiyo; Yano, Yoshihiko; Tanahashi, Toshihito; Enomoto, Masaru; Tamori, Akihiro; Kawada, Norifumi; Iwadate, Mitsuo; Umeyama, Hideaki

    2015-01-01

    The treatments for chronic hepatitis B (CHB) are interferon and nucleoside analogues reverse transcriptase (RT) inhibitors. Because both treatments are less than ideal, we conducted to identify novel anti-viral agents for HBV-reverse transcriptase (HBV-RT). We determined the ligand-binding site of the HBV-RT by conducting a homological search of the amino acid sequence and then we also determined not only structural arrangement of the target protein but the target protein-binding site of the ligand using known protein-ligand complexes in registered in the protein data bank (PDB). Finally we simulated binding between the ligand candidates and the HBV-RT and evaluated the degree of binding (in silico screening). PXB cells derived from human-mouse chimeric mouse liver, infected with HBV were administrated with the candidates, and HBVDNA in the culture medium was monitored by realtime qPCR. Among compounds from the AKosSamples database, twelve candidates that can inhibit RT were also identified, two of which seem to have the potential to control HBV replication in vitro. PMID:25446116

  8. Phosphatidylcholine alteration identified using MALDI imaging MS in HBV-infected mouse livers and virus-mediated regeneration defects.

    PubMed

    Park, Eun-Sook; Lee, Jeong Hwa; Hong, Ji Hye; Park, Yong Kwang; Lee, Joon Won; Lee, Won-Jae; Lee, Jae Won; Kim, Kwang Pyo; Kim, Kyun-Hwan

    2014-01-01

    In this study, we investigated whether hepatitis B virus (HBV) causes the alteration of lipid metabolism and composition during acute infection and liver regeneration in a mouse model. The liver controls lipid biogenesis and bile acid homeostasis. Infection of HBV causes various liver diseases and impairs liver regeneration. As there are very few reports available in the literature on lipid alterations by HBV infection or HBV-mediated liver injury, we have analyzed phospholipids that have important roles in liver regeneration by using matrix-assisted laser desorption/ionization (MALDI)-imaging mass spectrometry (IMS) in the livers of HBV model mice. As a result, we identified different phosphatidylcholines (PCs) showing significant changes in their composition as well as cationized ion adduct formation in HBV-infected mouse livers which are associated with virus-mediated regeneration defects. To find the factor of altered PCs, the expression kinetics of enzymes was also examined that regulate PC biosynthesis during liver regeneration. It is noteworthy that the expression of choline-phosphate cytidylyltransferase A (PCYT1A) was significantly delayed in wild type HBV-expressing livers. Moreover, the amount of hepatic total PC was also significantly decreased in wt HBV-expressing mice. These results suggest that infection of HBV alters the composition of PCs which may involve in HBV-mediated regeneration defects and liver disease. PMID:25101682

  9. Phosphatidylcholine Alteration Identified Using MALDI Imaging MS in HBV-Infected Mouse Livers and Virus-Mediated Regeneration Defects

    PubMed Central

    Park, Eun-Sook; Lee, Jeong Hwa; Hong, Ji Hye; Park, Yong Kwang; Lee, Joon Won; Lee, Won-Jae; Lee, Jae Won; Kim, Kwang Pyo; Kim, Kyun-Hwan

    2014-01-01

    In this study, we investigated whether hepatitis B virus (HBV) causes the alteration of lipid metabolism and composition during acute infection and liver regeneration in a mouse model. The liver controls lipid biogenesis and bile acid homeostasis. Infection of HBV causes various liver diseases and impairs liver regeneration. As there are very few reports available in the literature on lipid alterations by HBV infection or HBV-mediated liver injury, we have analyzed phospholipids that have important roles in liver regeneration by using matrix-assisted laser desorption/ionization (MALDI)-imaging mass spectrometry (IMS) in the livers of HBV model mice. As a result, we identified different phosphatidylcholines (PCs) showing significant changes in their composition as well as cationized ion adduct formation in HBV-infected mouse livers which are associated with virus-mediated regeneration defects. To find the factor of altered PCs, the expression kinetics of enzymes was also examined that regulate PC biosynthesis during liver regeneration. It is noteworthy that the expression of choline-phosphate cytidylyltransferase A (PCYT1A) was significantly delayed in wild type HBV-expressing livers. Moreover, the amount of hepatic total PC was also significantly decreased in wt HBV-expressing mice. These results suggest that infection of HBV alters the composition of PCs which may involve in HBV-mediated regeneration defects and liver disease. PMID:25101682

  10. Pharmacokinetics of Anti-HBV Polyoxometalate in Rats

    PubMed Central

    Qi, Yanfei; Li, Jinhua; Song, Xiuling; Li, Li; Yin, Dehui; Xu, Kun; Li, Juan

    2014-01-01

    Polyoxometalates are non-nucleoside analogs that have been proven to exhibit broad-spectrum antiviral activity. In particular, Cs2K4Na[SiW9Nb3O40].H2O 1 shows low toxicity and high activity against HBV. The preclinical pharmacokinetics of Compound 1 in rats were characterized by establishing and applying inductively coupled plasma-mass spectrometry method to determine the concentration of W in plasma, urine, feces, bile and organ samples. The quantitative ICP-MS method demonstrated good sensitivity and application in the pharmacokinetics study of polyoxometalates. The pharmacokinetic behavior of Compound 1 after intravenous or oral administration fit a two-compartment model. Tmax ranges from 0.1 h to 3 h and the T1/2 of Compound 1 is between 20 h and 30 h. The absolute bioavailability of Compound 1 at 45, 180 and 720 mg/kg groups were 23.68%, 14.67% and 11.93%, respectively. The rates of plasma protein binding of Compound 1 at 9, 18 and 36 mg/ml of Compound 1 are 62.139.41%, 71.2024.98% and 49.0025.59%, respectively. Compound 1 was widely distributed throughout the body, and high levels of compound 1 were found in the kidney and liver. The level of Compound 1 in excretion was lower: 30% for urine, 0.28% for feces and 0.42% for bile, respectively. For elaborate pharmacokinetic characteristics to be fully understood, the metabolism of Compound 1 needs to be studied further. PMID:24921932

  11. Comparison of Abbott and Da-an real-time PCR for quantitating serum HBV DNA

    PubMed Central

    Qiu, Ning; Li, Rui; Yu, Jian-Guo; Yang, Wen; Zhang, Wei; An, Yong; Li, Tong; Liu, Xue-En; Zhuang, Hui

    2014-01-01

    AIM: To compare the performance of the Da-an real-time hepatitis B virus (HBV) DNA assay and Abbott RealTime HBV assay. METHODS: HBV DNA standards as well as a total of 180 clinical serum samples from patients with chronic hepatitis B were measured using the Abbott and Da-an real-time polymerase chain reaction (PCR) assays. Correlation and Bland-Altman plot analysis was used to compare the performance of the Abbott and Da-an assays. The HBV DNA levels were logarithmically transformed for analysis. All statistical analyses were performed using SPSS for Windows version 18.0. The correlation between the two assays was analyzed by Pearson’s correlation and linear regression. The Bland-Altman plots were used for the analysis of agreement between the two assays. A P value of < 0.05 was considered statistically significant. RESULTS: The HBV DNA values measured by the Abbott or Da-an assay were significantly correlated with the expected values of HBV DNA standards (r = 0.999, for Abbott; r = 0.987, for Da-an, P < 0.001). A Bland-Altman plot showed good agreement between these two assays in detecting HBV DNA standards. Among the 180 clinical serum samples, 126 were quantifiable by both assays. Fifty-two samples were detectable by the Abbott assay but below the detection limit of the Da-an assay. Moreover, HBV DNA levels measured by the Abbott assay were significantly higher than those of the Da-an assay (6.23 ± 1.76 log IU/mL vs 5.46 ± 1.55 log IU/mL, P < 0.001). A positive correlation was observed between HBV DNA concentrations determined by the two assays in 126 paired samples (r = 0.648, P < 0.001). One hundred and fifteen of 126 (91.3%) specimens tested with both assays were within mean difference ± 1.96 SD of HBV DNA levels. CONCLUSION: The Da-an assay presented lower sensitivity and a narrower linear range as compared to the Abbott assay, suggesting the need to be improved. PMID:25206280

  12. Inflammation Promotes Expression of Stemness-Related Properties in HBV-Related Hepatocellular Carcinoma

    PubMed Central

    Wu, Yu-Chih; Liu, Jun-Jen; Kuo, Yung Che; Lee, Kam-Fai; Lin, Sin-Yi; Lin, Sey-En; Tung, Shui-Yi; Kuo, Liang-Mou; Tsai, Ying-Huang; Huang, Yen-Hua

    2016-01-01

    The expression of cancer stemness is believed to reduce the efficacy of current therapies against hepatocellular carcinoma (HCC). Understanding of the stemness-regulating signaling pathways incurred by a specific etiology can facilitate the development of novel targets for individualized therapy against HCC. Niche environments, such as virus-induced inflammation, may play a crucial role. However, the mechanisms linking inflammation and stemness expression in HCC remain unclear. Here we demonstrated the distinct role of inflammatory mediators in expressions of stemness-related properties involving the pluripotent octamer-binding transcription factor 4 (OCT4) in cell migration and drug resistance of hepatitis B virus-related HCC (HBV-HCC). We observed positive immunorecognition for macrophage chemoattractant protein 1 (MCP-1)/CD68 and OCT4/NANOG in HBV-HCC tissues. The inflammation-conditioned medium (inflamed-CM) generated by lipopolysaccharide-stimulated U937 human leukemia cells significantly increased the mRNA and protein levels of OCT4/NANOG preferentially in HBV-active (HBV+HBsAg+) HCC cells. The inflamed-CM also increased the side population (SP) cell percentage, green fluorescent protein (GFP)-positive cell population, and luciferase activity of OCT4 promoter-GFP/luciferase in HBV-active HCC cells. Furthermore, the inflamed-CM upregulated the expressions of insulin-like growth factor-I (IGF-I)/IGF-I receptor (IGF-IR) and activated IGF-IR/Akt signaling in HBV-HCC. The IGF-IR phosphorylation inhibitor picropodophyllin (PPP) suppressed inflamed-CM-induced OCT4 and NANOG levels in HBV+HBsAg+ Hep3B cells. Forced expression of OCT4 significantly increased the secondary sphere formation and cell migration, and reduced susceptibility of HBV-HCC cells to cisplatin, bleomycin, and doxorubicin. Taking together, our results show that niche inflammatory mediators play critical roles in inducing the expression of stemness-related properties involving IGF-IR activation, and the upregulation of OCT4 contributes to cancer migration and drug resistance of HBV-HCC cells. Findings in this paper would provide potential targets for a therapeutic strategy targeting on inflammatory environment for HBV-HCC. PMID:26919045

  13. Effective compounds screening from Rabdosia serra (Maxim) Hara against HBV and tumor in vitro.

    PubMed

    Chen, Cheng; Chen, Yang; Zhu, Hongyuan; Xiao, Yiyun; Zhang, Xiuzhen; Zhao, Jingfeng; Chen, Yuxiang

    2014-01-01

    The aim of this study was to screen and investigate the anti-HBV and anti-tumor activities of separated compounds from Rabdosia serra (Maxim.) Hara to lay the basis for further isolate active entity. Three kinds of extractions from Rabdosia serra using different solvents (petroleum ether, acetidin, butyl alcohol) were prepared and used to analyze their anti-HBV activity in HepG2.2.15 cells for further separation. The cytotoxicity of each extraction was tested by MTT assay, the levels of HBsAg, HBeAg and HBV DNA in supernatants from HepG2.2.15 cells were detected by ELISA and real-time quantitative polymerase chain reaction (PCR). Then, the most effective extraction was further separated, the anti-HBV activities of separated compounds were also tested by MTT and ELISA, and three compounds with highest cytotoxicity were selected to further identify their anti-tumor activities on MCF-7, BGC-823 and HepG2 cells. Acetidin extraction C2 had the most effective anti-HBV activity that was used to be further separated, it led to statistically significant reduction in HBsAg and HBeAg secretion and HBV DNA. The separation of C2 resulted in 14 compounds, A3 and A5 markedly inhibited HBsAg secretion, while A9 inhibited HBeAg secretion in a dose-dependent manner with higher TI comparing with C2. A6, A7, A11 had different anti-tumor activity against different tumor cells. These data showed that the extraction and their separated effective compounds had strong inhibitory effect on HBV replication so as to have anti-HBV activity, and further separation and purification could enhance anti-HBV activity. Meanwhile, some compounds have high cytotoxicities on different tumor cells. Our study could provide a theoretical basis for the next clinical use and the development of potential and efficient drugs for HBV and tumor therapy from Rabdosia serra. PMID:24600493

  14. Inflammation Promotes Expression of Stemness-Related Properties in HBV-Related Hepatocellular Carcinoma.

    PubMed

    Chang, Te-Sheng; Chen, Chi-Long; Wu, Yu-Chih; Liu, Jun-Jen; Kuo, Yung Che; Lee, Kam-Fai; Lin, Sin-Yi; Lin, Sey-En; Tung, Shui-Yi; Kuo, Liang-Mou; Tsai, Ying-Huang; Huang, Yen-Hua

    2016-01-01

    The expression of cancer stemness is believed to reduce the efficacy of current therapies against hepatocellular carcinoma (HCC). Understanding of the stemness-regulating signaling pathways incurred by a specific etiology can facilitate the development of novel targets for individualized therapy against HCC. Niche environments, such as virus-induced inflammation, may play a crucial role. However, the mechanisms linking inflammation and stemness expression in HCC remain unclear. Here we demonstrated the distinct role of inflammatory mediators in expressions of stemness-related properties involving the pluripotent octamer-binding transcription factor 4 (OCT4) in cell migration and drug resistance of hepatitis B virus-related HCC (HBV-HCC). We observed positive immunorecognition for macrophage chemoattractant protein 1 (MCP-1)/CD68 and OCT4/NANOG in HBV-HCC tissues. The inflammation-conditioned medium (inflamed-CM) generated by lipopolysaccharide-stimulated U937 human leukemia cells significantly increased the mRNA and protein levels of OCT4/NANOG preferentially in HBV-active (HBV+HBsAg+) HCC cells. The inflamed-CM also increased the side population (SP) cell percentage, green fluorescent protein (GFP)-positive cell population, and luciferase activity of OCT4 promoter-GFP/luciferase in HBV-active HCC cells. Furthermore, the inflamed-CM upregulated the expressions of insulin-like growth factor-I (IGF-I)/IGF-I receptor (IGF-IR) and activated IGF-IR/Akt signaling in HBV-HCC. The IGF-IR phosphorylation inhibitor picropodophyllin (PPP) suppressed inflamed-CM-induced OCT4 and NANOG levels in HBV+HBsAg+ Hep3B cells. Forced expression of OCT4 significantly increased the secondary sphere formation and cell migration, and reduced susceptibility of HBV-HCC cells to cisplatin, bleomycin, and doxorubicin. Taking together, our results show that niche inflammatory mediators play critical roles in inducing the expression of stemness-related properties involving IGF-IR activation, and the upregulation of OCT4 contributes to cancer migration and drug resistance of HBV-HCC cells. Findings in this paper would provide potential targets for a therapeutic strategy targeting on inflammatory environment for HBV-HCC. PMID:26919045

  15. Effective compounds screening from Rabdosia serra (Maxim) Hara against HBV and tumor in vitro

    PubMed Central

    Chen, Cheng; Chen, Yang; Zhu, Hongyuan; Xiao, Yiyun; Zhang, Xiuzhen; Zhao, Jingfeng; Chen, Yuxiang

    2014-01-01

    The aim of this study was to screen and investigate the anti-HBV and anti-tumor activities of separated compounds from Rabdosia serra (Maxim.) Hara to lay the basis for further isolate active entity. Three kinds of extractions from Rabdosia serra using different solvents (petroleum ether, acetidin, butyl alcohol) were prepared and used to analyze their anti-HBV activity in HepG2.2.15 cells for further separation. The cytotoxicity of each extraction was tested by MTT assay, the levels of HBsAg, HBeAg and HBV DNA in supernatants from HepG2.2.15 cells were detected by ELISA and real-time quantitative polymerase chain reaction (PCR). Then, the most effective extraction was further separated, the anti-HBV activities of separated compounds were also tested by MTT and ELISA, and three compounds with highest cytotoxicity were selected to further identify their anti-tumor activities on MCF-7, BGC-823 and HepG2 cells. Acetidin extraction C2 had the most effective anti-HBV activity that was used to be further separated, it led to statistically significant reduction in HBsAg and HBeAg secretion and HBV DNA. The separation of C2 resulted in 14 compounds, A3 and A5 markedly inhibited HBsAg secretion, while A9 inhibited HBeAg secretion in a dose-dependent manner with higher TI comparing with C2. A6, A7, A11 had different anti-tumor activity against different tumor cells. These data showed that the extraction and their separated effective compounds had strong inhibitory effect on HBV replication so as to have anti-HBV activity, and further separation and purification could enhance anti-HBV activity. Meanwhile, some compounds have high cytotoxicities on different tumor cells. Our study could provide a theoretical basis for the next clinical use and the development of potential and efficient drugs for HBV and tumor therapy from Rabdosia serra. PMID:24600493

  16. Expression quantitative trait loci for TNFRSF10 influence both HBV infection and hepatocellular carcinoma development.

    PubMed

    Wen, Juan; Song, Ci; Liu, Jibin; Chen, Jianguo; Zhai, Xiangjun; Hu, Zhibin

    2016-03-01

    Tumor necrosis factor receptor superfamily member 10 (TNFRSF10) is a death domain-containing receptor for the apoptotic ligand TNFSF10, which involves multiple processes, including hepatocarcinogenesis and immune response against HBV infection. Several single nucleotide polymorphisms (SNPs) were identified as expression quantitative trait loci (eQTLs) for TNFRSF10. To assess the association of TNFRSF10 eQTL SNPs with the risk of hepatocellular carcinoma (HCC) and chronic HBV infection, we designed a case-control study that included 1,300 HBV-related HCC patients, 1,344 chronic HBV carriers, and 1,344 subjects with HBV natural clearance, and then genotyped two TNFRSF10 eQTL SNPs (rs79037040 and rs2055822). We found that rs79037040 GT/TT genotypes were associated with a decreased HCC risk (adjusted odds ratio [OR] = 0.83, 95% confidence intervals [CIs] = 0.71-0.97, P = 0.021) but an increased chronic HBV infection risk of borderline significance (adjusted OR = 1.14, 95%CIs = 0.98-1.33, P = 0.085). In contrast, the rs2055822 G allele was a risk factor for HCC (adjusted OR = 1.12, 95%CIs = 1.00-1.25, P = 0.041) but a protective factor for chronic HBV infection (adjusted OR = 0.89, 95%CIs = 0.80-0.99, P = 0.038). Furthermore, we observed a dose-dependent relationship between the number of alleles (rs79037040-T and rs2055822-A) and the risk of HCC and chronic HBV infection. In comparison with "0" alleles, having "1-4" alleles was significantly associated with decreased HCC risk and increased HBV infection risk. These findings suggest that eQTL SNPs for TNFRSF10 may be susceptibility markers for HCC and chronic HBV infection. J. Med. Virol. 88:474-480, 2016. © 2015 Wiley Periodicals, Inc. PMID:26297860

  17. Hepatitis B virus (HBV) status of children born to HIV/HBV co-infected women in a French hospital: a cross-sectional study

    PubMed Central

    Sellier, Pierre; Schnepf, Nathalie; Amarsy, Rishma; Maylin, Sarah; Coutellier, Martin; Lopes, Amanda; Mazeron, Marie-Christine; Flateau, Clara; Morgand, Marjolaine; Ciraru-Vigneron, Nicole; Berthe, Aurore; Ricbourg, Aude; Dolores-Moreno, Anne-Marie; Simoneau, Guy; Evans, John; Souak, Safia; Matheron, Sophie; Mouly, Stephane; Benifla, Jean-Louis; Simon, Franois; Bergmann, Jean-Franois

    2014-01-01

    Introduction Human Immunodeficiency Virus (HIV) Mother-To-Child-Transmission (MTCT) and prevention by combined antiretroviral therapy (cART) have been extensively studied. Hepatitis B Virus (HBV) MTCT from HIV/HBV co-infected women and prevention by antiretroviral therapy with dual activity have been poorly studied. The aim of the study was to assess HBV MTCT from HIV/HBV co-infected women in a developed country with a large access to cART. Materials and Methods HIV/HBV co-infected pregnant women attending the Obstetrics Department from 1st January 2000 to 1st January 2012 could be included in the study (NCT02044068). Antiretroviral therapy during pregnancy, injection of immunoglobulin and/or vaccine to newborns was retrospectively recorded. We assessed HBV status of children at least as old as two years. Results Forty nine (9.2%) from 530 HIV-infected women followed in the hospital were HIV/HBV co-infected. 34 (69.4%) had given birth to 57 children in the hospital. 13 of these women (22 children) were lost-to-follow-up, 21 women (35 children) could be studied. Twenty six children (74.3%) had HBs Ab at a protective level, 22 of them had received immunoglobulin at birth; 24 had received a complete vaccine schedule during the first six months of life (with immunoglobulin in 21 cases). The women had been given lamivudine or tenofovir/emtricitabine during eight and nine pregnancies respectively. Eight children (22.8%) were tested negative for HBs Ag, HBs Ab and HBc Ab: 4 (11.4%) had received immunoglobulin and a complete vaccine schedule; in two children, immunoglobulin was uncertain; in one child, the vaccine schedule was incomplete; in the last one, data about immunoglobulin and the vaccine schedule were lacking. The women had been given lamivudine or tenofovir/emtricitabine during five and two pregnancies respectively. One child had HBc Ab and HBs Ab, immunoglobulin was uncertain and the vaccine schedule was incomplete. The woman had been given lamivudine during the last trimester. Conclusions Three quarters of the children were protected. HBs Ab were negative in more than a tenth of the children who had received immunoglobulin and a complete vaccine schedule, questioning on long-term protection and underlining the need of control. PMID:25394136

  18. HBV and HIV co-infection: Prevalence and clinical outcomes in tertiary care hospital Malaysia.

    PubMed

    Akhtar, Ali; Khan, Amer Hayat; Sulaiman, Syed Azhar Syed; Soo, Chow Ting; Khan, Kashifullah

    2016-03-01

    According to WHO, Malaysia has been classified as a concentrated epidemic country due to progression of HIV infection in the population of injecting drug users. The main objectives of current study are to determine the prevalence of HBV among HIV-positive individuals in a tertiary care hospital of Malaysia and to assess the predictors involved in the outcomes of HIV-HBV co-infected patients. A retrospective, cross-sectional study is conducted at Hospital Palau Pinang, Malaysia. The collection of socio-demographic data as well as clinical data is done with the help of data collection form. Data were analyzed after putting the collected values of required data by using statistical software SPSS version 20.0 and P > 0.05 is considered as significant. Results show that the overall prevalence of HBV was 86 (13%) including 495 (74.5%) males and 169 (25.5%) females among a total of 664 HIV-infected patients. It was observed that there is a high prevalence of HIV-HBV co-infection in males 76 (11.4%) as compared to females 10 (1.5%) (P = 0.002). The median age of the study population was 39 years. The statistical significant risk factors involved in the outcomes of HIV-HBV co-infected patients were observed in the variables of gender, age groups, and injecting drug users. The findings of the present study shows that the prevalence of HBV infection among HIV-positive patients was 13% and the risk factors involved in the outcomes of HIV-HBV co-infected patients were gender, age, and intravenous drug users. J. Med. Virol. 88:455-460, 2016. © 2015 Wiley Periodicals, Inc. PMID:26255632

  19. Is mother-to-infant transmission the most important factor for persistent HBV infection?

    PubMed Central

    Li, Zixiong; Hou, Xiaomei; Cao, Guangwen

    2015-01-01

    Of the infants born to hepatitis B surface antigen (HBsAg)-positive mothers globally, 42.1% who did not receive hepatitis B virus (HBV) passive-active immunoprophylaxis and 2.9% of infants who received the immunoprophylaxis acquired HBV infection perinatally. Moreover, perinatal infection occurred in 84.2% (18.8%–100%) and 8.7% (0.0–21.0%) of infants born to hepatitis B e-antigen (HBeAg)-positive mothers who did not and did receive immunoprophylaxis, respectively; by contrast, the infection rates were 6.7% (0.0–15.4%) and 0.4% (0.0–2.5%) for infants born to HBeAg-negative-carrier mothers, respectively. The chronicity rates of HBV infection acquired perinatally were 28.2% (17.4%–33.9%) in infants born to HBeAg-negative mothers and 64.5% (53.5%–100%) in infants born to HBeAg-positive mothers. HBV mother-to-child transmission was more frequent in East Asia relative to other areas. In addition to differences in the endemic HBV genotype, the interchange of allelic dominance in genetic polymorphisms in HLA class II and NF-κB between the Chinese and European populations may explain why chronic HBV infection frequently affects the Chinese. The risk of progressing into chronic infection was inversely related to the age of children at the time of horizontal transmission. To further diminish HBV chronic infection, it is necessary to enforce antiviral treatment after the 28th week of gestation for HBeAg-positive mothers and to improve the health habits of carrier mothers and household sanitary conditions. PMID:26060603

  20. Liver type I regulatory T cells suppress germinal center formation in HBV-tolerant mice.

    PubMed

    Xu, Long; Yin, Wenwei; Sun, Rui; Wei, Haiming; Tian, Zhigang

    2013-10-15

    The liver plays a critical role in inducing systemic immune tolerance, for example, during limiting hypersensitivity to food allergy and in rendering acceptance of allotransplant or even hepatotropic pathogens. We investigated the unknown mechanisms of liver tolerance by using an established hepatitis B virus (HBV)-carrier mouse model, and found that these mice exhibited an antigen-specific tolerance toward peripheral HBsAg vaccination, showing unenlarged draining lymph node (DLN), lower number of germinal centers (GC), and inactivation of GC B cells and follicular T helper (Tfh) cells. Both in vivo and in vitro immune responses toward HBsAg were suppressed by mononuclear cells from HBV-carrier mice, which were CD4(+) Foxp3(-) type 1 regulatory T (Tr1)-like cells producing IL-10. Using recipient Rag1(-/-) mice, hepatic Tr1-like cells from day 7 of HBV-persistent mice acquired the ability to inhibit anti-HBV immunity 3 d earlier than splenic Tr1-like cells, implying that hepatic Tr1-like cells were generated before those in spleen. Kupffer cell depletion or IL-10 deficiency led to impairment of Tr1-like cell generation, along with breaking HBV persistence. The purified EGFP(+)CD4(+) T cells (containing Tr1-like cells) from HBV-carrier mice trafficked in higher numbers to DLN in recipient mice after HBsAg vaccination, and subsequently inactivated both Tfh cells and GC B cells via secreting IL-10, resulting in impaired GC formation and anti-HB antibody production. Thus, our results indicate Tr1-like cells migrate from the liver to the DLN and inhibit peripheral anti-HBV immunity by negatively regulating GC B cells and Tfh cells. PMID:24089450

  1. Establishment of a new quantitative detection approach to adefovir-resistant HBV and its clinical application

    PubMed Central

    Zhao, Wei-Feng; Shao, You-Lin; Chen, Liang-Yun; Wu, Jin-Hua; Zhu, Yi-Ling; Gan, Jian-He; Xiong, Hui

    2010-01-01

    AIM: To establish the more feasible and sensitive assessment approach to the detection of adefovir (ADV) resistance-associated hepatitis B virus (HBV) quasispecies. METHODS: Based on the characteristics of rtA181V/T and rtN236T mutations, a new approach based on real-time fluorescent quantitative polymerase chain reaction (RT-PCR) was established for the detection of ADV-resistant HBV quasispecies, total HBV DNA, rtA181 and rtN236 mutations in blood samples from 32 chronic hepatitis B (CHB) patients with unsatisfactory curative effect on ADV and compared with routine HBV DNA sequencing. RESULTS: Both the sensitivity and specificity of this new detection approach to ADV-resistant HBV quasispecies were 100%, which were much higher than those of direct HBV DNA sequencing. The approach was able to detect 0.1% of mutated strains in a total plasmid population. Among the 32 clinical patients, single rtA181 and rtN236T mutation and double rtA181T and rtN236T mutations were detected in 20 and 8, respectively, while ADV-resistant mutations in 6 (including, rtA181V/T mutation alone in 5 patients) and no associated mutations in 26. CONCLUSION: This new approach is more feasible and efficient to detect ADV-resistant mutants of HBV and ADV-resistant mutations before and during ADV treatment with a specificity of 100% and a sensitivity of 100%. PMID:20222172

  2. KIR : HLA association with clinical manifestations of HBV infection in Madurai, south India.

    PubMed

    Kalyanaraman, Narayanan; Thayumanavan, Lakshmikanthan; Jayalakshmi, Mariakuttikan

    2016-03-01

    The antiviral action of natural killer (NK) cells is regulated by a wide repertoire of germ-line encoded membrane receptors which recognize the expression of certain self-molecules on target cells. Among the receptors, killer cell immunoglobulinlike receptor (KIR) which recognizes the expression of human leukocyte antigen (HLA) class I has a predominant role in regulating the effector functions of NK cells, particularly in viral infections.We studied a total of 128 hepatitis B virus (HBV) patients (15 acute, 43 asymptomatic, 27 chronic and 43 with other liver diseases) while attending the Department of Medical Gastroenterology, Government Rajaji Hospital, Madurai, India, and 128 ethnic matched control to find the association between the KIR : HLA genes and differential manifestations of HBV. KIR and its ligand HLA polymorphism were identified by DNAPCR methods. The activatory receptor KIR-2DS1 was significantly elevated in various disease categories, namely asymptomatic, chronic and other HBV, except acute HBV infection. Whereas, KIR 2DS3 in acute and chronic patients and KIR 2DS5 and 3DS1 in asymptomatic individuals. Among various KIR-HLA combinations, homozygous 2DS2:C1 and individuals with 3DSI:BW4 (OR = 3.23, CI = 1.55-6.7, Pc = 0.02) are associated with HBV asymptomatism, while most of the two domain inhibitory receptors with their ligands showed significant risk in other liver diseases. Further, KIR3DL1 : HLA Bw4Iso80 (OR = 3.89, 95% CI = 1.58-9.55, Pc = 0.004) is related with higher risk for asymptomatic infection when compared with chronic HBV. Thus, the select KIR : HLA alleles and combinations seem to direct the NK cell activities and immune response in different directions resulting in varied symptoms and manifestations in the subgroups of HBV-infected patients studied. PMID:27019428

  3. Hepatitis B vaccination with or without hepatitis B immunoglobulin at birth to babies born of HBsAg-positive mothers prevents overt HBV transmission but may not prevent occult HBV infection in babies: a randomized controlled trial.

    PubMed

    Pande, C; Sarin, S K; Patra, S; Kumar, A; Mishra, S; Srivastava, S; Bhutia, K; Gupta, E; Mukhopadhyay, C K; Dutta, A K; Trivedi, S S

    2013-11-01

    Vertical transmission of Hepatitis B virus HBV can result in a state of chronic HBV infection and its complications. HBV vaccination with or without hepatitis B immunoglobulin (HBIG) prevents transmission of overt infection to the babies. However, whether it also prevents occult HBV infection in babies is not known. Consecutive pregnant women of any gestation found to be HBsAg positive were followed till delivery, and their babies were included in the study. Immediately after delivery, babies were randomized to receive either HBIG or placebo in addition to recombinant HBV vaccine (at 0, 6, 10 and 14 weeks). The primary end-point of the study, assessed at 18 weeks of age, was remaining free of any HBV infection (either overt or occult) plus the development of adequate immune response to vaccine. The babies were further followed up for a median of 2 years of age to determine their eventual outcome. Risk factors for HBV transmission and for poor immune response in babies were studied. Of the 283 eligible babies, 259 were included in the trial and randomized to receive either HBIG (n=128) or placebo (n=131) in addition to recombinant HBV vaccine. Of the 222 of 259 (86%) babies who completed 18 weeks of follow-up, only 62/222 (28%) reached primary end-point. Of the remaining, 6/222 (3%) developed overt HBV infection, 142/222 (64%) developed occult HBV infection, and 12/222 (5%) had no HBV infection but had poor immune response. All 6 overt infections occurred in the placebo group (P=0.030), while occult HBV infections were more common in the HBIG group (76/106 [72%] vs. 66/116 [57%]; P=0.025). This may be due to the immune pressure of HBIG. There was no significant difference between the two groups in frequency of babies developing poor immune response or those achieving primary end-point. The final outcome of these babies at 24 months of age was as follows: overt HBV infection 4%, occult HBV infection 42%, no HBV infection but poor immune response 8% and no HBV infection with good immune response 28%. Women who were anti-HBe positive were a low-risk group, and their babies were most likely to remain free of HBV infection (occult or overt) and had good immune response to the vaccine. Maternal HBeAg-positive status and negativity for anti-HBe predicted not only overt but also any infection (both overt and occult) in babies. In addition, high maternal HBV DNA and treatment with vaccine alone were significant factors for overt HBV infection in babies. The current practice of administration of vaccine with HBIG at birth to babies born of HBsAg-positive mothers is not effective in preventing occult HBV infection in babies, which may be up to 40%. Because the most important risk factors for mother-to-baby transmission of HBV infection are the replicative status and high HBV DNA level in mothers; it will be worthwhile investigating the role of antivirals and HBIG administration during pregnancy to prevent mother-to-child transmission of HBV infection. PMID:24168259

  4. TOXIRAE PRO PID

    EPA Science Inventory

    The ToxiRAE Pro PID measures total volatile organic compounds (VOCs) using a photoionization detector (PID). This sensor can be programmed to measure concentrations of a specified compound automatically and has a real time reading of VOC concentrations in parts per million (ppm) ...

  5. Making pro formas perform.

    PubMed

    Bryan, Stephen; Lilien, Steven

    2003-10-01

    Regulators are trying to clear up the muddle created by earnings-report adjustments called "pro formas" that companies issue. Constraining such reporting, as the regulators seem bent on doing, isn't the solution. Firms should increase alternative reporting--and fully account for their accounting. PMID:14521095

  6. Clinical evaluation (phase I) of a combination of two human monoclonal antibodies to HBV: safety and antiviral properties.

    PubMed

    Galun, Eithan; Eren, Rachel; Safadi, Rifaat; Ashour, Yaffa; Terrault, Norah; Keeffe, Emmet B; Matot, Edith; Mizrachi, Sara; Terkieltaub, Dov; Zohar, Merav; Lubin, Ido; Gopher, Judith; Shouval, Daniel; Dagan, Shlomo

    2002-03-01

    Treatment of chronic hepatitis B virus (HBV) infection with interferon alfa and lamivudine is characterized by lack of viral clearance, loss of response, or emergence of drug-resistant mutants. Thus, new and multiple drug approaches are needed. We have developed two fully human monoclonal antibodies, directed against different epitopes of hepatitis B surface antigen (HBsAg) that bind to all major HBV subtypes. A phase I clinical study was conducted to evaluate the safety, tolerability, and efficacy of a mixture of these two monoclonal antibodies, HBV-AB(XTL). A total of 27 chronic HBV patients were enrolled. In part A of the study 15 patients in 5 cohorts received a single intravenous infusion of antibodies with doses ranging from 0.26 mg (260 IU) to 40 mg (40,000 IU). All patients completed 16 weeks of follow-up. In the second part of the study (part B), 12 patients in 4 cohorts received 4 weekly infusions of 10, 20, 40, or 80 mg each of HBV-AB(XTL) and were followed for 4 additional weeks. Administration of antibodies was well tolerated. Patients administered doses at an Ab:Ag molar ratio of 1:2 to 1:20 showed a rapid and significant decrease in HBsAg to undetectable levels, with a corresponding reduction of HBV-DNA levels. In part B, HBV-AB(XTL) induced a significant reduction in both HBsAg and HBV-DNA levels repeatedly after administration. In conclusion, these data suggest that HBV-AB(XTL) binds HBV particles and reduces serum viral titers and HBsAg levels. HBV-AB(XTL) could be combined with other monotherapies that are currently used to treat HBV carriers. PMID:11870383

  7. [Assessment of mother-to-child HBV transmission at the prenatal consultation in Vientiane, Laos].

    PubMed

    Xaydalasouk, K; Keomalaphet, S; Latthaphasavang, V; Souvong, V; Buisson, Y

    2016-02-01

    Chronic infection with hepatitis B virus (HBV) remains highly endemic in Laos, mainly related to mother to child transmission. Despite the introduction of the vaccination against HBV in the Expanded Programme on Immunization in 2001 and the administration of a vaccine birth dose as part of a 3-dose schedule since 2004, infant immunization coverage remains inadequate because most mothers are not aware of the risks. A survey was conducted in early 2013 in Vientiane capital among women who undergo serologic screening for hepatitis B at the prenatal consultation, to assess their knowledge and risk factors of HBV infection. It included the administration of a standardized questionnaire divided into four parts (socio-demographic data, knowledge about hepatitis B, risk factors and immunization status) and a screening test for the HBV surface antigen (HBsAg). A total of 200 pregnant women were recruited consecutively in Mahosot hospital. They were aged 14-39 years (mean 27 4.76 years), civil servants (37%) or housewives (33.5%) with a secondary or higher education level (80%). Most were multiparous (68.5%) and attended antenatal care in the third trimester of pregnancy (61%). Sixteen (8%) tested HBsAg positive. The HBsAg seroprevalence was higher in the 26-30 years age group, among women above the primary school education level and women practicing the profession of shopkeeper or civil servant, but these differences were not significant. Hepatitis B was known by a small majority (53%) but 26% could name the routes of transmission, 28% considered it as a serious illness and 24.5% were aware of the HBV vaccine. No risk factor for blood or sexual exposure to HBVinfection was significantly linked to the HBsAg carriage. In this sample of pregnant women mostly urban, educated and multiparous with access to a central hospital, the high rate of HBV infection and the low level of knowledge about the risk of mother-to-child HBV transmission reveals a major gap in information and advice that should be provided during prenatal visits. A large scale program of health education focused on the prevention of vertical transmission of HBV should be implemented, parallel to the extension of HBV vaccine coverage including a birth dose for the Lao children. PMID:26821371

  8. Mapping of histone modifications in episomal HBV cccDNA uncovers an unusual chromatin organization amenable to epigenetic manipulation.

    PubMed

    Tropberger, Philipp; Mercier, Alexandre; Robinson, Margaret; Zhong, Weidong; Ganem, Don E; Holdorf, Meghan

    2015-10-20

    Chronic hepatitis B virus (HBV) infection affects 240 million people worldwide and is a major risk factor for liver failure and hepatocellular carcinoma. Current antiviral therapy inhibits cytoplasmic HBV genomic replication, but is not curative because it does not directly affect nuclear HBV closed circular DNA (cccDNA), the genomic form that templates viral transcription and sustains viral persistence. Novel approaches that directly target cccDNA regulation would therefore be highly desirable. cccDNA is assembled with cellular histone proteins into chromatin, but little is known about the regulation of HBV chromatin by histone posttranslational modifications (PTMs). Here, using a new cccDNA ChIP-Seq approach, we report, to our knowledge, the first genome-wide maps of PTMs in cccDNA-containing chromatin from de novo infected HepG2 cells, primary human hepatocytes, and from HBV-infected liver tissue. We find high levels of PTMs associated with active transcription enriched at specific sites within the HBV genome and, surprisingly, very low levels of PTMs linked to transcriptional repression even at silent HBV promoters. We show that transcription and active PTMs in HBV chromatin are reduced by the activation of an innate immunity pathway, and that this effect can be recapitulated with a small molecule epigenetic modifying agent, opening the possibility that chromatin-based regulation of cccDNA transcription could be a new therapeutic approach to chronic HBV infection. PMID:26438841

  9. PTD-fused p53 as a potential antiviral agent directly suppresses HBV transcription and expression.

    PubMed

    Chu, Xiaoyu; Wu, Bo; Fan, Hongxia; Hou, Junwei; Hao, Junli; Hu, Jun; Wang, Baozhong; Liu, Guangze; Li, Changfei; Meng, Songdong

    2016-03-01

    In Hepatitis B virus (HBV) infection, the virus generates numerous viral mRNAs/proteins and viral loads, which plays a major role in driving T cell tolerance, viral persistence, and hepatocellular carcinoma. However, currently available anti-HBV agents have no direct effect on viral mRNA transcription and protein expression. In this study, we designed a recombinant fusion of p53 protein with the cell-penetrating peptide PTD (protein transduction domain of trans-activator of transcription), which mediated p53 internalization into hepatocytes. PTD-p53 effectively suppressed HBV transcription and antigen expression by interaction with viral enhancers. We further provide evidence that PTD-p53 counteracts the viral transcription feedback loop and effectively suppressed HBV production of viral mRNAs, as well as HBsAg, HBeAg, and HBcAg, both in vitro and in vivo. Our results thereby provide a basis for developing a new therapeutic approach against HBV infection. PMID:26784393

  10. Presence of anti-HBc is associated to high rates of HBV resolved infection and low threshold for Occult HBV Infection in HIV patients with negative HBsAg in Chile.

    PubMed

    Vargas, Jose Ignacio; Jensen, Daniela; Sarmiento, Valeska; Peirano, Felipe; Acuña, Pedro; Fuster, Felipe; Soto, Sabrina; Ahumada, Rodrigo; Huilcaman, Marco; Bruna, Mario; Jensen, Werner; Fuster, Francisco

    2016-04-01

    HBV-HIV coinfection is prevalent. Frequently, anti-HBc is the only serological marker of HBV, which can be indicative of HBV resolved infection, when found together with anti-HBs reactivity; or present as "isolated anti-HBc," related to HBV occult infection with presence of detectable DNA HBV, more prevalent in HIV-positive individuals. Regional data about this condition are scarce. Anti-HBc rapid test has been used as screening, but its performance has not been described in HIV-positive patients. The aim of this study was determine prevalence of anti-HBc in HIV-positive patients, serological pattern of HBV resolved infection and isolated anti-HBc, evaluating presence of HBV occult infection. Assess anti-HBc rapid test compared to ECLIA. Methods included measurement of anti-HBc and anti-HBs in HIV-positive patients with negative HBsAg. Serum HBV DNA quantification and HBV booster vaccination to "isolated anti-HBc" individuals. Detection of anti-HBc by rapid test and ECLIA. In 192 patients, prevalence of anti-HBc was 42.7% (82/192); associated to male gender, drug use, men-sex-men, positive-VDRL, and longer time HIV diagnosis. 34.4% (66/192) had presence of anti-HBs, mean titers of 637 ui/ml. Isolated anti-HBc in 8.3% (16/192), associated to detectable HIV viral load and no-use of HAART; in them, HBV DNA was undetectable, and 60% responded to HBV vaccination booster. Anti-HBc rapid test showed low sensibility (32.9%) compared to ECLIA. These results show that prevalence of anti-HBc in HIV-positive individuals is high, in most cases accompanied with anti-HBs as HBV resolved infection. Low prevalence of "isolated anti-HBc," with undetectable HBV DNA, and most had anamnestic response to HBV vaccination; suggest low possibility of occult HBV infection. Anti-HBc rapid test cannot be recommended as screening method for anti-HBc. J. Med. Virol. 88:639-646, 2016. © 2015 Wiley Periodicals, Inc. PMID:26381185

  11. Hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC): molecular mechanisms and novel paradigms.

    PubMed

    Brechot, C; Kremsdorf, D; Soussan, P; Pineau, P; Dejean, A; Paterlini-Brechot, P; Tiollais, P

    2010-08-01

    Chronic hepatitis B (HBV) infection is a major risk factor for hepatocellular carcinoma (HCC). Most HCCs complicate the evolution of an active or inactive cirrhosis. However, some tumors occur on livers with minimal histological changes; the prevalence of such cases varies from one geographical region to the other, being much higher in the Southern half of Africa (around 40% of HCCs) than in Asia, America and Europe, where at least 90% of HCCs are associated in the cirrhosis. This heterogeneity is probably a reflection of different environmental and genetic factors. This review will summarise the current knowledge on the mechanisms involved in HBV-related liver carcinogenesis. It will show in particular how viruses can be viewed as tools to discover and dissect new cellular pathways involved in cancer development and emphasize the potential synergistic effects between HBV and hepatitis C virus (HCV), as well as between viral infections and other environmental factors, such as alcohol. PMID:20667665

  12. Defective natural killer cell anti-viral capacity in paediatric HBV infection

    PubMed Central

    Heiberg, I L; Pallett, L J; Winther, T N; Hgh, B; Maini, M K; Peppa, D

    2015-01-01

    Natural killer (NK) cells exhibit dysregulated effector function in adult chronic hepatitis B virus (HBV) infection (CHB), which may contribute to virus persistence. The role of NK cells in children infected perinatally with HBV is less studied. Access to a unique cohort enabled the cross-sectional evaluation of NK cell frequency, phenotype and function in HBV-infected children relative to uninfected children. We observed a selective defect in NK cell interferon (IFN)-? production, with conserved cytolytic function, mirroring the functional dichotomy observed in adult infection. Reduced expression of NKp30 on NK cells suggests a role of impaired NK-dendritic cell (DC) cellular interactions as a potential mechanism leading to reduced IFN-? production. The finding that NK cells are already defective in paediatric CHB, albeit less extensively than in adult CHB, has potential implications for the timing of anti-viral therapy aiming to restore immune control. PMID:25311087

  13. HBV-induced ROS accumulation promotes hepatocarcinogenesis through Snail-mediated epigenetic silencing of SOCS3.

    PubMed

    Yuan, K; Lei, Y; Chen, H-N; Chen, Y; Zhang, T; Li, K; Xie, N; Wang, K; Feng, X; Pu, Q; Yang, W; Wu, M; Xiang, R; Nice, E C; Wei, Y; Huang, C

    2016-04-01

    Interleukin-6 (IL-6) has been demonstrated to be involved in Hepatitis B virus (HBV)-associated hepatocarcinogenesis through activation of the STAT3 pathway. The sustained activation of the IL-6/STAT3 pathway is frequently associated with repression of SOCS3, which is both a target gene and a negative regulator of STAT3. However, the silencing mechanism of SOCS3 in hepatocellular carcinoma (HCC) remains to be elucidated. Here, we showed that the repression of SOCS3 and sustained activation of IL-6/STAT3 pathway in HBV-producing HCC cells were caused by HBV-induced mitochondrial ROS accumulation. Mechanistic studies revealed that ROS-mediated DNA methylation resulted in the silencing of SOCS3. Decreased SOCS3 expression significantly promoted the proliferation of HCC cells and growth of tumor xenografts in mice. Further studies revealed that HBV-induced ROS accumulation upregulated the expression of the transcription factor, Snail, which bound to the E-boxes of SOCS3 promoter and mediated the epigenetic silencing of SOCS3 in association with DNMT1 and HDAC1. In addition, we found that the expression of Snail and SOCS3 were inversely correlated in HBV-associated HCC patients, suggesting that SOCS3 and/or Snail could be used as prognostic markers in HCC pathogenesis. Taken together, our data show that HBV-induced mitochondrial ROS production represses SOCS3 expression through Snail-mediated epigenetic silencing, leading to the sustained activation of IL-6/STAT3 pathway and ultimately contributing to hepatocarcinogenesis. PMID:26794444

  14. Inhibitory effect of emodin and Astragalus polysaccharide on the replication of HBV

    PubMed Central

    Dang, Shuang-Suo; Jia, Xiao-Li; Song, Ping; Cheng, Yan-An; Zhang, Xin; Sun, Ming-Zhu; Liu, En-Qi

    2009-01-01

    AIM: To evaluate the anti-viral effect of emodin plus Astragalus polysaccharide (APS) in hepatitis B virus (HBV) transgenic mice. METHODS: Sixty HBV transgenic mice (HBV TGM) whose weight varied between 18 and 24 g were randomly divided into 3 groups, with 20 mice in each group. Group A was the normal control, where the mice were treated with physiological saline; group B was the positive control where the mice were treated with lamivudine solution (100 mL/kg per day). Group C was the experimental group where the mice were treated with physiological saline containing emodin and APS (57.59 mg/kg per day and 287.95 mg/kg per day, respectively). The mice were treated daily for 3 wk. After 1 wk recovery time, the mice were sacrificed and serum as well as liver tissues were collected for ELISA and histological examination. RESULTS: After 21 d treatment, HBV DNA levels in group B and group C significantly declined when compared with group A (P < 0.05). However, a significant increase in HBV DNA content was observed in group B, whereas this phenomenon was not observed in group C. A reduction in the contents of HBsAg, HBeAg and HBcAg in the mice from group B and C was observed when compared with group A. CONCLUSION: Emodin and APS have a weak but persistent inhibitory effect on HBV replication in vivo, which may function as a supplementary modality in the treatment of hepatitis B infection. PMID:19960563

  15. HBV Induced HCC: Major Risk Factors from Genetic to Molecular Level

    PubMed Central

    Ayub, Ambreen; Ashfaq, Usman Ali; Haque, Asma

    2013-01-01

    Hepatocellular carcinoma (HCC) is a deadly and emerging disease leading to death in Asian countries. High hepatitis B virus (HBV) load and chronic hepatitis B (CHB) infection increase the risk of developing HCC. HBV is a DNA virus that can integrate DNA into host genome thereby increase the yield of transactivator protein HBxAg that may deregulate many pathways involving in metabolism of cells. Several monogenic and polygenic risk factors are also involved in HCC development. This review summarizes the mechanism involved in HCC development and discusses some promising therapies to make HCC curative. PMID:23991421

  16. Isolation of the neutralization ScFvs Against HBV infection from the Immunized Population.

    PubMed

    Bai, Yin; Chen, Yanmin; Zhang, Nan; Guo, Xiaochen; Zhao, Jingzhuang; Wang, Fuxiang; Xu, Pengfei; Yuan, Qingyan; Qi, Jianying; Wang, Wenfei; Li, Deshan; Ren, Guiping

    2015-01-01

    For a long time, researchers have attempted to replace human plasmaderived immunoglobulin against HBV with recombinant HBV antibodies for therapeutic purposes, but failed to develop the products. One of the reasons may be lack of high throughput antibody screening tool. In this study, we screened an antibody library from immunized subjects by a powerful bacterial display technology. The capacity of the ScFv library was 10(9), 117 individual clones against HBV pre- S1 were initially selected and sequenced, the homology of these clones ranged from 59.7% -68.7%. Ten clones were randomly selected based on florescence intensity by FACS. The ScFv antibodies were expressed in E.coli and purified to examine their neutralization ability. First, we tested the ability of these clones to block the binding of the pre-S1 polypeptide to the HBV sensitive cells Chang liver cells and HepG2 cells, then, we examined the ability of these clones to inhibit the infection of the Change liver cells by HBV released from HepG2.2.15 cells by detection of viral DNA and hepatitis B virus e antigen (HBeAg) in the supernatant of Chang liver cells. Results showed that 4 (clone 3, 7, 9 and 31) out of the ten clones could significantly reduce the binding of pre-S1 polypeptide to Chang liver cells in a dose-dependent manner. Treatment with the same clones (clone 3, 7, 9 and 31) could dramatically reduce the contents of HBV DNA in the media of the infected Chang liver cells by 29.4, 7.89, 58.8, 76.9, respectively, and the amount of HBeAg by 60.2%, 32.6%, 66.1% and 68.1%, respectively. These results suggest that these clones can neutralize HBV infection and have the potential to become therapeutic antibodies against HBV infection to replace the human plasma-derived immunoglobulin. PMID:26144596

  17. IL6 Inhibits HBV Transcription by Targeting the Epigenetic Control of the Nuclear cccDNA Minichromosome

    PubMed Central

    Palumbo, Gianna Aurora; Scisciani, Cecilia; Pediconi, Natalia; Lupacchini, Leonardo; Alfalate, Dulce; Guerrieri, Francesca; Calvo, Ludovica; Salerno, Debora; Di Cocco, Silvia; Levrero, Massimo; Belloni, Laura

    2015-01-01

    The HBV covalently closed circular DNA (cccDNA) is organized as a mini-chromosome in the nuclei of infected hepatocytes by histone and non-histone proteins. Transcription from the cccDNA of the RNA replicative intermediate termed pre-genome (pgRNA), is the critical step for genome amplification and ultimately determines the rate of HBV replication. Multiple evidences suggest that cccDNA epigenetic modifications, such as histone modifications and DNA methylation, participate in regulating the transcriptional activity of the HBV cccDNA. Inflammatory cytokines (TNF?, LT?) and the pleiotropic cytokine interleukin-6 (IL6) inhibit hepatitis B virus (HBV) replication and transcription. Here we show, in HepG2 cells transfected with linear HBV monomers and HBV-infected NTCP-HepG2 cells, that IL6 treatment leads to a reduction of cccDNA-bound histone acetylation paralleled by a rapid decrease in 3.5kb/pgRNA and subgenomic HBV RNAs transcription without affecting cccDNA chromatinization or cccDNA levels. IL6 repressive effect on HBV replication is mediated by a loss of HNF1? and HNF4? binding to the cccDNA and a redistribution of STAT3 binding from the cccDNA to IL6 cellular target genes. PMID:26580974

  18. Management of the HBV reactivation in isolated HBcAb positive patients affected with Non Hodgkin Lymphoma

    PubMed Central

    2014-01-01

    Background Occult HBV infection (OBI) is defined by the persistence of HBV in the liver without serum HBsAg and HBVDNA. It represents a life-threatening event during immunosuppressive chemotherapies. An OBI occurs in approximately 18% of HBcAb + patients. International guidelines suggest surveillance for HBV markers in immunosuppressed patients. In Non-Hodgkin Lymphoma (NHL), the prevalence of OBI reactivation remains to be established. Methods In order to determine the prevalence of occult HBV reactivation in a large cohort of patients during chemotherapy for NHL, we analysed 498 NHL patients in a centre of Southern Italy. We evaluated HBV markers, NHL type, treatment type and occurrence of HBV reactivation. Results Forty % of patients were treated with monoclonal antibodies and 60.3% without. Ninety-six patients were HBcAb+, HBsAg-. HBV reactivation occurred in ten subjects of this subgroup. All of them were successfully treated with Lamivudine. None of the patients experienced liver-related death. The prevalence of OBI reactivation was of 10.42% in HBcAb + HBsAb- patients. This event occurred in 50% of patients treated with mild immunosuppressive therapies. Each reactivation was treated with Lamivudine. Discussion This report suggests that a strict surveillance is important and cost-effective in HBcAb + HBsAg- NHL patients treated with mild immunosuppressive therapies, in order to detect an occult HBV reactivation. PMID:24533834

  19. Fine mapping analysis of HLA-DP/DQ gene clusters on chromosome 6 reveals multiple susceptibility loci for HBV infection.

    PubMed

    Tao, Jingjing; Su, Kunkai; Yu, Chengbo; Liu, Xiaoli; Wu, Wei; Xu, Wei; Jiang, Bingxun; Luo, Rui; Yao, Jian; Zhou, Jiawei; Zhan, Yan; Ye, Chao; Yuan, Wenji; Jiang, Xianzhong; Cui, Wenyan; Li, Ming D; Li, Lianjuan

    2015-12-01

    Recent genome-wide association studies have revealed the HLA region on chromosome 6p21 as a susceptibility locus for hepatitis B virus (HBV) infection, a finding subsequently replicated in independent samples. However, only limited single nucleotide polymorphisms (SNPs) were analyzed in most of these studies, and it remains to be determined which SNPs contribute to the detected association. After genotyping 140 SNPs within this genomic region in a total of 1657 HBV-positive patients and 1456 HBV-negative controls, we conducted a series of genetic epidemiological and bioinformatics analysis, including individual SNP-based association analysis, haplotype-based association analysis, and conditional analysis. We identified 76 SNPs and 5 LD blocks in HLA-DP/DQ clusters that are significantly associated with HBV infection, with the smallest P value being 3.88נ10(-18) for rs9277535 in HLA-DPB1. With conditional analysis, we further revealed that the genes contributing to the effects of variants in HLA-DP/DQ on infection are independent of each other, and the LD block 5 in the 3'-UTR region of HLA-DPB1 had a predominant effect in the association of HLA-DP with HBV infection. We also found that the SNPs in the 3'-UTR region of HLA-DPB1 were significant between the subgroups of inactive HBV carrier, chronic hepatitis B, or hepatic cirrhosis from the case group and the spontaneous HBV-clearance subgroup from the control group. Finally, we did further association analysis of SNPs in this region with different subgroups from the case group, which revealed no association of these SNPs with the progression of HBV-related diseases. In sum, we showed, for the first time, that the HLA-DP/DQ clusters contribute independently to HBV infection, and the 3'-UTR region of HLA-DPB1 represents an important functional region involved in HBV infection. PMID:26197724

  20. Anti-HBV hairpin ribozyme-mediated cleavage of target RNA in vitro

    PubMed Central

    Song, Yu-Hu; Lin, Ju-Sheng; Liu, Nan-Zhi; Kong, Xin-Juan; Xie, Na; Wang, Nan-Xia; Jin, You-Xin; Liang, Kuo-Huan

    2002-01-01

    AIM: To study the preparation and cleavage activity of HpRz directed against the transcript of HBV core gene in vitro. METHODS: HpRz gene designed by computer targeting the transcript of HBV core gene was cloned into the vector p1.5 between 5-cis-Rz and 3-cis-Rz. 32p-labeled HpRz transcript proved whether the vector fit for the preparation of hairpin ribozyme in vitro. 32p-labeled pKC transcript containing HBV core region as target-RNA was transcribed using T7 RNA polymerase and purified by denaturing PAGE. Cold HpRz transcript was incubated with 32p-labeled target-RNAs under different conditions and radio autographed after denaturing polyacrylamide gel electrophoresis. RESULTS: HpRz has the specific ability of cleavage of target RNA at 37 C and 12 mM MgCl2. Km = 26.31 nmol/L, Kcat = 0.18/min. These results revealed that the design of HpRz was correct. CONCLUSION: HpRz prepared in this study possesses specific catalytic activity from the identification of cleavage activity. These results indicate that hairpin ribozyme may intracellularly inhibit the replication of HBV, therefore it may become a novel potent weapon for the treatment of hepatitis B. PMID:11833079

  1. Clinical cancer chemoprevention: From the hepatitis B virus (HBV) vaccine to the human papillomavirus (HPV) vaccine.

    PubMed

    Tsai, Horng-Jyh

    2015-04-01

    Approximately 2 million new cancer cases are attributed to infectious agents each year worldwide. Vaccines for the hepatitis B virus (HBV), a risk factor of hepatocellular cancer, and human papillomavirus (HPV), a risk factor of cervical cancer, are considered major successes in clinical chemoprevention of cancer. In Taiwan, the first evidence of cancer prevention through vaccinations was provided by HBV vaccination data in infants. The Taiwanese HBV vaccination program has since become a model immunization schedule for newborns worldwide. Persistent infection with high-risk HPV is generally accepted as prerequisite for cervical cancer diagnosis; however, cervical cancer is a rare complication of HPV infections. This is due to the fact that such infections tend to be transient. The safety and efficacy of both available HPV quadrivalent vaccine and bivalent vaccine are not in doubt at the present time. Until a human cytomegalovirus (CMV) vaccine becomes available, simple hygienic practices, such as hand washing, can prevent CMV infection both before and during pregnancy. Each country should establish her official guidelines regarding which vaccines should be used to treat various conditions, the target population (i.e., universal or limited to a selected population), and the immunization schedules. After a vaccine is recommended, decisions regarding reimbursement by the public health care fund are evaluated. The guidelines become part of the immunization schedule, which is updated annually and published in the official bulletin. In conclusion, both HBV and HPV vaccines are considered major successes in the chemoprevention of cancer. PMID:25951712

  2. Modeling and Analyzing the Transmission Dynamics of HBV Epidemic in Xinjiang, China

    PubMed Central

    Zhang, Tailei; Wang, Kai; Zhang, Xueliang

    2015-01-01

    Hepatitis B is an infectious disease caused by the hepatitis B virus (HBV) which affects livers. In this paper, we formulate a hepatitis B model to study the transmission dynamics of hepatitis B in Xinjiang, China. The epidemic model involves an exponential birth rate and vertical transmission. For a better understanding of HBV transmission dynamics, we analyze the dynamic behavior of the model. The modified reproductive number σ is obtained. When σ < 1, the disease-free equilibrium is locally asymptotically stable, when σ > 1, the disease-free equilibrium is unstable and the disease is uniformly persistent. In the simulation, parameters are chosen to fit public data in Xinjiang. The simulation indicates that the cumulated HBV infection number in Xinjiang will attain about 600,000 cases unless there are stronger or more effective control measures by the end of 2017. Sensitive analysis results show that enhancing the vaccination rate for newborns in Xinjiang is very effective to stop the transmission of HBV. Hence, we recommend that all infants in Xinjiang receive the hepatitis B vaccine as soon as possible after birth. PMID:26422614

  3. Modeling and Analyzing the Transmission Dynamics of HBV Epidemic in Xinjiang, China.

    PubMed

    Zhang, Tailei; Wang, Kai; Zhang, Xueliang

    2015-01-01

    Hepatitis B is an infectious disease caused by the hepatitis B virus (HBV) which affects livers. In this paper, we formulate a hepatitis B model to study the transmission dynamics of hepatitis B in Xinjiang, China. The epidemic model involves an exponential birth rate and vertical transmission. For a better understanding of HBV transmission dynamics, we analyze the dynamic behavior of the model. The modified reproductive number σ is obtained. When σ < 1, the disease-free equilibrium is locally asymptotically stable, when σ > 1, the disease-free equilibrium is unstable and the disease is uniformly persistent. In the simulation, parameters are chosen to fit public data in Xinjiang. The simulation indicates that the cumulated HBV infection number in Xinjiang will attain about 600,000 cases unless there are stronger or more effective control measures by the end of 2017. Sensitive analysis results show that enhancing the vaccination rate for newborns in Xinjiang is very effective to stop the transmission of HBV. Hence, we recommend that all infants in Xinjiang receive the hepatitis B vaccine as soon as possible after birth. PMID:26422614

  4. HBV and HIV co-infection: Impact on liver pathobiology and therapeutic approaches

    PubMed Central

    Parvez, Mohammad Khalid

    2015-01-01

    The consequences of hepatitis B virus (HBV) and human immunodeficiency virus (HIV) co-infection on progression of severe liver diseases is a serious public health issue, worldwide. In the co-infection cases, about 90% of HIV-infected population is seropositive for HBV where approximately 5%-40% individuals are chronically infected. In HIV co-infected individuals, liver-related mortality is estimated over 17 times higher than those with HBV mono-infection. The spectrum of HIV-induced liver diseases includes hepatitis, steatohepatitis, endothelialitis, necrosis, granulomatosis, cirrhosis and carcinoma. Moreover, HIV co-infection significantly alters the natural history of hepatitis B, and therefore complicates the disease management. Though several studies have demonstrated impact of HIV proteins on hepatocyte biology, only a few data is available on interactions between HBV and HIV proteins. Thus, the clinical spectrum as well as the complexity of the co-infection offers challenging fronts to study the underlying molecular mechanisms, and to design effective therapeutic strategies. PMID:25625003

  5. Characterization of Hepatitis B virus (HBV) genotypes in patients from Rondnia, Brazil

    PubMed Central

    2010-01-01

    Background Hepatitis B virus (HBV) can be classified into nine genotypes (A-I) defined by sequence divergence of more than 8% based on the complete genome. This study aims to identify the genotypic distribution of HBV in 40 HBsAg-positive patients from Rondnia, Brazil. A fragment of 1306 bp partially comprising surface and polymerase overlapping genes was amplified by PCR. Amplified DNA was purified and sequenced. Amplified DNA was purified and sequenced on an ABI PRISM 377 Automatic Sequencer (Applied Biosystems, Foster City, CA, USA). The obtained sequences were aligned with reference sequences obtained from the GenBank using Clustal X software and then edited with Se-Al software. Phylogenetic analyses were conducted by the Markov Chain Monte Carlo (MCMC) approach using BEAST v.1.5.3. Results The subgenotypes distribution was A1 (37.1%), D3 (22.8%), F2a (20.0%), D4 (17.1%) and D2 (2.8%). Conclusions These results for the first HBV genotypic characterization in Rondnia state are consistent with other studies in Brazil, showing the presence of several HBV genotypes that reflects the mixed origin of the population, involving descendants from Native Americans, Europeans, and Africans. PMID:21073730

  6. Occult HBV Infection May Be Transmitted through Close Contact and Manifest as an Overt Infection

    PubMed Central

    Hu, Li-Ping; Liu, De-Ping; Chen, Qin-Yan; Harrison, Tim J.; He, Xiang; Wang, Xue-Yan; Li, Hai; Tan, Chao; Yang, Qing-Li; Li, Kai-Wen; Fang, Zhong-Liao

    2015-01-01

    The importance of transmission of occult HBV infection (OBI) via transfusion, organ transplantation and hemodialysis has been widely recognized. However, data regarding the transmission of OBI through close contact remain limited. In this study, serum samples were obtained from a child and his parents. The child had received the standard vaccination regimen at birth and produced protective antibody. Sera were tested for HBV serological markers. Nested PCR assays were used to detect HBV DNA and the amplicons were cloned and their sequences subjected to phylogenetic analysis. The results showed that both parents had occult infections while the child had an overt infection. Twelve, eleven and nine clones, from the father, mother and son, respectively, were sequenced. Serotypes adrq+, ayw1, ayw and ayr were found in the father and ayw1, adw2 and adwq+ in the mother; adrq+ was the only serotype in son. Genotype B, subgenotype C2 and a recombinant were identified in the father and genotype B, subgenotype C5 and three recombinants were found in the mother. Subgenotype C2 was the only genotype identified in the child. A phylogenetic tree showed that all of the childs sequences and most of the fathers sequences clustered together. However, none of mothers sequences clustered with those of the child. The surface gene from the child and his father had the same amino acid substitution pattern (T118K, T123N and G145A). We concluded that the father was the source of the sons HBV infection, suggesting that occult HBV infection may be transmitted through close contact and manifest as an overt infection. PMID:26457811

  7. Molecular analysis of HBV genotypes and subgenotypes in the Central-East region of Tunisia

    PubMed Central

    2010-01-01

    Background In Tunisia, country of intermediate endemicity for Hepatitis B virus (HBV) infection, most molecular studies on the virus have been carried out in the North of the country and little is known about other regions. The aim of this study was to determine HBV genotype and subgenotypes in Central-East Tunisia. A total of 217 HBs antigen positive patients were enrolled and determination of genotype was investigated in 130 patients with detectable HBV DNA. HBV genotyping methods were: PCR-RFLP on the pre-S region, a PCR using type-specific primers in the S region (TSP-PCR) and partial sequencing in the pre-S region. Results Three genotypes (D, B and A) were detected by the PCR-RFLP method and two (D and A) with the TSP-PCR method, the concordance between the two methods was 93%. Sequencing and phylogenetic analysis of 32 strains, retrieved the same genotype (D and A) for samples with concordant results and genotype D for samples with discordant results. The sequences of discordant genotypes had a restriction site in the pre-S gene which led to erroneous result by the PCR-RFLP method. Thus, prevalence of genotype D and A was 96% and 4%, respectively. Phylogenetic analysis showed the predominance of two subgenotypes D1 (55%) and D7 (41%). Only one strain clustered with D3 subgenotype (3%). Conclusions Predominance of subgenotype D7 appears to occur in northern regions of Africa with transition to subgenotype D1 in the East of the continent. HBV genetic variability may lead to wrong results in rapid genotyping methods and sequence analysis is needed to clarify atypical results. PMID:21050489

  8. Blocking peptides against HBV: PreS1 protein selected from a phage display library

    SciTech Connect

    Wang, Wei; Liu, Yang; Zu, Xiangyang; Jin, Rui; Xiao, Gengfu

    2011-09-09

    Highlights: {yields} Successfully selected specific PreS1-interacting peptides by using phage displayed library. {yields} Alignment of the positive phage clones revealed a consensus PreS1 binding motif. {yields} A highly enriched peptide named P7 had a strong binding ability for PreS1. {yields} P7 could block PreS1 attachment. -- Abstract: The PreS1 protein is present on the outermost part of the hepatitis B virus (HBV) surface and has been shown to have a pivotal function in viral infectivity and assembly. The development of reagents with high affinity and specificity for PreS1 is of great significance for early diagnosis and treatment of HBV infection. A phage display library of dodecapeptide was screened for interactions with purified PreS1 protein. Alignment of the positive phage clones revealed a putative consensus PreS1 binding motif of HX{sub n}HX{sub m}HP/R. Moreover, a peptide named P7 (KHMHWHPPALNT) was highly enriched and occurred with a surprisingly high frequency of 72%. A thermodynamic study revealed that P7 has a higher binding affinity to PreS1 than the other peptides. Furthermore, P7 was able to abrogate the binding of HBV virions to the PreS1 antibody, suggesting that P7 covers key functional sites on the native PreS1 protein. This newly isolated peptide may, therefore, be a new therapeutic candidate for the treatment of HBV. The consensus motif could be modified to deliver imaging, diagnostic, and therapeutic agents to tissues affected by HBV.

  9. The Early Results of a New Health Care Program Implementation in HBV Screening: an Iranian Experience.

    PubMed

    Sharifian, Afsaneh; Naderi, Nostratollah; Sanati, Azar; Mohebi, Seyed Reza; Azimzadeh, Pedram; Golmohamadi, Ali; Nori, Simin; Khanyaghma, Mahsa; Sheikhesmaeili, Farshad; Zali, Mohamad Reza

    2015-10-01

    BACKGROUND According to the reports of World Health Organization (WHO) and Centers for Disease Control and Prevention, the prevalence of chronic hepatitis B infection in Iran has decreased from 2-7% in 2001 to 1.3-0.8% in children aged 2-14 years. In 2010 the Institute of Medicine recommended more comprehensive screening by primary care physicians (PCPs) for evaluation, vaccination, and management of infected patients for further decrease in the prevalence of chronic HBV infection. Thus, with contribution of the Health Department, we developed a practical flowchart for PCPs to start active screening of hepatitis B virus (HBV) in all visited patients and refer the positive cases for further evaluation and management to Taleghani Hospital. METHODS With collaboration of Health Department of Shahid Beheshti University of Medical Sciences), physicians of health centers were asked to screen all their patients for HBsAg. Positive cases were referred to Taleghani Hospital. They were first registered and educated about their disease, life style, and prevention methods. Their first degree families were screened for HBV infection too and were referred for vaccination if needed. According to the results of lab tests, appropriate management was done by a hepatologist. RESULTS Since implementation of this program, we have encountered a significant rise in patient detection (even in high risk groups). Many of them were not aware of their disease and most of those who were aware of their disease were not managed appropriately. Family screening and vaccination were inadequate and need more emphasis. CONCLUSION Although health system is active about screening of HBV infection in high risk populations, it is not perfect. It seems that health system needs to upgrade the screening and management programs of HBV infection. PMID:26609351

  10. The Early Results of a New Health Care Program Implementation in HBV Screening: an Iranian Experience

    PubMed Central

    Sharifian, Afsaneh; Naderi, Nostratollah; Sanati, Azar; Mohebi, Seyed Reza; Azimzadeh, Pedram; Golmohamadi, Ali; Nori, Simin; Khanyaghma, Mahsa; Sheikhesmaeili, Farshad; Zali, Mohamad Reza

    2015-01-01

    BACKGROUND According to the reports of World Health Organization (WHO) and Centers for Disease Control and Prevention, the prevalence of chronic hepatitis B infection in Iran has decreased from 2-7% in 2001 to 1.3-0.8% in children aged 2-14 years. In 2010 the Institute of Medicine recommended more comprehensive screening by primary care physicians (PCPs) for evaluation, vaccination, and management of infected patients for further decrease in the prevalence of chronic HBV infection. Thus, with contribution of the Health Department, we developed a practical flowchart for PCPs to start active screening of hepatitis B virus (HBV) in all visited patients and refer the positive cases for further evaluation and management to Taleghani Hospital. METHODS With collaboration of Health Department of Shahid Beheshti University of Medical Sciences), physicians of health centers were asked to screen all their patients for HBsAg. Positive cases were referred to Taleghani Hospital. They were first registered and educated about their disease, life style, and prevention methods. Their first degree families were screened for HBV infection too and were referred for vaccination if needed. According to the results of lab tests, appropriate management was done by a hepatologist. RESULTS Since implementation of this program, we have encountered a significant rise in patient detection (even in high risk groups). Many of them were not aware of their disease and most of those who were aware of their disease were not managed appropriately. Family screening and vaccination were inadequate and need more emphasis. CONCLUSION Although health system is active about screening of HBV infection in high risk populations, it is not perfect. It seems that health system needs to upgrade the screening and management programs of HBV infection. PMID:26609351

  11. Anti-HBV efficacy of combined siRNAs targeting viral gene and heat shock cognate 70

    PubMed Central

    2012-01-01

    Background Hepatitis B virus (HBV) infection is a major health concern with more than two billion individuals currently infected worldwide. Because of the limited effectiveness of existing vaccines and drugs, development of novel antiviral strategies is urgently needed. Heat stress cognate 70 (Hsc70) is an ATP-binding protein of the heat stress protein 70 family. Hsc70 has been found to be required for HBV DNA replication. Here we report, for the first time, that combined siRNAs targeting viral gene and siHsc70 are highly effective in suppressing ongoing HBV expression and replication. Methods We constructed two plasmids (S1 and S2) expressing short hairpin RNAs (shRNAs) targeting surface open reading frame of HBV(HBVS) and one plasmid expressing shRNA targeting Hsc70 (siHsc70), and we used the EGFP-specific siRNA plasmid (siEGFP) as we had previously described. First, we evaluated the gene-silencing efficacy of both shRNAs using an enhanced green fluorescent protein (EGFP) reporter system and flow cytometry in HEK293 and T98G cells. Then, the antiviral potencies of HBV-specific siRNA (siHBV) in combination with siHsc70 in HepG2.2.15 cells were investigated. Moreover, type I IFN and TNF-α induction were measured by quantitative real-time PCR and ELISA. Results Cotransfection of either S1 or S2 with an EGFP plasmid produced an 80%–90% reduction in EGFP signal relative to the control. This combinational RNAi effectively and specifically inhibited HBV protein, mRNA and HBV DNA, resulting in up to a 3.36 log10 reduction in HBV load in the HepG2.2.15 cell culture supernatants. The combined siRNAs were more potent than siHBV or siHsc70 used separately, and this approach can enhance potency in suppressing ongoing viral gene expression and replication in HepG2.2.15 cells while forestalling escape by mutant HBV. The antiviral synergy of siHBV used in combination with siHsc70 produced no cytotoxicity and induced no production of IFN-α, IFN-β and TNF-α in transfected cells. Conclusions Our combinational RNAi was sequence-specific, effective against wild-type and mutant drug-resistant HBV strains, without triggering interferon response or producing any side effects. These findings indicate that combinational RNAi has tremendous promise for developing innovative therapy against viral infection. PMID:23158906

  12. HBx down-regulated Gld2 plays a critical role in HBV-related dysregulation of miR-122.

    PubMed

    Peng, Feng; Xiao, Xinqiang; Jiang, Yongfang; Luo, Kaizhong; Tian, Yi; Peng, Milin; Zhang, Min; Xu, Yun; Gong, Guozhong

    2014-01-01

    miR-122 is a liver-rich-specific microRNA that plays an important role in hepatic gene expression via post-transcription regulation, and it is potentially associated with the development of hepatocellular carcinoma. It has been confirmed that miR-122 is down-regulated during HBV infection; however, how HBV affects miR-122 is still debated. One research provided evidence that HBx could reduce the miR-122 transcription level, but the other insisted that HBV had no significant effect on miR-122 transcription level but reduce miR-122 level via binding and sequestering endogenous miR-122. It is determinate that Gld2 could increase the specific miRNA stabilization by monoadenylation which was a post-transcription regulation. In this study, we aimed to investigate the mechanism of HBV-induced reduction of miR-122 and examine whether Gld2 is involved in it. According to the results of a microRNA microarray, we found miR-122 was the most down-regulated microRNA in HepG2.2.15 compared to HepG2. As revealed by qRT-PCR and western blotting analyses, both miR-122 and Gld2 levels were reduced in hepatic cell lines with expression of HBV or HBx but not other proteins of HBV, and over-expression of Gld2 could abolish the effect of HBV and HBx on the miR-122 level. What's more, both HBV and HBx have no significant effect on pre-miR-122 levels. And the dual-luciferase assay implicated that HBx could reduce the Gld2 promoter activity but had no significant effect on miR-122 promoter activity. In conclusion, HBx is a critical protein derived from HBV, which regulates miR-122 via down-regulating Gld2. PMID:24667324

  13. Antiviral treatment including entecavir plus tenofovir disoproxil fumarate for HBV reactivation following a rituximab-based regimen.

    PubMed

    Rago, Angela; Lichtner, Miriam; Mecarocci, Sergio; Marocco, Raffaella; Cenfra, Natalia; Belvisi, Valeria; Del Borgo, Cosmo; Cimino, Giuseppe; Mastroianni, Claudio M

    2010-01-01

    Entecavir and tenofovir disoproxil fumarate are potent and effective antiviral drugs that now represent recommended treatment options for chronic HBV infection. However, no or very limited clinical evidence is currently available on these drugs for the management of HBV reactivation in patients with haematological malignancies. Herein, we report a case of HBV reactivation in a patient with non-Hodgkin's lymphoma following a rituximab-based regimen, and who was successfully treated with a combination antiviral treatment including entecavir and tenofovir disoproxil fumarate. PMID:20834107

  14. Role of IL-4 Gene Polymorphisms in HBV-Related Hepatocellular Carcinoma in a Chinese Population

    PubMed Central

    Peng, Qiliu; Ma, Liping; Zhang, Xiaolian; Zhao, Jiangyang; Qin, Xue; Li, Shan

    2014-01-01

    Background Interleukin-4 (IL-4) is best known as an important mediator and modulator of immune and inflammatory responses. Hepatocellular carcinoma (HCC) is a typical inflammation-related cancer, and genetic variations in the IL-4 gene may be associated with the risk of hepatitis B virus (HBV)-related HCC. However, few studies have been conducted on their association. Objectives To clarify the effects of IL-4 gene polymorphisms on the risk of HBV-related HCC, two common variants, −590C/T (rs2243250) and −33C/T (rs2070874), and their relationship with HBV-related disease risk were investigated in a Chinese population. Methods IL-4 −590C/T and −33C/T polymorphisms were examined in 154 patients with HBV-related HCC, 62 patients with HBV-induced liver cirrhosis (LC), 129 patients with chronic hepatitis B (CHB), and 94 healthy controls, using the polymerase chain reaction-restriction fragment length polymorphism method and DNA sequencing. Results Overall, no significant differences were observed regarding the IL-4 −590C/T and −33C/T polymorphism genotypes, alleles, or haplotypes between the patient groups and the healthy controls. However, the CC genotypes of IL-4 −590C/T and −33C/T polymorphisms were observed to be significantly associated with CHB in subgroup analysis in males [CC versus TT (OR: 4.193, 95% CI: 1.094–16.071, P = 0.037; and OR: 3.438, 95% CI: 1.032–11.458, P = 0.044) and CC versus TT+CT (OR: 4.09, 95% CI: 1.08–15.49, P = 0.038; and OR: 3.43, 95% CI: 1.04–11.28, P = 0.042)]. Conclusions These findings suggest that genetic variants in IL-4 −590C/T and −33C/T polymorphisms may be a risk factor for CHB in Chinese males but not for HBV-related LC or HCC. PMID:25295591

  15. IL28B Is Associated with Outcomes of Chronic HBV Infection

    PubMed Central

    Shi, Xiaodong; Chi, Xiumei; Pan, Yu; Gao, Yanhang; Li, Wanyu; Yang, Chen; Zhong, Jin; Xu, Damo; Zhang, Manna; Minuk, Gerald

    2015-01-01

    Purpose The role of IL28B gene variants and expression in hepatitis B virus (HBV) infections are not well understood. Here, we evaluated whether IL28B gene expression and rs12979860 variations are associated with HBV outcomes. Materials and Methods IL28B genetic variations (rs12979860) were genotyped by pyrosequencing of DNA samples from 137 individuals with chronic HBV infection [50 inactive carriers (IC), 34 chronic hepatitis B (CHB), 27 cirrhosis, 26 hepatocellular carcinoma (HCC)], and 19 healthy controls. IL28A/B mRNA expression in peripheral blood mononuclear cells was determined by qRT-PCR, and serum IL28B protein was measured by ELISA. Results Patients with IL28B C/C genotype had greater IL28A/B mRNA expression and higher IL28B protein levels than C/T patients. Within the various disease stages, compared to IC and healthy controls, IL28B expression was reduced in the CHB, cirrhosis, and HCC cohorts (CHB vs. IC, p=0.02; cirrhosis vs. IC, p=0.01; HCC vs. IC, p=0.001; CHB vs. controls, p<0.01; cirrhosis vs. controls, p<0.01; HCC vs. controls, p<0.01). When stratified with respect to serum HBV markers in the IC and CHB cohorts, IL28B mRNA and protein levels were higher in HBeAg-positive than negative individuals (p=0.01). Logistic regression analysis revealed that factors associated with high IL28B protein levels were C/C versus C/T genotype [p=0.016, odds ratio (OR)=0.25, 95% confidence interval (CI)=0.08-0.78], high alanine aminotransferase values (p<0.001, OR=8.02, 95% CI=2.64-24.4), and the IC stage of HBV infection (p<0.001). Conclusion Our data suggest that IL28B genetic variations may play an important role in long-term development of disease in chronic HBV infections. PMID:25837166

  16. Detection of Hepatitis B Virus (HBV) Genotype E CarriedEven in the Presence of High Titers of Anti-HBs Antibodiesby an Argentinean Patient of African Descent Who Had Received Vaccination against HBV

    PubMed Central

    Mathet, Vernica L.; Cuestas, Mara L.; Ruiz, Vanesa; Minassian, Mara L.; Rivero, Cintia; Trinks, Julieta; Daleoso, Graciela; Len, Liliana M.; Sala, Andrea; Libellara, Beatriz; Corach, Daniel; Oubia, Jos R.

    2006-01-01

    Genotype E hepatitis B virus (HBV) was detected in two Argentine sisters exhibiting an African mitochondrial lineage. One of them (who had been vaccinated against HBV) exhibited anti-HBs cocirculating antibodies without HBsAg escape mutants, while her unvaccinated sister showed a D144A HBsAg escape mutant without anti-HBs antibodies. Both sisters carried an unusual L209V substitution within HBsAg. PMID:16954295

  17. Adaptation of the HBV model for the study of drought propagation in European catchments

    NASA Astrophysics Data System (ADS)

    van Loon, A. F.; van Lanen, H. A. J.; Seibert, J.; Torfs, P. J. J. F.

    2009-04-01

    Drought propagation is the conversion of a meteorological drought signal into a hydrological drought (e.g. groundwater and streamflow) as it moves through the subsurface part of the hydrological cycle. The lag, attenuation and possibly pooling of parts of the signal are dependent on climate and catchment characteristics. The understanding of processes underlying drought propagation is still very limited. Our aim is to study these processes in small catchments across Europe with different climate conditions and physical structures (e.g. hard rock, porous rock, flat areas, steep slopes, snow, lakes). As measurements of soil moisture and groundwater storage are normally scarce, simulation of these variables using a lumped hydrological model is needed. However, although a simple model is preferable, many conceptual rainfall-runoff models are not suitable for this purpose because of their focus on fast reactions and therefore unrealistic black box approach of the soil moisture and groundwater system. We studied the applicability of the well-known semi-distributed rainfall-runoff model HBV for drought propagation research. The results show that HBV reproduces observed discharges fairly well. However, in simulating groundwater storage in dry periods, HBV has some conceptual weaknesses: 1) surface runoff is approximated by a quick flow component through the upper groundwater box; 2) the storage in the upper groundwater box has no upper limit; 3) lakes are simulated as part of the lower groundwater box; 4) the percolation from the upper to the lower groundwater box is not continuous, but either zero or constant. So, adaptation of the HBV model structure was needed to be able to simulate realistic groundwater storage in dry periods. The HBV Light model (Seibert et al., 2000) was used as basis for this work. As the snow and soil routines of this model have proven their value in previous (drought) studies, these routines are left unchanged. The lower part of HBV Light, the "response function" that transforms groundwater recharge into discharge, is replaced by a for this study adapted conceptual research model programmed in R. The structure of this conceptual research model is based on a number of coupled reservoirs representing storage in shallow and deep groundwater, and lakes. The recession characteristics of the catchment determine the model elements: i.e. number of reservoirs, linear vs. non-linear reservoirs, in series vs. parallel connections. We used data from Narsjø (Norway), Metuje and Sázava (Czech Republic) to select the proper configuration for the conceptual research model and to test the combined HBV Light-conceptual research model approach. The influence of different model configurations on drought characteristics is presented. Subsequently, the new approach was applied to 4-5 other European catchments with contrasting climate conditions and physical structures (including Nedožery (Slovakia), and Upper-Guadiana (Spain)). Our adapted model approach finally gives a better representation of groundwater storage during drought periods than the original HBV model, which makes it a useful tool for the study of processes underlying drought propagation. Simulated drought characteristics are shown to illustrate drought propagation for the different catchment conditions. Seibert, J., Unlenbrook, S., Leibundgut, C. and Halldin, S., 2000. Multiscale calibration and validation of a conceptual rainfall-runoff model. Physics and Chemistry of the Earth, Part B: Hydrology, Oceans and Atmosphere, 25(1): 59-64.

  18. [Seroepidemiologic case finding in HTLV III infection, lues and HBV in a prison].

    PubMed

    Borroni, G; Panuccio, A; Ballerini, P; Gelosa, L

    1986-01-01

    We report serological screening of 1217 prisoners for HTLV III antibodies, HBV markers and lues tests. The prevalence for HTLV III Abs on the whole of prisoners controlled is 30.8%, among the drug-users is 60.7%, with a relative risk (RR) of 1.18 between males and females in this group. It is been observed a significant association between aspecific positivity to VDRL and HTLV III Abs in the serum. PMID:3580142

  19. HBV light - A user-friendly catchment-runoff-model software

    NASA Astrophysics Data System (ADS)

    Seibert, J.; Vis, M.; Kser, D.

    2012-04-01

    Conceptual models are frequently used for catchment hydrology studies. Here we present a new version of the HBV model, which has been programmed in Visual Basic .NET. This software provides a user-friendly version which is especially useful for education. Different functionalities like an automatic calibration and the possibility to perform Monte Carlo runs make the software also interesting for research projects. Furthermore, a command line version is suitable for automating modeling procedures and for coupling with software such as PEST.

  20. Distinct patterns of hepcidin and iron regulation during HIV-1, HBV, and HCV infections

    PubMed Central

    Armitage, Andrew E.; Stacey, Andrea R.; Giannoulatou, Eleni; Marshall, Elizabeth; Sturges, Pamela; Chatha, Kamaljit; Smith, Nicola M. G.; Huang, XiaoJie; Xu, XiaoNing; Pasricha, Sant-Rayn; Li, Ning; Wu, Hao; Webster, Craig; Prentice, Andrew M.; Pellegrino, Pierre; Williams, Ian; Norris, Phillip J.; Drakesmith, Hal; Borrow, Persephone

    2014-01-01

    During HIV type-1 (HIV-1), hepatitis C virus (HCV), and hepatitis B virus (HBV) infections, altered iron balance correlates with morbidity. The liver-produced hormone hepcidin dictates systemic iron homeostasis. We measured hepcidin, iron parameters, cytokines, and inflammatory markers in three cohorts: plasma donors who developed acute HIV-1, HBV, or HCV viremia during the course of donations; HIV-1–positive individuals progressing from early to chronic infection; and chronically HIV-1–infected individuals (receiving antiretroviral therapy or untreated). Hepcidin increased and plasma iron decreased during acute HIV-1 infection, as viremia was initially detected. In patients transitioning from early to chronic HIV-1 infection, hepcidin in the first 60 d of infection positively correlated with the later plasma viral load set-point. Hepcidin remained elevated in individuals with untreated chronic HIV-1 infection and in subjects on ART. In contrast to HIV-1, there was no evidence of hepcidin up-regulation or hypoferremia during the primary viremic phases of HCV or HBV infection; serum iron marginally increased during acute HBV infection. In conclusion, hepcidin induction is part of the pathogenically important systemic inflammatory cascade triggered during HIV-1 infection and may contribute to the establishment and maintenance of viral set-point, which is a strong predictor of progression to AIDS and death. However, distinct patterns of hepcidin and iron regulation occur during different viral infections that have particular tissue tropisms and elicit different systemic inflammatory responses. The hypoferremia of acute infection is therefore a pathogen-specific, not universal, phenomenon. PMID:25092293

  1. Distinct patterns of hepcidin and iron regulation during HIV-1, HBV, and HCV infections.

    PubMed

    Armitage, Andrew E; Stacey, Andrea R; Giannoulatou, Eleni; Marshall, Elizabeth; Sturges, Pamela; Chatha, Kamaljit; Smith, Nicola M G; Huang, XiaoJie; Xu, XiaoNing; Pasricha, Sant-Rayn; Li, Ning; Wu, Hao; Webster, Craig; Prentice, Andrew M; Pellegrino, Pierre; Williams, Ian; Norris, Phillip J; Drakesmith, Hal; Borrow, Persephone

    2014-08-19

    During HIV type-1 (HIV-1), hepatitis C virus (HCV), and hepatitis B virus (HBV) infections, altered iron balance correlates with morbidity. The liver-produced hormone hepcidin dictates systemic iron homeostasis. We measured hepcidin, iron parameters, cytokines, and inflammatory markers in three cohorts: plasma donors who developed acute HIV-1, HBV, or HCV viremia during the course of donations; HIV-1-positive individuals progressing from early to chronic infection; and chronically HIV-1-infected individuals (receiving antiretroviral therapy or untreated). Hepcidin increased and plasma iron decreased during acute HIV-1 infection, as viremia was initially detected. In patients transitioning from early to chronic HIV-1 infection, hepcidin in the first 60 d of infection positively correlated with the later plasma viral load set-point. Hepcidin remained elevated in individuals with untreated chronic HIV-1 infection and in subjects on ART. In contrast to HIV-1, there was no evidence of hepcidin up-regulation or hypoferremia during the primary viremic phases of HCV or HBV infection; serum iron marginally increased during acute HBV infection. In conclusion, hepcidin induction is part of the pathogenically important systemic inflammatory cascade triggered during HIV-1 infection and may contribute to the establishment and maintenance of viral set-point, which is a strong predictor of progression to AIDS and death. However, distinct patterns of hepcidin and iron regulation occur during different viral infections that have particular tissue tropisms and elicit different systemic inflammatory responses. The hypoferremia of acute infection is therefore a pathogen-specific, not universal, phenomenon. PMID:25092293

  2. Seroprevalence of HIV, HBV, HCV, and HTLV among Pregnant Women in Southwestern Nigeria.

    PubMed

    Opaleye, Oluyinka Oladele; Igboama, Magdalene C; Ojo, Johnson Adeyemi; Odewale, Gbolabo

    2016-01-01

    Sexually transmitted infections (STIs) are major public health challenge especially in developing countries. This study was designed to determine the prevalence of Hepatitis B virus (HBV), Hepatitis C Virus (HCV), Human immunodeficiency virus (HIV), and Human T-cell lymphotropic Virus type I (HTLV-I) among pregnant women attending antenatal clinic, in Ladoke Akintola University Teaching Hospital, Osogbo, and South-Western Nigeria. One hundred and eighty two randomly selected pregnant women were screened for HBsAg, anti-HCV, anti-HIV and HTLV-1 IgM antibodies using commercially available ELISA kit. Of the182 blood samples of pregnant women screened whose age ranged from 15-49 years, 13 (7.1%), 5 (2.7%), 9 (4.9%), and 44 (24.2%) were positive for HBsAg, anti-HCV, anti-HIV, and HTLV-1 IgM antibodies, respectively. The co-infection rate of 0.5% was obtained for HBV/HCV, HBV/HIV, HIV/HTLV-1, and HCV/HTLV-1 while 1.1% and 0% was recorded for HBV/HTLV-1 and HCV/HIV co-infections, respectively. Expected risk factors such as history of surgery, circumcision, tattooing and incision showed no significant association with any of the viral STIs (P > 0.05). This study shows that there is the need for a comprehensive screening of all pregnant women for HBsAg, anti-HCV, anti-HIV and HTLV-1 to prevent mother to child transmission of these viral infections and its attending consequences. PMID:25879258

  3. Diagnostic value of serum Golgi protein 73 for HBV-related primary hepatic carcinoma

    PubMed Central

    Gao, Guosheng; Dong, Feibo; Xu, Xiaozhen; Hu, Airong; Hu, Yaoren

    2015-01-01

    Background: Alpha-fetoprotein (AFP) levels are routinely used for diagnosis and monitoring of hepatic diseases, but it has a limited value. Golgi protein 73 (GP73) has been suggested as a new marker for hepatic diseases. Objective: To explore the clinical value of serum GP73 in different diseases associated with hepatitis B virus (HBV) infection. Method: Between January 2010 and August 2014, serum samples from 88 patients with chronic hepatitis B (CHB), 78 patients with HBV-related liver cirrhosis (LC), and 194 patients with HBV-related primary hepatic cancer (PHC) were collected. Serum samples from 30 healthy volunteers were used as controls. ELISA and microparticle enzyme immunoassay were used to measure serum GP73 and AFP levels. Receiver operating characteristic (ROC) curves were used to analyze the diagnostic value of serum GP73 and AFP for PHC. Results: For the diagnosis of PHC, GP73 showed a sensitivity of 65.5% and specificity of 66.3%, while AFP levels showed sensitivity of 64.4% and specificity of 76.5%. Serial testing (both tests are positive) could increase the specificity (sensitivity of 45.9% and specificity of 85.5%) while parallel testing (any single positive test result) could increase the sensitivity (sensitivity of 84.0% and specificity of 57.2%). Serum GP73 and AFP levels were significantly different between Child-Pugh grades (P<0.001 for GP73 and P=0.044 for AFP). Significant differences in serum GP73 and AFP were found between TNM stages (all P<0.001). Conclusion: Serum GP73 had limited diagnostic value for HBV-related PHC. The combined use of serum GP73 and AFP levels improved the diagnostic efficacy. PMID:26617863

  4. Serum GP73, a marker for evaluating progression in patients with chronic HBV infections.

    PubMed

    Wei, Hongshan; Li, Boan; Zhang, Renwen; Hao, Xiaohua; Huang, Yubo; Qiao, Yong; Hou, Jun; Li, Xin; Li, Xingwang

    2013-01-01

    This study was designed to investigate the role of serum GP73 for diagnosing significant fibrosis in patients with chronic hepatitis B virus (HBV) infections. Two populations were enrollment. All subjects were patients with chronic HBV infections. First population included 761 patients, who received liver stiffness measurement; the second population included 633 patients, who undertaken liver biopsy, in which 472 patients with nearly normal ALT. All patients received serum GP73 test. The effect of GP73 recombinant protein to HepG2 cells and LX2 cells were observed in vitro. Results showed that serum GP73 concentration is correlated with liver stiffness (r = 0.601). The area under ROC curve is 0.76. The sensitivity and specificity of GP73 for significant fibrosis (≥F2) diagnosis were 62.81%, 80.05% respectively (cut off: 76.6 ng/ml). Serum GP73 concentration was significantly correlated with the grading of fibrosis (r = 0.32, and 0.35, in 633 and 472 patients, respectively.) GP73 had a striking performance for diagnosing S2 in patients with chronic HBV infections. In 472 patients with nearly normal ALT, the sensitivity and specificity of GP73 for S2 diagnosis were 62.5% and 80.0% respectively, where the cut-off was set at 82 ng/ml. GP73 recombinant protein may prompt LX2 cells proliferation at the concentration 10-100 ng/ml. The present results indicated that GP73 may be a marker for diagnosing significant fibrosis in patients with chronic HBV infections, and may be a new contributor to fibrogensis. PMID:23418424

  5. HBV-Related Health Behaviors in a Socio-Cultural Context: Perspectives from Khmers and Koreans

    PubMed Central

    Lee, Haeok; Kiang, Peter; Chea, Phala; Peou, Sonith; Tang, Shirley S.; Yang, JinHwang; Fawcett, Jacqueline; Hann, Hie-Won

    2014-01-01

    Purpose To explore factors influencing health and health care within the sociocultural context of Cambodian Americans (CAs or Khmers) and Korean Americans (KA) and to examine intergroup similarities and differences between CAs and KAs, focusing on hepatitis B virus (HBV) and liver cancer prevention behaviors. Methods The study used a qualitative design guided by the revised Network Episode Model (NEM) and informed by ethnographic analysis. Focus group interviews with key informants among CA community health leaders (CHLs, n=14) and individual interviews with key informants of KA CHLs (n=9) were audiotaped and transcribed. Results Three categories that influenced HBV and liver cancer prevention emerged from both CAs and KAs: the socio-cultural, individual, and behavioral. Four additional sub-categories (sub-themes) of sociocultural were identified as socio-history, socio-medicine, socio-linguistic, and socio-health resources. Both CAs and KAs, however, have low levels of knowledge and significant misunderstandings about HBV infection. Conclusions The study identifies and compares the social-cultural determinant for HBV and liver cancer and highlights the factors of education, intercultural communication, and interactions within socio-cultural contexts of CA and KA subgroups. In general, conceptual overlaps are apparent between Khmers (from now on, the terms, CA and Khmer, will be used interchangeably) and Koreans except for the sub-theme of socio-history. However, differences in concept-specific attributes point to the need to account for differing conceptualizations and implications of specific ethnic groups’ sociocultural contexts, and to design contextually-relevant outreach and educational interventions for targeted AAPI subgroups. PMID:24355416

  6. Treatment options beyond IFN? and NUCs for chronic HBV infection: expectations for tomorrow.

    PubMed

    Baltayiannis, G; Karayiannis, P

    2014-11-01

    Chronic hepatitis B virus (HBV) infection may progress to cirrhosis, hepatocellular carcinoma (HCC) and end-stage liver failure with time. Interruption of this process can only be achieved through effective antiviral treatment. This approach has so far involved the use of immunomodulators such as pegylated interferon alpha (Peg-IFN?) for a finite period of up to a year and nucleos-(t)ide analogues (NUCs) for treatment over much longer periods of time. The latter act by suppressing HBV replication at the level of DNA synthesis by inhibiting the viral reverse transcriptase/DNA polymerase and causing premature termination of DNA synthesis. The ideal treatment end point is loss of HBsAg in both HBeAg+ve and HBeAg-ve patients following monotherapy. This, however, is only achievable in a minority of patients. Secondary outcomes are durable HBeAg loss and seroconversion to anti-HBe, which occur in about 18-30% of HBeAg+ve patients depending on the antiviral used, and sustained suppression of HBV-DNA accompanied by biochemical normalization and histological improvement in non-HBeAg+ve seroconverting and HBeAg-ve patients. There is therefore a need for additional direct-acting antivirals (DAAs) targeting different stages of the life cycle of the virus, as well as immunotherapeutic approaches. Such developments may pave the way for their use either alone or more likely in combination in the fight against chronic HBV infection. Such drugs or approaches, which are currently undergoing preclinical or clinical testing, are the subject of this review. PMID:25271858

  7. The Impact of Gender Differences in Attitudes and Beliefs Concerning HBV Vaccination and Screening in the Lao Community.

    PubMed

    Akosionu, Odichinma; Virnig, Beth; Call, Kathleen T; Yuan, Jian-Min; Chanthanouvong, Sunny; Nguyen, Ruby H N

    2016-02-01

    Liver cancer incidence is increasing among Asian Americans. Laotians in the US have greater risk of liver cancer death compared to other Asian American groups. However, ethnicity is not the only disparity; Laotian men are at increased risk of liver cancer compared to Laotian women. Use of hepatitis B virus (HBV) vaccination and screening is low among Laotians. The impact of gender differences in attitudes and beliefs concerning HBV vaccination and screening is unknown. This secondary analysis of a cross-sectional community-based participatory research study. Although men were more likely to believe that infection with HBV is preventable, and treatable, causes liver cancer, and that healthy persons should be vaccinated, of those who thought people should get vaccinated, women were four times more likely to receive vaccine than men (adj. OR 4.0, CI 1.2-19). Understanding and addressing gender differences may increase HBV screening and vaccination uptake, thus reducing disparities within the Laotian community. PMID:25612922

  8. Epigenetic mechanism involved in the HBV/HCV-related hepatocellular carcinoma tumorigenesis.

    PubMed

    Rongrui, Liang; Na, Huang; Zongfang, Li; Fanpu, Ji; Shiwen, Jiang

    2014-01-01

    Hepatitis B virus (HBV) and hepatitis C virus (HCV) infection were known to be risk factors for HCC, they were suspected to promote its development by eliciting epigenetic changes. However, the precise gene targets and underlying mechanisms have not been elucidated. Epigenetic regulation of gene expression has emerged as a fundamental aspect of cancer development and progression. The molecular mechanisms of carcinogenesis in hepatocellular carcinoma involve a complex interplay of both genetic and epigenetic factors. DNA methylation, post-translational modifications of histone proteins, chromatin remodeling, and noncoding RNAs are four major types of mechanistic layers in the field of epigenetics. HBV infection could affect methylation on p16(INK4A), GSTP1, CDH1(E-cadherin), RASSF1A, p21(WAF1/CIP1) genes, which may play important roles in the development of HCC. HCV infection was related to aberrant methylation on SOCS-1, Gadd45?, MGMT, STAT1 and APC. Other epigenetic alterations included histone proteins, chromatin remodeling, and noncoding RNAs were described in literature. Uncovering the epigenetic alterations of HBV/HCV-induced HCC carcinogenesis could highlight a new strategy for deciphering the mechanism of HCC tumorigenesis and development, as well as a potential diagnostic advantage. PMID:23888939

  9. IL-10 producing regulatory B cells in the pathogenesis of chronic HBV infection12

    PubMed Central

    Das, Abhishek; Ellis, Gidon; Pallant, Celeste; Lopes, A. Ross; Khanna, Pooja; Peppa, Dimitra; Chen, Antony; Blair, Paul; Dusheiko, Geoffrey; Gill, Upkar; Kennedy, Patrick T; Brunetto, Maurizia; Lampertico, Pietro; Mauri, Claudia; Maini, Mala K.

    2012-01-01

    A regulatory subset of B cells has been found to modulate immune responses in autoimmunity, infection and cancer but has not been investigated in the setting of human persistent viral infection. IL-10 is elevated in patients with chronic hepatitis B virus infection (CHB)3 but its cellular sources and impact on antiviral T cells have not been addressed. We investigated the role of IL-10 and regulatory B cells in the pathogenesis of CHB. Serum IL-10 levels were studied longitudinally in patients with CHB undergoing spontaneous disease flares. There was a close temporal correlation between IL-10 levels and fluctuations in viral load or liver inflammation. Blockade of IL-10 in vitro rescued polyfunctional virus-specific CD8 T cell responses. To investigate the potential contribution of regulatory B cells, their frequency was measured directly ex vivo and after exposure to stimuli relevant to HBV (CpG or HBV antigens). IL-10-producing B cells were enriched in patients, and their frequency correlated temporally with hepatic flares, both after stimulation and directly ex vivo. Phenotypically, these cells were predominantly immature (CD19+CD24hiCD38hi) ex vivo; sorted CD19+CD24hiCD38hi cells suppressed HBV-specific CD8 T cell responses in an IL-10-dependent manner. In summary, these data reveal a novel IL-10-producing subset of B cells able to regulate T cell immunity in CHB. PMID:22972930

  10. NK cell receptor imbalance and NK cell dysfunction in HBV infection and hepatocellular carcinoma.

    PubMed

    Sun, Cheng; Sun, Haoyu; Zhang, Cai; Tian, Zhigang

    2015-05-01

    Hepatocellular carcinoma (HCC) is currently the third leading cause of cancer mortality and a common poor-prognosis malignancy due to postoperative recurrence and metastasis. There is a significant correlation between chronic hepatitis B virus (HBV) infection and hepatocarcinogenesis. As the first line of host defense against viral infections and tumors, natural killer (NK) cells express a large number of immune recognition receptors (NK receptors (NKRs)) to recognize ligands on hepatocytes, liver sinusoidal endothelial cells, stellate cells and Kupffer cells, which maintain the balance between immune response and immune tolerance of NK cells. Unfortunately, the percentage and absolute number of liver NK cells decrease significantly during the development and progression of HCC. The abnormal expression of NK cell receptors and dysfunction of liver NK cells contribute to the progression of chronic HBV infection and HCC and are significantly associated with poor prognosis for liver cancer. In this review, we focus on the role of NK cell receptors in anti-tumor immune responses in HCC, particularly HBV-related HCC. We discuss specifically how tumor cells evade attack from NK cells and how emerging understanding of NKRs may aid the development of novel treatments for HCC. Novel mono- and combination therapeutic strategies that target the NK cell receptor-ligand system may potentially lead to successful and effective immunotherapy in HCC.Cellular & Molecular Immunology advance online publication, 6 October 2014; doi:10.1038/cmi.2014.91. PMID:25308752

  11. Genotyping the hepatitis B virus with a fragment of the HBV DNA polymerase gene in Shenyang, China

    PubMed Central

    2011-01-01

    The hepatitis B virus (HBV) has been classified into eight genotypes (A-H) based on intergenotypic divergence of at least 8% in the complete nucleotide sequence or more than 4% in the S gene. To facilitate the investigation of the relationship between the efficacy of drug treatment and the mutation with specific genotype of HBV, we have established a new genotyping strategy based on a fragment of the HBV DNA polymerase gene. Pairwise sequence and phylogenetic analyses were performed using CLUSTAL V (DNASTAR) on the eight (A-H) standard full-length nucleotide sequences of HBV DNA from GenBank (NCBI) and the corresponding semi-nested PCR products from the HBV DNA polymerase gene. The differences in the semi-nested PCR fragments of the polymerase genes among genotypes A through F were greater than 4%, which is consistent with the intergenotypic divergence of at least 4% in HBV DNA S gene sequences. Genotyping using the semi-nested PCR products of the DNA polymerase genes revealed that only genotypes B, C, and D were present in the 50 cases, from Shenyang, China, with a distribution of 11 cases (22%), 25 cases (50%), and 14 cases (28%) respectively. These results demonstrate that our new genotyping method utilizing a fragment of the HBV DNA polymerase gene is valid and can be employed as a general genotyping strategy in areas with prevalent HBV genotypes A through F. In Shenyang, China, genotypes C, B, and D were identified with this new genotyping method, and genotype C was demonstrated to be the dominant genotype. PMID:21693069

  12. Genetic polymorphisms of C-reactive protein increase susceptibility to HBV-related hepatocellular carcinoma in a Guangxi male population

    PubMed Central

    Lao, Xianjun; Ren, Shan; Lu, Yu; Yang, Dongmei; Qin, Xue; Li, Shan

    2015-01-01

    C-reactive protein (CRP) is a biomarker of inflammation and the production has been shown to be influenced by genetic variation in CRP gene. HBV-related hepatocellular carcinoma (HCC) is a typical inflammation-related disease occurs mainly in men. The present study was designed to investigate the association between CRP polymorphisms and HBV-related HCC risk in a Chinese male population. The CRP rs2794521 and rs3093059 SNPs were genotyped by polymerase chain reaction-restriction fragment length polymorphism method (PCR-RFLP) in 158 HBV patients with HCC, 207 HBV patients without HCC, and 150 unrelated healthy controls. A significant increased HCC risk in HBV patients were observed for the rs3093059 SNP comparing with those without HCC (C allele vs. T allele: adjusted OR=1.56, 95% CI, 1.07-2.29, P=0.021; TC vs. TT: adjusted OR=1.77, 95% CI, 1.13-2.76, P=0.012; TC/CC vs. TT: adjusted OR=1.76, 95% CI, 1.14-2.71, P=0.011). However, we did not observe any significant association of rs3093059 polymorphism with HCC when compared with healthy controls. With respect to rs2794521 polymorphism, no significant associations of this polymorphism with HCC risk were found in this population. In haplotype analysis between HBV patients with HCC and HBV patients without HCC, the TC haplotype was found correlated with a significant increased HCC risk (OR=1.803, 95% CI, 1.237-2.335, P<0.001). We concluded that the CRP rs3093059 polymorphism may play a significant role in the development of HBV-related HCC in the Guangxi male population. PMID:26884882

  13. Prevalence and Characteristics of Hepatitis B Virus (HBV) Coinfection among HIV-Positive Women in South Africa and Botswana

    PubMed Central

    Matthews, Philippa C.; Beloukas, Apostolos; Malik, Amna; Carlson, Jonathan M.; Jooste, Pieter; Ogwu, Anthony; Shapiro, Roger; Riddell, Lynn; Chen, Fabian; Luzzi, Graz; Jaggernath, Manjeetha; Jesuthasan, Gerald; Jeffery, Katie; Ndung’u, Thumbi; Goulder, Philip J. R.; Geretti, Anna Maria; Klenerman, Paul

    2015-01-01

    There is progressive concern about the evolving burden of morbidity and mortality caused by coinfection with HIV-1 and hepatitis B virus (HBV) in sub-Saharan Africa, but the epidemiology and impact of this problem are not well defined. We therefore set out to assimilate more information about the nature of HBV/HIV coinfection in this region by undertaking a retrospective observational study of southern African adult women. We used samples from previously recruited HIV-1 positive women attending antenatal clinics in three settings in South Africa and Botswana (n = 950) and added a small cohort of HIV-negative antenatal South African women for comparison (n = 72). We tested for HBsAg and followed up HBsAg-positive samples by testing for HBeAg, HBV DNA, HBV genotype, presence of drug-resistance associated mutations (RAMs) and HDV. We identified HBsAg in 72 individuals (7% of the whole cohort), of whom 27% were HBeAg-positive, and the majority HBV genotypes A1 and A2. We did not detect any HDV coinfection. HBV prevalence was significantly different between geographically distinct cohorts, but did not differ according to HIV status. Among adults from South Africa, HBV/HIV coinfected patients had lower CD4+ T cell counts compared to those with HIV-monoinfection (p = 0.02), but this finding was not replicated in the cohort from Botswana. Overall, these data provide a snapshot of the coinfection problem at the heart of the HIV/HBV co-epidemic, and are important to inform public health policy, resource allocation, education, surveillance and clinical care. PMID:26218239

  14. Prevalence and Characteristics of Hepatitis B Virus (HBV) Coinfection among HIV-Positive Women in South Africa and Botswana.

    PubMed

    Matthews, Philippa C; Beloukas, Apostolos; Malik, Amna; Carlson, Jonathan M; Jooste, Pieter; Ogwu, Anthony; Shapiro, Roger; Riddell, Lynn; Chen, Fabian; Luzzi, Graz; Jaggernath, Manjeetha; Jesuthasan, Gerald; Jeffery, Katie; Ndung'u, Thumbi; Goulder, Philip J R; Geretti, Anna Maria; Klenerman, Paul

    2015-01-01

    There is progressive concern about the evolving burden of morbidity and mortality caused by coinfection with HIV-1 and hepatitis B virus (HBV) in sub-Saharan Africa, but the epidemiology and impact of this problem are not well defined. We therefore set out to assimilate more information about the nature of HBV/HIV coinfection in this region by undertaking a retrospective observational study of southern African adult women. We used samples from previously recruited HIV-1 positive women attending antenatal clinics in three settings in South Africa and Botswana (n = 950) and added a small cohort of HIV-negative antenatal South African women for comparison (n = 72). We tested for HBsAg and followed up HBsAg-positive samples by testing for HBeAg, HBV DNA, HBV genotype, presence of drug-resistance associated mutations (RAMs) and HDV. We identified HBsAg in 72 individuals (7% of the whole cohort), of whom 27% were HBeAg-positive, and the majority HBV genotypes A1 and A2. We did not detect any HDV coinfection. HBV prevalence was significantly different between geographically distinct cohorts, but did not differ according to HIV status. Among adults from South Africa, HBV/HIV coinfected patients had lower CD4+ T cell counts compared to those with HIV-monoinfection (p = 0.02), but this finding was not replicated in the cohort from Botswana. Overall, these data provide a snapshot of the coinfection problem at the heart of the HIV/HBV co-epidemic, and are important to inform public health policy, resource allocation, education, surveillance and clinical care. PMID:26218239

  15. Efficacy and safety of tenofovir disoproxil fumarate in pregnancy for the prevention of vertical transmission of HBV infection

    PubMed Central

    Celen, Mustafa Kemal; Mert, Duygu; Ay, Müzeyyen; Dal, Tuba; Kaya, Safak; Yildirim, Necmettin; Gulsun, Serda; Barcin, Tunga; Kalkanli, Sevgi; Dal, Mehmet Sinan; Ayaz, Celal

    2013-01-01

    AIM: To evaluate the effects of tenofovir disoproxil fumarate (TDF) use during late pregnancy to reduce hepatitis B virus (HBV) transmission in highly viremic mothers. METHODS: This retrospective study included 45 pregnant patients with hepatitis B e antigen (+) chronic hepatitis B and HBV DNA levels > 107 copies/mL who received TDF 300 mg/d from week 18 to 27 of gestation (n = 21). Untreated pregnant patients served as controls (n = 24). All infants received 200 IU of hepatitis B immune globulin (HBIG) within 24 h postpartum and 20 μg of recombinant HBV vaccine at 4, 8, and 24 wk. Perinatal transmission rate was determined by hepatitis B surface antigen and HBV DNA results in infants at week 28. RESULTS: At week 28, none of the infants of TDF-treated mothers had immunoprophylaxis failure, whereas 2 (8.3 %) of the infants of control mothers had immunoprophylaxis failure (P = 0.022). There were no differences between the groups in terms of adverse events in mothers or congenital deformities, gestational age, height, or weight in infants. At postpartum week 28, significantly more TDF-treated mothers had levels of HBV DNA < 250 copies/mL and normalized alanine aminotransferase compared with controls (62% vs none, P < 0.001; 82% vs 61%, P = 0.012, respectively). CONCLUSION: TDF therapy during the second or third trimester reduced perinatal transmission rates of HBV and no adverse events were observed in mothers or infants. PMID:24409065

  16. Characteristics of Adults in the Hepatitis B Research Network in North America Reflect Their Country of Origin and HBV Genotype

    PubMed Central

    Ghany, Marc; Perrillo, Robert; Li, Ruosha; Belle, Steven H.; Janssen, Harry L.A.; Terrault, Norah A.; Shuhart, Margaret C.; Lau, Daryl T-Y; Kim, W. Ray; Fried, Michael W.; Sterling, Richard K.; Di Bisceglie, Adrian M.; Han, Steven-Huy B.; Ganova-Raeva, Lilia Milkova; Chang, Kyong-Mi; Suk-Fong Lok, Anna

    2014-01-01

    Background & Aims Chronic hepatitis B virus (HBV) infection is an important cause of cirrhosis and hepatocellular carcinoma worldwide; populations that migrate to the US and Canada might be disproportionately affected. The Hepatitis B Research Network (HBRN) is a cooperative network of investigators from the United States and Canada, created to facilitate clinical, therapeutic, and translational research in adults and children with hepatitis B. We describe the structure of the network and baseline characteristics of adults with hepatitis B enrolled in the network. Methods The HBRN collected data on clinical characteristics of 1625 adults with chronic HBV infection who are not receiving antiviral therapy from 21 clinical centers in North America. Results Half of the subjects in the HBRN are male, and the mean age is 42 years; 72% are Asian, 15% are Black, and 11% are White, with 82% born outside of North America. The most common HBV genotype was B (39%); 745 of subjects were negative for the hepatitis B e antigen. The median serum level of HBV DNA when the study began was 3.6 log10 IU/mL; 68% of male subjects and 67% of female subjects had levels of alanine aminotransferase above the normal range. Conclusions The HBRN cohort will be used to address important clinical and therapeutic questions for North Americans infected with chronic HBV and to guide health policies on HBV prevention and management in North America. PMID:25010003

  17. Construction of HBV-specific ribozyme and its recombinant with HDV and their cleavage activity in vitro

    PubMed Central

    Wen, Shu-Juan; Xiang, Kai-Jun; Huang, Zhen-Hua; Zhou, Rong; Qi, Xue-Zhong

    2000-01-01

    AIM: To construct the recombinant of HDV cDNA and HBV-specific ribozyme gene by recombinant PCR in order to use HDV as a transporting vector carrying HBV-specific ribozyme into liver cells for inhibiting the replication of HBV. METHODS: We separately cloned the ribozyme (RZ) gene and recombinant DVRZ (comprising HDV cDNA and HBV-specific ribozyme gene) into the downstream of T7 promoter of pTAdv-T vector and studied the in vitro cleavage activity of their transcripts (rRZ, rDVRZ) on target RNA (rBVCF) from in vitro transcription of HBV C gene fragment(BVCF). RESULTS: Both the simple (rRZ) and the recombinant ribozyme rDVRZ could efficiently catalyze the cleavage of target RNA (rBVCF) under different temperatures (37 °C, 42 °C and 55 °C) and Mg2+ concentrations (10 mmol/L, 15 mmol/L and 20 mmol/L) and their catalytic activity tended to increase as the temperature was rising. But the activity of rRZ was evidently higher than that of rDVRZ. CONCLUSION: The recombinant of HDV cDNA and ribozyme gene had the potential of being further explored and used in gene therapy of HBV infection. PMID:11819602

  18. Efficacy Comparison of Tenofovir and Entecavir in HBeAg-Positive Chronic Hepatitis B Patients with High HBV DNA

    PubMed Central

    Shi, Hong; Huang, Mingxing; Lin, Guoli; Li, Xiangyong; Wu, Yuankai; Jie, Yusheng

    2016-01-01

    Objectives. To compare entecavir (ETV) and tenofovir disoproxil fumarate (TDF) effects in chronic hepatitis B (CHB) patients with high HBV DNA. Method. 96 patients treated initially with tenofovir (TDF group) or entecavir (ETV group) were included in this retrospective study. The following parameters were assessed: HBeAg and hepatitis B e antibody (anti-HBe) status, serum alanine aminotransferase (ALT), and HBV-DNA levels at weeks 4, 12, 24, 36, 48, 60, 72, and 96; time to ALT normalization, undetectable HBV-DNA levels, and HBeAg seroconversion; total duration of follow-up and adverse reactions. Results. The patients included 66 (69%) and 30 (31%) individuals administered ETV and TDF, respectively, comprising 75% males. They were 35.1 ± 4.5 and 33.7 ± 4.6 years old in ETV and TDF groups, respectively. At 36 weeks, the response rate was significantly higher in the TDF group than in ETV treated patients (90% versus 69.7%, p = 0.03). At 48 weeks, less patients administered ETV showed undetectable HBV-DNA levels compared with the TDF group (86.4% versus 96.7%), a non-statistically significant difference (p = 0.13). Only 1 ETV treated patient developed virological breakthrough at 48–96 w. No adverse reactions were found. Conclusion. ETV and TDF are comparable in efficacy and safety to suppress HBV-DNA replication in HBeAg-positive CHB patients with high HBV DNA.

  19. Association between metabolic abnormalities and HBV related hepatocelluar carcinoma in Chinese: A cross-sectional study

    PubMed Central

    2011-01-01

    Background Previous studies suggested that the abnormality of metabolism is a newly identified risk factor in HBV-related hepatocellular carcinoma (HCC). The association between metabolic factors and hepatocellular carcinoma (HCC) has not been clarified up to now. This study was conducted to investigate the prevalence of metabolic abnormalities in HCC and to probe the association between metabolic parameters and liver function as well, so as to evaluate the interactions between metabolism and the development of HBV-related HCC. Methods Totally 179 cases of HBV-related HCC, who were surgically treated and pathologically confirmed were enrolled. HBV carriers (n = 100) and healthy controls (n = 150) were recruited from routine physical examination during the same period. Body mass index (BMI) was obtained from medical documentation. All the metabolic-related parameters and liver function tests were determined with routine biochemical or immunological analytic methods. Malondialdehyde (MDA) and total antioxidant capacity(TAOC)were detected by chemical analytic methods. A stratified analysis was conducted according to BMI, glycated albumin (GA), free fatty acids (FFA), and the relationships between the metabolic-related parameters and liver functions were analyzed in HCC and control subjects. Results HCC group showed significantly high levels of mean BMI, serum glucose, low serum lipids levels than controls (P < 0.05). Acquired by stratified analysis, the higher the BMI, the higher level of insulin and homeostasis model assessment for insulin resistance (HOMA-IR) (P < 0.01) were found in HCC patients. Elevated level of MDA and ?-glutamyltransferase (GGT) were revealed in those with high serum FFA level for the first time. Strong associations between metabolic factors and liver function were shown in HCC (P < 0.05). Higher GA level was strongly associated with increased risk of cancer compared to healthy controls (OR = 9.87, 95% confidence interval: 1.86~52.29). Serum triglycerides (TG) and low-density lipoprotein cholesterol (LDL-C) levels were negative contributory factors for HCC (OR = 0.05, 95% confidence interval: 0.01~0.27 and OR = 0.32, 95% confidence interval, 0.11~0.95: respectively). Conclusions Metabolic abnormalities are closely associated with the occurrence and development of HBV-related HCC. Oxidative stress and/or lipid peroxidation might be involved in the pathogenesis and acceleration of liver function impairments in HCC. PMID:21569630

  20. Watershed Modeling of Nutrient Transport Covering the Country of Sweden - Scale Transfer in HBV-NP

    NASA Astrophysics Data System (ADS)

    Arheimer, B.; Andersson, L.

    2002-12-01

    Eutrophication of the Baltic Sea and its coastal zone is considered a serious environmental problem. The problems are mainly caused by excessive load of nitrogen (N) and phosphorus (P). To improve the situation new policies including watershed-based water management are implemented. However, this also demands watershed-based knowledge of nutrient transport proc-esses and appropriate tools for landscape planning. A watershed model (HBV-NP) that can be applied both on the local and the national scale has thus been developed to be used both for international reporting and scenario estimates for more efficient nutrient control strategies. The P part is presently developed within the Swedish Water Management Research Program (VASTRA), in which HBV-NP will be used for evaluation of best management practices, and for communication with local stake-holders. The model has recently been applied at the national scale for calculations of flow-normalized annual average of gross load, N retention and net transport, and source apportionment of the N load reaching the sea. In this application (called TRK) several submodels with different levels of process descriptions were linked together. Dynamic and detailed models were included for arable leaching (SOIL-N model), rainfall interpolation, atmospheric deposition (MATCH model), water balance (HBV), and nutrient transformation in groundwater, rivers and lakes (HBV-N). Based on landscape information in GIS, different leaching rates and emissions were assigned to the water discharge from similar landscape elements in 1000 subbasins covering Sweden. Scale transfer was mainly achieved through up-scaling procedures and by using the conceptual model approach for watershed hydrology, including variability parameters that are calibrated for regions. The modeled river flow and N concentrations were validated against time-series from several independent-monitoring stations. A similar national system is now under development for P, including the ICECREAM model for arable leaching, routines for erosion and algae growth. Several applications with scenario evaluation for N have shown that the HBV-NP model is a very useful tool that facilitates discussions among local actors, acceptance of management plans and implementation of measures for nutrient reduction in watersheds.

  1. Characterization of Treatment-Naive HIV/HBV Co-Infected Patients Attending ART Clinic of a Tertiary Healthcare Centre in Eastern India

    PubMed Central

    Biswas, Avik; Panigrahi, Rajesh; Sarkar, Neelakshi; Sarkar, Jayeeta; Pal, Manisha; Guha, Subhasish Kamal; Saha, Bibhuti; Chakrabarti, Sekhar; Chakravarty, Runu

    2013-01-01

    Objective The study was designed to assess the hepatitis B virus (HBV) and hepatitis C virus (HCV) co-infection scenario among the human immunodeficiency virus (HIV) infected patients attending a tertiary healthcare unit in eastern India. Additionally, clinical and virological characterization of these viruses, prior to antiretroviral therapy (ART) initiation was also done for better understanding of the disease profile. Methods Pool of ART-naive HIV/HBV co-infected and HIV mono-infected patients, participating in two different studies, were included in this study. HBV DNA was detected by nested-PCR amplification followed by HBV genotype determination and HBV reverse transcriptase (RT) region amplification and direct sequencing for detecting drug resistance. Results The prevalence of HBsAg (11.3%) was higher compared to anti-HCV (1.9%) among the HIV infected ART-naive patients. Moreover, majority of the HBeAg positive HIV/HBV co-infected patients (87.7%) had HBV DNA ?20,000 IU/ml with median HBV DNA significantly higher than that of HBeAg negative subjects (5.7 log10 IU/ml vs. 4.2 log10 IU/ml; p<0.0001). Multivariate analysis also showed that HBeAg-positive status was independently associated with higher HBV DNA level (p?=?<0.001). Notably, 60.9% of the HBeAg negative co-infected subjects had HBV DNA ?2,000 IU/ml of which 37.0% had HBV DNA ?20,000 IU/ml. Genotype HBV/D (68.2%) was the predominant genotype followed by HBV/A (24.3%) and HBV/C (7.5%). Anti-HBV drug resistant mutations were detected in two (3.8%) of the ART-naive patients. Conclusion The prevalence of HIV/HBV co-infection was relatively higher in our study subjects. HBeAg testing might provide clue for early treatment initiation. Furthermore, HBeAg negative patients are also associated with high HBV DNA levels and therefore require appropriate medical attention. Pre-treatment screening for anti-HBV drug resistant mutations is not necessary before ART initiation. PMID:24023688

  2. The prevalence of HBV infection in the cohort of IDPs of war against terrorism in Malakand Division of Northern Pakistan

    PubMed Central

    2011-01-01

    Background Hepatitis B is an important public health problem in the Pakistani population and is the major cause of chronic hepatitis, cirrhosis, fibrosis and hepatocellular carcinoma. High prevalence of HBV infections has been observed especially in areas of low economic status. In spite of effective immunization programs, no significant change has been observed in the epidemiology of HBV in the rural areas of Pakistan (~67.5% of the total population) mainly due to lack of interest from government authorities and poor hygienic measures. The current study was aimed at estimating the prevalence and risk factors associated with HBV infection within internally displaced persons (IDPs) due to war against terrorism in the Malakand Division of Northern Pakistan. Methods Blood samples from 950 IDPs suspected with HBV infection (including both males and females) were collected and processed with commercial ELISA kits for HBsAg, Anti HBs, HBeAg, Anti HBe antibodies. The samples positive by ELISA were confirmed for HBV DNA by real-time PCR analysis. Results The overall prevalence of HBV observed was 21.05% of which 78.5% were males and 21.5% were females. Most confirmed HBV patients belong to the Malakand and Dir (lower) district. High-risk of infection was found in the older subjects 29.13% (46-60 years), while a lower incidence (11.97%) was observed in children aged <15 years. Lack of awareness, socioecomic conditions, sexual activities and sharing of razor blades, syringes and tattooing needles were the most common risk factors of HBV infection observed during the cohort of patients. Conclusion The present study, revealed for the first time a high degree of prevalence of HBV infection in rural areas of Northern Pakistan. The noticed prevalence is gender- and age-dependent that might be due to their high exposures to the common risk factors. To avoid the transmission of HBV infection proper awareness about the possible risk factors and extension of immunization to the rural areas are recommended. PMID:21689435

  3. Liver Fibrosis Regression Measured by Transient Elastography in Human Immunodeficiency Virus (HIV)-Hepatitis B Virus (HBV)-Coinfected Individuals on Long-Term HBV-Active Combination Antiretroviral Therapy

    PubMed Central

    Audsley, Jennifer; Robson, Christopher; Aitchison, Stacey; Matthews, Gail V.; Iser, David; Sasadeusz, Joe; Lewin, Sharon R.

    2016-01-01

    Background. Advanced fibrosis occurs more commonly in human immunodeficiency virus (HIV)-hepatitis B virus (HBV) coinfected individuals; therefore, fibrosis monitoring is important in this population. However, transient elastography (TE) data in HIV-HBV coinfection are lacking. We aimed to assess liver fibrosis using TE in a cross-sectional study of HIV-HBV coinfected individuals receiving combination HBV-active (lamivudine and/or tenofovir/tenofovir-emtricitabine) antiretroviral therapy, identify factors associated with advanced fibrosis, and examine change in fibrosis in those with >1 TE assessment. Methods. We assessed liver fibrosis in 70 HIV-HBV coinfected individuals on HBV-active combination antiretroviral therapy (cART). Change in fibrosis over time was examined in a subset with more than 1 TE result (n = 49). Clinical and laboratory variables at the time of the first TE were collected, and associations with advanced fibrosis (≥F3, Metavir scoring system) and fibrosis regression (of least 1 stage) were examined. Results. The majority of the cohort (64%) had mild to moderate fibrosis at the time of the first TE, and we identified alanine transaminase, platelets, and detectable HIV ribonucleic acid as associated with advanced liver fibrosis. Alanine transaminase and platelets remained independently advanced in multivariate modeling. More than 28% of those with >1 TE subsequently showed liver fibrosis regression, and higher baseline HBV deoxyribonucleic acid was associated with regression. Prevalence of advanced fibrosis (≥F3) decreased 12.3% (32.7%–20.4%) over a median of 31 months. Conclusions. The observed fibrosis regression in this group supports the beneficial effects of cART on liver stiffness. It would be important to study a larger group of individuals with more advanced fibrosis to more definitively assess factors associated with liver fibrosis regression. PMID:27006960

  4. Variations in the core promoter/pre-core region in HBV genotype C in Japanese and Northern Vietnamese patients.

    PubMed

    Truong, Bui Xuan; Yano, Yoshihiko; Seo, Yasushi; Phuong, Tran Minh; Tanaka, Yasuhito; Kato, Hirotaka; Miki, Akira; Utsumi, Takako; Azuma, Takeshi; Trach, Nguyen Khanh; Mizokami, Masashi; Hayashi, Yoshitake; Kasuga, Masato

    2007-09-01

    Hepatitis B virus (HBV) subgenotypes Cs (C1) and Ce (C2) are common in East Asia. To investigate the genomic difference of HBV genotype C between two separated regions, 50 subgenotype Cs-infected Vietnamese and 70 subgenotype Ce-infected Japanese patients were enrolled for analysis. The patients were categorized to either a hepatocellular carcinoma group (HCC) or a non-HCC group including liver cirrhosis, chronic hepatitis, and asymptomatic carriers. HBV serology, HBV-DNA level, and variations in core promoter/pre-core region were examined. Phylogenetic analysis based on the full genome sequences and nucleotide sequences partly in the S gene and in the P gene revealed that all Japanese strains (70/70) were subgenotype Ce, and nearly all of the Vietnamese strains (50/51) were subgenotype Cs, excluding one subgenotype C5. C1858 and G1775 were common in the Vietnamese (64% and 40%) but not in the Japanese (0%). The prevalence of C/A1753 in Vietnamese was higher than that in the Japanese (32% vs. 17.1%), however the frequency of A1896 in the Japanese was significantly higher (32.9% vs. 12%, P < 0.05). Most of the Vietnamese patients with HCC had a high level of HBV-DNA, the Japanese HCC had a relatively low level. In the Vietnamese, C/A1753 and C1858 were associated closely with T1762A1764, higher HBV-DNA levels and higher HCC incidence. The multivariate analysis revealed that male, T1653 and C/A1753 were independent risk factors for HCC. The subgenotypes and unique mutations of HBV genotype C in the Vietnamese and Japanese differed, and C/A1753 and C1858 variants might play a role in the pathogenesis of liver disease in Vietnamese patients. PMID:17607788

  5. Serum Golgi Protein 73 (GP73) is a Diagnostic and Prognostic Marker of Chronic HBV Liver Disease

    PubMed Central

    Xu, Zhengju; Liu, Liguan; Pan, Xingnan; Wei, Kaipeng; Wei, Meijuan; Liu, Lifei; Yang, Huanwen; Liu, Qian

    2015-01-01

    Abstract Alanine aminotransferase (ALT) is the most commonly used marker of liver injury, but normal ALT levels are seen in a proportion of chronic hepatitis B virus (HBV)-infected patients with severe liver injury. Golgi protein 73 (GP73) is a promising alternative marker of liver injury. This study assessed the relation between GP73 levels and liver disease severity, monitored the kinetic changes in GP73 levels in chronic HBV patients receiving entecavir (ETV) therapy, and investigated the potential diagnostic and prognostic values of serum GP73 as a new liver injury biomarker in chronic HBV infections. This study enrolled 1150 patients with chronic HBV infections, 200 of whom were retrospectively enrolled in this study after receiving 1 year of ETV treatment. GP73 expression in liver tissue was detected by immunohistochemistry. GP73 levels in single or serial serum samples were measured by enzyme-linked immunosorbent assay. Immunohistochemical analysis indicated that GP73 protein expression in the liver increased progressively with pathologic progression from nonexistent or mild hepatitis to severe hepatitis and cirrhosis during chronic HBV infection. Serum GP73 levels were positively correlated with the disease severity of chronic HBV infections (r = 0.58, P < 0.001). In patients with normal ALT levels, serum GP73 concentrations were significantly higher in patients with prominent hepatic inflammatory injury and fibrosis than in patients without hepatic inflammatory injury or fibrosis. Serum GP73 concentrations and GP73 protein expression were decreased in the liver tissues of patients whose ALT levels normalized after 1 year of ETV antiviral therapy. Changes in serum GP73 levels were closely associated with changes in liver injury severity, and, therefore, GP73 may be an effective new liver inflammatory injury biomarker, and could be useful for monitoring the prognosis of chronic HBV infectious patients with normal ALT levels. PMID:25816035

  6. Serum Golgi protein 73 (GP73) is a diagnostic and prognostic marker of chronic HBV liver disease.

    PubMed

    Xu, Zhengju; Liu, Liguan; Pan, Xingnan; Wei, Kaipeng; Wei, Meijuan; Liu, Lifei; Yang, Huanwen; Liu, Qian

    2015-03-01

    Alanine aminotransferase (ALT) is the most commonly used marker of liver injury, but normal ALT levels are seen in a proportion of chronic hepatitis B virus (HBV)-infected patients with severe liver injury. Golgi protein 73 (GP73) is a promising alternative marker of liver injury. This study assessed the relation between GP73 levels and liver disease severity, monitored the kinetic changes in GP73 levels in chronic HBV patients receiving entecavir (ETV) therapy, and investigated the potential diagnostic and prognostic values of serum GP73 as a new liver injury biomarker in chronic HBV infections. This study enrolled 1150 patients with chronic HBV infections, 200 of whom were retrospectively enrolled in this study after receiving 1 year of ETV treatment. GP73 expression in liver tissue was detected by immunohistochemistry. GP73 levels in single or serial serum samples were measured by enzyme-linked immunosorbent assay. Immunohistochemical analysis indicated that GP73 protein expression in the liver increased progressively with pathologic progression from nonexistent or mild hepatitis to severe hepatitis and cirrhosis during chronic HBV infection. Serum GP73 levels were positively correlated with the disease severity of chronic HBV infections (r = 0.58, P < 0.001). In patients with normal ALT levels, serum GP73 concentrations were significantly higher in patients with prominent hepatic inflammatory injury and fibrosis than in patients without hepatic inflammatory injury or fibrosis. Serum GP73 concentrations and GP73 protein expression were decreased in the liver tissues of patients whose ALT levels normalized after 1 year of ETV antiviral therapy. Changes in serum GP73 levels were closely associated with changes in liver injury severity, and, therefore, GP73 may be an effective new liver inflammatory injury biomarker, and could be useful for monitoring the prognosis of chronic HBV infectious patients with normal ALT levels. PMID:25816035

  7. An in-house real-time polymerase chain reaction: standardisation and comparison with the Cobas Amplicor HBV monitor and Cobas AmpliPrep/Cobas TaqMan HBV tests for the quantification of hepatitis B virus DNA

    PubMed Central

    Santos, Ana Paula de Torres; Levi, José Eduardo; Lemos, Marcilio Figueiredo; Calux, Samira Julien; Oba, Isabel Takano; Moreira, Regina Célia

    2016-01-01

    This study aimed to standardise an in-house real-time polymerase chain reaction (rtPCR) to allow quantification of hepatitis B virus (HBV) DNA in serum or plasma samples, and to compare this method with two commercial assays, the Cobas Amplicor HBV monitor and the Cobas AmpliPrep/Cobas TaqMan HBV test. Samples from 397 patients from the state of São Paulo were analysed by all three methods. Fifty-two samples were from patients who were human immunodeficiency virus and hepatitis C virus positive, but HBV negative. Genotypes were characterised, and the viral load was measure in each sample. The in-house rtPCR showed an excellent success rate compared with commercial tests; inter-assay and intra-assay coefficients correlated with commercial tests (r = 0.96 and r = 0.913, p < 0.001) and the in-house test showed no genotype-dependent differences in detection and quantification rates. The in-house assay tested in this study could be used for screening and quantifying HBV DNA in order to monitor patients during therapy. PMID:26872342

  8. Associations between activation-induced cytidine deaminase/apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like cytidine deaminase expression, hepatitis B virus (HBV) replication and HBV-associated liver disease (Review)

    PubMed Central

    HE, XIUTING; LI, JIE; WU, JING; ZHANG, MANLI; GAO, PUJUN

    2015-01-01

    The hepatitis B virus (HBV) infection is a major risk factor in the development of chronic hepatitis (CH) and hepa-tocellular carcinoma (HCC). The activation-induced cytidine deaminase (AID)/apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like (APOBEC) family of cytidine deaminases is significant in innate immunity, as it restricts numerous viruses, including HBV, through hypermutation-dependent and -independent mechanisms. It is important to induce covalently closed circular (ccc)DNA degradation by interferon-α without causing side effects in the infected host cell. Furthermore, organisms possess multiple mechanisms to regulate the expression of AID/APOBECs, control their enzymatic activity and restrict their access to DNA or RNA substrates. Therefore, the AID/APOBECs present promising targets for preventing and treating viral infections. In addition, gene polymorphisms of the AID/APOBEC family may alter host susceptibility to HBV acquisition and CH disease progression. Through G-to-A hypermutation, AID/APOBECs also edit HBV DNA and facilitate the mutation of HBV DNA, which may assist the virus to evolve and potentially escape from the immune responses. The AID/APOBEC family and their associated editing patterns may also exert oncogenic activity. Understanding the effects of cytidine deaminases in CH virus-induced hepatocarcinogenesis may aid with developing efficient prophylactic and therapeutic strategies against HCC. PMID:26398702

  9. An in-house real-time polymerase chain reaction: standardisation and comparison with the Cobas Amplicor HBV monitor and Cobas AmpliPrep/Cobas TaqMan HBV tests for the quantification of hepatitis B virus DNA.

    PubMed

    Santos, Ana Paula de Torres; Levi, Jos Eduardo; Lemos, Marcilio Figueiredo; Calux, Samira Julien; Oba, Isabel Takano; Moreira, Regina Clia

    2016-02-01

    This study aimed to standardise an in-house real-time polymerase chain reaction (rtPCR) to allow quantification of hepatitis B virus (HBV) DNA in serum or plasma samples, and to compare this method with two commercial assays, the Cobas Amplicor HBV monitor and the Cobas AmpliPrep/Cobas TaqMan HBV test. Samples from 397 patients from the state of So Paulo were analysed by all three methods. Fifty-two samples were from patients who were human immunodeficiency virus and hepatitis C virus positive, but HBV negative. Genotypes were characterised, and the viral load was measure in each sample. The in-house rtPCR showed an excellent success rate compared with commercial tests; inter-assay and intra-assay coefficients correlated with commercial tests (r = 0.96 and r = 0.913, p < 0.001) and the in-house test showed no genotype-dependent differences in detection and quantification rates. The in-house assay tested in this study could be used for screening and quantifying HBV DNA in order to monitor patients during therapy. PMID:26872342

  10. Epidemiology of Hepatitis C Virus Infection in Highly Endemic HBV Areas in China

    PubMed Central

    Wang, Tingcai; Xiao, Dan; Zhang, Jingxia; Guo, Zhiwen; Wang, Bo; Yan, Yongping

    2013-01-01

    Background Wuwei City has the highest prevalence of hepatitis B virus (HBV) in China. From 2007 to 2011, the average reported incidence rate of hepatitis B was 634.56/100,000 people. However, studies assessing the epidemic features and risk factors of HCV in the general population of Wuwei City are limited. Methods A total of 7189 people were interviewed and screened for HCV antibodies. HCV RNA and HCV genotypes were analyzed by PCR. Relevant information was obtained from the general population using a standardized questionnaire, and association and logistic regression analyses were conducted. Results The anti-HCV prevalence was 1.64% (118/7189), and HCV-RNA was detected in 37.29% (44/118) of the anti-HCV positive samples. The current HCV infection rate was 0.61% (44/7189) in the Wuwei general population. Hepatitis C infection rate was generally higher in the plains regions (?2?=?27.54,P<0.05), and the most predominant HCV genotypes were 2a (59.1%) and 1b (34.1%). The concurrent HCV and HBV infection rate was 1.37%, and a history of blood transfusion (OR?=?17.9, 95% CI: 6.1 to 52.6, p<0.001) was an independent risk factor for HCV positivity. Conclusions Although Wuwei is a highly endemic area for HBV, the anti-HCV positive rate in the general population is low. More than one-third of HCV-infected people were unaware of their infection; this may become an important risk factor for hepatitis C prevalence in the general population. Maintaining blood safety is important in order to help reduce the burden of HCV infection in developing regions of China. PMID:23372775

  11. Extraction of protoporphyrin disodium and its inhibitory effects on HBV-DNA

    PubMed Central

    Li, Chao-Pin; Xu, Li-Fa; Liu, Qun-Hong; Zhang, Chao; Wang, Jian; Zhu, Yu-Xia

    2004-01-01

    AIM: To explore an ideal method for extracting protoporphyrin disodium (PPN) from unanticoagulated animal blood, and to study the inhibitory effects of PPN on HBV-DNA duplication and its cytotoxicity to 2.2.15 cell strain. METHODS: Protoporphyrin methyl ester and other intermediate products were prepared with protoheme separated from protein hydrolysates of coagulated animal blood, which were finally made into PPN and detected quantitatively with an ultraviolet fluorescent analyzer. Ten ?g/ml, 20 ?g/ml, 40 ?g/ml, 80 ?g/ml and 160 ?g/ml of PPN-aqueous solution were added into culture medium for 2.2.15 cells respectively. Eight days later, the drug concentration in supernatant from the culture medium was detected when inhibition rate of HBeAg, cell survival rate when inhibition rate of HBeAg was 50% (ID50), and when survival cells in experimental group were 50% of those in control group (CD50), and the therapeutic index (TI) was also detected. PPN with different concentration of 10 ?g/ml, 20 ?g/ml, 40 ?g/ml, 80 ?g/ml and 160 ?g/ml was respectively mixed and cultivated with HepG2 2.2.15 cell suspension, and then the inhibition of PPN against HBV-DNA was judged by PCR. RESULTS: The extract of henna crystal was identified to be PPN. When the concentrations of PPN were 160 ?g/ml and 80 ?g/ml, the inhibition rates of HBeAg were 89.8% and 82.4%, and the cell survival rates were 98.7% and 99.2%. CONCLUSION: It is suggested that PPN can be extracted from unanticoagulated animal blood. PPN can inhibit HBV-DNA expression and duplication in vitro, and has no cytotoxicity to liver cells. Further study and application of PPN are warranted. PMID:14760773

  12. Phylogenetic analysis of complete genome sequences of hepatitis B virus from an Afro-Colombian community: presence of HBV F3/A1 recombinant strain

    PubMed Central

    2012-01-01

    Background Hepatitis B virus (HBV) infection is one of the most prevalent viral infections in humans and represents a serious public health problem. In Colombia, our group reported recently the presence of subgenotypes F3, A2 and genotype G in Bogotá. The aim of this study was to characterize the HBV genotypes circulating in Quibdó, the largest Afro-descendant community in Colombia. Sixty HBsAg-positive samples were studied. A fragment of 1306 bp (S/POL) was amplified by nested PCR. Positive samples to S/POL fragment were submitted to PCR amplification of the HBV complete genome. Findings The distribution of HBV genotypes was: A1 (52.17%), E (39.13%), D3 (4.3%) and F3/A1 (4.3%). An HBV recombinant strain subgenotype F3/A1 was found for the first time. Conclusions This study is the first analysis of complete HBV genome sequences from Afro-Colombian population. It was found an important presence of HBV/A1 and HBV/E genotypes. A new recombinant strain of HBV genotype F3/A1 was reported in this population. This fact may be correlated with the introduction of these genotypes in the times of slavery. PMID:23092209

  13. TP53 Mutations and HBX Status Analysis in Hepatocellular Carcinomas from Iran: Evidence for Lack of Association between HBV Genotype D and TP53 R249S Mutations

    PubMed Central

    Abedi-Ardekani, Behnoush; Gouas, Doriane; Villar, Stephanie; Sotoudeh, Masoud; Hainaut, Pierre

    2011-01-01

    High incidence of HCC is mostly due to the combination of two major risk factors, chronic infection with hepatitis B (HBV) and/or C (HCV) viruses and exposure to the mycotoxin aflatoxin B1, which induces a particular mutation at codon 249 in TP53 (R249S). Eight genotypes of HBV are diversely found in high and low incidence areas. Regardless of documented strong associations between TP53 R249S mutation and HBV genotypes B, C, A or E, there is no report of such association for genotype D despite of the presence of aflatoxin in areas with high prevalence of HBV genotype D. In Iran, 3% of the population is chronically infected with HBV, predominantly genotype D. Twenty-one histologically confirmed HCC cases from Iran were analyzed for TP53 R249S and HBV double mutations 1762T/1764A, hallmarks of more pathogenic forms of HBV. We did not detect any of these mutations. In addition, we report the only case identified so far carrying both R249S mutation and chronic HBV genotype D, a patient from The Gambia in West Africa. This paper suggests that association between HBV genotype D and aflatoxin-induced TP53 mutation is uncommon, explaining the relatively lower incidence of HCC in areas where genotype D is highly prevalent. PMID:21869931

  14. Immunization with adenovirus LIGHT-engineered dendritic cells induces potent T cell responses and therapeutic immunity in HBV transgenic mice.

    PubMed

    Jiang, Wenzheng; Chen, Ran; Kong, Xiaobo; Long, Fengying; Shi, Yaru

    2014-07-31

    LIGHT, a TNF superfamily member (TNFSF14), is a type II transmembrane protein expressed on activated T cells and immature dendritic cells (DCs). However, the expression of LIGHT on mature DCs is down-regulated. Recent studies demonstrated that LIGHT provides potent costimulatory activity for T cells, enhancing proliferation and the production of Th1 cytokines independently of the B7-CD28 pathway. Here, we evaluated the effectiveness of peptide-pulsed DC-mediated antiviral immunity in HBV transgenic mice and the immunoadjuvant effect of LIGHT. The bone marrow-derived DCs were modified in vitro with an adenovirus (Ad) vector expressing mouse LIGHT (Ad-LIGHT), the expression of costimulatory molecules was up-regulated and the secretion of cytokines IL-12 and IFN-? increased. LIGHT-modified DCs enhanced allostimulation for T cells in mixed lymphocyte reaction (MLR). HBV peptide-pulsed DCs elicited HBV specific CD8+ T cell response and reduced the level of HBsAg and HBV DNA in sera of HBV transgenic mice. Importantly, LIGHT-modified DCs could induce stronger antiviral immunity. These results support the concept that genetic modification of DCs with a recombinant LIGHT adenovirus vector may be a useful strategy for antiviral immunotherapy. PMID:24951859

  15. Epidemiology study of HBV genotypes and antiviral drug resistance in multi-ethnic regions from Western China

    PubMed Central

    Zhang, Qi; Liao, Yun; Chen, Jie; Cai, Bei; Su, Zhenzhen; Ying, Binwu; Lu, Xiaojun; Tao, Chuanmin; Wang, Lanlan

    2015-01-01

    Hepatitis B virus (HBV) infection is a critical global health issue and moderately epidemic in Western China, but HBV molecular epidemiology characteristics are still limited. We conducted this study to investigate HBV genotypes and antiviral resistant mutations in this multi-ethnic area. A total of 1316 HBV patients were recruited from four ethnic groups from 2011 to 2013. Genotypes and resistant mutations were determined by Sanger sequencing. Four genotypes (B, C, D and C/D) were identified. Genotype B and C were common in Han population, while genotype D was predominant in Uygurs. Genotype C was the major genotype in both Tibetans and Yis, and recombinant C/D was found in Tibetans only. Lamivudine resistance was common in all populations, especially in Hans with prevalence of 42.8%. Entecavir resistance was barely observed regardless of ethnicity. Genotype C isolates had higher rates of rtA181T/V than genotype B (13.5% vs. 5.1%, P?HBV genotypes and resistance-conferring mutations had different geographic and demographic distributions in Western China, which provided molecular epidemiology data for clinical management. PMID:26612031

  16. The direct and indirect roles of HBV in liver cancer: prospective markers for HCC screening and potential therapeutic targets.

    PubMed

    Ringelhan, Marc; O'Connor, Tracy; Protzer, Ulrike; Heikenwalder, Mathias

    2015-01-01

    Chronic hepatitis B virus (HBV) infection remains the number one risk factor for hepatocellular carcinoma (HCC), accounting for more than 600 000 deaths/year. Despite highly effective antiviral treatment options, chronic hepatitis B (CHB), subsequent end-stage liver disease and HCC development remain a major challenge worldwide. In CHB, liver damage is mainly caused by the influx of immune cells and destruction of infected hepatocytes, causing necro-inflammation. Treatment with nucleoside/nucleotide analogues can effectively suppress HBV replication in patients with CHB and thus decrease the risk for HCC development. Nevertheless, the risk of HCC in treated patients showing sufficient suppression of HBV DNA replication is significantly higher than in patients with inactive CHB, regardless of the presence of baseline liver cirrhosis, suggesting direct, long-lasting, predisposing effects of HBV. Direct oncogenic effects of HBV include integration in the host genome, leading to deletions, cis/trans-activation, translocations, the production of fusion transcripts and generalized genomic instability, as well as pleiotropic effects of viral transcripts (HBsAg and HBx). Analysis of these viral factors in active surveillance may allow early identification of high-risk patients, and their integration into a molecular classification of HCC subtypes might help in the development of novel therapeutic approaches. PMID:25196558

  17. Epidemiology study of HBV genotypes and antiviral drug resistance in multi-ethnic regions from Western China.

    PubMed

    Zhang, Qi; Liao, Yun; Chen, Jie; Cai, Bei; Su, Zhenzhen; Ying, Binwu; Lu, Xiaojun; Tao, Chuanmin; Wang, Lanlan

    2015-01-01

    Hepatitis B virus (HBV) infection is a critical global health issue and moderately epidemic in Western China, but HBV molecular epidemiology characteristics are still limited. We conducted this study to investigate HBV genotypes and antiviral resistant mutations in this multi-ethnic area. A total of 1316 HBV patients were recruited from four ethnic groups from 2011 to 2013. Genotypes and resistant mutations were determined by Sanger sequencing. Four genotypes (B, C, D and C/D) were identified. Genotype B and C were common in Han population, while genotype D was predominant in Uygurs. Genotype C was the major genotype in both Tibetans and Yis, and recombinant C/D was found in Tibetans only. Lamivudine resistance was common in all populations, especially in Hans with prevalence of 42.8%. Entecavir resistance was barely observed regardless of ethnicity. Genotype C isolates had higher rates of rtA181T/V than genotype B (13.5% vs. 5.1%, P?HBV genotypes and resistance-conferring mutations had different geographic and demographic distributions in Western China, which provided molecular epidemiology data for clinical management. PMID:26612031

  18. IL-17 and IL-22 genetic polymorphisms in HBV vaccine non- and low-responders among healthcare workers

    PubMed Central

    Borzooy, Zohreh; Streinu-Cercel, Adrian; Mirshafiey, Abbass; Khamseh, Azam; Mahmoudie, Masoud Karkhaneh; Navabi, Shadi Sadat; Nosrati, Marjan; Najafi, Zahra; Hosseini, Mostafa; Jazayeri, Seyed Mohammad

    2016-01-01

    Background Healthcare workers constitute a population at high risk for HBV infection. Efficient vaccination options are available; however, the individual response to HBV vaccination may vary widely between subjects, potentially due to cytokine profiles and genetic variations. In the present study, we investigated the relationship between IL-17 and IL-22 gene polymorphisms versus non- and low-responsiveness to HBV vaccination in healthcare workers. Methods We selected the following IL-17 and IL-22 polymorphisms: rs4711998 (A/G) from IL-17 and rs2227501 (A/T), rs2227503 (A/G), rs1026786 (A/G) from IL-22 sequences genes. These were determined by polymerase chain reaction restriction fragment length polymorphisms. Results The IL-17 rs4711998 GG genotype had a significantly lower frequency in non-responders compared to low-responders (p=0.025). However, we did not identify a relationship between IL-22 rs1026780, rs2227501 and rs2227503 genotypes and the anti-HBs response following HBV vaccination. Conclusion These data suggest that genetic variation in rs4711998 polymorphisms in the IL-17 cytokine may influence vaccine-induced immune responses to HBV vaccine in healthcare workers.

  19. Recombinant HBV vaccine enhances the rate of sustained virological response when early initiated after anti-HCV combination therapy.

    PubMed

    Hanafy, Amr Shaaban; Farag, Alaa Ahmad; Hassanin, Hassan Mahmoud; Hassaneen, Ahmad Mahmoud

    2016-01-01

    The overall SVR rate for chronic hepatitis C genotype 4 using the Standard of care is 54.3%. HBV infection can be prevented by the administration of effective and safe vaccine. Evaluation of the vaccination-induced anti-HBs response rates in a cohort of HCV Egyptian patients after being exposed to antiviral combination therapy and the magnitude of its effect on the rate of SVR through its putative role in induction of crossed immunity. (A) 500 HCV patients who had completed the course of antiviral therapy and achieved ETR were retrospectively analyzed and received 20??g of recombinant DNA vaccine for hepatitis B at time intervals (0, 1, and 4 months). The first dose of the vaccine was initiated one month post treatment. (B) Laboratory analysis: Included routine preliminary investigations to anti viral therapy and specific investigations as determination of anti-HBs antibodies 2 months following the third dose of vaccine. 433 patients showed protective response (86.6%), 67 patients were non-responders (13.4%) (P?=?0.003). Adding HBV vaccine 1 month post-treatment increased SVR (400 patients, 80%) (?(2) ?=?40.3, P?=?0.000). Diabetes affect response to HBV vaccine (P?=?0.0001). Adding HBV vaccine to the post treatment care of patients with HCV after termination of antiviral therapy gain two benefits; protection from HBV and significant increase in rates of SVR. PMID:26147509

  20. ProC: Process Coordinator

    NASA Astrophysics Data System (ADS)

    Planck software team

    2016-01-01

    ProC (short for Process Coordinator) is a versatile workflow engine that allows the user to build, run and manage workflows with just a few clicks. It automatically documents every processing step, making every modification to data reproducible. ProC provides a graphical user interface for constructing complex data processing workflows out of a given set of computer programs. The user can, for example, specify that only data products which are affected by a change in the input data are updated selectively, avoiding unnecessary computations. The ProC suite is flexible and satisfies basic needs of data processing centers that have to be able to restructure their data processing along with the development of a project.

  1. Clinical Analysis of the HBV Infection Status of 135 Patients with Diffuse Large B Cell Lymphoma Treated with R-CHOP or CHOP/CHOP-Like Chemotherapy

    PubMed Central

    Guo, Wei; Zhang, Wenxian; Liu, Chunshui; Song, Yuanyuan; Bai, Ou

    2015-01-01

    Objectives This study aimed to determine the HBV infection status of 135 patients with DLBCL (diffuse large B cell lymphoma), to analyze the overall survival (OS) and progression-free survival (PFS) of the different HBV infection status groups, and to discuss the relationship between HBV serological test results and the prognosis of DLBCL patients. Methods A retrospective analysis was performed of the clinical data, HBV serological test results, and PFS/OS of 135 DLBCL patients who were initially diagnosed and treated with more than 3 cycles of an R-CHOP/CHOP/CHOP-like regimen at our center from January 1, 2008 to December 31, 2012. Results The patients in the HBV infection group were older at disease onset (≥60 years old) and were more likely to present with stage 3-4 disease compared with the HBV-free group (P = 0.030 and P = 0.025, respectively). Approximately 50% of the patients with an active HBV infection required a reduction in the chemotherapy dose, and 66.7% of the patients in this group received more than 1 line of therapy; these rates were significantly higher than those in the no infection group (P = 0.003 and P = 0.011, respectively). Although HBV infection had no obvious influence on the outcome of first-line therapy, patients with an inactive infection had a higher relapse/progression rate within 3 months after a CR/PR than patients with an active infection (14/20 vs. 1/12, P = 0.001). The PFS at 1 year, 3 years and OS rates at 1 year, 3 years were significantly lower in the active HBV infection group than in the HBV-free group (P = 0.008, P = 0.002, P = 0.004, and P = 0.002, respectively). The PFS rates at 1 year and 3 year in HBV-free group were higher than those in the HBV infection group (80.5% and 52.9% P = 0.001, 78.1% and 44.4% P = 0.002). The lymphoma-related mortality rates were 2.7% in the no infection group, 19.2% in the HBV infection group (P = 0.004), and 28.6% in the active HBV infection group (P = 0.001). Among the patients treated with MabThera, the PFS in the HBV infection group was 11 months in the HBV infection group and 67 months in the infection-free group (P = 0.000). A Cox regression model of PFS revealed that age ≥60 years and HBV infection were independent prognostic factors (age: P = 0.019, HR = 2.002, 95% CI 1.123-3.567; HBV infection: P = 0.026, HR = 0.494, 95% CI 0.265-0.919). Conclusion Compared with the patients in HBV-free group, those in the HBV infection group were older at disease onset, and the active infection patients presented with more advanced disease and had a lower PFS at 1, 3 years as well as a lower OS at 3 years. The patients in the inactive infection group had a higher progression/relapse rate within 3 months after a CR/PR than those in the active infection group. HBV infection was an unfavorable factor for PFS in the MabThera group. An age ≥60 years and HBV infection were independent unfavorable prognostic factors for PFS. PMID:26053951

  2. An MLP Classifier for Prediction of HBV-Induced Liver Cirrhosis Using Routinely Available Clinical Parameters

    PubMed Central

    Hu, Zhi-De; Liu, Xiao-Fei; Deng, An-Mei

    2013-01-01

    Background. Liver cirrhosis (LC) is the final stage of most of chronic liver diseases and is almost caused by chronic hepatitis B (CHB) in China. Liver biopsy is the reference method for the evaluation of liver cirrhosis. However, it is an invasive procedure with inherent risk. The aim of this study was to construct a new classifier based on the routine clinical markers for the prediction of HBV-induced LC. Subjects and Methods. We collected routine clinical parameters from 124 LC patients with CHB and 115 with CHB. Training set (n = 120) and test set (n = 119) were built for model construction and evaluation, respectively. Results. We describe a new classifier, MLP, for prediction of LC with CHB. MLP was built with seven routinely available clinical parameters, including age, ALT, AST, PT, PLT, HGB, and RDW. With optimal cutoff, we obtained a sensitivity of 95.2%, a specificity of 84.2%, and an overall accuracy of 89.9% on an independent test set, which were superior to those of FIB-4 and APRI. Conclusions. Our study suggests that the MLP classifier can be implemented for discriminating LC and non-LC cohorts by using machine learning method based on the routine available clinical parameters. It could be used for clinical practice in HBV-induced LC assessment. PMID:24302810

  3. Review of 8 years of experience with Infanrix hexa (DTPa-HBV-IPV/Hib hexavalent vaccine).

    PubMed

    Zepp, Fred; Schmitt, Heinz-Josef; Cleerbout, Jan; Verstraeten, Thomas; Schuerman, Lode; Jacquet, Jeanne-Marie

    2009-06-01

    Combination vaccines that include multiple antigens within one formulation are now widely accepted as an effective means of eliciting protection against several diseases at the same time. Owing to improvements in quality and convenient modes of administration, they have become part of routine pediatric practice. Hexavalent vaccines, including diphtheria, tetanus, pertussis, hepatitis B, polio and Haemophilus influenzae type b antigens represent the latest advance in the development of combination vaccines. Over 8 years since its first licensure, this review looks at the immunogenicity, efficacy and safety profile of the only hexavalent pediatric vaccine currently in use--Infanrix hexa (diphtheria, tetanus, acellular pertusis-hepatitis B virus-inactivated poliovirus vaccine/Haemophilus influenzae type b vaccine [DTPa-HBV-IPV/Hib]; GlaxoSmithKline Biologicals, Rixensart, Belgium)--through published clinical trials and postmarketing surveillance data. These data show DTPa-HBV-IPV/Hib to be highly immunogenic and well tolerated across a range of different primary and booster vaccination schedules, as well as when administered concomitantly with other licensed vaccines (e.g., pneumococcal conjugate vaccine). Additional issues surrounding the use of hexavalent vaccines are also reviewed. PMID:19485747

  4. A new lignan with anti-HBV activity from the roots of Bombax ceiba.

    PubMed

    Wang, Guo Kai; Lin, Bin Bin; Rao, Rao; Zhu, Kan; Qin, Xiao Ying; Xie, Guo Yong; Qin, Min Jian

    2013-08-01

    A new lignan bombasinol A (1), together with three known compounds was obtained from the ethanol (95%) extract of roots of Bombax ceiba L. through its being subjected to silica gel and Sephadex LH-20 chromatography. Their structures were elucidated as 4-(4-(3,5-dimethoxyphenyl)hexahydrofuro[3,4-c]furan-1-yl)-2-methoxy-phenol (1), 5,6-dihydroxymatairesinol (2), (+)-pinoresinol (3) and matairesinol (4) on the basis of spectroscopic methods, including 1-D and 2-D NMR (HSQC and HMBC) experiments and by comparison of the data with those previously reported literatures. All these compounds were the first reported from Bombacaceae. The anti-Hepatitis B Virus (HBV) activity of all compounds isolated from B. ceiba in the research was evaluated. From the results of the HBV assay, these tested compounds showed inhibitory activity against HepG2 2.2.15 cell lines. Compounds 1-4 showed relative differences in their abilities to inhibit HBsAg secretion, with IC50 values of 118.3, 123.7, 118.9 and 218.2 mM, respectively. PMID:23140388

  5. Acute hepatitis B caused by a vaccine-escape HBV strain in vaccinated subject: sequence analysis and therapeutic strategy.

    PubMed

    Luongo, Monica; Critelli, Rosina; Grottola, Antonella; Gitto, Stefano; Bernabucci, Veronica; Bevini, Mirco; Vecchi, Chiara; Montagnani, Giuliano; Villa, Erica

    2015-01-01

    HBV vaccine contains the 'a' determinant region, the major immune-target of antibodies (anti-HBs). Failure of immunization may be caused by vaccine-induced or spontaneous 'a' determinant surface gene mutants. Here, we evaluate the possible lack of protection by HBV vaccine, describing the case of an acute hepatitis B diagnosed in a 55-year-old Caucasian male unpaid blood donor, vaccinated against HBV. Sequencing data for preS-S region revealed multiple point mutations. Of all the substitutions found, Q129H, located in the "a" determinant region of HBsAg, can alter antigenicity, leading to mutants. This mutant may cause vaccine failure especially when associated with high viremia of infecting source. PMID:25542480

  6. A Rare HBV Subgenotype D4 with Unique Genomic Signatures Identified in North-Eastern India –An Emerging Clinical Challenge?

    PubMed Central

    Banerjee, Priyanka; Mondal, Rajiv Kumar; Nandi, Madhuparna; Ghosh, Sumantra; Khatun, Mousumi; Chakraborty, Nabendu; Bhattacharya, Swatilekha; RoyChoudhury, Arindam; Banerjee, Soma; Santra, Amal; Sil, Samir; Chowdhury, Abhijit; Bhaumik, Pradip; Datta, Simanti

    2014-01-01

    Background/Aims HBV has been classified into ten genotypes (A–J) and multiple subgenotypes, some of which strongly influence disease outcome and their distribution also correlate with human migration. HBV infection is highly prevalent in India and its diverse population provides an excellent opportunity to study the distinctiveness of HBV, its evolution and disease biology in variegated ethnic groups. The North-East India, having international frontiers on three sides, is one of the most ethnically and linguistically diverse region of the country. Given the paucity of information on molecular epidemiology of HBV in this region, the study aimed to carry out an in-depth genetic characterization of HBV prevailing in North-East state of Tripura. Methods From sera of chronically HBV infected patients biochemical/serological tests, HBV DNA quantification, PCR-amplification, sequencing of PreS/S or full-length HBV genomes were done. HBV genotype/subgenotype determination and sequence variability were assessed by MEGA5-software. The evolutionary divergence times of different HBV subgenotypes were estimated by DNAMLK/PHYLIP program while jpHMM method was used to detect any recombination event in HBV genomes. Results HBV genotypes D (89.5%), C (6.6%) and A (3.9%) were detected among chronic carriers. While all HBV/A and HBV/C isolates belonged to subgenotype-A1 and C1 respectively, five subgenotypes of HBV/D (D1–D5) were identified including the first detection of rare D4. These non-recombinant Indian D4 (IndD4) formed a distinct phylogenetic clade, had 2.7% nucleotide divergence and recent evolutionary radiation than other global D4. Ten unique amino acids and 9 novel nucleotide substitutions were identified as IndD4 signatures. All IndD4 carried T120 and R129 in ORF-S that may cause immune/vaccine/diagnostic escape and N128 in ORF-P, implicated as compensatory Lamivudine resistance mutation. Conclusions IndD4 has potential to undermine vaccination programs or anti-viral therapy and its introduction to North-East India is believed to be linked with the settlement of ancient Tibeto-Burman migrants from East-Asia. PMID:25295865

  7. Genotype and variations in core promoter and pre-core regions are related to progression of disease in HBV-infected patients from Northern Vietnam.

    PubMed

    Truong, Bui Xuan; Seo, Yasushi; Yano, Yoshihiko; Ho, Pham Thi Thu; Phuong, Tran Minh; Long, Dao Van; Son, Nguyen Truong; Long, Nguyen Cong; Kato, Hirotaka; Hayashi, Yoshitake; Trach, Nguyen Khanh; Kasuga, Masato

    2007-02-01

    Vietnam is one of the countries with a high rate of hepatitis B virus (HBV) infection, but there are only a few reports about relation of HBV genotypes and mutations to clinical course in Northern Vietnam. The characteristics of HBV and its relationship to clinical outcome in patients from Northern Vietnam were analyzed. Serum samples were collected from 183 HBV-infected Vietnamese patients. They were clinically categorized into 4 groups: hepatocellular carcinoma (HCC), liver cirrhosis (LC), chronic hepatitis (CH), and asymptomatic carriers (ASC). HBV serology, alpha-fetoprotein, HBV genotypes, HBV-DNA level and mutations in the core promoter and pre-core regions of HBV-DNA were examined. The majority of sera contained HBV genotype B (67.8%) and C (27.9%). The median age was matched between genotype B and C (38.2 vs. 42.9 years). The rates of HBeAg seroconversion and G1896A for genotype B were significantly higher than those for genotype C (P<0.05). Genotype C had a higher HBV-DNA level than genotype B. C1858 was frequent, especially in genotype C (62.7%). The most prevalent genotype in ASC and CH was genotype B. The presence of the mutation A1762T/G1764A correlated with disease progression. The triple mutation T1753C/A1762T/ G1764A was quite common and was more prevalent in LC and HCC than in CH and ASC. In Northern Vietnamese, HBV genotypes B and C were prevalent. Genotype C and mutations in the core promoter region were associated with progressive, severe liver diseases. PMID:17203204

  8. Hepatitis B Virus (HBV) Variants in Untreated and Tenofovir Treated Chronic Hepatitis B (CHB) Patients during Pregnancy and Post-Partum Follow-Up

    PubMed Central

    Virine, Boris; Osiowy, Carla; Gao, Shan; Wang, Tong; Castillo, Eliana; Martin, Steven R.; Lee, Samuel S.; Simmonds, Kimberley; van Marle, Guido; Coffin, Carla S.

    2015-01-01

    Background Chronic hepatitis B (CHB) is a dynamic disease that may be affected by immune changes in pregnancy. Guidelines suggest consideration of nucleos/tide analogs (NA), i.e., tenofovir, (TDF) in highly viremic mothers to reduce vertical transmission risk. HBV variability affects CHB outcome, but little is known about HBV genetic changes in pregnancy due to immune or NA selection. Objectives To evaluate HBV diversity in NA treated or untreated pregnant vs. post-partum CHB carriers. Study Design In plasma collected from 21 mothers (7 matching pre/post-partum), HBV serological tests, genotype and viral load were assayed. The HBV pre-surface (S) /S overlapping polymerase (P) (N = 20), pre-core (C) /C (N = 11) and/or full genome PCR amplicons (N = 3) underwent clonal sequence analysis. Results The median age was 31 y, 71% Asian, 68% genotype B or C, 33% HBV eAg+, 5 received TDF (median HBV DNA 8.5 log IU/ml). In untreated mothers, median antepartum vs. post-partum ALT was 21 vs. 24 U/L and HBV DNA was 2.7 vs. 2.4 log(10) IU/ml. ALT and/or HBV DNA flares occurred during pregnant and/or post-partum period in 47% (10/21). Clonal sequencing antepartum showed the presence of minor “a determinant” and/or vaccine escape mutants (VEM) but drug resistant variants were infrequent. Analysis of pregnant vs. post-partum samples showed different HBV variants and viral diversity. Conclusions Differences in immune and/or by NA selective pressures during pregnancy may affect HBV evolution during pregnancy. The presence of minor VEM warrant infant follow-up. PMID:26474400

  9. Dealing with Pro Se Patrons

    ERIC Educational Resources Information Center

    Pettinato, Tammy R.

    2008-01-01

    The problem of the "pro se" patrons (people who are representing themselves in a legal dispute or transaction) has received significant attention in the legal information literature, and many excellent suggestions have been offered to aid law librarians in dealing with this population group. However, these suggestions can be usefully applied in

  10. InterPro protein classification.

    PubMed

    McDowall, Jennifer; Hunter, Sarah

    2011-01-01

    Improvements in nucleotide sequencing technology have resulted in an ever increasing number of nucleotide and protein sequences being deposited in databases. Unfortunately, the ability to manually classify and annotate these sequences cannot keep pace with their rapid generation, resulting in an increased bias toward unannotated sequence. Automatic annotation tools can help redress the balance. There are a number of different groups working to produce protein signatures that describe protein families, functional domains or conserved sites within related groups of proteins. Protein signature databases include CATH-Gene3D, HAMAP, PANTHER, Pfam, PIRSF, PRINTS, ProDom, PROSITE, SMART, SUPERFAMILY, and TIGRFAMs. Their approaches range from characterising small conserved motifs that can identify members of a family or subfamily, to the use of hidden Markov models that describe the conservation of residues over entire domains or whole proteins. To increase their value as protein classification tools, protein signatures from these 11 databases have been combined into one, powerful annotation tool: the InterPro database (http://www.ebi.ac.uk/interpro/) (Hunter et al., Nucleic Acids Res 37:D211-D215, 2009). InterPro is an open-source protein resource used for the automatic annotation of proteins, and is scalable to the analysis of entire new genomes through the use of a downloadable version of InterProScan, which can be incorporated into an existing local pipeline. InterPro provides structural information from PDB (Kouranov et al., Nucleic Acids Res 34:D302-D305, 2006), its classification in CATH (Cuff et al., Nucleic Acids Res 37:D310-D314, 2009) and SCOP (Andreeva et al., Nucleic Acids Res 36:D419-D425, 2008), as well as homology models from ModBase (Pieper et al., Nucleic Acids Res 37:D347-D354, 2009) and SwissModel (Kiefer et al., Nucleic Acids Res 37:D387-D392, 2009), allowing a direct comparison of the protein signatures with the available structural information. This chapter reviews the signature methods found in the InterPro database, and provides an overview of the InterPro resource itself. PMID:21082426

  11. Sequence analysis of pre-S/surface and pre-core/core promoter genes of hepatitis B virus in chronic hepatitis C patients with occult HBV infection.

    PubMed

    Kao, Jia-Horng; Chen, Pei-Jer; Lai, Ming-Yang; Chen, Ding-Shinn

    2002-10-01

    Although occult hepatitis B virus (HBV) infection in individuals without detectable hepatitis B surface antigen (HBsAg) may occur and has been reported to be common in patients with chronic hepatitis C, the related molecular mechanisms remain unknown. With the polymerase chain reaction, serum HBV DNA was sought in 100 HBsAg-negative patients with chronic hepatitis C virus (HCV)-infection. In those with occult HBV infection, possible genomic variability of HBV was evaluated by amplification and direct sequencing of pre-S, surface, and pre-core/core promoter genes. In total, 10 of the 100 patients (10%) had detectable serum HBV DNA, documenting an occult HBV infection. A deletion mutant in the pre-S gene was found in one patient and mutations of the a determinant of HBsAg were observed in 2. In addition, a novel core promoter mutant (a dinucleotide substitution: T-to-C at nucleotide 1,802 and T-to-G at nucleotide 1,803, T1802C/T1803G) was found frequently in patients with occult HBV infection as compared to sex- and age-matched HBsAg-positive patients (80 vs. 10%, P < 0.001). In conclusion, the data suggest occult HBV infection is not uncommon in chronic hepatitis C patients in Taiwan, and a novel core promoter mutant may be associated with the absence of circulating HBsAg in these patients. PMID:12210410

  12. Corner Office: ProQuest's Marty Kahn

    ERIC Educational Resources Information Center

    Fialkoff, Francine; Oder, Norman

    2009-01-01

    In a scant three years at ProQuest, Marty Kahn, CEO, has moved a company coming out of a financial morass back onto solid ground. He came on board after the purchase of ProQuest Information and Learning by the (mostly) privately owned Cambridge Information Group in late 2006 and the merger of ProQuest and CSA to form ProQuest CSA. (It's now just…

  13. Corner Office: ProQuest's Marty Kahn

    ERIC Educational Resources Information Center

    Fialkoff, Francine; Oder, Norman

    2009-01-01

    In a scant three years at ProQuest, Marty Kahn, CEO, has moved a company coming out of a financial morass back onto solid ground. He came on board after the purchase of ProQuest Information and Learning by the (mostly) privately owned Cambridge Information Group in late 2006 and the merger of ProQuest and CSA to form ProQuest CSA. (It's now just

  14. Inhibition of HBV Replication in HepG2.2.15 Cells by Human Peripheral Blood Mononuclear Cell-Derived Dendritic Cells.

    PubMed

    Liu, Tao; Song, Hong-Li; Zheng, Wei-Ping; Shen, Zhong-Yang

    2015-09-01

    Anti-HBV therapy is essential for patients awaiting liver transplantation. This study aimed to explore the effects of dendritic cells (DCs) derived from the peripheral blood of hepatitis B patients on the replication of HBV in vivo and to evaluate the biosafety of DCs in clinical therapy. Peripheral blood mononuclear cells (PBMCs) were isolated from HBV-infected patients and maturation-promoting factors and both HBsAg and HBcAg were used to induce DC maturation. Mature DCs and lymphocytes were co-cultured with human hepatocyte cell HL-7702 or HBV-producing human hepatocellular carcinoma cell HepG2.2.15. We found that mature lymphocytes exposed to DCs in vitro did not influence morphology or activities of HL-7702 and HepG2.2.15 cells. Liver function indexes and endotoxin levels in the cell supernatants did not change in these co-cultures. Additionally, supernatant and intracellular HBV DNA levels were reduced when HepG2.2.15 cells were co-cultured with mature lymphocytes that had been cultured with DCs, and HBV covalently closed circular DNA (cccDNA) levels in HepG2.2.15 cells also decreased. Importantly, DC-mediated immunotherapy had no mutagenic effect on HBV genomic DNA by gene sequencing of the P, S, X, and C regions of HBV genomic DNA. We conclude that PBMC-derived DCs from HBV-infected patients act on autologous lymphocytes to suppress HBV replication and these DC clusters showed favorable biosafety. PMID:26586699

  15. BNP and NT-proBNP Test

    MedlinePLUS

    ... Peptides Formal name: B-type Natriuretic Peptide; N-terminal pro b-type Natriuretic Peptide Related tests: Cardiac ... for B-type natriuretic peptide (BNP) or N-terminal pro b-type natriuretic peptide (NT-proBNP) is ...

  16. Astershionones A-F, six new anti-HBV shionane-type triterpenes from Aster tataricus.

    PubMed

    Zhou, Wen-Bing; Zeng, Guang-Zhi; Xu, Hui-Min; He, Wen-Jun; Zhang, Yu-Mei; Tan, Ning-Hua

    2014-03-01

    Six new shionane-type triterpenes, astershionones A-F (1-6), were obtained from the roots and rhizomes of Aster tataricus. Their structures were elucidated on the basis of spectroscopic data, mainly NMR and MS data. The absolute configuration of 1 was determined by single crystal X-ray diffraction analysis and CD analysis. 3 showed inhibitory activity against HBsAg and HBeAg secretion with IC50 values of 23.0 and 23.1 ?M, and cytotoxicity against HepG 2.2.15 cells with a CC50 value of 170.5 ?M. 3 also exhibited inhibitory activity against HBV DNA replication with an IC50 value of 22.4 ?M. PMID:24393620

  17. Modeling of HBV and HCV hepatitis with Hepatocyte-like cells.

    PubMed

    Bengrine, Abderrahmane; Brochot, Etienne; Louchet, Marie; Herpe, Yves Edouard; Duverlie, Gilles

    2016-01-01

    Chronic liver diseases caused by either hepatitis B or C viruses are a major health problem around the world. Despite major advances accomplished in recent years in understanding the physiology of both viruses usingin vitroand/orin vivomodels, there is no vaccine for HCV available. Moreover, susceptibility to acute and chronic infection and the response to treatments are different between HBV or HCV infected patients. Crucial information can be collected using a robust cell model that permits the culture of clinical isolates along with the investigation of the virus-host interaction. The recent progress in the field of cell reprogramming and differentiation has opened new opportunities in viral hepatitis research raising the hopes of developing new improved therapeutics. In this review, we discuss current models for hepatitis B and C studies and their limitations, and also the iPSC model, and its relevance to the viral host cell interactions. PMID:26709899

  18. Effect and mechanisms of curdlan sulfate on inhibiting HBV infection and acting as an HB vaccine adjuvant.

    PubMed

    Li, Pingli; Tan, Haining; Xu, Dongqing; Yin, Fengxin; Cheng, Yanna; Zhang, Xinke; Liu, Yuhong; Wang, Fengshan

    2014-09-22

    In this study, the effect and mechanisms of curdlan sulfate (CS3) on hepatitis B virus (HBV) infection and promoting immune response of the mice immunized with recombinant hepatitis B surface protein (HBsAg) were investigated. The results showed that CS3 could inhibit HBV infection of HepG2 and HepaRG cells, especially the process of HBV particle binding to the cell surfaces. The surface plasmon response (SPR) technology indicated that CS3 could bind with recombinant HBsAg and the binding ability depended on the content of sulfate groups on the polysaccharide chains. Co-administration of CS3 to BALB/c mice immunized with HBsAg significantly enhanced the influx of macrophages and dendritic cells in spleen, increased antigen-specific CD4+ and CD8+ cell numbers, and promoted splenocyte proliferation. The titer of HBsAg-specific antibodies was also augmented by use of CS3 as a vaccine adjuvant. The higher expression of interferon (IFN)-γ, lower expression of interleukin (IL)-4, and higher IgG2a/IgG1 ratio within the anti-HBsAg antibodies in mice immunized with HBsAg plus CS3 than those in mice receiving HBsAg alone indicated that CS3 induced a shift toward a Th1-biased immune response. These results presented that CS3 could be developed as an immunotherapy agent or vaccine adjuvant for HBV infection treatment or prevention. PMID:24906778

  19. Clinicopathological features of cryoglobulinemic glomerulonephritis associated with HBV infection: a retrospective analysis of 8 cases in China

    PubMed Central

    Wang, Chen; Ye, Zi-Yin; Zeng, De-Hua; Xie, Fei-Lai; Qu, Li-Juan; Zheng, Zhi-Yong

    2015-01-01

    Aims: We retrospectively analyzed clinicopathologic features of 8 cases of hepatitis B virus-associated glomerulonephritis with hyaline thrombi, to confirm the diagnosis of cryoglobulinemic glomerulonephritis (CRYGN) associated with HBV infection. Methods: Retrospective analysis was carried out with demographic information, clinical manifestations, laboratory parameters, pathological and prognostic features. Results: The median age of 8 patients was 30.5 years (range, 21-75 years), including 6 males and 2 femles (M:F = 3:1). One patient had Raynaud’s syndrome. Cryoglobulin testing was performed in 4 cases of our series, and 3 cases had elevated cryocrit (>256). Serum C4 decreased in all detected cases. Histopathologically, all cases showed hyaline thrombi occluded in capillary lumina; Co-deposit of IgG, IgM, IgA, Fib, C3d, C4d, C1q, HBsAg and HBcAb were identified in hyaline deposit/hyaline thrombi with polyclonal Igκ and Igλ staining. Ultrastructural examination confirmed the hyaline thrombi to be huge electron-dense bodies, which were a homogeneous texture. Conclusions: The results suggest that 8 cases in the series are CRYGN associated with HBV infection. The incidence of CRYGN associated HBV was extremely low. Our series suggested that prognosis of CRYGN associated HBV was better in patients with mild symptoms, but it was poor in elder patients with severe vasculitis. PMID:26617757

  20. HBV and HCV Coinfection among HIV/AIDS Patients in the National Hospital of Tropical Diseases, Vietnam.

    PubMed

    Huy, Bi V?; Vernavong, Kanxay; Knh, Nguy?n V?n

    2014-01-01

    Aim. To examine prevalence and characterization of HBV and HCV coinfection among HIV/AIDS patients. Methods. This cross-sectional, retrospective study analyzed 724 HIV/AIDS patients in the HIV clinic at the National Hospital of Tropical Diseases (NHTD), from 5/2005 to 4/2011. Results. The prevalence of HBV, HCV, and HIV coinfection was 50.3% (364/724), of which HbsAg, HCV, and both of HbsAg, and HCV positivity were 8.4%, 35.4%, and 6.5%, respectively. The cohort (364 patients) with HBV, HCV, and HIV coinfection live in the 30 provinces/cities in the North and Central area of Vietnam. We found statistically significant associations between heightened risk of coinfection with HIV and HCV in the age group 30-39 years (P < 0.001), male gender (P < 0.001), never married patients (P < 0.001), patients with a history of injection drug use (P < 0.001), and clinical stages 2-4 (P < 0.001). Coinfection with HBV/HIV was statistically significant associations between heightened risk of marital status (never married) (P < 0.001) and those who reported transmission through sexual intercourse. Conclusion. Coinfection with viral hepatitis is common in HIV patients; further study of the impact and evolution of coinfection is necessary to find effective treatment algorithms. PMID:25580287

  1. HBV and HCV Coinfection among HIV/AIDS Patients in the National Hospital of Tropical Diseases, Vietnam

    PubMed Central

    Huy, Bi V?; Vernavong, Kanxay; Knh, Nguy?n V?n

    2014-01-01

    Aim. To examine prevalence and characterization of HBV and HCV coinfection among HIV/AIDS patients. Methods. This cross-sectional, retrospective study analyzed 724 HIV/AIDS patients in the HIV clinic at the National Hospital of Tropical Diseases (NHTD), from 5/2005 to 4/2011. Results. The prevalence of HBV, HCV, and HIV coinfection was 50.3% (364/724), of which HbsAg, HCV, and both of HbsAg, and HCV positivity were 8.4%, 35.4%, and 6.5%, respectively. The cohort (364 patients) with HBV, HCV, and HIV coinfection live in the 30 provinces/cities in the North and Central area of Vietnam. We found statistically significant associations between heightened risk of coinfection with HIV and HCV in the age group 3039 years (P < 0.001), male gender (P < 0.001), never married patients (P < 0.001), patients with a history of injection drug use (P < 0.001), and clinical stages 24 (P < 0.001). Coinfection with HBV/HIV was statistically significant associations between heightened risk of marital status (never married) (P < 0.001) and those who reported transmission through sexual intercourse. Conclusion. Coinfection with viral hepatitis is common in HIV patients; further study of the impact and evolution of coinfection is necessary to find effective treatment algorithms. PMID:25580287

  2. A novel HBV genotypes detecting system combined with microfluidic chip, loop-mediated isothermal amplification and GMR sensors.

    PubMed

    Zhi, Xiao; Deng, Min; Yang, Hao; Gao, Guo; Wang, Kan; Fu, Hualin; Zhang, Yixia; Chen, Di; Cui, Daxiang

    2014-04-15

    Genotyping of hepatitis B virus (HBV) can be used for clinical effective therapeutic drug-selection. A novel microfluidic biochip for HBV genotyping has been fabricated, for the first time, integrating loop-mediated isothermal amplification (LAMP), line probes assay (LiPA) and giant magnetoresistive (GMR) sensors. Coupling LAMP with LiPA in microfluidic chip shortened reaction time substantially, and combining LAMP with GMR sensor enabled limit of detection to attain 10 copies mL(-1) target HBV DNA molecules in 1 h. Furthermore, the independent designed GMR sensors and microfluidic chip can decrease manufacturing cost and patient's test-cost, and facilitate GMR detector repeating use for signal detection. In addition, the detection system has a lower background signal owing to application of superparamagnetic nanoclusters. And it can be expected to use for multiple target molecules synchronous detection in microfluidic chip based on a characteristic of stationary reaction temperature of LAMP. In conclusion, the neoteric detecting system is well suitable for quick genotyping diagnosis of clinical HBV and other homothetic biomolecule detection in biological and medical fields. PMID:24292142

  3. Runoff simulation in the Ferghana Valley (Central Asia) using conceptual hydrological HBV-light model

    NASA Astrophysics Data System (ADS)

    Radchenko, Iuliia; Breuer, Lutz; Forkutsa, Irina; Frede, Hans-Georg

    2013-04-01

    Glaciers and permafrost on the ranges of the Tien Shan mountain system are primary sources of water in the Ferghana Valley. The water artery of the valley is the Syr Darya River that is formed by confluence of the Naryn and Kara Darya rivers, which originate from the mountain glaciers of the Ak-Shyrak and the Ferghana ranges accordingly. The Ferghana Valley is densely populated and main activity of population is agriculture that heavily depends on irrigation especially in such arid region. The runoff reduction is projected in future due to global temperature rise and glacier shrinkage as a consequence. Therefore, it is essential to study climate change impact on water resources in the area both for ecological and economic aspects. The evaluation of comparative contribution of small upper catchments (n=24) with precipitation predominance in discharge and the large Naryn and Karadarya River basins, which are fed by glacial melt water, to the Fergana Valley water balance under current and future climatic conditions is general aim of the study. Appropriate understanding of the hydrological cycle under current climatic conditions is significant for prognosis of water resource availability in the future. Thus, conceptual hydrological HBV-light model was used for analysing of the water balance of the small upper catchments that surround the Ferghana Valley. Three trial catchments (the Kugart River basin, 1010 km²; the Kurshab River basin, 2010 km2; the Akbura River basin, 2260 km²) with relatively good temporal quality data were chosen to setup the model. Due to limitation of daily temperature data the MODAWEC weather generator, which converts monthly temperature data into daily based on correlation with rainfall, was tested and applied for the HBV-light model.

  4. Epidemiological patterns of hepatitis B virus (HBV) in highly endemic areas.

    PubMed Central

    Edmunds, W. J.; Medley, G. F.; Nokes, D. J.; O'Callaghan, C. J.; Whittle, H. C.; Hall, A. J.

    1996-01-01

    This paper uses meta-analysis of published data and a deterministic mathematical model of hepatitis B virus (HBV) transmission to describe the patterns of HBV infection in high endemicity areas. We describe the association between the prevalence of carriers and a simple measure of the rate of infection, the age at which half the population have been infected (A50), and assess the contribution of horizontal and perinatal transmission to this association. We found that the two main hyper-endemic areas of sub-Saharan Africa and east Asia have similar prevalences of carriers and values of A50, and that there is a negative nonlinear relationship between A50 and the prevalence of carriers in high endemicity areas (Spearman's Rank, P = 0.0086). We quantified the risk of perinatal transmission and the age-dependent of infection to allow a comparison between the main hyper-endemic areas. East Asia was found to have higher prevalences of HBeAg positive mothers and a greater risk of perinatal transmission from HBeAg positive mothers than sub-Saharan Africa, though the differences were not statistically significant. However, the two areas have similar magnitudes and age-dependent rates of horizontal transmission. Results of a simple compartmental model suggest that similar rates of horizontal transmission are sufficient to generate the similar patterns between A50 and the prevalences of carriers. Interrupting horizontal transmission by mass immunization is expected to have a significant, nonlinear impact on the rate of acquisition of new carriers. PMID:8870629

  5. Attempted therapeutic immunization in a chimpanzee chronic HBV carrier with a high viral load

    PubMed Central

    Shata, Mohamed Tarek M.; Pfahler, Wolfram; Brotman, Betsy; Lee, Dong-Hun; Tricoche, Nancy; Murthy, Krishna; Prince, Alfred M.

    2006-01-01

    Background We previously reported successful therapeutic immunization in a chimpanzee having a relatively low viral load, which was immunized with recombinant plasmid hepatitis B surface antigen (HBsAg) DNA and boosted with recombinant HBsAg encoding canarypox virus. In the present study, we attempted to confirm these findings in an animal with a high virus load. Methods and Results We tested three immunization strategies successively over a 3-year period. In the first of these, we administered four monthly injections of DNA encoding HBsAg + PreS2 + hepatitis B core antigen (HBcAg) + DNA encoding interleukin (IL)-12, (given 3 days later), and boosted with canarypox expressing all of the above HBV genes 6 months after initial immunization. No reduction in viral load was observed. In the second trial, we administered lamivudine for 8 weeks, and then began monthly DNA-based immunization with plasmids expressing the above viral genes; however, viral loads rebounded 1 week after termination of lamivudine therapy. In a third trial, we continued lamivudine therapy for 30 weeks and immunized with vaccinia virus expressing the above viral genes 18 and 23 weeks after the start of lamivudine therapy. Again viral loads rebounded shortly after cessation of lamivudine treatment. Analysis of cell-mediated immune responses, and their avidity, revealed that DNA-based immunization produced the strongest enhancement of high avidity T-cell responses, while recombinant vaccinia immunization during lamivudine therapy enhanced low avidity responses only. The strongest low and high avidity responses were directed to the middle surface antigen. Conclusions Three strategies for therapeutic immunization failed to control HBV viremia in a chronically infected chimpanzee with a high viral load. PMID:16764675

  6. Co-infection of Toxoplasma gondii with HBV in HIV-infected and uninfected pregnant women in Burkina Faso.

    PubMed

    Ouermi, D; Simpore, J; Belem, A M G; Sanou, D S; Karou, D S; Ilboudo, D; Bisseye, C; Onadja, S M; Pietra, V; Pignatelli, S; Gnoula, C; Nikiema, J B; Kabre, G B

    2009-09-01

    Toxoplasma gondii infections can induce serious complications in HIV-infected pregnant women, leading to miscarriage; favour the mother-to-child transmission of HBV and HIV and birth defects. The purposes of this study were: (1) to quantify IgM and IgG antibodies to Toxoplasma gondii in HIV-seropositive and seronegative pregnant women, (2) to identify hepatitis B antigens (HBsAg) in pregnant women and (3) to determine T. gondii and HBV co-infections among these patients. The study was conducted at Centre Medical Saint Camille, in Burkina Faso from January to June 2009. A total of 276 HIV-infected and uninfected pregnant women were included. All women had less than 32 weeks of amenorrhoea and were aged from 19 to 42 years. Toxoplasma gondii antibodies and HBsAg were detected using ELISA method. In addition, women freely agreed to answer a questionnaire. The results of our investigations revealed that, among these pregnant women, 38.8% were illiterates, 50.4% were housewives and only 5.4% were civil servants. Positive T. gondii-specific IgM (4.7%) and IgG (27.2%) were detected. In this study, we found that HIV-seropositive status seem to be associated with great prevalence rates of both T. gondii (31.9 vs. 22.5%) and HBV (13.0 vs. 5.8%). The elevated co-infection rate in HIV-positive women suggested that they are exposed to T. gondii and HBV infections prevalently because of their immune depression. Therefore, to reduce the prevalence of T. gondii and HBV among HIV-seropositive pregnant women, lamivudine could be included in their HEART and women should follow healthy lifestyle formation. PMID:19943453

  7. HBV cccDNA: viral persistence reservoir and key obstacle for a cure of chronic hepatitis B.

    PubMed

    Nassal, Michael

    2015-12-01

    At least 250 million people worldwide are chronically infected with HBV, a small hepatotropic DNA virus that replicates through reverse transcription. Chronic infection greatly increases the risk for terminal liver disease. Current therapies rarely achieve a cure due to the refractory nature of an intracellular viral replication intermediate termed covalently closed circular (ccc) DNA. Upon infection, cccDNA is generated as a plasmid-like episome in the host cell nucleus from the protein-linked relaxed circular (RC) DNA genome in incoming virions. Its fundamental role is that as template for all viral RNAs, and in consequence new virions. Biosynthesis of RC-DNA by reverse transcription of the viral pregenomic RNA is now understood in considerable detail, yet conversion of RC-DNA to cccDNA is still obscure, foremostly due to the lack of feasible, cccDNA-dependent assay systems. Conceptual and recent experimental data link cccDNA formation to cellular DNA repair, which is increasingly appreciated as a critical interface between cells and viruses. Together with new in vitro HBV infection systems, based on the identification of the bile acid transporter sodium taurocholate cotransporting polypeptide as an HBV entry receptor, this offers novel opportunities to decipher, and eventually interfere with, formation of the HBV persistence reservoir. After a brief overview of the role of cccDNA in the HBV infectious cycle, this review aims to summarise current knowledge on cccDNA molecular biology, to highlight the experimental restrictions that have hitherto hampered faster progress and to discuss cccDNA as target for new, potentially curative therapies of chronic hepatitis B. PMID:26048673

  8. Intestinal microbiota was assessed in cirrhotic patients with hepatitis B virus infection. Intestinal microbiota of HBV cirrhotic patients.

    PubMed

    Lu, Haifeng; Wu, Zhongwen; Xu, Wei; Yang, Jiezuan; Chen, Yunbo; Li, Lanjuan

    2011-04-01

    To unravel the profile of intestinal microecological parameters in Chinese patients with asymptomatic carriage of hepatitis B virus (HBV), chronic hepatitis B, decompensated HBV cirrhosis, and health controls and to establish their correlation with liver disease progression, we performed quantitative PCR and immunological techniques to investigate fecal parameters, including population of fecal predominant bacteria and the abundance of some virulence genes derived from Escherichia coli, Bacteroides fragilis, Clostridium difficile, and Clostridium perfringens in fecal crude DNA and some immunological parameters in extracts of all fecal samples. Data analysis indicated that 16S rRNA gene copy numbers for Faecalibacterium prausnitzii, Enterococcus faecalis, Enterobacteriaceae, bifidobacteria, and lactic acid bacteria (Lactobacillus, Pediococcus, Leuconostoc, and Weissella) showed marked variation in the intestine of HBV cirrhotic patients. The Bifidobacteria/Enterobacteriaceae (B/E) ratio, which may indicate microbial colonization resistance of the bowel, was decreased significantly in turn from 1.15??0.11 in healthy controls, 0.99??0.09 in asymptomatic carriers, and 0.76??0.08 in patients with chronic hepatitis B to 0.64??0.09 in patients with decompensated HBV cirrhosis (for all, P?HBV cirrhotic patients were present at higher levels than in other groups, which indicates that a complicated autoregulatory system tries to achieve a new intestinal microecological balance. PMID:21286703

  9. Serum LncRNAs Profiles Serve as Novel Potential Biomarkers for the Diagnosis of HBV-Positive Hepatocellular Carcinoma

    PubMed Central

    Shi, Jie; Tang, Yu fu; Shen, Feng; Wu, Meng chao; Liu, Shan rong; Cheng, Shu qun

    2015-01-01

    Background Hepatocellular carcinoma (HCC) is a common malignancy that has a poor prognosis because there is lack of methods for early diagnosis. We aimed to utilize two serum long non-coding RNAs (lncRNAs), uc001ncr and AX800134, to diagnose hepatitis B virus (HBV)positive HCC. Methods lncRNA microarrays were utilized to measure the differential expression of lncRNAs between tumor tissues and corresponding non-tumor tissues in HBV-positive hapatocellular carcinoma. uc001ncr and AX800134 were selected as candidate lncRNAs and detected in three independent cohorts containing a total of 684 participants (healthy individuals and chronic HBV patients and HBV-positive HCC patients) who were recruited between March 2011 and December 2012. A logistic regression model was constructed using a training cohort (n = 353) and validated using an independent cohort (n = 181). The area under the receiver operating characteristic curve (AUC) was utilized to evaluate the diagnostic accuracy. Results We determined that a panel based on the expression of uc001ncr and AX800134 accurately diagnosed HBV-positive HCC (AUC values of 0.9494 and 0.9491 for the training and validation cohorts, respectively). The diagnostic performance of the panel remained high in patients with AFP?400 ng/ml (AUC values of 0.9371 and 0.9527 for the training and validation cohorts, respectively). The panel also diagnosed early HCC (AUC values of 0.9450 and 0.9564 for the training and validation cohorts, respectively). Conclusion Our results indicated that the serum expression of uc001ncr and AX800134 has potential as novel potential biomarker for the diagnosis of HCC, especially in patients with AFP?400 ng/ml or early-stage disease (BCLC 0+A). PMID:26674525

  10. Hyperimmune anti-HBs plasma as alternative to commercial immunoglobulins for prevention of HBV recurrence after liver transplantation

    PubMed Central

    2010-01-01

    Background Hepatitis B immune globulins (HBIG) in combination with nucleos(t)ide analogues (NA) are effectively used for the prevention of hepatitis B virus (HBV) recurrence after liver transplantation (LT). However, associated treatment costs for HBIG are exceedingly high. Methods Fresh frozen plasma obtained from blood donors with high anti-HBs levels (hyperimmune plasma, HIP) containing at least 4,500 IU anti-HBs was used as alternative treatment for HBV recurrence prophylaxis post-LT. Results Twenty-one HBV-related LT recipients received HIP starting at transplantation, followed by long-term combination treatment with NA. Mean follow-up time was 4.5 years (range 0.5-12.6) and each patient received on average 8.2 HIP per year (range 5.8-11.4). Anti-HBs terminal elimination kinetic after HIP administration was 20.6 days (range 13.8-30.9), which is comparable to values reported for commercial HBIG products. All 21 patients remained free of HBV recurrence during follow-up and no transfusion-transmitted infection or other serious complication was observed. Seven patients developed reversible mild transfusion reactions. The cost for one HIP unit was US$140; average yearly HBIG treatment cost was US$1,148 per patient, as compared to US$25,000-100,000 for treatment with commercial HBIG. Conclusion The results of this study suggest that the use of HIP may be a useful and economical approach for the prevention of HBV recurrence post-LT if used in combination with NA. Additional prospective controlled studies in larger populations are needed to confirm these results. PMID:20598161

  11. AST to platelet ratio index as a prospective predictor of hepatocellular carcinoma risk in patients with chronic HBV infection

    PubMed Central

    Lai, Yinzhi; Hann, Richard S.; Myers, Ronald E.; Patel, Fenil; Zhang, Kejin; Ye, Zhong; Wang, Chun; Yang, Hushan

    2015-01-01

    Background APRI (aspartate aminotransferase [AST] to platelet ratio index) is widely used to assess fibrosis and cirrhosis risk, especially in HCV-infected patients. Few studies have evaluated APRI and HBV-related hepatocellular carcinoma (HCC) risk. Prospective evidence is needed to assess whether APRI predicts HCC risk in HBV patients. Method In a prospectively enrolled clinical cohort of 855 HBV patients with a 1-year exclusion window (followed for >1 year and did not develop HCC within 1 year), the predictive value of APRI in HCC risk was evaluated by Cox proportional hazards model using univariate and multivariate analyses and longitudinal analysis. Results Higher APRI prospectively conferred a significantly increased risk of HCC in univariate analysis (quartile analysis, P trend=2.910?7). This effect remained highly significant after adjusting for common host characteristics but not cirrhosis (P trend=7.110?5), and attenuated when cirrhosis is adjusted (P trend=0.021). The effect remained prominent when the analysis was restricted to patients with a more stringent 2-year exclusion window (P trend=0.008 in quartile analysis adjusting all characteristics including cirrhosis), indicating that the association was unlikely due to including undetected HCC patients in the cohort, thus minimizing the reverse-causation limitation in most retrospective studies. Longitudinal comparison demonstrated a persistently higher APRI value in HBV patients who developed HCC during follow-up than those remaining cancer-free. Conclusion APRI might be a marker of HCC risk in HBV patients in cirrhosis-dependent and independent manners. Further studies are warranted to validate this finding and test its clinical applicability in HCC prevention. PMID:24995497

  12. ProMAT: protein microarray analysis tool

    SciTech Connect

    White, Amanda M.; Daly, Don S.; Varnum, Susan M.; Anderson, Kevin K.; Bollinger, Nikki; Zangar, Richard C.

    2006-04-04

    Summary: ProMAT is a software tool for statistically analyzing data from ELISA microarray experiments. The software estimates standard curves, sample protein concentrations and their uncertainties for multiple assays. ProMAT generates a set of comprehensive figures for assessing results and diagnosing process quality. The tool is available for Windows or Mac, and is distributed as open-source Java and R code. Availability: ProMAT is available at http://www.pnl.gov/statistics/ProMAT. ProMAT requires Java version 1.5.0 and R version 1.9.1 (or more recent versions) which are distributed with the tool.

  13. Screening differential expression of serum proteins in AFP-negative HBV-related hepatocellular carcinoma using iTRAQ -MALDI-MS/MS.

    PubMed

    He, X; Wang, Y; Zhang, W; Li, H; Luo, R; Zhou, Y; Li, C; Liao, M; Huang, H; Lv, X; Xie, Z; He, M

    2013-09-20

    Hepatocellular carcinoma?(HCC) is serious?condition associated with a?high morbidity and mortality. Therefore is an urgent need to develop novel noninvasive techniques for early diagnosis, particularly for patients with AFP-negative [AFP(-)] HCC. In this study, iTRAQ-MALDI-MS/MS was used to identify differentially expressed proteins in AFP(-) HBV-related HCC compared with non-cancerous hepatitis B?virus (HBV) and healthy controls subjects.Serum was obtained from 18 patients with AFP(-) HBV-related HCC, 18 matched patients with HBV without HCC and 18 healthy control subjects. High abundance proteins were removed from serum and the differentially expressed proteins from the three groups were screened out using iTRAQ-MALDI-MS/MS. The Gene Ontology (GO) function and the interaction networks of differentially expressed proteins were then analyzed. A total of 24 expressed differential proteins associated with AFP(-) HBV-related HCC were screened out, 15 proteins were up-regulated and 9 down-regulated. The most common molecular function of the 24 differentially expressed proteins was enzyme inhibition. Interaction network of the 24 differentially expressed proteins showed that 14 proteins (C5, KNG1, FN1, LRG1, HRG, SERPINC1, CRP, APOB, SAA1, APCS, C4BPA, CFI, CFB and GSN) were central to the functional network. The expression levels of the GSN protein were down-regulated in AFP(-) HBV-related HCC subjects compared with healthy controls and the HBV group (p<0.01), consistent with the iTRAQ results.The 14 proteins from the serum of AFP(-) HBV-related HCC appeared at the fulcrum of the functional network and were differentially expressed compare to HBV and healthy controls suggesting a?possible association with HCC progression. Keywords: HCC, AFP Negative, iTRAQ, GSN. PMID:24050542

  14. Screening differential expression of serum proteins in AFP-negative HBV-related hepatocellular carcinoma using iTRAQ -MALDI-MS/MS.

    PubMed

    He, X; Wang, Y; Zhang, W; Li, H; Luo, R; Zhou, Y; Liao, C Li M; Huang, H; Lv, X; Xie, Z; He, M

    2014-01-01

    Hepatocellular carcinoma(HCC) is serious condition associated with a high morbidity and mortality. Therefore is an urgent need to develop novel noninvasive techniques for early diagnosis, particularly for patients with AFP-negative [AFP(-)] HCC. In this study, iTRAQ-MALDI-MS/MS was used to identify differentially expressed proteins in AFP(-) HBV-related HCC compared with non-cancerous hepatitis B virus (HBV) and healthy controls subjects.Serum was obtained from 18 patients with AFP(-) HBV-related HCC, 18 matched patients with HBV without HCC and 18 healthy control subjects. High abundance proteins were removed from serum and the differentially expressed proteins from the three groups were screened out using iTRAQ-MALDI-MS/MS. The Gene Ontology (GO) function and the interaction networks of differentially expressed proteins were then analyzed. A total of 24 expressed differential proteins associated with AFP(-) HBV-related HCC were screened out, 15 proteins were up-regulated and 9 down-regulated. The most common molecular function of the 24 differentially expressed proteins was enzyme inhibition. Interaction network of the 24 differentially expressed proteins showed that 14 proteins (C5, KNG1, FN1, LRG1, HRG, SERPINC1, CRP, APOB, SAA1, APCS, C4BPA, CFI, CFB and GSN) were central to the functional network. The expression levels of the GSN protein were down-regulated in AFP(-) HBV-related HCC subjects compared with healthy controls and the HBV group (p<0.01), consistent with the iTRAQ results.The 14 proteins from the serum of AFP(-) HBV-related HCC appeared at the fulcrum of the functional network and were differentially expressed compare to HBV and healthy controls suggesting a possible association with HCC progression. PMID:24195504

  15. Towards the complete eradication of mother-to-child HIV/HBV coinfection at Saint Camille Medical Centre in Burkina Faso, Africa.

    PubMed

    Ilboudo, Denise; Simpore, Jacques; Ouermi, Djeneba; Bisseye, Cyrille; Sagna, Tani; Odolini, Silvia; Buelli, Fabio; Pietra, Virginio; Pignatelli, Salvatore; Gnoula, Charlemagne; Nikiema, Jean-Baptiste; Musumeci, Salvatore

    2010-01-01

    The coinfection of HIV and hepatitis B virus (HBV) and their vertical transmission constitute a public health problem in sub-Saharan countries of Africa. The objectives of this research are: i) identify the pregnant women that are coinfected by HIV and HBV at Saint Camille Medical Centre; ii) use three antiretroviral drugs (zidovudine, nevirapine and lamivudine) to interrupt the vertical transmission of HIV and HBV from infected mothers; and iii) use the PCR technique to diagnose children who are vertically infected by these viruses in order to offer them an early medical assistance. At Saint Camille Medical Centre, 115 pregnant women, aged from 19 to 41 years, were diagnosed as HIV-positive and, among them, 14 coinfected with HBV. They had at least 32 weeks of amenorrhoea and all of them received the HAART, which contained lamivudine. Two to six months after childbirth, the babies underwent PCR diagnosis for HIV and HBV. The results revealed that, among these mothers, 64.4% were housewives, 36.5% were illiterates, and only 1.7% had a university degree. The rate of vertical transmission of HIV and HBV was 0.0% (0/115) and 21.4% (3/14), respectively. The 3 mothers who transmitted the HBV to their children had all HBsAg, HbeAg, and HBV DNA positive. An antiretroviral therapy that in addition to zidovudine and nevirapine includes lamivudine could, as in the present study, block or reduce the vertical transmission in HIV positive pregnant women who are coinfected with HBV. PMID:20835503

  16. A Genetic Variant in the Promoter Region of miR-106b-25 Cluster and Risk of HBV Infection and Hepatocellular Carcinoma

    PubMed Central

    Wen, Juan; Liu, Li; Zhai, Xiangjun; Liu, Jibin; Pan, Shandong; Chen, Jianguo; Shen, Hongbing; Hu, Zhibin

    2012-01-01

    Background MiR-106b-25 cluster, hosted in intron 13 of MCM7, may play integral roles in diverse processes including immune response and tumorigenesis. A single nucleotide polymorphism (SNP), rs999885, is located in the promoter region of MCM7. Methods We performed a case-control study including 1300 HBV-positive hepatocellular carcinoma (HCC) cases, 1344 HBV persistent carriers and 1344 subjects with HBV natural clearance to test the association between rs999885 and the risk of HBV persistent infection and HCC. We also investigated the genotype-expression correlation between rs999885 and miR-106b-25 cluster in 25 pairs of HCC and adjacent non-tumor liver tissues. Results Compared with the HBV natural clearance subjects carrying rs999885 AA genotype, those with AG/GG genotypes had a decreased risk of chronic HBV infection with an adjusted odds ratio (OR) of 0.79 [95% confidence intervals (CIs) = 0.67–0.93]. However, the AG/GG genotypes were significantly associated with an increased HCC risk in HBV persistent carriers (adjusted OR = 1.25, 95% CIs = 1.06–1.47). Expression analysis revealed that the expression level of miR-106b-25 cluster was significantly higher in AG/GG carriers than those in AA carriers in non-tumor liver tissues. Conclusions These findings indicate that the A to G base change of rs999885 may provide a protective effect against chronic HBV infection but an increased risk for HCC in HBV persistent carriers by altering the expression of the miR-106b-25 cluster. PMID:22393390

  17. Evaluation of neonatal Toll-like receptors 3 (c.1377C/T) and 9 (G2848A) gene polymorphisms in HBV intrauterine transmission susceptibility.

    PubMed

    Gao, Y; Guo, J; Zhang, F; Guo, Z; Zhang, L R; Wang, T; Wang, B; Feng, S Y; Wang, S P

    2015-07-01

    To investigate whether single nucleotide polymorphisms (SNPs) in Toll-like receptors (TLRs) 3 and 9 affect the susceptibility of hepatitis B virus (HBV) intrauterine transmission, we genotyped 399 neonates for TLR3 (c.1377C/T) [rs3775290] and TLR9 (G2848A) [rs352140] using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). A femoral venous blood sample was obtained from these subjects. Hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) were measured using chemiluminescence immunoassay kits and hepatitis B virus DNA (HBV DNA) levels were determined by fluorescence quantitative PCR assay. Our results showed that when adjusting for maternal HBeAg, maternal HBV DNA and mode of delivery, allele 'T' for SNP c.1377C/T was significantly associated with HBV intrauterine transmission susceptibility [adjusted OR (aOR) 0.55, 95% confidence interval (CI) 0.34-0.91, P = 0.020] and the TT genotype decreased the risk of HBV intrauterine transmission (aOR 0.28, 95% CI 0.09-0.91, P = 0.033). Allele 'A' for SNP G2848A was significantly associated with HBV intrauterine transmission susceptibility (aOR 0.62, 95% CI 0.39-1.00, P = 0.048) and the GA genotype protected neonates from HBV intrauterine transmission (aOR 0.45, 95% CI 0.22-0.93, P = 0.031). The TLR3 (c.1377C/T) and TLR9 (G2848A) polymorphisms may be relevant for HBV intrauterine transmission susceptibility, although the reduction in risk to HBV intrauterine transmission is modest and the biological mechanism of the observed association merits further investigation. PMID:25388852

  18. Multi-purpose calibration of HBV models for the Rhine with OpenDA

    NASA Astrophysics Data System (ADS)

    van Verseveld, W. J.; Sperna-Weiland, F.; Meissner, D.; Winsemius, H. C.; Weerts, A. H.; Hummel, S.; Sumihar, J. H.; Hegnauer, M.

    2012-04-01

    Calibration strategies for hydrological models nearly always depend on user interests. These interests are strongly determined by the eventual practical application of the model: what information should the model primarily provide, e.g. low flows, high flows, or accumulated inflows; what spatial and temporal information density is available in terms of data, and what information needed in terms of practical use; should parameter uncertainty estimation of the hydrological model be included? The Open-source Data Assimilation toolbox (OpenDA) is an open software framework for calibration and data-assimilation of hydrological models. In this contribution, we show that OpenDA can be used to rapidly calibrate a hydrological model, which is to be used for different purposes or under different circumstances such as mentioned above. To this end, OpenDA includes a number of calibration algorithms, can communicate with a multitude of hydrological and hydraulic models, and can handle multiple calibration signals in one calibration experiment. It can therefore be employed in complex calibration experiments. New algorithms and models can be included efficiently in the software. Our case study focuses on an HBV model structure for the international Rhine basin (area ~ 185.000 km2), consisting of 134 sub-catchment units containing many different gauging stations. This model is embedded in Delft-FEWS, an operational forecasting system which can also be used for offline data management and model integration. We performed a recalibration focussing on two applications: FEWS-Rivers / FEWS-BfG (operational forecasting): Simulations of snow pack and melt within HBV performed poorly in this application. The model was optimized on hourly time scale. Parameters, related to snow processes were identified and optimized on a large number of available gauge data sets, using the Shuffled Complex Evolution algorithm. FEWS-GRADE (extreme discharges for dike design): In this application, very long synthetic discharge series are simulated on a daily basis. Because of the high return periods of interest (1/1250 years), uncertainty of these estimates should be taken into account. Therefore, calibration has been performed using the GLUE algorithm. GLUE is used to select an ensemble of parameter sets, rather than one single set. Parameter performance was tested with specific criteria for extreme high discharges.

  19. A Tat-conjugated Peptide Nucleic Acid Tat-PNA-DR Inhibits Hepatitis B Virus Replication In Vitro and In Vivo by Targeting LTR Direct Repeats of HBV RNA.

    PubMed

    Zeng, Zhengyang; Han, Shisong; Hong, Wei; Lang, Yange; Li, Fangfang; Liu, Yongxiang; Li, Zeyong; Wu, Yingliang; Li, Wenxin; Zhang, Xianzheng; Cao, Zhijian

    2016-01-01

    Hepatitis B virus (HBV) infection is a major cause of chronic active hepatitis, cirrhosis, and primary hepatocellular carcinoma, all of which are severe threats to human health. However, current clinical therapies for HBV are limited by potential side effects, toxicity, and drug-resistance. In this study, a cell-penetrating peptide-conjugated peptide nucleic acid (PNA), Tat-PNA-DR, was designed to target the direct repeat (DR) sequences of HBV. Tat-PNA-DR effectively inhibited HBV replication in HepG2.2.15 cells. Its anti-HBV effect relied on the binding of Tat-PNA-DR to the DR, whereby it suppressed the translation of hepatitis B e antigen (HBeAg), HBsAg, HBV core, hepatitis B virus x protein, and HBV reverse transcriptase (RT) and the reverse transcription of the HBV genome. Furthermore, Tat-PNA-DR administered by intravenous injection efficiently cleared HBeAg and HBsAg in an acute hepatitis B mouse model. Importantly, it induced an 80% decline in HBV DNA in mouse serum, which was similar to the effect of the widely used clinical drug Lamivudine (3TC). Additionally, a long-term hydrodynamics HBV mouse model also demonstrated Tat-PNA-DR's antiviral effect. Interestingly, Tat-PNA-DR displayed low cytotoxicity, low mouse acute toxicity, low immunogenicity, and high serum stability. These data indicate that Tat-PNA-DR is a unique PNA and a promising drug candidate against HBV. PMID:26978579

  20. Combination versus sequential monotherapy in chronic HBV infection: a mathematical approach.

    PubMed

    Bertacchi, Daniela; Zucca, Fabio; Foresti, Sergio; Mangioni, Davide; Gori, Andrea

    2015-12-01

    Sequential monotherapy is the most widely used therapeutic approach in the treatment of hepatitis B virus (HBV) chronic infection. Unfortunately, under therapy, in some patients the hepatitis virus mutates and gives rise to variants which are drug resistant. We wonder whether those patients would have benefited from the choice of combination therapy instead of sequential monotherapy. To study the action of these two therapeutic approaches and to explain the emergence of drug resistance, we propose a stochastic model for the infection within a patient who is treated with two drugs, either sequentially or contemporaneously, and who, under the first kind of therapy develops a strain of the virus which is resistant to both drugs. Our stochastic model has a deterministic approximation which is a slight modification of a classic three-strain model. We discuss why stochastic simulations are more suitable than the study of the deterministic approximation, when modelling the rise of mutations (this is mainly due to the amplitude of the stochastic fluctuations). We run stochastic simulations with suitable parameters and compare the time when, under the two therapeutic approaches, the resistant strain first reaches detectability in the serum viral load. Our results show that the best choice is to start an early combination therapy, which allows one to stay drug resistance free for a longer time and in many cases leads to viral eradication. PMID:25398978

  1. [New Strategy for anti-HBV therapy: blocking P-8 interaction].

    PubMed

    Huang, Ya-yun; Hu, Kang-hong

    2014-11-01

    Clinically being applied treatment against chronic hepatitis has three limitations: low response rates, severe adverse effects and a high rate of drug resistance. Hence, novel targets for antiviral therapy need to be developed so as to provide an armory of different strategies. During the replication of hepatitis B virus, the interaction of viral polymerase (P protein, also called P) and epsilonRNA is indispensable for the initiation of reverse transcription via protein priming and the pregenome RNA (pgRNA) packaging. Three strategies are currently developed for blocking P-epsilon interaction: heat shock protein inhibitors, epsilonaptamers and chemical compounds for blocking formation of P-epsilon complex. Previously, our group has for the first time worldwide in vitro screened several aptamers, which are able to interfere with the P-epsilon interaction. A strong inhibition against HBV was observed in vitro and in vivo experiments, respectively. In conclusion, the so far developed chemicals suppressing the P-epsilon interaction may bypass or overcome the viral resistance problems during clinic treatment and represent a highly attractive option for therapeutic intervention. PMID:25868288

  2. Relative predictive factors for hepatocellular carcinoma after HBeAg seroconversion in HBV infection

    PubMed Central

    Murata, Kazumoto; Sugimoto, Kazushi; Shiraki, Katsuya; Nakano, Takeshi

    2005-01-01

    AIM: To determine the predictive factors for hepatocellular carcinoma (HCC) development in patients after spontaneous or therapeutic HBeAg seroconversion. METHODS: In 48 patients who seroconverted to anti-HBe positive during follow-up, the background factors for HCC development were analyzed. RESULTS: HCC was developed in six patients during follow-up (average follow-up after HBeAg seroconversion: 10.95.4 years). The incidence of HCC evaluated by KaplanMeier analysis was significantly higher in patients with abnormal aspartate aminotransferase (AST> 40 IU/L) level, lower platelet counts (PLT<10104/L), lower albumin level (Alb<30 g/L), positive HBV-DNA or older age at seroconversion (>40 years). However, lower platelet count was the only predictive factor for HCC development shown by multivariate proportional-hazard analysis. CONCLUSION: Active hepatitis or advanced hepatitis at HBeAg seroconversion or progressive hepatitis even after HBeAg seroconversion would be the risk factors for HCC development. These predictive factors should be taken into account in determining the frequency of biochemical study or imaging studies for HCC surveillance. PMID:16425395

  3. Validation of Virus NAT for HIV, HCV, HBV and HAV Using Post-Mortal Blood Samples

    PubMed Central

    Gubbe, Knut; Scharnagl, Yvonne; Grosch, Steffi; Tonn, Torsten; Schmidt, Michael; Hourfar, Kai M.; Karl, Andreas; Seifried, Erhard; Wilkemeyer, Ina; Kalus, Ulrich

    2012-01-01

    Summary Objective Commercial available NAT systems are usually not validated for screening of post-mortem blood samples. NAT testing might be challenging due to inhibitory substances in the cadaveric blood sample that cause false-negative test results. Validation studies have to be performed to show the performance characteristics of the NAT assays for testing cadaveric blood. Methods A set of 32 post-mortem serum and plasma samples from cornea donors and 40 control samples from blood donors, serologically and NAT negative for all investigated parameters, were spiked with defined concentrations of WHO reference material and tested for HIV-1, HCV, HBV, and HAV by NAT using DRK Baden-Wrttemberg-Hesse CE PCR kits. Analytical sensitivity, analytical specificity and reproducibility/precision were validated and compared with each other in both groups of samples. Results The analytical sensitivity was 100% for control and post-mortem specimens when spiked with virus standards at concentrations of 3 level of detection (LOD). Invalid results did not occur. The analytical specificity rate for all assays was 100%. Intra-assay variation was analyzed as a function of sample material and sampling time post mortem. Values of % coefficient of variation (%CV) were comparable for serum and plasma but slightly higher for post-mortem samples especially for those samples collected more than 24 h post mortem. Conclusion Based on the presented validation, postmortem donor samples can be tested with the automated DRK Baden-Wrtemberg-Hesse NAT system. PMID:23801525

  4. The role of DCs in the immunopathogenesis of chronic HBV infection and the methods of inducing DCs maturation.

    PubMed

    Sun, Hai-Hua; Zhou, Dong-Fang; Zhou, Jun-Ying

    2016-01-01

    Chronic hepatitis B virus (HBV) infection is the result of an inadequate immune response towards the virus. Dendritic cells (DCs), as the most efficient professional antigen-presenting cells (APCs), possess the strongest antigen presenting the effect in the body and can stimulate the initial T cell activation and proliferation. DCs of patients with chronic HBV infection are impaired, resulting in more tolerogenic rather than immunogenic responses, which may contribute to viral persistence. Recently, numerous methods have been developed to induce DCs maturation. To date, recombinant human granulocyte-macrophage colony stimulating factor (rhGM-CSF) combined with interleukin-4 (rhIL-4) has been a classic culture combination to DCs. The recently classified type III interferon group interferon-? (IFN-?) displays antiviral, antitumor, and immunoregulatory activity. In our laboratory, we demonstrate that IFN-?1 combined with rhGM-CSF and rhIL-4 can significantly increase the expression of DC surface molecules and the secretion of interleukin-12 (IL-12) and interferon-? (IFN-?) in patients with chronic hepatitis B infection. In this review, we emphasize on the role of DCs in the immunopathogenesis of chronic HBV infection. Importantly, we systematic review that the latest update in the current status of knowledge on the methods of inducing DCs maturation in anti-HBV immunity. What's more, we conclude that IFN-?1 combined with GM-CSF and IL-4 can induce DCs maturation, which could become a possibility to be applied to the autologus dendritic cell vaccine to treat chronic hepatitis B. PMID:26104380

  5. The association between three IL-6 polymorphisms and HBV-related liver diseases: a meta-analysis

    PubMed Central

    Chang, Lei; Lan, Tian; Wu, Long; Li, Cuicui; Yuan, Yufeng; Liu, Zhisu

    2015-01-01

    Background: A quantity of case-control studies have been performed to address the association between the three interleukin-6 (IL-6) polymorphisms (-572G/C, -597G/A and -174G/C) and the risk of HBV related liver diseases. However, previous research results are inconsistent. We conducted this meta-analysis to clarify the correlation between these IL-6 polymorphisms and HBV related liver diseases. Methods: We searched in PubMed, EMBASE, Cochrane Library as well as Chinese databases including China National Knowledge Infrastructure (CNKI) and WanFang database for all the relevant studies up to April 15, 2015. The data were extracted by two independent authors. Odds ratios (ORs) and 95% confidence intervals (95% CI) were calculated. Results: A total of 10 studies consisting of 3879 cases and 2812 controls were included in this metaanalysis. For IL-6 polymorphism -572G/C, an association with increased chronic hepatitis B (CHB) risk was observed under in allelic, homozygous, heterozygous, dominant and recessive model. However, IL-6 polymorphisms (-572G/C) were not related to Inactive Carrier (IC), Liver Cirrhosis (LC) and Hepatocellular Carcinoma (HCC) risk in this study. We also found that IL-6 polymorphisms (-597G/A) were related to CHB in allelic, heterozygous, recessive model. For IL-6 polymorphism -174G/C, we did not find any association with CHB risk. Conclusion: The present meta-analysis indicated that IL-6 polymorphisms -572G/C and -597G/A significantly associate with CHB risk, but might not be significantly related to the progressive HBV such as LC and HCC. IL-6 polymorphisms -174G/C might not significantly associate with HBV related liver diseases.

  6. Development of a Multiplex Real-Time PCR Assay for the Detection of Treponema pallidum, HCV, HIV-1, and HBV.

    PubMed

    Zhou, Li; Gong, Rui; Lu, Xuan; Zhang, Yi; Tang, Jingfeng

    2015-11-20

    Treponema pallidum, hepatitis C virus (HCV), human immunodeficiency virus (HIV)-1, and hepatitis B virus (HBV) are major causes of sexually transmitted diseases passed through blood contact. The development of a sensitive and efficient method for detection is critical for early diagnosis and for large-scale screening of blood specimens in China. This study aims to establish an assay to detect these pathogens in clinical serum specimens. We established a TaqMan-locked nucleic acid (LNA) real-time polymerase chain reaction (PCR) assay for rapid, sensitive, specific, quantitative, and simultaneous detection and identification. The copy numbers of standards of these 4 pathogens were quantified. Standard curves were generated by determining the mean cycle threshold values versus 10-fold serial dilutions of standards over a range of 10(6) to 10(1) copies/?L, with the lowest detection limit of the assay being 10(1) copies/?L. The assay was applied to 328 clinical specimens and compared with enzyme-linked immunosorbent assay (ELISA) and commercial nucleic acid testing (NAT) methods. The assay identified 39 T. pallidum-, 96 HCV-, 13 HIV-1-, 123 HBV-, 5 HBV/HCV-, 1 T. pallidum/HBV-, 1 HIV-1/HCV-, and 1 HIV-1/T. pallidum-positive specimens. The high sensitivity of the assay confers strong potential for its use as a highly reliable, cost-effective, and useful molecular diagnostic tool for large-scale screening of clinical specimens. This assay will assist in the study of the pathogenesis and epidemiology of sexually transmitted blood diseases. PMID:25866106

  7. Cimetidine synergizes with Praziquantel to enhance the immune response of HBV DNA vaccine via activating cytotoxic CD8(+) T cell.

    PubMed

    Xie, Xiaoping; Geng, Shuang; Liu, Hu; Li, Chaofan; Yang, Yuqin; Wang, Bin

    2014-01-01

    Previously, we have reported that either CIM or PZQ, 2 clinical drugs, could be used to develop as adjuvants on HBV DNA vaccine to elicit both humoral and cellular immune responses. Here, we demonstrate that combinations of CIM and PZQ as adjuvants for a HBV DNA vaccine, could induce much stronger antigen specific CD4(+) and CD8(+) T cell responses compared either with CIM or PZQ alone. The synergistic effects of CIM plus PZQ to HBV DNA vaccine were observed on a higher IgG2a/IgG1 ratio, an increase of HBsAg-specific CD4(+) T cells capable of producing IFN-? or IL-17A and a robust IFN-?-, IL-17A-, or TNF-?-producing CD8(+) T cells to HBsAg. Most importantly, the antigen-specific CTL response was also elevated significantly, which is critical for the eradication of hepatitis B virus (HBV) infected cells. Using an HBsAg transgenic mouse model, the expression of HBsAg in the hepatic cells was also significantly reduced after immunized with pCD-S 2 in the presence of 0.5% CIM and 0.25% PZQ. Further investigations demonstrated that the synergistic effects of combination of CIM and PZQ were dependent on enhanced cytotoxic CD8(+) T cells, which was correlated with impaired activities of regulatory T cells. Therefore, combinations of CIM and PZQ have great potential to be used as effective adjuvants on DNA-based vaccinations for the treatment of chronic hepatitis B. PMID:24643207

  8. Cost-Effectiveness of HBV and HCV Screening Strategies – A Systematic Review of Existing Modelling Techniques

    PubMed Central

    Geue, Claudia; Wu, Olivia; Xin, Yiqiao; Heggie, Robert; Hutchinson, Sharon; Martin, Natasha K.; Fenwick, Elisabeth; Goldberg, David

    2015-01-01

    Introduction Studies evaluating the cost-effectiveness of screening for Hepatitis B Virus (HBV) and Hepatitis C Virus (HCV) are generally heterogeneous in terms of risk groups, settings, screening intervention, outcomes and the economic modelling framework. It is therefore difficult to compare cost-effectiveness results between studies. This systematic review aims to summarise and critically assess existing economic models for HBV and HCV in order to identify the main methodological differences in modelling approaches. Methods A structured search strategy was developed and a systematic review carried out. A critical assessment of the decision-analytic models was carried out according to the guidelines and framework developed for assessment of decision-analytic models in Health Technology Assessment of health care interventions. Results The overall approach to analysing the cost-effectiveness of screening strategies was found to be broadly consistent for HBV and HCV. However, modelling parameters and related structure differed between models, producing different results. More recent publications performed better against a performance matrix, evaluating model components and methodology. Conclusion When assessing screening strategies for HBV and HCV infection, the focus should be on more recent studies, which applied the latest treatment regimes, test methods and had better and more complete data on which to base their models. In addition to parameter selection and associated assumptions, careful consideration of dynamic versus static modelling is recommended. Future research may want to focus on these methodological issues. In addition, the ability to evaluate screening strategies for multiple infectious diseases, (HCV and HIV at the same time) might prove important for decision makers. PMID:26689908

  9. The Inhibitory Effect of the Hepatitis B Virus Singly-Spliced RNA-Encoded p21.5 Protein on HBV Nucleocapsid Formation

    PubMed Central

    Wang, Yi-Ling; Liou, Gan-Guang; Lin, Chao-Hsiung; Chen, Mong-Liang; Kuo, Tzer-Min; Tsai, Kuen-Nan; Huang, Chien-Choao; Chen, Ya-Ling; Huang, Li-Rung; Chou, Yu-Chi; Chang, Chungming

    2015-01-01

    Hepatitis B virus (HBV) is the smallest DNA virus and the major cause of acute and chronic hepatitis. The 3.2 kb HBV viral genome generates four major species of unspliced viral transcript as well as several alternatively spliced RNAs. A 2.2 kb singly-spliced RNA is the most abundant spliced RNA and is widely expressed among all HBV genotypes. The expression of the singly-spliced RNA, as well as that of its encoded protein HBSP, is strongly associated with hepatopathology during HBV infection. Here, we report a novel inhibitory role of a p21.5 protein, which is encoded by a 2.2 kb singly-spliced RNA, in the modulation of HBV replication. We show that overexpression of the singly-spliced RNA is able to efficiently inhibit HBV replication. Furthermore, a mutation in the ATG start codon of the precore region completely abolishes the inhibitory effect of the singly-spliced RNA, indicating that a viral protein (p21.5) derived from the singly-spliced RNA is the mediator of the inhibition. Furthermore, p21.5 is able to form a homodimer that interacts with core dimers forming hybrid viral assembly components. Sucrose gradient fractionation revealed that co-expression of p21.5 resulted in a spread distribution pattern of core proteins ranging from low to high sucrose densities. When compared with p22, p21.5 is almost ten times more efficient at destabilizing HBV nucleocapsid assembly in Huh7 cells overexpressing either p21.5 or p22 protein. Moreover, in vivo expression of p21.5 protein by tail vein injection was found to decrease the amount of nucleocapsid in the livers of HBV-expressing BALB/c mice. In conclusion, our study reveals that the HBV 2.2 kb singly-spliced RNA encodes a 21.5 kDa viral protein that significantly interferes with the assembly of nucleocapsids during HBV nucleocapsid formation. These findings provide a possible strategy for elimination of HBV particles inside cells. PMID:25785443

  10. Association of Single Nucleotide Polymorphisms in VDR and DBP Genes with HBV-Related Hepatocellular Carcinoma Risk in a Chinese Population

    PubMed Central

    Lao, Xianjun; Li, Ruolin; Chen, Zhiping; Wang, Jian; Qin, Xue; Li, Shan

    2014-01-01

    Background Polymorphisms of genes encoding components of the vitamin D pathway including vitamin D receptor (VDR) and vitamin D binding protein (DBP) have been widely investigated because of the complex role played by vitamin D in cancer tumorogenesis. In this study, we investigated the association between VDR and DBP gene polymorphisms and HBV-related HCC risk in a Chinese population. Methods Study subjects were divided into three groups: 184 HBV patients with HCC, 296 HBV patients without HCC, and 180 healthy controls. The VDR rs2228570, and rs3782905 and the DBP rs7041 polymorphisms were genotyped using PCR-RFLP and the VDR rs11568820 polymorphism was genotyped by PCR-SSP, respectively. DNA sequencing was performed to validate the genotype results. Results We found that there were significant differences in the genotype and allele frequencies of the VDR rs2228570 and DBP rs7041 polymorphisms between HBV patients with HCC and healthy controls. The rs2228570 T allele was associated with a significant increased HBV-related HCC risk as compared with the C allele. The rs2228570 TT and TT/TC genotypes were correlated with a significant increased HBV-related HCC risk when compared with the wild-type CC homozygote. Similarly, the rs7041 G allele was associated with a significant increased HBV-related HCC risk as compared with the T allele. The rs7041 GG and GG/TG genotypes were correlated with a significant increased HBV-related HCC risk when compared with the wild-type TT homozygote. However, we did not observe any significant effect of VDR rs11568820, and rs3782905 polymorphisms on HBV-related HCC risk in this population. In haplotype analysis, we also did not find any significant differences in haplotype frequencies of the VDR gene between HBV patients with HCC and the healthy controls. Conclusions We conclude that the VDR rs2228570 and DBP rs7041 polymorphisms may contribute to increased susceptibility to HBV-related HCC in the Chinese population. Due to the marginal significance, further large and well-designed studies in diverse ethnic populations are needed to confirm our results. PMID:25541958

  11. Genetic editing of HBV DNA by monodomain human APOBEC3 cytidine deaminases and the recombinant nature of APOBEC3G.

    PubMed

    Henry, Michel; Gutard, Denise; Suspne, Rodolphe; Rusniok, Christophe; Wain-Hobson, Simon; Vartanian, Jean-Pierre

    2009-01-01

    Hepatitis B virus (HBV) DNA is vulnerable to editing by human cytidine deaminases of the APOBEC3 (A3A-H) family albeit to much lower levels than HIV cDNA. We have analyzed and compared HBV editing by all seven enzymes in a quail cell line that does not produce any endogenous DNA cytidine deaminase activity. Using 3DPCR it was possible to show that all but A3DE were able to deaminate HBV DNA at levels from 10(-2) to 10(-5)in vitro, with A3A proving to be the most efficient editor. The amino terminal domain of A3G alone was completely devoid of deaminase activity to within the sensitivity of 3DPCR ( approximately 10(-4) to 10(-5)). Detailed analysis of the dinucleotide editing context showed that only A3G and A3H have strong preferences, notably CpC and TpC. A phylogenic analysis of A3 exons revealed that A3G is in fact a chimera with the first two exons being derived from the A3F gene. This might allow co-expression of the two genes that are able to restrict HIV-1Deltavif efficiently. PMID:19169351

  12. Pokemon siRNA Delivery Mediated by RGD-Modified HBV Core Protein Suppressed the Growth of Hepatocellular Carcinoma.

    PubMed

    Kong, Jing; Liu, Xiaoping; Jia, Jianbo; Wu, Jinsheng; Wu, Ning; Chen, Jun; Fang, Fang

    2015-10-01

    Hepatocellular carcinoma (HCC) is a deadly human malignant tumor that is among the most common cancers in the world, especially in Asia. Hepatitis B virus (HBV) infection has been well established as a high risk factor for hepatic malignance. Studies have shown that Pokemon is a master oncogene for HCC growth, suggesting it as an ideal therapeutic target. However, efficient delivery system is still lacking for Pokemon targeting treatment. In this study, we used core proteins of HBV, which is modified with RGD peptides, to construct a biomimetic vector for the delivery of Pokemon siRNAs (namely, RGD-HBc-Pokemon siRNA). Quantitative PCR and Western blot assays revealed that RGD-HBc-Pokemon siRNA possessed the highest efficiency of Pokemon suppression in HCC cells. In vitro experiments further indicated that RGD-HBc-Pokemon-siRNA exerted a higher tumor suppressor activity on HCC cell lines, evidenced by reduced proliferation and attenuated invasiveness, than Pokemon-siRNA or RGD-HBc alone. Finally, animal studies demonstrated that RGD-HBc-Pokemon siRNA suppressed the growth of HCC xenografts in mice by a greater extent than Pokemon-siRNA or RGD-HBc alone. Based on the above results, Pokemon siRNA delivery mediated by RGD-modified HBV core protein was shown to be an effective strategy of HCC gene therapy. PMID:26356810

  13. Protective immune barrier against hepatitis B is needed in individuals born before infant HBV vaccination program in China.

    PubMed

    Yang, Shigui; Yu, Chengbo; Chen, Ping; Deng, Min; Cao, Qing; Li, Yiping; Ren, Jingjing; Xu, Kaijin; Yao, Jun; Xie, Tiansheng; Wang, Chencheng; Cui, Yuanxia; Ding, Cheng; Tian, Guo; Wang, Bing; Zhang, Xiaoyan; Ruan, Bing; Li, Lanjuan

    2015-01-01

    The hepatitis B prevalence rate in adults is still at a high to intermediate level in China. Our purpose was to explore the incidence rate and protective immune barrier against hepatitis B in adults in China. A sample of 317961 participants was multi-screened for hepatitis B surface antigens (HBsAg) in a large-scale cohort of the National Hepatitis B Demonstration Project. A total of 5401 persons were newly-infected, representing an incidence rate of 0.81 (95%?CI: 0.77-0.85) per 100 person-years after adjusted by gender and age. History of acquired immune deficiency syndrome, birth prior to 1992, coastal residence, family history of HBV, and migrant worker status were significantly associated with higher incidence, while HBV vaccination and greater exercise with lower incidence. The hepatitis B surface antibody (HBsAb) positive rate was negatively correlated with the incidence rate of hepatitis B (r?=?-0.826). Linear fitting yielded an incidence rate of 1.23 plus 0.02 multiplied by HBsAb positive rate. The study firstly identified the HBsAg incidence rate, which was reduced to 0.1 per 100 person-years after vaccination coverage of about 64%. The protective immune barrier against hepatitis B needs to be established in individuals born prior to the advent of infant HBV vaccination. PMID:26655735

  14. Protective immune barrier against hepatitis B is needed in individuals born before infant HBV vaccination program in China

    PubMed Central

    Yang, Shigui; Yu, Chengbo; Chen, Ping; Deng, Min; Cao, Qing; Li, Yiping; Ren, Jingjing; Xu, Kaijin; Yao, Jun; Xie, Tiansheng; Wang, Chencheng; Cui, Yuanxia; Ding, Cheng; Tian, Guo; Wang, Bing; Zhang, Xiaoyan; Ruan, Bing; Li, Lanjuan

    2015-01-01

    The hepatitis B prevalence rate in adults is still at a high to intermediate level in China. Our purpose was to explore the incidence rate and protective immune barrier against hepatitis B in adults in China. A sample of 317961 participants was multi-screened for hepatitis B surface antigens (HBsAg) in a large-scale cohort of the National Hepatitis B Demonstration Project. A total of 5401 persons were newly-infected, representing an incidence rate of 0.81 (95% CI: 0.77–0.85) per 100 person-years after adjusted by gender and age. History of acquired immune deficiency syndrome, birth prior to 1992, coastal residence, family history of HBV, and migrant worker status were significantly associated with higher incidence, while HBV vaccination and greater exercise with lower incidence. The hepatitis B surface antibody (HBsAb) positive rate was negatively correlated with the incidence rate of hepatitis B (r = −0.826). Linear fitting yielded an incidence rate of 1.23 plus 0.02 multiplied by HBsAb positive rate. The study firstly identified the HBsAg incidence rate, which was reduced to 0.1 per 100 person-years after vaccination coverage of about 64%. The protective immune barrier against hepatitis B needs to be established in individuals born prior to the advent of infant HBV vaccination. PMID:26655735

  15. Recognition of core-derived epitopes from a novel HBV-targeted immunotherapeutic by T-cells from patients infected by different viral genotypes.

    PubMed

    Godon, Ophelie; Evlachev, Alexei; Bourgine, Maryline; Meritet, Jean-Franois; Martin, Perrine; Inchauspe, Genevieve; Michel, Marie-Louise

    2015-08-26

    Hepatitis B virus (HBV) infects millions of people worldwide and is a leading cause of liver cirrhosis and hepatocellular carcinoma. Current therapies based on nucleos(t)ide analogs or pegylated-interferon-? lead to control of viral replication in most patients but rarely achieve cure. A potential strategy to control chronic hepatitis B is to restore or induce functional anti-HBV T-cell immune responses using HBV-specific immunotherapeutics. However, viral diversity is a challenge to the development of this class of products as HBV genotypes display a sequence diversity of up to 8%. We have developed a novel HBV-targeted immunotherapeutic, TG1050, based on a non-replicative Adenovirus vector encoding a unique and large fusion protein composed of multiple antigenic regions derived from a HBV genotype D sequence. Using peripheral blood mononuclear cells from 23 patients chronically infected by five distinct genotypes (gt A, B, C, D and E) and various sets of peptides encompassing conserved versus divergent regions of HBV core we have measured ability of TG1050 genotype D core-derived peptides to be recognized by T-cells from patients infected by various genotypes. Overall, PBMCs from 78% of genotype B or C- and 100% genotype A or E-infected patients lead to detection of HBV core-specific T-cells recognizing genotype D antigenic domains located both in conserved and variable regions. This proof-of-concept study supports the clinical development of TG1050 in large patient populations independently of infecting genotypes. PMID:26209840

  16. PD-1 mRNA expression is associated with clinical and viral profile and PD1 3'-untranslated region polymorphism in patients with chronic HBV infection.

    PubMed

    Zhang, Guoyu; Li, Na; Zhang, Pingping; Li, Fang; Yang, Cuiling; Zhu, Qianqian; Han, Qunying; Lv, Yi; Zhou, Zhihua; Liu, Zhengwen

    2014-11-01

    Programmed cell death-1 (PD-1) is involved in hepatitis B virus (HBV) infection and single-nucleotide polymorphism (SNP) rs10204525 in the 3'-untranslated region (3' UTR) of PD1 gene was shown to be associated with the disease course of HBV infection. This study examined the associations of PD-1 mRNA expression with the clinical and viral profiles and the genotypes of rs10204525 in HBV infection. PD-1 mRNA levels in peripheral blood nuclear cells were determined by real-time quantitative reverse transcription polymerase chain reaction (PCR). PD1 rs10204525 was genotyped by bidirectional PCR amplification of specific alleles. The results showed that patients with chronic HBV infection had significantly elevated PD-1 mRNA levels than healthy controls. Patients with chronic hepatitis and hepatocellular carcinoma had significantly higher PD-1 mRNA levels than healthy controls. HBeAg (+) patients had significantly higher PD-1 mRNA levels than HBeAg (-) patients (P<0.001). PD-1 mRNA levels were sequentially increased with the elevation of HBV DNA levels. In HBV patients, but not in healthy controls, PD-1 mRNA levels were sequentially decreased from rs10204525 genotypes AA, AG to GG and the levels in genotype AA were significantly higher than in genotype GG (P=0.039). These findings suggest that increased PD-1 expression may affect the disease course of chronic HBV infection by facilitating HBV viral replication, and this may at least partially relate to PD1 3' UTR polymorphism. PMID:25218665

  17. Lower baseline ALT cut-off values and HBV DNA levels better differentiate HBeAg(-) chronic hepatitis B patients from inactive chronic carriers

    PubMed Central

    Assy, Nimer; Beniashvili, Zaza; Djibre, Agness; Nasser, Gattas; Grosovski, Maria; Nseir, William

    2009-01-01

    AIM: To determine whether new cut-off values for alanine aminotransferase (ALT) and baseline hepatitis B virus (HBV) DNA levels better differentiate HBeAg(-) chronic hepatitis B (CHB) patients from inactive chronic carriers. METHODS: Ninety-one patients [32 HBeAg(+) CHB, 19 inactive carriers and 40 HBeAg(-) CHB] were followed up for 2 years and were tested for HBV DNA levels by a PCR-based assay. ALT was tested twice during the last 6 mo using new cut-off values: ULN (upper limit of normal) 30 IU/L for males, 19 IU/L for females. Diagnostic accuracy, sensitivity, specificity, positive and negative predictive values were calculated by discriminant analysis. RESULTS: When using the revised ALT cut-off values, the lowest optimal HBV DNA level that differentiated HBeAg(-) CHB patients from inactive carriers was 50?000 copies/mL. The diagnostic accuracy of HBV DNA to determine inactive carriers with a cut-off of 50?000 copies/mL was similar to the previously recommended cut-off of 100?000 copies/mL (91%). HBV DNA levels were lower than the cut-off value in 95% of inactive carriers and in 28% of HBeAg(-) CHB patients. With ALT < 30 IU/L in men and < 19 IU/L in women and HBV DNA levels < 100?000 copies/mL, the risk of CHB is 5%. On the other hand, if ALT values were > 30 IU in men and > 19 IU in women and baseline HBV DNA levels were > 100?000 copies/mL, the risk is 86%. CONCLUSION: New cut-off values for ALT together with HBV DNA levels proposed by AASLD (American Association for the Study of Liver Diseases) and NIH (National Institute of Health) consensus seem appropriate to characterize inactive carriers. PMID:19554656

  18. Telomerase activated thymidine analogue pro-drug is a new molecule targeting hepatocellular carcinoma

    PubMed Central

    Tarocchi, Mirko; Polvani, Simone; Peired, Anna Julie; Marroncini, Giada; Calamante, Massimo; Ceni, Elisabetta; Rhodes, Daniela; Mello, Tommaso; Pieraccini, Giuseppe; Quattrone, Alessandro; Luchinat, Claudio; Galli, Andrea

    2014-01-01

    Background & Aims Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide. Although hepatectomy and transplantation have significantly improved survival, there is no effective chemotherapeutic treatment for HCC and its prognosis remains poor. Sustained activation of telomerase is essential for the growth and progression of HCC, suggesting that telomerase is a rational target for HCC therapy. Therefore, we developed a thymidine analogue pro-drug, acycloguanosyl-5?-thymidyltriphosphate (ACV-TP-T), which is specifically activated by telomerase in HCC cells and investigated its anti-tumour efficacy. Methods First, we verified in vitro whether ACV-TP-T was a telomerase substrate. Second, we evaluated proliferation and apoptosis in murine (Hepa1-6) and human (Hep3B, HuH7, HepG2) hepatic cancer cells treated with ACV-TP-T. Next, we tested the in vivo treatment efficacy in HBV transgenic mice that spontaneously develop hepatic tumours, and in a syngeneic orthotopic murine model where HCC cells were implanted directly in the liver. Results In vitro characterization provided direct evidence that the pro-drug was actively metabolized in liver cancer cells by telomerase to release the active form of acyclovir. Alterations in cell cycle and apoptosis were observed following in vitro treatment with ACV-TP-T. In the transgenic and orthotopic mouse models, treatment with ACV-TP-T reduced tumour growth, increased apoptosis, and reduced the proliferation of tumour cells. Conclusions ACV-TP-T is activated by telomerase in HCC cells and releases active acyclovir that reduces proliferation and induces apoptosis in human and murine liver cancer cells. This pro-drug holds a great promise for the treatment of HCC. PMID:24862448

  19. The PRO-ACT database

    PubMed Central

    Berry, James; Shui, Amy; Zach, Neta; Sherman, Alexander; Sinani, Ervin; Walker, Jason; Katsovskiy, Igor; Schoenfeld, David; Cudkowicz, Merit; Leitner, Melanie

    2014-01-01

    Objective: To pool data from completed amyotrophic lateral sclerosis (ALS) clinical trials and create an open-access resource that enables greater understanding of the phenotype and biology of ALS. Methods: Clinical trials data were pooled from 16 completed phase II/III ALS clinical trials and one observational study. Over 8 million de-identified longitudinally collected data points from over 8,600 individuals with ALS were standardized across trials and merged to create the Pooled Resource Open-Access ALS Clinical Trials (PRO-ACT) database. This database includes demographics, family histories, and longitudinal clinical and laboratory data. Mixed effects models were used to describe the rate of disease progression measured by the Revised ALS Functional Rating Scale (ALSFRS-R) and vital capacity (VC). Cox regression models were used to describe survival data. Implementing Bonferroni correction, the critical p value for 15 different tests was p = 0.003. Results: The ALSFRS-R rate of decline was 1.02 (2.3) points per month and the VC rate of decline was 2.24% of predicted (6.9) per month. Higher levels of uric acid at trial entry were predictive of a slower drop in ALSFRS-R (p = 0.01) and VC (p < 0.0001), and longer survival (p = 0.02). Higher levels of creatinine at baseline were predictive of a slower drop in ALSFRS-R (p = 0.01) and VC (p < 0.0001), and longer survival (p = 0.01). Finally, higher body mass index (BMI) at baseline was associated with longer survival (p < 0.0001). Conclusion: The PRO-ACT database is the largest publicly available repository of merged ALS clinical trials data. We report that baseline levels of creatinine and uric acid, as well as baseline BMI, are strong predictors of disease progression and survival. PMID:25298304

  20. Mutations in pre-core and basal-core promoter regions of hepatitis B virus in chronic HBV patients from Golestan, Iran

    PubMed Central

    Moradi, Abdolvahab; Zhand, Sareh; Ghaemi, Amir; Javid, Naeme; Bazouri, Masoud; Tabarraei, Alijan

    2014-01-01

    Objective(s): It has been reported that the mutation of the pre-core (PC) and basal-core promoter (BCP) may play an important role in the development of HBV-related hepatocellular carcinoma (HCC). In this study the PC and BCP mutations were investigated in chronic HBV patients. Materials and Methods: In this study, 120 chronic HBV patients from Golestan, Northeast of Iran who were not vaccinated against HBV, were recruited from the year 2008 to 2012. HBV-DNA extraction from plasma and PCR were performed and positive PCR products were subjected to automated sequencing. Results: One hundred out of 120 (83.3%) patients were HBeAg negative. Comparison of our nucleotide sequences with reference sequence showed high rate mutation in BCP and PC region (96.66%). Frame shift mutation was found in 78 (65%) of patients in BCP region, among them 8 (6.6%) patients showed mutation in PC region. Conclusion: Our results demonstrated high rate of mutations in BCP and PC regions among HBV chronic patients in Northeast of Iran. PMID:24967066

  1. Integrated Programs and Pro-Environmental Behaviour

    ERIC Educational Resources Information Center

    Smith, Tiffany

    2008-01-01

    Research suggested that "nature experience as an education method played a role in developing environmental value and attitudes, and was influential in pro-environmental behaviour." Few of these studies however, assessed the long-term influences of outdoor education experiences on participants' pro-environmental behaviour. The Outward Bound Canada…

  2. Epidemiology, Risk Factors and Genotypes of HBV in HIV-Infected Patients in the Northeast Region of Colombia: High Prevalence of Occult Hepatitis B and F3 Subgenotype Dominance

    PubMed Central

    Bautista-Amorocho, Henry; Castellanos-Domnguez, Yeny Zulay; Rodrguez-Villamizar, Laura Andrea; Velandia-Cruz, Sindi Alejandra; Becerra-Pea, Jeysson Andrey; Farfn-Garca, Ana Elvira

    2014-01-01

    Introduction Chronic hepatitis B virus (HBV) infection is an increasing cause of morbidity and mortality in human immunodeficiency virus (HIV)-infected individuals. HIV-positive patients are commonly co-infected with HBV due to shared routes of transmission. Objectives Our aim was to determine the risk factors, prevalence, genotypes, and mutations of the Surface S gene of HBV, and occult hepatitis B infection (OBI) among patients infected with HIV in a northeastern Colombian city. Methods A cross-sectional study was conducted with 275 HIV-positive patients attending an outpatient clinic in Bucaramanga, Colombia during 20092010. Blood samples were collected and screened for serological markers of HBV (anti-HBs, anti-HBc and HBsAg) through ELISA assay. Regardless of their serological profile, all samples were tested for the HBV S gene by nested-PCR and HBV genotypes were determined by phylogenetic inference. Clinical records were used to examine demographic, clinical, virological, immunological and antiretroviral therapy (ART) variables of HIV infection. Results Participants were on average 3711 years old and 65.1% male. The prevalence of HIV-HBV coinfection was 12% (95%CI 8.416.4) of which 3.3% had active HBV infection and 8.7% OBI. The prevalence of HIV-HBV coinfection was associated with AIDS stage and ART treatment. Sequence analysis identified genotype F, subgenotype F3 in 93.8% of patients and genotype A in 6.2% of patients. A C149R mutation, which may have resulted from failure in HBsAg detection, was found in one patient with OBI. Conclusions The present study found a high prevalence of HIV-HBV coinfection with an incidence of OBI 2.6-fold higher compared to active HBV infection. These findings suggest including HBV DNA testing to detect OBI in addition to screening for HBV serological markers in HIV patients. PMID:25462190

  3. Optical diagnostic of hepatitis B (HBV) and C (HCV) from human blood serum using Raman spectroscopy

    NASA Astrophysics Data System (ADS)

    Anwar, Shahzad; Firdous, Shamaraz

    2015-06-01

    Hepatitis is the second most common disease worldwide with half of the cases arising in the developing world. The mortality associated with hepatitis B and C can be reduced if the disease is detected at the early stages of development. The aim of this study was to investigate the potential of Raman spectroscopy as a diagnostic tool to detect biochemical changes accompanying hepatitis progression. Raman spectra were acquired from 20 individuals with six hepatitis B infected patients, six hepatitis C infected patients and eight healthy patients in order to gain an insight into the determination of biochemical changes for early diagnostic. The human blood serum was examined at a 532 nm excitation laser source. Raman characteristic peaks were observed in normal sera at 1006, 1157 and 1513 cm-1, while in the case of hepatitis B and C these peaks were found to be blue shifted with decreased intensity. New Raman peaks appeared in HBV and HCV infected sera at 1194, 1302, 844, 905, 1065 and 1303 cm-1 respectively. A Mat lab subroutine and frequency domain filter program is developed and applied to signal processing of Raman scattering data. The algorithms have been successfully applied to remove the signal noise found in experimental scattering signals. The results show that Raman spectroscopy displays a high sensitivity to biochemical changes in blood sera during disease progression resulting in exceptional prediction accuracy when discriminating between normal and malignant. Raman spectroscopy shows enormous clinical potential as a rapid non-invasive diagnostic tool for hepatitis and other infectious diseases.

  4. Pro-Anorexia and Pro-Recovery Photo Sharing: A Tale of Two Warring Tribes

    PubMed Central

    Yom-Tov, Elad; Weber, Ingmar; Crain, Steven P

    2012-01-01

    Background There is widespread use of the Internet to promote anorexia as a lifestyle choice. Pro-anorexia content can be harmful for people affected or at risk of having anorexia. That movement is actively engaged in sharing photos on social networks such as Flickr. Objective To study the characteristics of the online communities engaged in disseminating content that encourages eating disorders (known as “pro-anorexia”) and to investigate if the posting of such content is discouraged by the posting of recovery-oriented content. Methods The extraction of pro-anorexia and pro-recovery photographs from the photo sharing site Flickr pertaining to 242,710 photos from 491 users and analyzing four separate social networks therein. Results Pro-anorexia and pro-recovery communities interact to a much higher degree among themselves than what is expected from the distribution of contacts (only 59-72% of contacts but 74-83% of comments are made to members inside the community). Pro-recovery users employ similar words to those used by pro-anorexia users to describe their photographs, possibly in order to ensure that their content appears when pro-anorexia users search for images. Pro-anorexia users who are exposed to comments from the opposite camp are less likely to cease posting pro-anorexia photographs than those who do not receive such comments (46% versus 61%), and if they cease, they do so approximately three months later. Our observations show two highly active communities, where most interaction is within each community. However, the pro-recovery community takes steps to ensure that their content is visible to the pro-anorexia community, both by using textual descriptions of their photographs that are similar to those used by the pro-anorexia group and by commenting to pro-anorexia content. The latter activity is, however, counterproductive, as it entrenches pro-anorexia users in their stance. Conclusions Our results highlight the nature of pro-anorexia and pro-recovery photo sharing and accentuate the need for clinicians to be aware of such content and its effect on their patients. Our findings suggest that some currently used interventions are not useful in helping pro-anorexia users recover. Thus, future work should focus on new intervention methods, possibly tailored to individual characteristics. PMID:23134671

  5. Pro-sociality without empathy

    PubMed Central

    Vasconcelos, Marco; Hollis, Karen; Nowbahari, Elise; Kacelnik, Alex

    2012-01-01

    Empathy, the capacity to recognize and share feelings experienced by another individual, is an important trait in humans, but is not the same as pro-sociality, the tendency to behave so as to benefit another individual. Given the importance of understanding empathy's evolutionary emergence, it is unsurprising that many studies attempt to find evidence for it in other species. To address the question of what should constitute evidence for empathy, we offer a critical comparison of two recent studies of rescuing behaviour that report similar phenomena but are interpreted very differently by their authors. In one of the studies, rescue behaviour in rats was interpreted as providing evidence for empathy, whereas in the other, rescue behaviour in ants was interpreted without reference to sharing of emotions. Evidence for empathy requires showing that actor individuals possess a representation of the receiver's emotional state and are driven by the psychological goal of improving its wellbeing. Proving psychological goal-directedness by current standards involves goal-devaluation and causal sensitivity protocols, which, in our view, have not been implemented in available publications. Empathy has profound significance not only for cognitive and behavioural sciences but also for philosophy and ethics and, in our view, remains unproven outside humans. PMID:22859561

  6. UPLC-MS/MS method for the simultaneous quantification of anti-HBV nucleos(t)ides analogs: Entecavir, lamivudine, telbivudine and tenofovir in plasma of HBV infected patients.

    PubMed

    De Nicol, Amedeo; Simiele, Marco; Pensi, Debora; Boglione, Lucio; Allegra, Sarah; Di Perri, Giovanni; D'Avolio, Antonio

    2015-10-10

    Hepatitis B infection affects two billion people worldwide and 350 million of these are chronically infected. Chronic hepatitis B virus is one of the most important cause of mortality and morbidity worldwide. If it is left untreated, about one-third of affected people will develop progressive and possibly fatal liver disease, like hepatic cirrhosis and primary hepatocellular carcinoma. Currently, five nucleos(t)ide analogs are approved for the treatment of chronic HBV infection. They are: lamivudine, adefovir dipivoxil, telbivudine, entecavir and tenofovir disoproxil fumarate. In this work, we developed and validated an UPLC-Tandem mass spectrometry assay method capable of monitoring lamivudine, telbivudine, tenofovir and entecavir plasma concentrations. Both standards and quality controls (high, medium and low) were prepared in human plasma. Each sample was added with internal standard (5'amino-5'deoxy-thymidine) and then drugs were extracted through a protein precipitation protocol with acetonitrile+0.1% formic acid and then dried. The extracts were resuspended in water and then injected into the chromatographic system. The chromatographic separation was performed on an Acquity UPLC HSS T3 1.8 ?m 2.1 150 mm column, with a gradient of water and acetonitrile, both added with formic acid (0.05%). Accuracy, intra-day and inter-day precision at quality controls levels fitted all FDA guidelines for all analytes, while matrix effects and recoveries resulted stable between samples for each analyte. Finally, we tested this method by monitoring plasma concentrations in 30 HBV+ patients with good results. This simple analytical method could represent a useful tool for the management of anti-HBV therapy. PMID:26037161

  7. Immune memory to hepatitis B virus in 4-9-year old children vaccinated in infancy with four doses of hexavalent DTPa-HBV-IPV/Hib vaccine.

    PubMed

    Zinke, Michael; Kappes, Rudolf; Kindler, Klaus; Paulus-Koschik, Anke; Goering, Uwe; Disselhoff, Johann; Soemantri, Peter; Grunert, Detlef; Laakmann, Karl Heinz; Gunasekaran, Ramakrishnan; Gartner, Britta; Jacquet, Jeanne-Marie

    2009-09-01

    The combined hexavalent diphtheria-tetanus-acellular pertussis-hepatitis B-inactivated polio Haemophilus influenzae type b (DTPa-HBV-IPV/Hib) vaccine produces similar hepatitis B responses as the HBV monovalent vaccine. Booster vaccination of immunocompetent individuals primed against hepatitis B in infancy is currently not recommended. We investigated persisting immunity to hepatitis B in 4-6 (Study A; 106745) and 7-9 (Study B; 106744) year-old children primed in infancy and boosted in the second year of life with DTPa-HBV-IPV/Hib. Immunity was assessed by measuring persisting anti-HBs antibodies and evaluating the response to a challenge dose of HBV vaccine. At 4-6 years of age 86.0% of 186 subjects had persisting anti-HBs > or =10 mIU/ml increasing to 98.4% after the challenge. At 7-9 years of age, 78.0% of 186 subjects continued to have anti-HBs antibody concentrations > or =10 mIU/ml, increasing to 98.9% after the challenge. In both studies anti-HBs antibody GMC rose >80-fold. An anamnestic response to the HBV challenge was observed in 95.7% and 98.9% of subjects in Studies A and B, respectively. In both studies, 87% of 38 subjects with initially undetectable circulating anti-HBs antibodies (>3.3 IU/ml) achieved the 10 mIU/ml threshold after challenge; > or =97.0% of subjects with detectable antibodies before the challenge at least quadrupled their concentration. Post-vaccination anti-HBs concentrations were directly related to persisting antibody concentrations and the concentrations achieved after the booster dose in the second year of life. The HBV vaccine challenge dose was well tolerated. These studies show that primary and booster vaccination with combined DTPa-HBV-IPV/Hib (Infanrix hexa) induces sustained immune memory against hepatitis B up to age 9 years. PMID:19535920

  8. ProCoS: Protein composition server.

    PubMed

    Rishishwar, Lavanya; Mishra, Neha; Pant, Bhasker; Pant, Kumud; Pardasani, Kamal Raj

    2010-01-01

    ProCoS is a free online tool for computing different combinations of peptide compositions. It is developed as an applet and a server with a capability to handle multiple FASTA sequences. The generalized algorithm for computing poly-amino acid composition forms the core of ProCoS. It produces output in different formats for easy visualization of results. It also allows composition analysis of sequences in full or in specific parts. Thus, ProCoS is user-friendly, flexible and unique. PMID:21364804

  9. Manduca sexta proprophenoloxidase activating proteinase-3 (PAP3) stimulates melanization by activating proPAP3, proSPHs, and proPOs

    PubMed Central

    Wang, Yang; Lu, Zhiqiang; Jiang, Haobo

    2014-01-01

    Melanization participates in various insect physiological processes including antimicrobial immune responses. Phenoloxidase (PO), a critical component of the enzyme system catalyzing melanin formation, is produced as an inactive precursor prophenoloxidase (proPO) and becomes active via specific proteolytic cleavage by proPO activating proteinase (PAP). In Manduca sexta, three PAPs can activate proPOs in the presence of two serine proteinase homologs (SPH1 and SPH2). While the hemolymph proteinases (HPs) that generate the active PAPs are known, it is unclear how the proSPHs (especially proSPH1) are activated. In this study, we isolated from plasma of bar-stage M. sexta larvae an Ile-Glu-Ala-Arg-p-nitroanilide hydrolyzing enzyme that cleaved the proSPHs. This proteinase, PAP3, generated active SPH1 and SPH2, which function as cofactors for PAP3 in proPO activation. Cleavage of the purified recombinant proSPHs by PAP3 yielded 38 kDa bands similar in mobility to the SPHs formed in vivo. Surprisingly, PAP3 also can activate proPAP3 to stimulate melanization in a direct positive feedback loop. The enhanced proPO activation concurred with the cleavage activation of proHP6, proHP8, proPAP1, proPAP3, proSPH1, proSPH2, proPOs, but not proHP14 or proHP21. These results indicate that PAP3, like PAP1, is a key factor of the self-reinforcing mechanism in the proPO activation system, which is linked to other immune responses in M. sexta. PMID:24768974

  10. Hepatitis B virus DNA is more powerful than HBeAg in predicting peripheral T-lymphocyte subpopulations in chronic HBV-infected individuals with normal liver function tests

    PubMed Central

    You, Jing; Sriplung, Hutcha; Geater, Alan; Chongsuvivatwong, Virasakdi; Zhuang, Lin; Chen, Hong-Ying; Huang, Jun-Hua; Tang, Bao-Zhang

    2008-01-01

    AIM: To investigate the peripheral T-lymphocyte subpopulation profile, and its correlations with hepatitis B virus (HBV) replication level in chronic HBV-infected (CHI) individuals with normal liver function tests (LFTs). METHODS: Frequencies of T-lymphocyte subpopu-lations in peripheral blood were measured by flow cytometry in 216 CHI individuals. HBV markers were detected with ELISA. Serum HBV DNA load was assessed with quantitative real-time PCR. Information of age at HBV infection, and maternal HBV infection status was collected. ANOVA linear trend test and linear regression were used in statistical analysis. RESULTS: CHI individuals had significantly decreased relative frequencies of CD3+, CD4+ subpopulations and CD4+/CD8+ ratio, and increased CD8+ subset percentage compared with uninfected individuals (all P < 0.001). There was a significant linear relationship between the load of HBV DNA and the parameters of T-lymphocyte subpopulations (ANOVA linear trend test P < 0.01). The parameters were also significantly worse among individuals whose mothers were known to be HBV carriers, and those having gained infection before the age of 8 years. In multiple regressions, after adjustment for age at HBV infection and status of maternal HBV infection, log copies of HBV DNA maintained its highly significant predictive coefficient on T-lymphocyte subpopulations, whereas the effect of HBeAg was not significant. CONCLUSION: HBV DNA correlates with modification in the relative T-lymphocyte subpopulation frequencies. High viral load is more powerful than HBeAg in predicting the impaired balance of T-cell subsets. PMID:18595137

  11. Hepatocellular Carcinoma Risk of Compensated Cirrhosis Patients with Elevated HBV DNA Levels according to Serum Aminotransferase Levels

    PubMed Central

    Lee, Junggyu; Sinn, Dong Hyun; Kim, Jung Hee; Gwak, Geum-Youn; Kim, Hye Seung; Jung, Sin-Ho; Paik, Yong-Han; Choi, Moon Seok; Lee, Joon Hyeok; Koh, Kwang Cheol; Yoo, Byung Chul

    2015-01-01

    Sometimes, hepatitis B virus (HBV)-related cirrhotic patients with normal aminotransferase levels are closely followed-up for the elevation of aminotransferase levels instead of prompt antiviral therapy (AVT). We analyzed the long-term hepatocellular carcinoma (HCC) risk according to the aminotransferase levels in a retrospective cohort of 1,468 treatment-nave, HBV-related, compensated cirrhosis patients with elevated HBV DNA levels (?2,000 IU/mL). Based on aminotransferase levels, patients were categorized into normal (< 40 U/L, n = 364) and elevated group (?40 U/L, n = 1,104). During a median of 5.3 yr of follow-up (range: 1.0-8.2 yr), HCC developed in 296 (20%) patients. The 5-yr cumulative HCC incidence rate was higher in patients with elevated aminotransferase level, but was not low in normal aminotransferase level (17% vs. 14%, P = 0.004). During the follow-up, 270/364 (74%) patients with normal aminotransferase levels experienced elevation of aminotransferase levels, and AVT was initiated in 1,258 (86%) patients. Less patients with normal aminotransferase levels received AVT (70% vs. 91%, P < 0.001) and median time to start AVT was longer (17.9 vs. 2.4 months, P < 0.001). AVT duration was an independent factor associated with HCC, and median duration of AVT was shorter (4.0 vs. 2.6 yr, P < 0.001) in patients with normal aminotransferase levels. The HCC risk of compensated cirrhosis patients with normal aminotransferase level is not low, and AVT duration is associated with lowered HCC risk, indicating that prompt AVT should be strongly considered even for those with normal aminotransferase levels. PMID:26539006

  12. Efficiency and safety of lamivudine therapy in patients with chronic HBV infection, dialysis or after kidney transplantation

    PubMed Central

    Lapinski, Tadeusz Wojciech; Flisiak, Robert; Jaroszewicz, Jerzy; Michalewicz, Małgorzata; Kowalczuk, Oksana

    2005-01-01

    AIM: To analyze the effectiveness and safety of lamivudine treatment in patients with chronic HBV infection undergoing hemodialysis or after kidney transplantation, and to study the frequency of tyrosine - methionine - aspartate - aspartate (YMDD) mutation occurrence after lamivudine treatment. METHODS: We analyzed 91 patients with chronic hepatitis B, among whom, 16 patients underwent hemodialysis, 7 patients had kidney transplantation and 68 patients had normal function of kidney. The hemodialysis patients were treated by lamivudine 300 mg/wk. Patients after kidney transplantation and patients with normal function of kidney were treated with lamivudine 100 mg/d. Therapy lasted for 12 mo. HBV-DNA, HBsAg, HBeAg and anti-HBe, and anti-HCV antibodies were assessed in sera of patients. The analysis was performed before and 6 mo after the end of lamivudine treatment. Before, during and after the lamivudine therapy, the number of erythrocytes, leukocytes, platelets and hemoglobin concentration, ALT and AST activity, as well as bilirubin, urea and creatinine concentrations were analyzed in sera from patients. RESULTS: After the 12-mo lamivudine treatment, elimination of HBV - DNA was observed in 56% patients undergoing hemodialysis and in 53% patients with normal kidney function. Only 1 from 7 (14%) kidney-transplanted patients eliminated HBV-DNA. Furthermore, HBeAg elimination was observed in 36% hemodialysis patients, in 51% patients with normal function of kidneys and in 43% kidney-transplanted patients. Among the patients undergoing dialysis, no YMDD mutation was found after 12 mo of therapy, while it was detected in 9 patients (13%) with normal function of kidney and in 2 kidney-transplanted patients (29%, P<0.006). We did not observe significant side effects of lamivudine treatment in studied patients. CONCLUSION: Effectiveness of lamivudine therapy in dialysis patients is comparable with that in patients with normal function of kidney. Lamivudine treatment is well tolerated and safe in patients with renal insufficiency undergoing hemodialysis and kidney-transplantation. However, in the latter group, high incidence of YMDD mutation after lamivudine treatment was observed. PMID:15637753

  13. New Susceptibility and Resistance HLA-DP Alleles to HBV-Related Diseases Identified by a Trans-Ethnic Association Study in Asia

    PubMed Central

    Kashiwase, Koichi; Minami, Mutsuhiko; Sugiyama, Masaya; Seto, Wai-Kay; Yuen, Man-Fung; Posuwan, Nawarat; Poovorawan, Yong; Ahn, Sang Hoon; Han, Kwang-Hyub; Matsuura, Kentaro; Tanaka, Yasuhito; Kurosaki, Masayuki; Asahina, Yasuhiro; Izumi, Namiki; Kang, Jong-Hon; Hige, Shuhei; Ide, Tatsuya; Yamamoto, Kazuhide; Sakaida, Isao; Murawaki, Yoshikazu; Itoh, Yoshito; Tamori, Akihiro; Orito, Etsuro; Hiasa, Yoichi; Honda, Masao; Kaneko, Shuichi; Mita, Eiji; Suzuki, Kazuyuki; Hino, Keisuke; Tanaka, Eiji; Mochida, Satoshi; Watanabe, Masaaki; Eguchi, Yuichiro; Masaki, Naohiko; Murata, Kazumoto; Korenaga, Masaaki; Mawatari, Yoriko; Ohashi, Jun; Kawashima, Minae; Tokunaga, Katsushi; Mizokami, Masashi

    2014-01-01

    Previous studies have revealed the association between SNPs located on human leukocyte antigen (HLA) class II genes, including HLA-DP and HLA-DQ, and chronic hepatitis B virus (HBV) infection, mainly in Asian populations. HLA-DP alleles or haplotypes associated with chronic HBV infection or disease progression have not been fully identified in Asian populations. We performed trans-ethnic association analyses of HLA-DPA1, HLA-DPB1 alleles and haplotypes with hepatitis B virus infection and disease progression among Asian populations comprising Japanese, Korean, Hong Kong, and Thai subjects. To assess the association between HLA-DP and chronic HBV infection and disease progression, we conducted high-resolution (4-digit) HLA-DPA1 and HLA-DPB1 genotyping in a total of 3,167 samples, including HBV patients, HBV-resolved individuals and healthy controls. Trans-ethnic association analyses among Asian populations identified a new risk allele HLA-DPB1*09∶01 (P = 1.36×10−6; OR = 1.97; 95% CI, 1.50–2.59) and a new protective allele DPB1*02∶01 (P = 5.22×10−6; OR = 0.68; 95% CI, 0.58–0.81) to chronic HBV infection, in addition to the previously reported alleles. Moreover, DPB1*02∶01 was also associated with a decreased risk of disease progression in chronic HBV patients among Asian populations (P = 1.55×10−7; OR = 0.50; 95% CI, 0.39–0.65). Trans-ethnic association analyses identified Asian-specific associations of HLA-DP alleles and haplotypes with HBV infection or disease progression. The present findings will serve as a base for future functional studies of HLA-DP molecules in order to understand the pathogenesis of HBV infection and the development of hepatocellular carcinoma. PMID:24520320

  14. Risk of Severe Acute Exacerbation of Chronic HBV Infection Cancer Patients Who Underwent Chemotherapy and Did Not Receive Anti-Viral Prophylaxis

    PubMed Central

    Shih, Chih-An; Chen, Wen-Chi; Yu, Hsien-Chung; Cheng, Jin-Shiung; Lai, Kwok-Hung; Hsu, Jui-Ting; Chen, Hui-Chun; Hsu, Ping-I

    2015-01-01

    Background Reactivation of HBV replication with an increase in serum HBV DNA and alanine aminotransferase (ALT) activity has been reported in 2050% of hepatitis B carriers undergoing cytotoxic chemotherapy for cancer treatment. Manifestation of HBV reactivation ranges from asymptomatic self-limiting hepatitis to severe progressive hepatic failure and fatal consequences. Aim To investigate the risk of severe acute exacerbation of chronic HBV infection in HBsAg-positive cancer patients with solid tumors or hematological malignancies who underwent chemotherapy without antiviral prophylaxis. Methods A retrospective review of charts was conducted for HBsAg-positive cancer patients in our institution who underwent chemotherapy and did not receive anti-viral prophylaxis between the periods of July 2007 to January 2013. We investigate the incidence of severe acute exacerbation of chronic HBV infection if these patients with a variety of solid tumors and hematological malignancies. Results A total of 156 patients (hematological malignancies: 16; solid tumors: 140) were included. The incidence of severe acute HBV exacerbation in the patients with hematological malignancy was higher than that in solid tumors (25.0% [4/16] vs 4.3% [6/140]); P = 0.005). Additionally, patients receiving rituximab-based chemotherapy had higher acute exacerbation rate than those with non-rituximab-based chemotherapy (40.0% vs 4.1%, P = 0.001). Among the patients with solid tumors, the incidences of severe acute exacerbation of chronic HBV in hepatocellular carcinoma, colorectal cancer, lung cancer, breast cancer, gynecological cancer, urological tract cancer, head/neck cancer and other solid malignancies were 2.3%, 4.0%, 7.1%, 9.0%, 16.7%, 6.7%, 0% and 0%, respectively. Conclusion Severe acute exacerbation of chronic HBV infection may occur in HBsAg-positive patients with a variety of solid tumors who received chemotherapy without adequate anti-viral prophylaxis. Hematological malignancy and rituximab-based chemotherapy are the risk factors related to severe acute exacerbation of chronic HBV infection in HBsAg-positive cancer patients undergoing chemotherapy. PMID:26274393

  15. Pro Libra Makes the Impossible Happen.

    ERIC Educational Resources Information Center

    Cherry, Susan Spaeth

    1981-01-01

    Pro Libra Associates, Inc. in South Orange, New Jersey, is a cadre of some 200 carefully screened professionals and clerical workers who perform a variety of library tasks on a contract basis. (Author/LLS)

  16. Hepatitis B Virus (HBV) and Hepatitis C Virus (HCV) Co-Infection Among HIV Infected Individuals at Tertiary Care Hospital in Western Nepal

    PubMed Central

    Gokhale, Shishir; Sathian, Brijesh; Bhatta, Dharma Raj

    2015-01-01

    Background The HIV, HBV and HCV viruses are the major public health concern all over the world including Nepal. The aim of the study is to determine the rate of HBV and HCV co-infections in patients with HIV infection. Methods The study cohort included 218 consecutive HIV infected patients who were examined for co-infection with HBV or HCV or both at Manipal teaching hospital, Western Nepal. The demographic data of the subjects was collected retrospectively. The data was analyzed with SPSS software and EPI Info to measure the correlation of variables and infection rates. Results In the course of six years study period, a total of 25,708 samples were collected for HIV screening test. The 218 (0.8%) screen test positive for HIV were confirmed as per WHO guidelines. The overall rate of co-infection with HBV and or HCV was 7.3% (16 of 218 patients). Only 7 (3.2% [CI 1.3, 6.5]) were positive for both HIV and HBV infection markers and 9 (4.1% [CI 1.9, 7.7]) were positive for HIV and HCV infection markers. None were positive of all three virus markers. Conclusion It is advisable to implementregular screening for Hepatitis B Virus and Hepatitis C Virus among all HIV infected individuals and their sexual partners. PMID:26913208

  17. Immunogenicity and safety of 3-dose primary vaccination with combined DTPa-HBV-IPV/Hib vaccine in Canadian Aboriginal and non-Aboriginal infants.

    PubMed

    Scheifele, David W; Ferguson, Murdo; Predy, Gerald; Dawar, Meena; Assudani, Deepak; Kuriyakose, Sherine; Van Der Meeren, Olivier; Han, Htay-Htay

    2015-04-15

    This study compared immune responses of healthy Aboriginal and non-Aboriginal infants to Haemophilus influenzae type b (Hib) and hepatitis B virus (HBV) components of a DTaP-HBV-IPV/Hib combination vaccine, 1 month after completing dosing at 2, 4 and 6 months of age. Of 112 infants enrolled in each group, 94 Aboriginal and 107 non-Aboriginal infants qualified for the immunogenicity analysis. Anti-PRP concentrations exceeded the protective minimum (?0.15 ?g/ml) in ?97% of infants in both groups but geometric mean concentrations (GMCs) were higher in Aboriginal infants (6.12 ?g/ml versus 3.51 ?g/ml). All subjects were seroprotected (anti-HBs ?10 mIU/mL) against HBV, with groups having similar GMCs (1797.9 versus 1544.4 mIU/mL, Aboriginal versus non-Aboriginal, respectively). No safety concerns were identified. We conclude that 3-dose primary vaccination with DTaP-HBV-IPV/Hib combination vaccine elicited immune responses to Hib and HBV components that were at least as high in Aboriginal as in non-Aboriginal Canadian infants. Clinical Trial Registration NCT00753649. PMID:25701314

  18. Technology evaluation: PRO-542, Progenics Pharmaceuticals inc.

    PubMed

    Mukhtar, M; Parveen, Z; Pomerantz, R J

    2000-12-01

    Progenics's rCD4-IgG2 (PRO-542) is a recombinant fusion protein, which has been developed using the company's Universal Antiviral Binding (UnAB) technology, and is in phase I/II clinical trials for the treatment of human immunodeficiency virus type I (HIV-1) infection [273391]. At the beginning of 1997, Progenics received a Phase II Small Business Innovation Research Program (SBIR) grant from the National Institute of Allergy and Infectious diseases (NIAID) to fund the development of PRO-542 [236048]. A further grant of $2.7 million was awarded in August 1998 for the clinical evaluation of PRO-542 and other anti-HIV therapies [294200]. Progenics is collaborating with the Aaron Diamond AIDS Research Center (ADARC) in New York and the Center for Disease Control and Prevention in Atlanta [178410]. In February 2000, Progenics and Genzyme Transgenics Corp signed an agreement to continue the development of a transgenic source of PRO-542. Genzyme will develop transgenic goats that produce PRO-542 in their milk in exchange for undisclosed fees and milestone payments. Genzyme will supply PRO-542 to Progenics for clinical trials with a possibility for eventual commercial supply [357291]. Following on from this, in October 2000, Progenics received an SBIR grant to fund a two-year project with Genzyme Transgenics into the development of cost-effective methods for the manufacture of PRO-542, by optimization of the production of the drug in the milk of transgenic dairy animals [385982]. In August 2000, Punk, Ziegel & Company predicted that Progenics Pharmaceuticals will become sustainably profitable in 2003 following the launch of PRO-542 and GMK (Progenics Pharmaceuticals) in 2002 [390063]. PMID:11249748

  19. A new fluorescent based screening system for high throughput screening of drugs targeting HBV-core and HBsAg interaction.

    PubMed

    Suresh, V; Krishnakumar, K A; Asha, V V

    2015-03-01

    The existing screening systems for anti-hepatitis B virus (anti-HBV) drug discovery is time-consuming mainly due to the laborious detection system it is using. A new fluorescence based screening system for high throughput anti-HBV drug discovery was created by tagging hepatitis B surface antigen (HBsAg) with monomeric red fluorescent protein and hepatitis B virus (HBV) core protein with enhanced green fluorescent protein. The two constructs were co-transfected on to Hep3B cells and the transfection was stabilized by fluorescent activated cell sorter (FACS). The fusion proteins expressed through the secretory protein pathway as evidenced by localization with ER-Tracker and tubulin tracker. The new system has given analogues results like that of conventional enzyme-linked immunosorbent assay (ELISA). Hence it can be of very high potential for large scale drug screening systems. PMID:25776516

  20. 19 CFR 141.85 - Pro forma invoice.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 19 Customs Duties 2 2010-04-01 2010-04-01 false Pro forma invoice. 141.85 Section 141.85 Customs... (CONTINUED) ENTRY OF MERCHANDISE Invoices 141.85 Pro forma invoice. A pro forma invoice submitted in accordance with any provision of this chapter shall be in substantially the following form: Pro Forma...

  1. Immunological persistence in 5 y olds previously vaccinated with hexavalent DTPa-HBV-IPV/Hib at 3, 5, and 11 months of age.

    PubMed

    Silfverdal, Sven A; Assudani, Deepak; Kuriyakose, Sherine; Van Der Meeren, Olivier

    2014-01-01

    The combined diphtheria-tetanus-acellular pertussis-hepatitis B-poliomyelitis/Haemophilus influenza vaccine (DTPa-HBV-IPV/Hib: Infanrix hexa, GlaxoSmithKline Vaccines) is used for primary vaccination of infants in a range of schedules world-wide. Antibody persistence after 4 DTPa-HBV-IPV/Hib doses in the first 2 y of life has been documented, but long-term persistence data following the 3, 5, 11-12 months (3-5-11) infant vaccination schedule, employed for example in Nordic countries, are limited. We assessed antibody persistence in 57 5-year-old children who had received either DTPa-HBV-IPV/Hib or DTPa-IPV/Hib (Infanrix-IPV/Hib, GlaxoSmithKline Vaccines) in the 3-5-11 schedule. Among DTPa-HBV-IPV/Hib recipients, 7/12 retained seroprotective antibody concentrations for diphtheria, 10/12 for tetanus, 5/12 for hepatitis and 10/12 for Hib. Detectable antibodies were observed for 0/12 children for pertussis toxin (PT), 12/12 for filamentous haemagglutinin (FHA) and 8/12 for pertactin (PRN). Among DTPa-IPV/Hib recipients, 28/45 retained seroprotective anti-diphtheria concentrations, 34/44 for tetanus and 40/45 for Hib. Detectable antibodies were observed for 9/45 children for PT, 41/45 for FHA and 34/45 for PRN. Antibody persistence in DTPa-HBV-IPV/Hib and DTPa-IPV/Hib-vaccinees appeared similar in 5 y olds to that previously observed in children of a similar age who had received 4 prior doses of DTPa-HBV-IPV/Hib (or DTPa-IPV/Hib). As in subjects primed with 4 prior doses, we observed that antibodies markedly declined by 5 y of age, calling for the administration of a pre-school booster dose in order to ensure continued protection against pertussis. PMID:25483640

  2. Across-sectional study on anxiety and stress in pregnant women with chronic HBV infection in the Peoples Republic of China

    PubMed Central

    Zhou, Fen; Li, Jianju; Lin, Keke; Ji, Ping; Sun, Yumei

    2015-01-01

    Purpose To investigate the anxiety and pregnancy-associated stress of pregnant women with chronic hepatitis B virus (HBV) infection in the Peoples Republic of China and analyze the relationship between anxiety and pregnancy-associated stress in the hope of finding ways to reduce the stress or improve the coping skills for these mothers-to-be during pregnancy. Methods A cross-sectional study was conducted. One hundred and sixty chronic HBV-infected pregnant women (HBV group) and 160 healthy pregnant women (control group) selected from three Peking University-affiliated hospitals participated in the study, and completed the State-Trait Anxiety Inventory (STAI) and Pregnancy Stress Rating Scale (PSRS) survey. Results The mean scores of STAI and PSRS for the HBV group were higher than for the control group. Factor 2 of PSRS (stress caused by worrying about mother and childs health and safety) was the highest, and was significantly higher in the HBV group than in the control group. Correlation analysis showed STAI scores were significantly correlated with economic status and diagnosis, as well as the total score, factor 1 (stress about identifying with the role of mother), and factor 2 of PSRS, but not significantly correlated with factor 3 of PSRS (stress caused by the changes of body shape and physical activity). Conclusion Pregnant women with chronic HBV infection experienced higher levels of anxiety and stress than healthy pregnant women. Their major stress came from concerns for the health and safety of the mother and the child. PMID:26346004

  3. Human melioidosis reported by ProMED

    PubMed Central

    Nasner-Posso, Katherinn Melissa; Cruz-Calderón, Stefania; Montúfar-Andrade, Franco E.; Dance, David A.B.; Rodriguez-Morales, Alfonso J.

    2015-01-01

    Summary Objective There are limited sources describing the global burden of emerging diseases. A review of human melioidosis reported by ProMED was performed and the reliability of the data retrieved assessed in comparison to published reports. The effectiveness of ProMED was evaluated as a source of epidemiological data by focusing on melioidosis. Methods Using the keyword ‘melioidosis’ in the ProMED search engine, all of the information from the reports and collected data was reviewed using a structured form, including the year, country, gender, occupation, number of infected individuals, and number of fatal cases. Results One hundred and twenty-four entries reported between January 1995 and October 2014 were identified. A total of 4630 cases were reported, with death reported in 505 cases, suggesting a misleadingly low overall case fatality rate (CFR) of 11%. Of 20 cases for which the gender was reported, 12 (60%) were male. Most of the cases were reported from Australia, Thailand, Singapore, Vietnam, and Malaysia, with sporadic reports from other countries. Conclusions Internet-based reporting systems such as ProMED are useful to gather information and synthesize knowledge on emerging infections. Although certain areas need to be improved, ProMED provided good information about melioidosis. PMID:25975651

  4. DTPa-HBV-IPV/Hib Vaccine (Infanrix hexa): A Review of its Use as Primary and Booster Vaccination.

    PubMed

    Dhillon, Sohita

    2010-05-28

    Infanrix hexa, administered intramuscularly, is a diphtheria, tetanus, acellular pertussis, hepatitis B (HBV), inactivated poliomyelitis and Haemophilus influenzae type b (Hib) conjugate vaccine, indicated for primary and booster vaccination of infants. Infanrix hexa should be administered as a two- or three-dose primary vaccination course in infants aged HBV or Hib vaccines. In large clinical studies, Infanrix hexa elicited a strong immune response against vaccine toxoids/antigens, as indicated by high seroprotection/seropositivity/vaccine response rates and geometric mean titres. Moreover, antibodies against vaccine toxoids/antigens persisted for up to a mean of approximately 6 years after booster vaccination, and the vaccine induced long-term immune memory against hepatitis B surface antigen and Hib antigen. A strong immune response against Infanrix hexa toxoids/antigens after primary vaccination was also induced in infants who had received a dose of HBV vaccine at birth and in pre-term infants, although the response in the latter group was somewhat lower than that in full-term infants. In addition, when coadministered with other childhood vaccines, the immunogenicity of Infanrix hexa or that of the concomitantly administered vaccine was generally not altered. Hexavalent vaccines, including Infanrix hexa, were protective against invasive Hib disease; Infanrix hexa is also expected to be protective against pertussis. Most solicited local and general symptoms with Infanrix hexa were mild to moderate in intensity and the vaccine was associated with few unsolicited adverse events. Available clinical data from more than 10 years' experience with the vaccine suggest that Infanrix hexa as primary and booster vaccination is a safe and useful option for providing protection against the common childhood diseases of diphtheria, tetanus, poliomyelitis, pertussis, hepatitis B and invasive Hib disease. PMID:20481658

  5. A comparison of SRM and HBV models for real time runoff forecasting in the Upper Euphrates Basin, Turkey

    NASA Astrophysics Data System (ADS)

    Sorman, A. A.; Sensoy, A.; Yamankurt, E.; Gozel, E.

    2012-04-01

    Predicting snowmelt runoff in the mountainous eastern part of Turkey at a daily time step is important in water resource management as it constitutes nearly 2/3 in volume of the total yearly runoff during spring and early summer months. Keeping track of snow dynamics as well as forecasting the amount and timing of snowmelt runoff in the headwaters of the trans-boundary Euphrates River, where large dams are located, is a crucial and challenging task concerning the practical importance and great demand for real time forecasting of melt water. In mountainous regions, data limitations prevent detailed understanding of the variability of snow cover and melt. In situ snowpack measurements are sparsely distributed relative to snowpack heterogeneity therefore, to supplement ground measurement networks, remotely sensed images of snow covered area (SCA) provide useful information for runoff prediction during the snowmelt season. SCA has been used as a direct input to hydrological models such as Snowmelt Runoff Model (SRM) or as a means of assimilating hydrologic model snowpack and checking the internal validity as in the case of HBV model. Alternative ways of handling melt water modeling using satellite derived SCA is discussed, with emphasis on the contrasting treatments in two widely used hydrologic models, SRM and HBV. The greatest similarity between the two models is that each uses a temperature index method to predict melt rate whereas the greatest difference lies in the way snow cover is handled. Moderate Resolution Imaging Spectroradiometer (MODIS) daily snow cover products with 500 m spatial resolution are used to derive SCA data in this study. Since the cloud obscuring problem degrades the use of satellites with optical sensors, a special combination and filtering methodology is utilized to reduce cloud coverage of the product. Both models are used to simulate runoff for the years 2001-2010 with model efficiency above 0.86 and volume difference less than 2.5%. Finally, operational snowmelt runoff forecasting is carried out for 2011 ablation season using numerical weather prediction (Mesoscale Model 5) data as forcing input variables. Discussion of results are supervised to reflect the general debates in hydrologic modeling in terms of parameters and calibration, internal validation, the value and limitations of using satellite derived and numerical weather prediction data. Key words: snow, SRM, HBV, forecasting, Upper Euphrates Basin

  6. FRUITS OF TRANSGENIC TOMATO PLANTS PRODUCING TBI-HBSAG CHIMERIC PROTEIN CAN BE USED AS AN ORAL VACCINE AGAINST HIV AND HBV AS SHOWN IN EXPERIMENTAL MICE

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Human immunodeficiency (HIV) and hepatitis B (HBV) viruses are pathogens causing dangerous diseases. These infections are spreading at a high rate, reaching the level of a worldwide epidemic. According to the WHO data, 2–3 million people die annually of acquired immunodeficiency syndrome (AIDS)...

  7. Performance evaluation of new automated hepatitis B viral markers in the clinical laboratory: two quantitative hepatitis B surface antigen assays and an HBV core-related antigen assay.

    PubMed

    Park, Yongjung; Hong, Duck Jin; Shin, Saeam; Cho, Yonggeun; Kim, Hyon-Suk

    2012-05-01

    We evaluated quantitative hepatitis B surface antigen (qHBsAg) assays and a hepatitis B virus (HBV) core-related antigen (HBcrAg) assay. A total of 529 serum samples from patients with hepatitis B were tested. HBsAg levels were determined by using the Elecsys (Roche Diagnostics, Indianapolis, IN) and Architect (Abbott Laboratories, Abbott Park, IL) qHBsAg assays. HBcrAg was measured by using Lumipulse HBcrAg assay (Fujirebio, Tokyo, Japan). Serum aminotransferases and HBV DNA were respectively quantified by using the Hitachi 7600 analyzer (Hitachi High-Technologies, Tokyo, Japan) and the Cobas AmpliPrep/Cobas TaqMan test (Roche). Precision of the qHBsAg and HBcrAg assays was assessed, and linearity of the qHBsAg assays was verified. All assays showed good precision performance with coefficients of variation between 4.5% and 5.3% except for some levels. Both qHBsAg assays showed linearity from 0.1 to 12,000.0 IU/mL and correlated well (r = 0.9934). HBsAg levels correlated with HBV DNA (r = 0.3373) and with HBcrAg (r = 0.5164), and HBcrAg also correlated with HBV DNA (r = 0.5198; P < .0001). This observation could provide impetus for further research to elucidate the clinical usefulness of the qHBsAg and HBcrAg assays. PMID:22523216

  8. HIV, HCV, HBV, HSV, and syphilis prevalence among female sex workers in Tehran, Iran, by using respondent-driven sampling.

    PubMed

    Moayedi-Nia, Saeedeh; Bayat Jozani, Zahra; Esmaeeli Djavid, Gholamreza; Entekhabi, Fatemeh; Bayanolhagh, Saeed; Saatian, Minoo; Sedaghat, Abbas; Nikzad, Rana; Jahanjoo Aminabad, Fatemeh; Mohraz, Minoo

    2016-04-01

    To find out the prevalence of HIV, HCV, HBV, HSV, and syphilis infections among female sex workers (FSWs) in Tehran, a cross-sectional study by using respondent-driven sampling (RDS) method was conducted. From December 2012 to April 2013 FSWs in Tehran were recruited. Inclusion criteria consisted of trading sex during the 12 months prior to this study and selling sex for at least 6 months in participants' lifetime. Among 161 consenting participants, 5% were infected with HIV. Moreover, 8.1% of FSWs were HCV positive, 37.9% were of HSV type1/type2, 1.2% of participants were infected with HBV, and none of the participants were infected with syphilis. HIV-positive participants were significantly more likely to be co-infected with HSV type1/type2, be younger, have more sexual partners and especially more clients during seven days prior to this study and report more history of having at least one of sexually transmitted infections symptoms in 12 months prior the study. In the multiple logistic regression analysis, being infected with HSV and also being under 25 years of age were found to be independently associated with HIV infection. Compared with the prevalence of HIV among general population of Tehran, relatively high prevalence of HIV and other viral infections among FSWs should be considered. All in all, it is critical to commence effective counter-measures for this high-risk group if the aim is to prevent spreading of these viruses to general population. PMID:26565671

  9. Evaluation of a novel commercial quaternary ammonium compound for eradication of Mycobacteria, HCV and HBV in Egypt.

    PubMed

    Elkholy, Yasmine Samy; Hegab, Asmaa Sayed; Ismail, Dalia Kadry; Hassan, Reem Mostafa

    2016-01-01

    Endoscopes are a common source of outbreaks of healthcare-associated infections. It is therefore important to identify high-level disinfectants capable of eliminating or killing all vegetative bacteria, mycobacteria, and viruses. Aldehydebased disinfectants are most commonly used in clinical practice but resistance has recently been detected and side effects associated with these disinfectants are well documented. In this study, we evaluated Virusolve+ EDS, a novel quaternary ammonium compound formulation supplied by Amity international, against Mycobacterium bovis (ATCC-27289), hepatitis C virus (HCV)-positive serum and hepatitis B surface antigen-positive serum. We also compared its efficacy against Cidex (glutaraldehyde 2%), an aldehyde-based disinfectant. M. bovis showed no growth after 10 weeks with either Virusolve+ or Cidex. Virusolve+ achieved a 10(4)- fold reduction in the initial 10(6) HCV load under clean conditions (without red blood cells) for 20 min, whereas Cidex achieved this reduction under clean and dirty conditions (without and with red blood cells, respectively) after both 10 and 20 min. Both Virusolve+ and Cidex were able to eradicate hepatitis B virus (HBV) infectivity under clean conditions after 10 and 20 min, whereas under dirty conditions they were only able to eradicate virus infectivity after 20 min. Virusolve+ EDS when compared with Cidex showed equal mycobactericidal activity completely eradicating M. bovis. However, both showed comparable virucidal activity against HBV, which was more effective under clean conditions, emphasizing the importance of the cleaning step in endoscope reprocessing. Cidex was more effective at eradicating HCV under dirty conditions after a short contact time. PMID:26727900

  10. Pro-brain natriuretic peptide (ProBNP) levels in North Indian children with Kawasaki disease.

    PubMed

    Reddy, Mounika; Singh, Surjit; Rawat, Amit; Sharma, Avinash; Suri, Deepti; Rohit, Manoj Kumar

    2016-04-01

    The diagnosis of Kawasaki disease (KD), a common pediatric vasculitis, is based solely on clinical criteria. There is a need for a robust laboratory marker that can help differentiate KD from other acute, febrile, childhood illnesses and also to predict cardiac involvement. We conducted a cross-sectional study of 25 consecutive patients admitted with diagnosis of KD from January 2013 to April 2014 and compared them with age- and sex-matched febrile controls. We studied the serum pro-brain natriuretic peptide (ProBNP) [ProBNP and N-terminal pro-B-type natriuretic peptide (NT-ProBNP) levels], a marker of myocardial dysfunction, in children with KD in acute and convalescent phases of disease. These levels were also estimated in febrile controls for comparison. The ProBNP (ProBNP and NT-ProBNP) levels were much higher in the acute phase of the KD patients compared to levels in the convalescent phase of KD (p = 0.000014). Similarly, the levels in the acute phase were higher when compared to the age- and sex-matched febrile controls (p = 0.000126). The receiver operating curve (ROC) analysis for the ProBNP levels in the acute phase of KD yielded an area under the curve of 0.954 ± 0.034 (p < 0.000, 95 % CI 0.886-1.0). Based on ROC analysis, a cutoff of 1025 pg/mL for ProBNP levels in the acute phase of KD had 88 % sensitivity and 96 % specificity for the diagnosis of KD. A lower cut-off of 514 pg/mL yielded a 100 % sensitivity and 80 % specificity for the diagnosis of KD. The ProBNP levels were higher in those with coronary artery abnormalities (CAA) compared to those without CAA in both acute (p = 0.013) and convalescent (p = 0.045) phases. ProBNP levels may be used as a surrogate marker for the differentiation of KD from other febrile, infectious illnesses and may also predict the involvement of coronary arteries. PMID:26849890

  11. Hepatitis B (HBV), Hepatitis C (HCV) and Hepatitis Delta (HDV) Viruses in the Colombian Population—How Is the Epidemiological Situation?

    PubMed Central

    Alvarado-Mora, Mónica Viviana; Gutierrez Fernandez, María Fernanda; Gomes-Gouvêa, Michele Soares; de Azevedo Neto, Raymundo Soares; Carrilho, Flair José; Pinho, João Renato Rebello

    2011-01-01

    Background Viral hepatitis B, C and delta still remain a serious problem worldwide. In Colombia, data from 1980s described that HBV and HDV infection are important causes of hepatitis, but little is known about HCV infection. The aim of this study was to determine the currently frequency of HBV, HCV and HDV in four different Colombian regions. Methodology/Principal Findings This study was conducted in 697 habitants from 4 Colombian departments: Amazonas, Chocó, Magdalena and San Andres Islands. Epidemiological data were obtained from an interview applied to each individual aiming to evaluate risk factors related to HBV, HCV or HDV infections. All samples were tested for HBsAg, anti-HBc, anti-HBs and anti-HCV markers. Samples that were positive to HBsAg and/or anti-HBc were tested to anti-HDV. Concerning the geographical origin of the samples, the three HBV markers showed a statistically significant difference: HBsAg (p = 0.033) and anti-HBc (p<0.001) were more frequent in Amazonas and Magdalena departments. Isolated anti-HBs (a marker of previous vaccination) frequencies were: Chocó (53.26%), Amazonas (32.88%), Magdalena (17.0%) and San Andrés (15.33%) - p<0.001. Prevalence of anti-HBc increased with age; HBsAg varied from 1.97 to 8.39% (p = 0.033). Amazonas department showed the highest frequency for anti-HCV marker (5.68%), while the lowest frequency was found in San Andrés Island (0.66%). Anti-HDV was found in 9 (5.20%) out of 173 anti-HBc and/or HBsAg positive samples, 8 of them from the Amazonas region and 1 from them Magdalena department. Conclusions/Significance In conclusion, HBV, HCV and HDV infections are detected throughout Colombia in frequency levels that would place some areas as hyperendemic for HBV, especially those found in Amazonas and Magdalena departments. Novel strategies to increase HBV immunization in the rural population and to strengthen HCV surveillance are reinforced by these results. PMID:21559488

  12. microRNA-122 Abundance in Hepatocellular Carcinoma and Non-Tumor Liver Tissue from Japanese Patients with Persistent HCV versus HBV Infection

    PubMed Central

    Spaniel, Carolyn; Honda, Masao; Selitsky, Sara R.; Yamane, Daisuke; Shimakami, Tetsuro; Kaneko, Shuichi; Lanford, Robert E.; Lemon, Stanley M.

    2013-01-01

    Mechanisms of hepatic carcinogenesis in chronic hepatitis B and hepatitis C are incompletely defined but often assumed to be similar and related to immune-mediated inflammation. Despite this, several studies hint at differences in expression of miR-122, a liver-specific microRNA with tumor suppressor properties, in hepatocellular carcinoma (HCC) associated with hepatitis B virus (HBV) versus hepatitis C virus (HCV) infection. Differences in the expression of miR-122 in these cancers would be of interest, as miR-122 is an essential host factor for HCV but not HBV replication. To determine whether the abundance of miR-122 in cancer tissue is influenced by the nature of the underlying virus infection, we measured miR-122 by qRT-PCR in paired tumor and non-tumor tissues from cohorts of HBV- and HCV-infected Japanese patients. miR-122 abundance was significantly reduced from normal in HBV-associated HCC, but not in liver cancer associated with HCV infection. This difference was independent of the degree of differentiation of the liver cancer. Surprisingly, we also found significant differences in miR-122 expression in non-tumor tissue, with miR-122 abundance reduced from normal in HCV- but not HBV-infected liver. Similar differences were observed in HCV- vs. HBV-infected chimpanzees. Among HCV-infected Japanese subjects, reductions in miR-122 abundance in non-tumor tissue were associated with a single nucleotide polymorphism near the IL28B gene that predicts poor response to interferon-based therapy (TG vs. TT genotype at rs8099917), and correlated negatively with the abundance of multiple interferon-stimulated gene transcripts. Reduced levels of miR-122 in chronic hepatitis C thus appear to be associated with endogenous interferon responses to the virus, while differences in miR-122 expression in HCV- versus HBV-associated HCC likely reflect virus-specific mechanisms contributing to carcinogenesis. The continued expression of miR-122 in HCV-associated HCC may signify an important role for HCV replication late in the progression to malignancy. PMID:24130799

  13. Maternal chronic HBV infection would not increase the risk of pregnancy-induced hypertension--results from pregnancy cohort in Liuyang rural China.

    PubMed

    Huang, Xin; Tan, Hongzhuan; Li, Xun; Zhou, Shujin; Wen, Shi Wu; Luo, Meiling

    2014-01-01

    The relationship between maternal HBV (hepatitis B virus) infection and pregnancy-induced hypertension (PIH) is inconclusive. Few studies have been conducted in rural areas of China. In order to examine the association between maternal chronic HBV infection and risk of PIH in Liuyang rural area China, we enrolled 6,195 eligible pregnant women in 2010-2011 in selected 14 towns of Liuyang on their first prenatal visit to local maternity care unit. A total of 461 subjects (7.44% (95%CI: 6.79%, 8.10%)) were identified with positive HBsAg status (exposed group) and 5734 were non-HBV carriers (unexposed group). Multivariate log-binomial regression models were used to estimate the risk of PIH, gestational hypertension (GH), and preeclampsia (PE) in relation to maternal chronic HBV infection. There are total of 455 subjects diagnosed with PIH (7.34% (95%CI: 6.70%, 7.99%)), including 371 GH (5.99% (95%CI: 5.40%, 6.58%)) and 81 PE (1.31% (95%CI: 1.07%, 1.64%)). The crude risk ratio between PIH, GH, PE and maternal HBV infection were 1.20 (95%CI: 0.88, 1.64), 1.30(95%CI: 0.93, 1.81) and 0.79 (95%CI: 0.32, 1.93), respectively. After adjustment for gravidity history, abortion history, family history of Diabetes Mellitus (DM) and family history of hypertension, positive HBsAg status was still not significantly associated with PIH (RR = 1.18, 95%CI: 0.87, 1.62), GH (RR = 1.27, 95%CI: 0.91, 1.78) or PE (RR = 0.79, 95%CI: 0.32, 1.95). Additional adjustment for maternal age, marital status, parity history, family history of DM, Body Mass Index at first antenatal visit, folic acid supplementation, smoking status during pregnancy and economic status of living area, multivariate analysis provided similar results. In conclusion, our study found that maternal chronic HBV infection prevalence rate is 7.4% among Liuyang rural area and there is no significant association between maternal HBV infection and the risk of PIH, GH or PE. PMID:25479003

  14. Network of hydrogen bonds in Pro-Ala-Pro and Pro-Phe-Pro diamides: A first principles study of Ala-->Phe point mutation in proline environment

    NASA Astrophysics Data System (ADS)

    Wang, Hui; Csizmadia, Imre G.; Marsi, Istvan; Chasse, Gregory A.; Fang, DeCai; Viskolcz, Bela

    2009-07-01

    Intramolecular hydrogen bonding in the Pro-Ala-Pro and Pro-Phe-Pro tripeptides has been characterized using Bader's atoms in molecule (AIM) analyses of relevant electron density topologies. The properties of hydrogen bonds with corresponding ring strains were investigated. Good correlations along the decrease in electron densities at ring critical points were examined from five- to ten-membered hydrogen-bound ring sizes; seven-membered rings being the most energetically favored. AIM analysis confirms the logical conclusion that the molecule has to become very compact to form as many hydrogen bonds as possible. The relatively large hydrogen bond stabilization attributed to the pronounced network of interactions comes at the "energetic expense" of a relatively large internal repulsion due to the compactness of the structures. The net balanced result was a very modest increase in the zero point corrected conformation energy (ΔEZPEC). These findings aid in establishing hydrogen bonding rules in reductionist "bottoms-up" approaches to peptide and protein folding.

  15. Beneficial potential of casein hydrolysate containing Val-Pro-Pro and Ile-Pro-Pro on central blood pressure and hemodynamic index: a preliminary study.

    PubMed

    Nakamura, Teppei; Mizutani, Jun; Sasaki, Kouichi; Yamamoto, Naoyuki; Takazawa, Kenji

    2009-12-01

    Pharmaceutical angiotensin-converting enzyme (ACE) inhibitors have been shown to reduce arterial stiffness; the possible effect of food-derived putative ACE inhibitory peptides on this degenerative process, however, has not been reported. In the present study, casein hydrolysate containing the lactotripeptides, Val-Pro-Pro (VPP) and Ile-Pro-Pro (IPP), which has been found to have an antihypertensive effect in a number of clinical studies, was investigated for its ability to improve hemodynamic parameters, including central systolic blood pressure (cSBP), in hypertensive subjects. Twelve hypertensive subjects who were not on prescribed medication were monitored for various hemodynamic parameters, including brachial blood pressure (peripheral blood pressure), cSBP, and augmentation index (AI), at the start and then after 3, 6, and 9 weeks of a daily treatment comprising four tablets containing VPP and IPP. Compared with basal levels, treatment with casein hydrolysate for 6 and/or 9 weeks showed a significant reduction in peripheral systolic and diastolic blood pressure, AI, and cSBP, but not in heart rate or pulse pressure. cSBP showed a reduction sooner and greater (-21.8 mm Hg) than did brachial systolic blood pressure (-16.4 mm Hg) during the 9-week treatment. Although small and not placebo-controlled, this study suggests that continuous intake of VPP and IPP might have the potential to improve arterial stiffness as well as cSBP and peripheral brachial blood pressure. PMID:19821692

  16. HBV, HCV and HIV seroprevalence among blood donors in Istanbul, Turkey: how effective are the changes in the national blood transfusion policies?

    PubMed

    Acar, Ali; Kemahli, Sabri; Altunay, Husnu; Kosan, Erdogan; Oncul, Oral; Gorenek, Levent; Cavuslu, Saban

    2010-01-01

    The national blood transfusion policies have been changed significantly in recent years in Turkey. The purpose of this study was to determine the prevalence of HBV, HCV, and HIV in blood donors at the Red Crescent Center in Istanbul and to evaluate the effect of changes in the national blood transfusion policies on the prevalence of these infections. The screening results of 72695 blood donations at the Red Crescent Center in Istanbul between January and December 2007 were evaluated retrospectively. HBsAg, anti-HCV, and anti-HIV-1/2 were screened by microparticle enzyme immunoassay (MEIA) method. Samples found to be positive for anti-HIV 1/2 and anti-HCV were confirmed by Inno-Lia HCV Ab III and Inno-Lia HIV I/II Score, respectively. The seropositivity rates for HBsAg, anti-HCV, and anti-HIV-1/2 were determined as 1.76%, 0.07%, and 0.008%, respectively. Compared to the previously published data from Red Crescent Centers in Turkey, it was found that HBV and HCV seroprevalances decreased and HIV seroprevalance increased in recent years. In conclusion, we believe that the drop in HBV and HCV prevalence rates are likely multifactorial and may have resulted from more diligent donor questioning upon screening, a higher level of public awareness on viral hepatitis as well as the expansion of HBV vaccination coverage in Turkey. Another factor to contribute to the decreased prevalence of HCV stems from the use of more sensitive confirmation testing on all reactive results, thereby eliminating a fair amount of false positive cases. Despite similar transmission routes, the increase in HIV prevalence in contrast to HBV and HCV may be linked to the increase in AIDS cases in Turkey in recent years. PMID:20428653

  17. Rapid screening and identification of dominant B cell epitopes of HBV surface antigen by quantum dot-based fluorescence polarization assay

    NASA Astrophysics Data System (ADS)

    Meng, Zhongji; Song, Ruihua; Chen, Yue; Zhu, Yang; Tian, Yanhui; Li, Ding; Cui, Daxiang

    2013-03-01

    A method for quickly screening and identifying dominant B cell epitopes was developed using hepatitis B virus (HBV) surface antigen as a target. Eleven amino acid fragments from HBV surface antigen were synthesized by 9-fluorenylmethoxy carbonyl solid-phase peptide synthesis strategy, and then CdTe quantum dots were used to label the N-terminals of all peptides. After optimizing the factors for fluorescence polarization (FP) immunoassay, the antigenicities of synthetic peptides were determined by analyzing the recognition and combination of peptides and standard antibody samples. The results of FP assays confirmed that 10 of 11 synthetic peptides have distinct antigenicities. In order to screen dominant antigenic peptides, the FP assays were carried out to investigate the antibodies against the 10 synthetic peptides of HBV surface antigen respectively in 159 samples of anti-HBV surface antigen-positive antiserum. The results showed that 3 of the 10 antigenic peptides may be immunodominant because the antibodies against them existed more widely among the samples and their antibody titers were higher than those of other peptides. Using three dominant antigenic peptides, 293 serum samples were detected for HBV infection by FP assays; the results showed that the antibody-positive ratio was 51.9% and the sensitivity and specificity were 84.3% and 98.2%, respectively. In conclusion, a quantum dot-based FP assay is a very simple, rapid, and convenient method for determining immunodominant antigenic peptides and has great potential in applications such as epitope mapping, vaccine designing, or clinical disease diagnosis in the future.

  18. Rapid screening and identification of dominant B cell epitopes of HBV surface antigen by quantum dot-based fluorescence polarization assay

    PubMed Central

    2013-01-01

    A method for quickly screening and identifying dominant B cell epitopes was developed using hepatitis B virus (HBV) surface antigen as a target. Eleven amino acid fragments from HBV surface antigen were synthesized by 9-fluorenylmethoxy carbonyl solid-phase peptide synthesis strategy, and then CdTe quantum dots were used to label the N-terminals of all peptides. After optimizing the factors for fluorescence polarization (FP) immunoassay, the antigenicities of synthetic peptides were determined by analyzing the recognition and combination of peptides and standard antibody samples. The results of FP assays confirmed that 10 of 11 synthetic peptides have distinct antigenicities. In order to screen dominant antigenic peptides, the FP assays were carried out to investigate the antibodies against the 10 synthetic peptides of HBV surface antigen respectively in 159 samples of anti-HBV surface antigen-positive antiserum. The results showed that 3 of the 10 antigenic peptides may be immunodominant because the antibodies against them existed more widely among the samples and their antibody titers were higher than those of other peptides. Using three dominant antigenic peptides, 293 serum samples were detected for HBV infection by FP assays; the results showed that the antibody-positive ratio was 51.9% and the sensitivity and specificity were 84.3% and 98.2%, respectively. In conclusion, a quantum dot-based FP assay is a very simple, rapid, and convenient method for determining immunodominant antigenic peptides and has great potential in applications such as epitope mapping, vaccine designing, or clinical disease diagnosis in the future. PMID:23452727

  19. Sequencing of PCR amplified HBV DNA pre-c and c regions in the 2.2.15 cells and antiviral action by targeted antisense oligonucleotide directed against sequence

    PubMed Central

    Zhong, Sen; Wen, Shou-Ming; Zhang, Ding-Feng; Wang, Quan-Li; Wang, Seng-Qi; Ren, Hong

    1998-01-01

    AIM: To study the specific inhibition of HBV gene expression by liver-targeting antisense oligonucleotide (ASON) directed against pre-c and cregious in a sequence specific manner. METHODS: According to the result of direct sequencing of PCR amplified products, a 16-mer phosphorothioate analogue of the antisense oligonucleotide (PS-ASOn) directed against the HBV U-5-like region was synthesized and then linked with one live-targeting ligand, the galactosylated poly-L-lysine.Their effect on the expression of HBV gene was observed using the 2.2.15 cells. RESULTS: HBV DNA in the 2.2.15 cells was from HBV with surface antigen subtype ayw 1 by sequencing so that antisense oligonucleotides could bind specifically to the target sequence through base piring. Under the same experimental conditions, the inhibitory rates of PS-ASON to HBsAg and HBeAg were 70% and 58% at a concentration of 10 ?mol/L, while by ligand-PS-ASON they were 96% and 82%, the amount of HBV DNA in cultured supernatant and cells was reduced significantly. An unrelated sequence oligonucleotide showed no effectiveness. All the oligonucleotides had no cytotoxicity. CONCLUSION: Antisense oligonucleotides complexed by the liver-targeting ligand can be targeted to cells via asialoglycoprotein receptors, resulting in supecific inhibition of HBV gene expression and replication. PMID:11819339

  20. A randomized, dose-ranging assessment of the immunogenicity and safety of a booster dose of a combined diphtheria-tetanus-whole cell pertussis-hepatitis B-inactivated poliovirus-Hemophilus influenzae type b (DTPw-HBV-IPV/Hib) vaccine vs. co-administration of DTPw-HBV/Hib and IPV vaccines in 12 to 24 months old Filipino toddlers

    PubMed Central

    Quiambao, Beatriz; Van Der Meeren, Olivier; Kolhe, Devayani; Gatchalian, Salvacion

    2012-01-01

    As progress toward global poliovirus eradication continues, more and more countries are moving away from use of oral poliovirus vaccines (OPV) to inactivated poliovirus vaccines (IPV) in national vaccination schedules. Reduction of antigen dose in IPV could increase manufacturing capacity and facilitate the change from OPV to IPV. Combination vaccines reduce the number of injections required to complete vaccination, thus playing an important role in maintaining high vaccine coverage with good public acceptability. Three formulations of a combined, candidate hexavalent diphtheria-tetanus-whole cell pertussis-hepatitis B-inactivated poliovirus-Hemophilus influenzae type b conjugate vaccine (DTPw-HBV-IPV/Hib, GlaxoSmithKline Biologicals) differing only in IPV antigen content (full-dose, half-dose and one-third dose as compared with available stand-alone IPV vaccines), were evaluated when administered to healthy toddlers. Controls received separately administered licensed DTPw-HBV/Hib and IPV vaccines. Immunogenicity was assessed before and one month after vaccination. Safety and reactogenicity data were assessed for 30 d after vaccination. A total of 312 Filipino children were vaccinated in their second year of life. Each DTPw-HBV-IPV/Hib formulation was non-inferior to control in terms of pre-defined criteria for IPV immunogenicity. Post-vaccination GMTs against each poliovirus type were increased between 4.2- and 37.9-fold over pre-vaccination titers. Non-inferiority to other vaccine antigens was also demonstrated. The safety profile of the 3 DTPw-HBV-IPV/Hib formulations resembled licensed DTPw-HBV/Hib Kft and IPV in terms of the frequency and intensity of adverse reactions after vaccination. Further investigation of DTPw-HBV-IPV/Hib containing reduced quantity of IPV antigen for primary vaccination in infants is warranted.   This study is registered at www.clinicaltrials.gov NCT number: NCT01106092 PMID:22330958

  1. Lasting immune memory against hepatitis B in children after primary immunization with 4 doses of DTPa-HBV-IPV/Hib in the first and 2nd year of life

    PubMed Central

    2010-01-01

    Background Few studies have assessed long term persisting immunity against hepatitis B virus (HBV) in children vaccinated during infancy with combined vaccines containing recombinant HBV surface antigen (HBs). We assessed antibody persistence and immune memory in children 4-5 years of age, previously vaccinated with four doses of combined hexavalent DTPa-HBV-IPV/Hib vaccine (Infanrix hexa). Methods Immune memory was assessed in 301 children through administration of a challenge dose of monovalent HBV vaccine. Results At 4-5 years of age, 85.3% of subjects had persisting anti-HBs antibody concentrations ? 10 mIU/mL, rising to 98.6% after the HBV challenge dose. All but 12 subjects (95.8%) achieved post-challenge anti-HBs concentrations ? 100 mIU/mL. The post-challenge anti-HBs GMC rose by 100-fold compared to pre-challenge concentrations. An anamnestic response to the HBV vaccine challenge was observed in 96.8% of subjects, including 17/21 (81.0%) of children with initially undetectable antibodies (<3.3 mIU/mL). All but 4 of 42 subjects (90.5%) with anti-HBs antibodies <10 mIU/mL prior to the challenge dose, achieved seroprotective levels afterwards. A 4-fold rise in antibody concentration after the challenge dose was observed in 259/264 (98.1%) of initially seropositive subjects. The magnitude of the post-challenge responses was proportional to pre-challenge anti-HBs levels. No serious adverse events were reported during the study. Conclusion The combined DTPa-HBV-IPV/Hib vaccine induced lasting immune memory against hepatitis B. Long term protection afforded by DTPa-HBV-IPV/Hib is likely to be similar to that observed following priming with monovalent HBV vaccines. Trial registration http://www.clinicaltrials.gov 106789 NCT00411697 PMID:20078876

  2. 31 CFR 50.92 - Determination of pro rata share.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 31 Money and Finance: Treasury 1 2010-07-01 2010-07-01 false Determination of pro rata share. 50.92 Section 50.92 Money and Finance: Treasury Office of the Secretary of the Treasury TERRORISM RISK INSURANCE PROGRAM Cap on Annual Liability 50.92 Determination of pro rata share. (a) Pro rata...

  3. 26 CFR 1.1377-1 - Pro rata share.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 26 Internal Revenue 11 2013-04-01 2013-04-01 false Pro rata share. 1.1377-1 Section 1.1377-1...) INCOME TAXES (CONTINUED) Small Business Corporations and Their Shareholders 1.1377-1 Pro rata share. (a) Computation of pro rata shares(1) In general. For purposes of subchapter S of chapter 1 of the...

  4. 31 CFR 50.93 - Application of pro rata share.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 31 Money and Finance: Treasury 1 2010-07-01 2010-07-01 false Application of pro rata share. 50.93... PROGRAM Cap on Annual Liability 50.93 Application of pro rata share. An insurer shall apply the PRLP to determine the pro rata share of each insured loss to be paid by the insurer on all insured losses...

  5. 31 CFR 50.92 - Determination of pro rata share.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 31 Money and Finance: Treasury 1 2011-07-01 2011-07-01 false Determination of pro rata share. 50... INSURANCE PROGRAM Cap on Annual Liability 50.92 Determination of pro rata share. (a) Pro rata loss... support of an insurer's claim for the Federal share of compensation will be reviewed for the...

  6. 31 CFR 50.93 - Application of pro rata share.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 31 Money and Finance: Treasury 1 2011-07-01 2011-07-01 false Application of pro rata share. 50.93... PROGRAM Cap on Annual Liability 50.93 Application of pro rata share. An insurer shall apply the PRLP to determine the pro rata share of each insured loss to be paid by the insurer on all insured losses...

  7. 26 CFR 1.1377-1 - Pro rata share.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 26 Internal Revenue 11 2012-04-01 2012-04-01 false Pro rata share. 1.1377-1 Section 1.1377-1...) INCOME TAXES (CONTINUED) Small Business Corporations and Their Shareholders 1.1377-1 Pro rata share. (a) Computation of pro rata shares(1) In general. For purposes of subchapter S of chapter 1 of the...

  8. 26 CFR 1.1377-1 - Pro rata share.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 26 Internal Revenue 11 2014-04-01 2014-04-01 false Pro rata share. 1.1377-1 Section 1.1377-1...) INCOME TAXES (CONTINUED) Small Business Corporations and Their Shareholders 1.1377-1 Pro rata share. (a) Computation of pro rata shares(1) In general. For purposes of subchapter S of chapter 1 of the...

  9. 26 CFR 1.1377-1 - Pro rata share.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 26 Internal Revenue 11 2010-04-01 2010-04-01 true Pro rata share. 1.1377-1 Section 1.1377-1...) INCOME TAXES Small Business Corporations and Their Shareholders 1.1377-1 Pro rata share. (a) Computation of pro rata shares(1) In general. For purposes of subchapter S of chapter 1 of the...

  10. Pro-moieties of antimicrobial peptide prodrugs.

    PubMed

    Forde, Eanna; Devocelle, Marc

    2015-01-01

    Antimicrobial peptides (AMPs) are a promising class of antimicrobial agents that have been garnering increasing attention as resistance renders many conventional antibiotics ineffective. Extensive research has resulted in a large library of highly-active AMPs. However, several issues serve as an impediment to their clinical development, not least the issue of host toxicity. An approach that may allow otherwise cytotoxic AMPs to be used is to deliver them as a prodrug, targeting antimicrobial activity and limiting toxic effects on the host. The varied library of AMPs is complemented by a selection of different possible pro-moieties, each with their own characteristics. This review deals with the different pro-moieties that have been used with AMPs and discusses the merits of each. PMID:25591121

  11. Cryogenic system for BERLinPro

    SciTech Connect

    Anders, W.; Hellwig, A.; Knobloch, J.; Pflückhahn, D.; Rotterdam, S.

    2014-01-29

    In 2010 Helmholtz-Zentrum Berlin (HZB) received funding to design and build the Berlin Energy Recovery Linac Project BERLinPro. The goal of this compact Energy recovery linac (ERL) is to develop the accelerator physics and technology required to generate and accelerate a 100-mA, 1-mm mrad emittance electron beam. The BERLinPro know-how can then be transferred to various ERL-based applications. All accelerating RF cavities including the electron source are based on superconducting technology operated at 1.8 K. A Linde L700 helium liquefier is supplying 4.5 K helium. The subatmospheric pressure of 16 mbar of the helium bath of the cavities will be achieved by pumping with a set of cold compressors and warm vacuum pumps. While the L700 is already in operating, the 1.8 K system and the helium transfer system are in design phase.

  12. [Radiation Anticarcinogenesis by Thiazolidine Pro-drug

    NASA Technical Reports Server (NTRS)

    Warters, Raymond L.; Roberts, Jeanette C.; Fain, Heidi

    1999-01-01

    The original goal of this work was to determine the capacity of selected aminothiols to modulate radiation induced cytotoxicity, mutagenesis and carcinogenesis in a human mammary epithelial cell line. The conclusions from this work are that WR-1065 is the "gold standard" for protection against radiation induced cytotoxicity, mutagenesis and carcinogenesis. While a potent radiation protector, WR-1065 is cytotoxic in vitro and in vivo. Our rationale for a study of the thiazolidine pro-drugs was that these compounds are neither toxic in vitro or in vivo. The results obtained during this funding period indicate that the thiazolidine pro-drugs are as potent as WR-1065 as protectors against radiation induced mutation induction, and thus presumably against radiation induced carcinogenesis. Our results indicate that the thiazolidine prodrugs are excellent candidates to test as non-toxic anticarcinogens for protecting astronauts from cancer induction during space travel.

  13. Cryogenic system for BERLinPro

    NASA Astrophysics Data System (ADS)

    Anders, W.; Hellwig, A.; Knobloch, J.; Pflckhahn, D.; Rotterdam, S.

    2014-01-01

    In 2010 Helmholtz-Zentrum Berlin (HZB) received funding to design and build the Berlin Energy Recovery Linac Project BERLinPro. The goal of this compact Energy recovery linac (ERL) is to develop the accelerator physics and technology required to generate and accelerate a 100-mA, 1-mm mrad emittance electron beam. The BERLinPro know-how can then be transferred to various ERL-based applications. All accelerating RF cavities including the electron source are based on superconducting technology operated at 1.8 K. A Linde L700 helium liquefier is supplying 4.5 K helium. The subatmospheric pressure of 16 mbar of the helium bath of the cavities will be achieved by pumping with a set of cold compressors and warm vacuum pumps. While the L700 is already in operating, the 1.8 K system and the helium transfer system are in design phase.

  14. Abbott RealTime HBV Assay Is More Sensitive in Detection of Low Viral Load and Little Impacted by Drug Resistant Mutation in Chronic Hepatitis B Patients under Nucleot(s)ide Analogues Therapy

    PubMed Central

    Yeh, Ming-Lun; Huang, Chung-Feng; Huang, Ching-I; Liu, Shu-Fen; Yang, Hua-Ling; Hsieh, Ming-Yen; Huang, Jee-Fu; Dai, Chia-Yen; Chuang, Wan-Long; Yu, Ming-Lung

    2014-01-01

    Background Selection of drug-resistant strains may lead to failure of HBV antiviral therapy. There is little information whether there is detection difference in drug resistant mutations between different viral load assays of HBV. Objectives This study is aimed to investigate whether there is drug-resistant strains related detection difference between Abbott RealTime HBV (RealTime) and CobasAmpliPrep/CobasTaqMan HBV assays 2.0 (TaqMan). Study Design One hundred and thirty-four CHB patients who received HBV anti-viral therapy were enrolled. HBV virological markers were tested 3 months apart regularly. Serum HBV DNA levels were determined using the TaqMan and RealTime. YMDD (rt180M and rt204V) mutation was checked in patients who experienced virologic breakthrough (VBT). Results The correlation of HBV DNA observed between the RealTime and TaqMan was good for all 571 samples (R2 = 0.797; P<0.001). However, the correlation in the 434 samples with HBV DNA level <3 log10 IU/ml was not as good as in all samples (R2 = 0.457). Overall, 21.5% of samples had a detection difference of ≥1 log10 IU/ml with 91.9% of these having HBV DNA level <3 log10 IU/ml. Twenty-four patients experiencedVBT. Three of these patients had acquired the YMDD mutation and exhibited discordant viral load results between the two methods tested. In each case, persistent HBV DNA was detected by RealTime and undetectable with TaqMan. Of the patients who experienced a VBT and had acquired YMDD mutation, 4.7% had undetectable HBV DNA by TaqMan while all were detectable with RealTime. Conclusions RealTime assay is more sensitive and is little impacted by the development of drug resistant mutation. PMID:25000502

  15. Calibrating the Prominence Magnetometer (ProMag)

    NASA Astrophysics Data System (ADS)

    Fox, Lewis; Casini, R.

    2013-07-01

    The Prominence Magnetometer (ProMag) is a dual-channel, dual-beam, slit-scanning, full Stokes spectro-polarimeter designed by the High Altitude Observatory at the National Center for Atmospheric Research (HAO/NCAR) for the study of the magnetism of solar prominences and filaments. It was deployed in August 2009 at the 40 cm coronagraph of the Evans Solar Facility (ESF) of the National Solar Observatory on Sacramento Peak (NSO/SP). In its standard mode of operation it acquires spectro-polarimetric maps of solar targets simultaneously in the two chromospheric lines of He I at 587.6 nm and 1083.0 nm. Since August 2011 ProMag has operated in patrol mode with a dedicated observer. We aim to routinely measure the vector magnetic field in prominences. The electro-optic modulator and polarization analyzer are integrated into a single mechanical unit located at the coude feed of the telescope. This location was necessary for proper co-alignment of the dual beams, but complicates the precise polarimeter calibration necessary to achieve the sensitivity required for prominence measurements (< 10^-3). At this sensitivity, small variations in optical alignment can become significant. We present a calibration method for ProMag, using a polarizer and retarder at coronagraph prime focus. Calibrations are recorded before and after observations. We discuss the success of this method and its limitations.

  16. Sensitivity Analysis of a Conceptual HBV Ra?nfall-Runoff MODEL Using Eumetsat Snow Covered Area Product

    NASA Astrophysics Data System (ADS)

    Akyurek, Z.; Surer, S.; Parajka, J.

    2014-12-01

    HBV is a conceptual hydrological model extensively used in operational hydrological forecasting and water balance studies. In this study, we apply the HBV model on the upper Euphrates basin in Turkey, which has 10 624 km2 area. The Euphrates basin is largely fed from snow precipitation whereby nearly two-thirds occur in winter and may remain in the form of snow for half of the year. We analyze individual sensitivity of the parameters by calibrating the model using the Multi-Objective Shuffled Complex Evolution (MOSCEM) algorithm. The calibration is performed against snow cover area (SCA) in addition to runoff data for the water years 2009, 2010, 2011, 2012 and 2013. The SCA product has been developed in the framework of the European Organization for the Exploitation of Meteorological Satellites (EUMETSAT), Satellite Application Facility on Support to Operational Hydrology and Water Management (H-SAF) Project. The product is generated by using data from Spinning Enhanced Visible and InfraRed Imager (SEVIRI) instrument making observations from a geostationary satellite Meteosat Second Generation (MSG). In the previous study evaluation of the model was done with commonly used statistical performance metrics (Nash-Sutcliffe) for high and low flows, volume error and root mean square error (RMSE). In this study signature metrics, which are based on the flow duration curve (FDC) are used to see the performance of the model for low flows. In order to consider a fairly balanced evaluation between high and low flow phases we divided the flow duration curve into segments of high, medium and low flow phases, and additionally into very high and very low phases. Root mean square error (RMSE) is used to evaluate the performance in these segments. The sensitivity analysis of the parameters around the calibrated optimum points showed that parameters of the soil moisture and evapotranspiration (FC, beta and LPrat) have a strong effect in the total volume error of the model. The parameters from the response and transformation routines (LSUZ, K1, K0 and bmax) have a significant influence on the peak flows. It is observed that the parameters of snow routine (Tmelt, CSF and DDF) have strong effect in high flows and total volume. The parameters FC, K0, K1 And K2 are found to have effect on low flows from the signature metrics.

  17. A comparison of SRM and HBV models for real time runoff forecasting in the Upper Euphrates Basin, Turkey

    NASA Astrophysics Data System (ADS)

    Sorman, A.; Sensoy, A.; Gozel, E.; Yamankurt, E.; Sorman, U.

    2011-12-01

    Predicting snowmelt runoff in the mountainous eastern part of Turkey at a daily timescale is important in water resource management as it constitutes nearly 2/3 in volume of the total yearly runoff during spring and early summer months. Keeping track of snow dynamics and forecasting the amount and the timing of snowmelt runoff in the headwaters of the trans-boundary Euphrates River, where large dams are located, is a crucial and challenging task concerning the practical importance and great demand for real time forecasting of meltwater. In mountainous regions, data limitations prevent detailed understanding of the variability of snow cover and melt. In situ snowpack measurements are sparsely distributed relative to snowpack heterogeneity therefore to supplement ground measurement networks, remotely derived images of snow covered area (SCA) provides useful information for runoff prediction during the snowmelt season. SCA has been used as a direct input to hydrological models such as Snowmelt Runoff Model (SRM) or as a means of updating hydrologic model snowpack simulations and checking the internal validity of snowmelt runoff model as in the case of HBV model. Alternative ways of handling meltwater modeling using satellite derived SCA is discussed, with emphasis on the contrasting treatments in two widely used models, HBV and SRM. The greatest similarity between two models is that each uses a temperature index method to predict melt rate and the greatest difference between the models is in the way snow cover is handled. Moderate Resolution Imaging Spectroradiometer (MODIS) daily snow cover products with 500 m spatial resolution are used to derive SCA data in this study. Since the cloud obscuring problem degrades the use of satellites with optical sensors, a special combination and filtering methodology is used to reduce cloud coverage of the product. Both models are used to simulate runoff for the years 2003-2010 with model efficiency above 0.85 and volume difference around 2.5% and model parameters are calibrated in these applications. Finally, an operational snowmelt runoff forecasting is carried out for 2011 ablation season using numerical weather prediction Mesoscale Model 5 (MM5) data as forcing input variables. Discussion of results are supervised to reflect the general debates in hydrological modeling in terms of parameters and calibration, internal validation, the value and limitations of using satellite derived data.

  18. Perl Embedded in PTC's Pro/ENGINEER, Version 1

    SciTech Connect

    2003-12-22

    Pro-PERL (AKA Pro/PERL) is a Perl extension to the PTC Pro/TOOLKIT API to the PTC Pro/ENGINEER CAD application including an embedded interpreter. It can be used to automate and customize Pro/ENGINEER, create Vendor Neutral Archive (VNA) format files and re-create CAD models from the VNA files. This has applications in sanitizing classified CAD models created in a classified environment for transfer to an open environment, creating template models for modification to finished models by non-expert users, and transfer of design intent data to other modeling technologies.

  19. Perl Embedded in PTC's Pro/ENGINEER, Version 1

    Energy Science and Technology Software Center (ESTSC)

    2003-12-22

    Pro-PERL (AKA Pro/PERL) is a Perl extension to the PTC Pro/TOOLKIT API to the PTC Pro/ENGINEER CAD application including an embedded interpreter. It can be used to automate and customize Pro/ENGINEER, create Vendor Neutral Archive (VNA) format files and re-create CAD models from the VNA files. This has applications in sanitizing classified CAD models created in a classified environment for transfer to an open environment, creating template models for modification to finished models by non-expertmore » users, and transfer of design intent data to other modeling technologies.« less

  20. Freeze-Drying of Plant Tissue Containing HBV Surface Antigen for the Oral Vaccine against Hepatitis B

    PubMed Central

    Milczarek, Magdalena; Pajtasz-Piasecka, Elżbieta; Wietrzyk, Joanna

    2014-01-01

    The aim of this study was to develop a freeze-drying protocol facilitating successful processing of plant material containing the small surface antigen of hepatitis B virus (S-HBsAg) while preserving its VLP structure and immunogenicity. Freeze-drying of the antigen in lettuce leaf tissue, without any isolation or purification step, was investigated. Each process step was consecutively evaluated and the best parameters were applied. Several drying profiles and excipients were tested. The profile of 20°C for 20 h for primary and 22°C for 2 h for secondary drying as well as sucrose expressed efficient stabilisation of S-HBsAg during freeze-drying. Freezing rate and postprocess residual moisture were also analysed as important factors affecting S-HBsAg preservation. The process was reproducible and provided a product with VLP content up to 200 µg/g DW. Assays for VLPs and total antigen together with animal immunisation trials confirmed preservation of antigenicity and immunogenicity of S-HBsAg in freeze-dried powder. Long-term stability tests revealed that the stored freeze-dried product was stable at 4°C for one year, but degraded at elevated temperatures. As a result, a basis for an efficient freeze-drying process has been established and a suitable semiproduct for oral plant-derived vaccine against HBV was obtained. PMID:25371900

  1. Osteopontin and latent-TGF ? binding-protein 2 as potential diagnostic markers for HBV-related hepatocellular carcinoma.

    PubMed

    da Costa, Andre Nogueira; Plymoth, Amelie; Santos-Silva, Daniela; Ortiz-Cuaran, Sandra; Camey, Suzy; Guilloreau, Paule; Sangrajrang, Suleeporn; Khuhaprema, Thiravud; Mendy, Maimuna; Lesi, Olufunmilayo A; Chang, Hee-Kyung; Oh, Jin-Kyoung; Lee, Duk-Hee; Shin, Hai-Rim; Kirk, Gregory D; Merle, Philippe; Beretta, Laura; Hainaut, Pierre

    2015-01-01

    Chronic Hepatitis B (HB) is the main risk factor for chronic liver disease (CLD) and hepatocellular carcinoma (HCC) in many low-resource countries, where diagnosis is constrained by lack of clinical, histopathological and biomarker resources. We have used proteomics to detect plasma biomarkers that outperform ?-Fetoprotein (AFP), the most widely used biomarker for HCC diagnosis in low-resource contexts. Deep-plasma proteome analysis was performed in HCC patients, patients with CLD and in HB-carrier controls from Thailand (South-East Asia) and The Gambia (West-Africa). Mass spectrometry profiling identified latent-transforming growth factor ? binding-protein 2 (LTBP2) and Osteopontin (OPN) as being significantly elevated in HCC versus CLD and controls. These two proteins were further analyzed by ELISA in a total of 684 plasma samples, including 183 HCC, 274 CLD and 227 asymptomatic controls. When combined, LTBP2 and OPN showed an area under the receiver operating curve of 0.85 in distinguishing HCC from CLD in subjects with AFP <20 ng/mL. In a prospective cohort of 115 CLD patients from Korea, increased plasma levels of LTBP2 and/or OPN were detected in plasma collected over 2 years prior to diagnosis in 21 subjects who developed HCC. Thus, the combination of LTBP2 and OPN outperformed AFP for diagnosis and prediction of HCC and may therefore improve biomarker-based detection of HBV-related HCC. PMID:24803312

  2. Hot-spot mutations in HBV pre-C region in HBeAg-negative patients with severe hepatitis B.

    PubMed

    Lin, Yu-Long; Hou, Jin-Lin; Wang, Zhan-Hui; Sun, Jian; Yan, Li; Luo, Kang-Xian

    2001-01-01

    OBJECTIVE: To investigate the association of hot-spot mutations in hepatitis B virus (HBV) pre-C region with the occurrence and outcome of severe hepatitis B. METHODS: A total of 68 patients with severe hepatitis B negative for hepatits B e antigen (HBeAg) were enrolled in this study, including 6 cases of acute, 38 cases of subacute and 24 chronic severe hepatitis B, with another 44 HBeAg-positive patients with chronic hepatitis B serving as control. Mismatch PCR and restriction fragment length polymorphism analysis were employed to examine the mutations of T1862 and A1896 in this 2 groups of patients. RESULTS: The mutation rates at A1896 and T1862 were 66.7% (4/6) and 0 (0/6) respectively in acute severe hepatitis B cases, 42.1% (16/38) and 15.8% (6/38) in subacute severe hepatitis, 25.0% (6/24) and 16.7% (4/24) in chronic severe hepatitis, and 45.5% (20/24) and 2.3% (1/44) in chronic hepatitis cases. There were significant differences in terms of T1862 mutation between patients with severe hepatitis and chronic hepatitis (P<0.01). CONCLUSION: T1862 mutation is closely related to the exacerbation of chronic hepatitis, while the role of A1896 mutation in this process requires further investigation. PMID:12426191

  3. Aberrant expression and dysfunction of TLR2 and its soluble form in chronic HBV infection and its regulation by antiviral therapy.

    PubMed

    Huang, Zuxiong; Ge, Jun; Pang, Jinke; Liu, Hongyan; Chen, Jinjun; Liao, Baolin; Huang, Xuan; Zuo, Daming; Sun, Jian; Lu, Mengji; Zhang, Xiaoyong; Hou, Jinlin

    2015-06-01

    Toll-like receptor 2 (TLR2) plays an important role in the immunopathogenesis of hepatitis B virus (HBV) infection. The relationship between TLR2 expression and clinical outcome of chronic HBV infection is not yet elucidated in details so far. Here, we employed clinical cohorts to investigate TLR2 expression and function in different phases of HBV infection and dynamic changes of TLR2 expression in HBeAg-positive chronic hepatitis B (CHB) patients during antiviral therapy. TLR2 was mainly expressed in monocytes and its ligand stimulation resulted in TNF-?, IL-6 and IL-10 production. Serum soluble TLR2 (sTLR2) levels were negatively correlated with TLR2 mRNA in PBMCs. As compared with immunotolerant carriers and inactive carriers, CHB patients showed an elevated TLR2 expression and TNF-?, IL-6 induction in PBMC, but had a decreased level of sTLR2 in serum. However, TLR2 expression and TNF-? induction in monocytes of CHB patients remained lower than healthy controls. Furthermore, higher TLR2 expression in PBMCs and lower level of sTLR2 in serum at baseline were predictive of a complete response to 52 weeks of telbivudine (LdT) therapy. Temporal dynamic analysis showed that TLR2 expression was restored with viral suppression and ALT normalization from week 12 to 24. However, peg-IFN-?-2a therapy induced a slightly decline in TLR2 expression. In conclusion, TLR2 expression and function in monocytes were impaired by chronic HBV infection. Higher TLR2 expression in PBMC and lower level of sTLR2 in serum at baseline were associated with a complete response to LdT therapy, and dynamic TLR2 expression was differently regulated by LdT and peg-IFN-?-2a therapy. PMID:25771704

  4. [Analysis of the results of the HIV-1, HCV and HBV viral load of SEIMC External Quality Control Program. Year 2013].

    PubMed

    Orta Mira, Nieves; Del Remedio Guna Serrano, Mara; Latorre Martnez, Jos-Carlos; Medina Gonzlez, Rafael; Rosario Ovies, Mara; Poveda, Marta; Ruiz de Gopegui, Enrique; Gimeno Cardona, Concepcin

    2015-07-01

    Human immunodeficiency virus type 1 (HIV-1) and hepatitis B (HBV) and C virus (HCV) viral load determinations are among the most relevant markers for the follow up of patients infected with these viruses. External quality control tools are crucial to ensure the accuracy of results obtained by microbiology laboratories. This article summarized the results obtained from the 2013 SEIMC External Quality Control Programme for HIV-1, HCV, and HBV viral loads. In the HIV-1 program, a total of five standards were sent. One standard consisted in seronegative human plasma, while the remaining four contained plasma from three different viremic patients, in the range of 2-5 log10 copies/mL; two of these standards were identical aiming to determine repeatability. A significant proportion of the laboratories (25% on average) obtained values out of the accepted range (mean 0.25 log10 copies/mL), depending on the standard and on the method used for quantification. Repeatability was excellent, with up to 98.9% of laboratories reporting results within the limits (D < 0.5 log10 copies/mL). The HBV and HCV program consisted of two standards with different viral load contents. Most of the participants, 82% in the case of HCV and 78% in the HBV, obtained all the results within the accepted range (mean 1.96 SD log10 UI/mL). Data from this analysis reinforce the utility of proficiency programmes to ensure the quality of the results obtained by a particular laboratory, as well as the importance of the post-analytical phase on the overall quality. Due to the remarkable interlaboratory variability, it is advisable to use the same method and the same laboratory for patient follow up. PMID:26320990

  5. The Prevalence and Risk Factors of Hepatitis Delta Virus in HIV/HBV Co-Infected Patients in Shiraz, Iran, 2012.

    PubMed

    Motamedifar, Mohammad; Taheri, Mohammad; Lankarani, Kamran Bagheri; Gholami, Mina; Lari, Mahmood Amini; Faramarzi, Hossein; Sarvari, Jamal

    2015-09-01

    Evidence has shown that liver disease caused by hepatitis viruses can be more aggressive and severe in HIV infected subjects. Therefore, the present cross-sectional study aimed to evaluate the seroprevalence of HDV infection among HIV/HBV co-infected clients in Shiraz, southwest Iran. In this study, 178 patients co-infected with HBV and HIV individuals were enrolled. The diagnosis of HIV infection was documented based on serological assays. The demographic and complementary data were collected by a questionnaire. HBsAg and HDV Ab were detected by commercial quantitative enzyme linked immunosorbent assay kits according to the manufacturer's instructions. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were also measured. The mean age of the participants was 37.47.4 years (range 22-63). 175 (98.4 %) patients were male and 3 (1.6 %) were female. Among 178 patients co-infected with HIV/HBV, 35 cases (19.7%, 95% CI: 14%-25%) were anti-HDV? positive and 143 (80.3%) were negative for anti-HDV. HDV exposure in HIV/HBV co-infected patients was associated with blood transfusion (P=0.002, OR: 14.3) and prison history (P=0.01, OR: 2.31) but not with age, marital status, unsafe sex contact, and injection drug abuse. Our data showed a relatively high prevalence of HDV infection in HIV infected population in Shiraz, Iran. The high frequency of HDV Ab in patients with blood transfusion and prison history reveals that HDV transmission occurs more frequently in the parental route than sexual contacts; therefore, blood screening for HDV diagnosis in the high-risk group is recommended. PMID:26379352

  6. The Prevalence and Risk Factors of Hepatitis Delta Virus in HIV/HBV Co-Infected Patients in Shiraz, Iran, 2012

    PubMed Central

    Motamedifar, Mohammad; Taheri, Mohammad; Lankarani, Kamran Bagheri; Gholami, Mina; Lari, Mahmood Amini; Faramarzi, Hossein; Sarvari, Jamal

    2015-01-01

    Evidence has shown that liver disease caused by hepatitis viruses can be more aggressive and severe in HIV infected subjects. Therefore, the present cross-sectional study aimed to evaluate the seroprevalence of HDV infection among HIV/HBV co-infected clients in Shiraz, southwest Iran. In this study, 178 patients co-infected with HBV and HIV individuals were enrolled. The diagnosis of HIV infection was documented based on serological assays. The demographic and complementary data were collected by a questionnaire. HBsAg and HDV Ab were detected by commercial quantitative enzyme linked immunosorbent assay kits according to the manufacturers instructions. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were also measured. The mean age of the participants was 37.47.4 years (range 22-63). 175 (98.4 %) patients were male and 3 (1.6 %) were female. Among 178 patients co-infected with HIV/HBV, 35 cases (19.7%, 95% CI: 14%-25%) were anti-HDV? positive and 143 (80.3%) were negative for anti-HDV. HDV exposure in HIV/HBV co-infected patients was associated with blood transfusion (P=0.002, OR: 14.3) and prison history (P=0.01, OR: 2.31) but not with age, marital status, unsafe sex contact, and injection drug abuse. Our data showed a relatively high prevalence of HDV infection in HIV infected population in Shiraz, Iran. The high frequency of HDV Ab in patients with blood transfusion and prison history reveals that HDV transmission occurs more frequently in the parental route than sexual contacts; therefore, blood screening for HDV diagnosis in the high-risk group is recommended. PMID:26379352

  7. Inactivated ORF virus shows antifibrotic activity and inhibits human hepatitis B virus (HBV) and hepatitis C virus (HCV) replication in preclinical models.

    PubMed

    Paulsen, Daniela; Urban, Andreas; Knorr, Andreas; Hirth-Dietrich, Claudia; Siegling, Angela; Volk, Hans-Dieter; Mercer, Andrew A; Limmer, Andreas; Schumak, Beatrix; Knolle, Percy; Ruebsamen-Schaeff, Helga; Weber, Olaf

    2013-01-01

    Inactivated orf virus (iORFV), strain D1701, is a potent immune modulator in various animal species. We recently demonstrated that iORFV induces strong antiviral activity in animal models of acute and chronic viral infections. In addition, we found D1701-mediated antifibrotic effects in different rat models of liver fibrosis. In the present study, we compare iORFV derived from two different strains of ORFV, D1701 and NZ2, respectively, with respect to their antifibrotic potential as well as their potential to induce an antiviral response controlling infections with the hepatotropic pathogens hepatitis C virus (HCV) and hepatitis B virus (HBV). Both strains of ORFV showed anti-viral activity against HCV in vitro and against HBV in a transgenic mouse model without signs of necro-inflammation in vivo. Our experiments suggest that the absence of liver damage is potentially mediated by iORFV-induced downregulation of antigen cross-presentation in liver sinus endothelial cells. Furthermore, both strains showed significant anti-fibrotic activity in rat models of liver fibrosis. iORFV strain NZ2 appeared more potent compared to strain D1701 with respect to both its antiviral and antifibrotic activity on the basis of dosages estimated by titration of active virus. These results show a potential therapeutic approach against two important human liver pathogens HBV and HCV that independently addresses concomitant liver fibrosis. Further studies are required to characterize the details of the mechanisms involved in this novel therapeutic principle. PMID:24066148

  8. Managing HBV in pregnancy. Prevention, prophylaxis, treatment and follow-up: position paper produced by Australian, UK and New Zealand key opinion leaders.

    PubMed

    Visvanathan, Kumar; Dusheiko, Geoff; Giles, Michelle; Wong, May-Ling; Phung, Nghi; Walker, Susan; Le, Suong; Lim, Seng Gee; Gane, Ed; Ngu, Meng; Hardikar, Winita; Cowie, Ben; Bowden, Scott; Strasser, Simone; Levy, Miriam; Sasaduesz, Joe

    2016-02-01

    Hepatitis B during pregnancy presents unique management issues for both the mother and fetus. These include the lack of a current cohesive strategy for treatment and follow-up of mothers and their babies; the uncertain risk of postpartum HBV flares; the lack of randomised trial data on the safety and efficacy of antiviral treatment in pregnancy; the lack of head-to-head studies comparing different antivirals in pregnancy; and the lack of epidemiologic information regarding infection across different populations globally. This position paper provides a comprehensive review of the management of women with HBV infection prior to conception, throughout each stage of pregnancy and postpartum, as well as recommendations and clinical approaches for the follow-up of children born to infected mothers, based on available evidence in the literature and recommendations from international experts. Prevention of perinatal transmission is an important component of global efforts to reduce the burden of chronic HBV since vertical transmission is responsible for most of the chronic infection worldwide. PMID:26475631

  9. Immune memory to hepatitis B persists in children aged 7-8 years, who were vaccinated in infancy with 4 doses of hexavalent DTPa-HBV-IPV/Hib (Infanrix hexa) vaccine.

    PubMed

    Van Der Meeren, Olivier; Bleckmann, Gerhard; Crasta, Priya D

    2014-01-01

    Protection against hepatitis B disease relies on either protective serum antibodies or on the ability of the immune system to mount an anamnestic response when confronted with the hepatitis B virus (HBV). This open multicenter study (EUDRACT: 2010-022538-10) measured antibodies to HBV surface antigen (anti-HBs) in 7-8-year-old children who had received 4 doses of hexavalent diphtheria-tetanus-acellular pertussis-HBV-inactivated poliovirus-Hemophilus influenzae type b conjugate vaccine (DTPa-HBV-IPV/Hib: Infanrix hexa; GlaxoSmithKline Vaccines) in the first 2 years of life through routine vaccine services in Germany. The ability of these children to mount an anamnestic response to a challenge dose of monovalent HBV vaccine (Engerix B Kinder; GlaxoSmithKline Vaccines) was also assessed. Before the challenge dose, 78.5% of children had anti-HBs levels ?6.2 mIU/mL (seropositive) and 72.2% had anti-HBs levels ?10 mIU/mL (seroprotected). Post-challenge, 98.9% had anti-HBs levels ?10 mIU/mL and 95.8% had anti-HBs ?100 mIU/mL. An anamnestic response to the challenge was observed in 96.6% of all subjects. The challenge dose was well tolerated, with a reactogenicity and safety profile consistent with published data. DTPa-HBV-IPV/Hib induces long-lasting immune memory to HBV that appears very similar to that induced by monovalent HBV vaccines. Protection against hepatitis B may be conferred through immune memory in subjects who responded to primary vaccination, even when they subsequently lose detectable levels of circulating anti-HBs antibodies. PMID:24637296

  10. Photoelectron spectrum of PrO-

    NASA Astrophysics Data System (ADS)

    Kafader, Jared O.; Ray, Manisha; Jarrold, Caroline Chick

    2015-08-01

    The photoelectron (PE) spectrum of PrO- exhibits a short 835 20 cm-1 vibrational progression of doublets (210 30 cm-1 splitting) assigned to transitions from the 4f2 [3H4] ?6s2 ? = 4 anion ground state to the 4f2 [3H4] ?6s ? = 3.5 and 4.5 neutral states. This assignment is analogous to that of the recently reported PE spectrum of CeO-, though the 82 cm-1 splitting between the 4f [2F2.5] ?6s ? = 2 and ? = 3 CeO neutral states could not be resolved [Ray et al., J. Chem. Phys. 142, 064305 (2015)]. The origin of the transition to the ? = 3.5 neutral ground state is 0.96 0.01 eV, which is the adiabatic electron affinity of PrO. Density functional theory calculations on the anion and neutral molecules support the assignment. The appearance of multiple, irregularly spaced and low-intensity features observed ca. 1 eV above the ground state cannot be reconciled with low-lying electronic states of PrO that are accessible via one-electron detachment. However, neutral states correlated with the 4f2 [3H4] 5d superconfiguration are predicted to be approximately 1 eV above the 4f2 [3H4] ?6s ? = 3.5 neutral ground state, leading to the assignment of these features to shake-up transitions to the excited neutral states. Based on tentative hot band transition assignments, the term energy of the previously unobserved 4f2 [3H4] ?6s ? = 2.5 neutral state is determined to be 1840 110 cm-1.

  11. Educational Opportunities in Pro-Am Collaboration

    NASA Astrophysics Data System (ADS)

    Fienberg, R. T.; Stencel, R. E.

    2006-08-01

    While many backyard stargazers take up the hobby just for fun, many others are attracted to it because of their keen interest in learning more about the universe. The best way to learn science is to do science. Happily, the technology available to today's amateur astronomers — including computer-controlled telescopes, CCD cameras, powerful astronomical software, and the Internet — gives them the potential to make real contributions to scientific research and to help support local educational objectives. Meanwhile, professional astronomers are losing access to small telescopes as funding is shifted to larger projects, including survey programs that will soon discover countless interesting objects needing follow-up observations. Clearly the field is ripe with opportunities for amateurs, professionals, and educators to collaborate. Amateurs will benefit from mentoring by expert professionals, pros will benefit from observations and data processing by increasingly knowledgeable amateurs, and educators will benefit from a larger pool of skilled talent to help them carry out astronomy-education initiatives. We will look at some successful pro-am collaborations that have already borne fruit and examine areas where the need and/or potential for new partnerships is especially large. In keeping with the theme of this special session, we will focus on how pro-am collaborations in astronomy can contribute to science education both inside and outside the classroom, not only for students of school age but also for adults who may not have enjoyed particularly good science education when they were younger. Because nighttime observations with sophisticated equipment are not always possible in formal educational settings, we will also mention other types of pro-am partnerships, including those involving remote observing, data mining, and/or distributed computing.

  12. Establishment of Real Time Allele Specific Locked Nucleic Acid Quantitative PCR for Detection of HBV YIDD (ATT) Mutation and Evaluation of Its Application

    PubMed Central

    Wang, Wei; Su, Mingkuan; Lin, Jinpiao; Chen, Huijuan; Jiang, Ling; Chen, Jing; Yang, Bin; Ou, Qishui

    2014-01-01

    Background Long-term use of nucleos(t)ide analogues can increase risk of HBV drug-resistance mutations. The rtM204I (ATT coding for isoleucine) is one of the most important resistance mutation sites. Establishing a simple, rapid, reliable and highly sensitive assay to detect the resistant mutants as early as possible is of great clinical significance. Methods Recombinant plasmids for HBV YMDD (tyrosine-methionine-aspartate-aspartate) and YIDD (tyrosine-isoleucine-aspartate-aspartate) were constructed by TA cloning. Real time allele specific locked nucleic acid quantitative PCR (RT-AS-LNA-qPCR) with SYBR Green I was established by LNA-modified primers and evaluated with standard recombinant plasmids, clinical templates (the clinical wild type and mutant HBV DNA mixture) and 102 serum samples from nucleos(t)ide analogues-experienced patients. The serum samples from a chronic hepatitis B (CHB) patient firstly received LMV mono therapy and then switched to LMV + ADV combined therapy were also dynamically analyzed for 10 times. Results The linear range of the assay was between 1×109 copies/μl and 1×102 copies/μl. The low detection limit was 1×101 copies/μl. Sensitivity of the assay were 10−6, 10−4 and 10−2 in the wild-type background of 1×109 copies/μl, 1×107 copies/μl and 1×105 copies/μl, respectively. The sensitivity of the assay in detection of clinical samples was 0.03%. The complete coincidence rate between RT-AS-LNA-qPCR and direct sequencing was 91.2% (93/102), partial coincidence rate was 8.8% (9/102), and no complete discordance was observed. The two assays showed a high concordance (Kappa = 0.676, P = 0.000). Minor variants can be detected 18 weeks earlier than the rebound of HBV DNA load and alanine aminotransferase level. Conclusions A rapid, cost-effective, high sensitive, specific and reliable method of RT-AS-LNA-qPCR with SYBR Green I for early and absolute quantification of HBV YIDD (ATT coding for isoleucine) variants was established, which can provide valuable information for clinical antiretroviral regimens. PMID:24587198

  13. IRRIGATOR PRO 1.0 VS. IRRIGATOR PRO 2.0

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Irrigator Pro is an expert system marketed by the Peanut Foundation for scheduling irrigation and certain pest control practices for peanut production. Version 1.0 was developed using new concepts and different strategies for each of the 2 yield potentials, 3 variety (maturity) groups, 3 soil grou...

  14. Autophagy and the (Pro)renin Receptor

    PubMed Central

    Binger, Katrina J.; Muller, Dominik N.

    2013-01-01

    The (pro)renin receptor (PRR) is a newly reported member of the renin-angiotensin system (RAS); a hormonal cascade responsible for regulating blood pressure. Originally, identification of PRR was heralded as the next drug target of the RAS, of which such therapies would have increased benefits against target-organ damage and hypertension. However, in the years since its discovery, several conditional knockout mouse models of PRR have demonstrated an essential role for this receptor unrelated to the RAS and blood pressure. Specific deletion of PRR in podocytes or cardiomyocytes resulted in the rapid onset of organ failure and subsequently animal mortality after only a matter of weeks. In both cell types, loss of PRR resulted in the intracellular accumulation of autophagosomes and misfolded proteins, indicating a disturbance in autophagy. In light of the fact that the majority of PRR is located intracellularly, this molecular function appears to be more relevant than its ability to bind to high, non-physiological concentrations of (pro)renin. This review will focus on the role of PRR in autophagy and its importance in maintaining cellular homeostasis. Understanding the link between PRR, autophagy and how its loss results in cell death will be essential for deciphering its role in physiology and pathology. PMID:24155743

  15. Communicating stigma: the pro-ana paradox.

    PubMed

    Yeshua-Katz, Daphna; Martins, Nicole

    2013-01-01

    This study explores the personal experience of pro-ana bloggers, members of an online community for people with eating disorders. Using Erving Goffman's work on stigma, this study explores the motivations, benefits, and drawbacks of blogging about a stigmatized mental illness, as taken from the bloggers' own perceptive. We conducted 33 interviews with bloggers from seven different countries via phone, Skype, and e-mail. Participants were motivated to blog because they found social support, a way to cope with a stigmatized illness, and means of self-expression. Participants described blogging as a cathartic experience and perceived the social support they received from other members of the pro-ana community as a benefit. The fear that the eating disorder will be revealed if the blog is exposed and the concern that the blog encourages disordered eating were the perceived negative consequences of maintaining such a blog. Thus, blogging about anorexia serves to both alleviate and trigger anxiety about living with this stigmatized illness. Recommendations for future research are made. PMID:22873763

  16. Pro-neurotrophins, sortilin, and nociception

    PubMed Central

    Lewin, Gary R; Nykjaer, Anders

    2014-01-01

    Nerve growth factor (NGF) signaling is important in the development and functional maintenance of nociceptors, but it also plays a central role in initiating and sustaining heat and mechanical hyperalgesia following inflammation. NGF signaling in pain has traditionally been thought of as primarily engaging the classic high-affinity receptor tyrosine kinase receptor TrkA to initiate sensitization events. However, the discovery that secreted proforms of nerve NGF have biological functions distinct from the processed mature factors raised the possibility that these proneurotrophins (proNTs) may have distinct function in painful conditions. ProNTs engage a novel receptor system that is distinct from that of mature neurotrophins, consisting of sortilin, a type I membrane protein belonging to the VPS10p family, and its co-receptor, the classic low-affinity neurotrophin receptor p75NTR. Here, we review how this new receptor system may itself function with or independently of the classic TrkA system in regulating inflammatory or neuropathic pain. PMID:24494677

  17. Pro-Anorexia and Anti-Pro-Anorexia Videos on YouTube: Sentiment Analysis of User Responses

    PubMed Central

    Garcia, David; Sirola, Anu; Näsi, Matti; Kaakinen, Markus; Keipi, Teo; Räsänen, Pekka

    2015-01-01

    Background Pro-anorexia communities exist online and encourage harmful weight loss and weight control practices, often through emotional content that enforces social ties within these communities. User-generated responses to videos that directly oppose pro-anorexia communities have not yet been researched in depth. Objective The aim was to study emotional reactions to pro-anorexia and anti-pro-anorexia online content on YouTube using sentiment analysis. Methods Using the 50 most popular YouTube pro-anorexia and anti-pro-anorexia user channels as a starting point, we gathered data on users, their videos, and their commentators. A total of 395 anorexia videos and 12,161 comments were analyzed using positive and negative sentiments and ratings submitted by the viewers of the videos. The emotional information was automatically extracted with an automatic sentiment detection tool whose reliability was tested with human coders. Ordinary least squares regression models were used to estimate the strength of sentiments. The models controlled for the number of video views and comments, number of months the video had been on YouTube, duration of the video, uploader’s activity as a video commentator, and uploader’s physical location by country. Results The 395 videos had more than 6 million views and comments by almost 8000 users. Anti-pro-anorexia video comments expressed more positive sentiments on a scale of 1 to 5 (adjusted prediction [AP] 2.15, 95% CI 2.11-2.19) than did those of pro-anorexia videos (AP 2.02, 95% CI 1.98-2.06). Anti-pro-anorexia videos also received more likes (AP 181.02, 95% CI 155.19-206.85) than pro-anorexia videos (AP 31.22, 95% CI 31.22-37.81). Negative sentiments and video dislikes were equally distributed in responses to both pro-anorexia and anti-pro-anorexia videos. Conclusions Despite pro-anorexia content being widespread on YouTube, videos promoting help for anorexia and opposing the pro-anorexia community were more popular, gaining more positive feedback and comments than pro-anorexia videos. Thus, the anti-pro-anorexia content provided a user-generated counterforce against pro-anorexia content on YouTube. Professionals working with young people should be aware of the social media dynamics and versatility of user-generated eating disorder content online. PMID:26563678

  18. The representation of protein complexes in the Protein Ontology (PRO)

    PubMed Central

    2011-01-01

    Background Representing species-specific proteins and protein complexes in ontologies that are both human- and machine-readable facilitates the retrieval, analysis, and interpretation of genome-scale data sets. Although existing protin-centric informatics resources provide the biomedical research community with well-curated compendia of protein sequence and structure, these resources lack formal ontological representations of the relationships among the proteins themselves. The Protein Ontology (PRO) Consortium is filling this informatics resource gap by developing ontological representations and relationships among proteins and their variants and modified forms. Because proteins are often functional only as members of stable protein complexes, the PRO Consortium, in collaboration with existing protein and pathway databases, has launched a new initiative to implement logical and consistent representation of protein complexes. Description We describe here how the PRO Consortium is meeting the challenge of representing species-specific protein complexes, how protein complex representation in PRO supports annotation of protein complexes and comparative biology, and how PRO is being integrated into existing community bioinformatics resources. The PRO resource is accessible at http://pir.georgetown.edu/pro/. Conclusion PRO is a unique database resource for species-specific protein complexes. PRO facilitates robust annotation of variations in composition and function contexts for protein complexes within and between species. PMID:21929785

  19. Pro-sociality and strategic reasoning in economic decisions

    PubMed Central

    Arruñada, Benito; Casari, Marco; Pancotto, Francesca

    2015-01-01

    We study the relationship between pro-social preferences and strategic reasoning. These aspects are typically studied separately but little is known about their joint distribution. In an experiment, for each participant we elicit individual concerns toward pro-sociality—inequality aversion and efficiency—as well as the number of steps of reasoning through a guessing game. We report that self-regarding and pro-social participants exhibit similar levels of strategic reasoning, which supports the view that pro-sociality and strategic reasoning can be studied independently. PMID:26074799

  20. Pro-sociality and strategic reasoning in economic decisions.

    PubMed

    Arruada, Benito; Casari, Marco; Pancotto, Francesca

    2015-01-01

    We study the relationship between pro-social preferences and strategic reasoning. These aspects are typically studied separately but little is known about their joint distribution. In an experiment, for each participant we elicit individual concerns toward pro-sociality-inequality aversion and efficiency-as well as the number of steps of reasoning through a guessing game. We report that self-regarding and pro-social participants exhibit similar levels of strategic reasoning, which supports the view that pro-sociality and strategic reasoning can be studied independently. PMID:26074799

  1. Pro-eating disorder websites: users' opinions.

    PubMed

    Csipke, Emese; Horne, Outi

    2007-05-01

    The phenomenon of 'pro-eating disorder' websites remains relatively unexplored by researchers in published formats. Supporters of the sites claim beneficial effects but health professionals worry that the sites propagate disordered behaviours. The present study addressed visitor characteristics and perceived impact of visits. A 24-item questionnaire supplemented with the Eating Attitudes Test-26 (EAT-26) was developed and posted on the website of the UK mental health charity SANE. Participants who interacted with others on the sites and sought emotional support reported improved mental state after visiting, and for them, evidence was found of reduced impact from potentially damaging content. 'Silent browsing' in order to sustain a disorder was found to be mainly harmful. 'Silent browsers' may be particularly vulnerable to a worsening of their symptoms in the absence of beneficial effects from emotional support, but those who interact and find support could face a danger of a different sort. PMID:17676689

  2. Autophagy as a pro-death pathway.

    PubMed

    Denton, Donna; Xu, Tianqi; Kumar, Sharad

    2015-01-01

    The evolutionarily conserved catabolic process of autophagy involves the degradation of cytoplasmic components through lysosomal enzymes. Basal levels of autophagy maintain cellular homeostasis and under stress conditions high levels of autophagy are induced. It is often under such stress conditions that high levels of autophagy and cell death have been observed, leading to the idea that autophagy may act as an executioner of cell death. However the notion of autophagy as a cell death mechanism has been controversial and remains mechanistically undefined. There is now growing evidence that in specific contexts autophagy can indeed facilitate cell death. The pro-death role of autophagy is however complicated due to the extensive cross-talk between different signalling pathways. This review summarises the examples of where autophagy acts as a means of cell death and discusses the association of autophagy with the different cell death pathways. PMID:25331550

  3. French Pro/Am collaborations in exoplanet

    NASA Astrophysics Data System (ADS)

    Santerne, A.; Moutou, C.; Vanhuysse, M.; Bouchy, F.; Buil, C.; Cochard, F.; Thizy, O.; Martinez, P.; Desnoux, V.; Pujol, M.; Colas, F.

    2011-10-01

    Amateur astronomers have access to huge telescope time and can reach photometric precision up to a few mmag as well as radial velocity precision up to 50m.s-1 on brightest stars. We will first present some results of french amateur astronomers in transit photometry and radial velocity and then, we will present an over-view of all the collaborations which can be done between professional and amateur astronomers in the competitive exoplanet domain, and especially the current collaboration between french Pro & Am astronomers which was used in publication in A&A. Finally, we will present a new internet wiki page which goal is to develop such collaboration in different countries.

  4. Emergence of lamivudine resistance hepatitis B virus mutations in pregnant women infected with HBV and HIV receiving antiretroviral prophylaxis for the prevention of mother-to-infant transmission in Malawi.

    PubMed

    Galluzzo, Clementina; Liotta, Giuseppe; Andreotti, Mauro; Luhanga, Richard; Jere, Haswell; Mancinelli, Sandro; Maulidi, Martin; Sagno, Jean-Baptiste; Pirillo, Maria; Erba, Fulvio; Amici, Roberta; Ceffa, Susanna; Marazzi, Maria Cristina; Vella, Stefano; Palombi, Leonardo; Giuliano, Marina

    2012-10-01

    HIV/HBV co-infection is highly prevalent in sub-Saharan Africa. The aim of this study was to determine if the use of triple combination lamivudine-containing prophylaxis for the prevention of mother-to-infant HIV transmission was associated with the emergence of lamivudine HBV mutations. The study included 21 pregnant co-infected women in Malawi who received either zidovudine or stavudine plus lamivudine and nevirapine from week 25 of gestation until 6 months after delivery or indefinitely if they met the criteria for treatment (CD4+ <350/mm(3)). HBV-DNA was determined using the Roche COBAS assay. Resistance mutations were assessed by the Trugene assay (Siemens Diagnostics). At baseline 33% of the women were HBeAg positive and had HBV-DNA > 10(4) IU/ml. Median CD4 count was 237 cells/mm(3) and median HIV-RNA was 3.8 log(10) copies/ml. After a median of 259 days of treatment, HBV-DNA was detectable in 9 out of 21 patients (42.8%). In three cases the HBV-DNA level was >10(4) IU/ml. Resistance mutations (M204I in five cases and L180M + M204I/V in one case) were present in 6 (28.6%) patients. Women with a resistant virus had significantly higher baseline HBV-DNA levels than those not developing resistance (1.1 10(7) IU/ml vs. 20.8 IU/ml, P = 0.022). Levels of ALT and AST were higher in women with resistant viruses compared to those retaining a wild-type virus. A high rate of lamivudine resistance was seen in this cohort of pregnant women. Follow-up of these patients will clarify if the presence of resistance has a significant impact on liver disease. PMID:22930502

  5. Is it necessary to delay antiviral therapy for 3-6 months to anticipate HBeAg seroconversion in patients with HBeAg-positive chronic hepatitis B in endemic areas of HBV genotype C?

    PubMed Central

    Cho, Yoo-Kyung; Jwa, Hyeyoung; Choi, Eun Kwang; Kim, Heung Up; Song, Hyun Joo; Na, Soo-Young; Boo, Sun-Jin; Jeong, Seung Uk

    2014-01-01

    Background/Aims Spontaneous HBeAg seroconversion occurs frequently in the immune reactive phase in HBeAg-positive chronic hepatitis B (CHB). Therefore, observation for 3-6 months before commencing antiviral therapy is recommended in patients with alanine aminotransferase (ALT) levels that exceed twice the upper limit of normal (ULN). However, HBeAg seroconversion occurs infrequently in patients infected with hepatitis B virus (HBV) genotype C. The aim of the present study was to determine whether the waiting policy is necessary in endemic areas of HBV genotype C infection. Methods Ninety patients with HBeAg-positive CHB were followed prospectively without administering antiviral therapy for 6 months. Antiviral therapy was initiated promptly at any time if there was any evidence of biochemical (i.e., acute exacerbation of HBV infection or aggravation of jaundice) or symptomatic deterioration. After 6 months of observation, antiviral therapy was initiated according to the patient's ALT and HBV DNA levels. Results Only one patient (1.1%) achieved spontaneous HBeAg seroconversion. Biochemical and symptomatic deterioration occurred before 6 months in 17 patients (18.9%) and 5 patients, respectively. High ALT and HBV DNA levels were both independent risk factors for biochemical deterioration. Of 15 patients with HBV DNA ≥5.1×107 IU/mL and ALT ≥5×ULN, biochemical deterioration occurred in 7 (46.7%), including 1 patient receiving liver transplantation due to liver failure. Conclusions Spontaneous HBeAg seroconversion in patients with HBeAg-positive CHB is rare within 6 months. Biochemical deterioration was common and may lead to liver failure. Immediate antiviral therapy should be considered, especially in patients with high ALT and HBV DNA levels in endemic areas of genotype C infection. PMID:25548741

  6. Pro-death and pro-survival properties of ouabain in U937 lymphoma derived cells

    PubMed Central

    2012-01-01

    Background Epidemiological studies revealed significantly lower mortality rates in cancer patients receiving cardiac glycosides, which turned on interest in the anticancer properties of these drugs. However, cardiac glycosides have also been shown to stimulate cell growth in several cell types. In the present investigation we analyzed the pro-death and pro-survival properties of ouabain in the human lymphoma derived cell line U937. Methods ROS, intracellular Ca++, cell cycle were evaluated by loading the cells with fluorescent probes under cytofluorimetry. Cell counts and evaluation of trypan blue-excluding cells were performed under optic microscope. Protein detection was done by specific antibodies after protein separation from cellular lysates by SDS-PAGE and transfer blot. Results High doses of ouabain cause ROS generation, elevation of [Ca++]i and death of lymphoma derived U937 cells. Lower doses of OUA activate a survival pathway in which plays a role the Na+/Ca++-exchanger (NCX), active in the Ca++ influx mode rather than in the Ca++ efflux mode. Also p38 MAPK plays a pro-survival role. However, the activation of this MAPK does not appear to depend on NCX. Conclusion This investigation shows that the cardiac glycoside OUA is cytotoxic also for the lymphoma derived cell line U937 and that can activate a survival pathway in which are involved NCX and p38 MAPK. These molecules can represent potential targets of combined therapy. PMID:23153195

  7. Pro-Market Educational Governance: Is Argentina a Black Swan?

    ERIC Educational Resources Information Center

    Beech, Jason; Barrenechea, Ignacio

    2011-01-01

    In this article we explore ways in which pro-market discourses have been interpreted in policy initiatives in Argentina since the 1970s. Our argument is that even though pro-market discourses have guided reforms in many aspects of public policies in Argentina, the arena of education has overall been resistant to taking them up. The first part of…

  8. 48 CFR 352.237-70 - Pro-Children Act.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 48 Federal Acquisition Regulations System 4 2012-10-01 2012-10-01 false Pro-Children Act. 352.237...-Children Act. As prescribed in 337.103-70(a), the Contracting Officer shall insert the following clause: Pro-Children Act (January 2006) (a) Public Law 103-227, Title X, Part C, also known as the...

  9. 48 CFR 352.237-70 - Pro-Children Act.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 48 Federal Acquisition Regulations System 4 2010-10-01 2010-10-01 false Pro-Children Act. 352.237...-Children Act. As prescribed in 337.103-70(a), the Contracting Officer shall insert the following clause: Pro-Children Act (January 2006) (a) Public Law 103-227, Title X, Part C, also known as the...

  10. 48 CFR 352.237-70 - Pro-Children Act.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 48 Federal Acquisition Regulations System 4 2011-10-01 2011-10-01 false Pro-Children Act. 352.237...-Children Act. As prescribed in 337.103-70(a), the Contracting Officer shall insert the following clause: Pro-Children Act (January 2006) (a) Public Law 103-227, Title X, Part C, also known as the...

  11. 48 CFR 352.237-70 - Pro-Children Act.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 48 Federal Acquisition Regulations System 4 2014-10-01 2014-10-01 false Pro-Children Act. 352.237...-Children Act. As prescribed in 337.103-70(a), the Contracting Officer shall insert the following clause: Pro-Children Act (January 2006) (a) Public Law 103-227, Title X, Part C, also known as the...

  12. 48 CFR 352.237-70 - Pro-Children Act.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 48 Federal Acquisition Regulations System 4 2013-10-01 2013-10-01 false Pro-Children Act. 352.237...-Children Act. As prescribed in 337.103-70(a), the Contracting Officer shall insert the following clause: Pro-Children Act (January 2006) (a) Public Law 103-227, Title X, Part C, also known as the...

  13. 17 CFR 210.8-05 - Pro forma financial information.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... FORM AND CONTENT OF AND REQUIREMENTS FOR FINANCIAL STATEMENTS, SECURITIES ACT OF 1933, SECURITIES... Statements of Smaller Reporting Companies § 210.8-05 Pro forma financial information. (a) Pro forma information showing the effects of the acquisition shall be furnished if financial statements of a...

  14. Pro-Market Educational Governance: Is Argentina a Black Swan?

    ERIC Educational Resources Information Center

    Beech, Jason; Barrenechea, Ignacio

    2011-01-01

    In this article we explore ways in which pro-market discourses have been interpreted in policy initiatives in Argentina since the 1970s. Our argument is that even though pro-market discourses have guided reforms in many aspects of public policies in Argentina, the arena of education has overall been resistant to taking them up. The first part of

  15. Body composition of transgenic pigs expressing the myostatin pro domain

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Previous results have shown that male mice expressing a myostatin pro domain construct (MLC-Pro) have increased body weight, more total body lean mass, and lower percentage of total body fat. Founder transgenic (TG) pigs were generated by standard pronuclear microinjection techniques using the sam...

  16. Peanuts & Crackerjacks: Economics of Pro Team Sports. Teacher's Guide.

    ERIC Educational Resources Information Center

    Federal Reserve Bank of Boston, MA.

    This teacher's guide presents instructional materials which examine issues in professional sports for students in high school economics and social studies classes. The issues include how the pro sports market evolved; how leagues gained market power; why athletes earn as much as they do; what are the sources of pro sports revenues; why tickets…

  17. 19 CFR 122.74 - Incomplete (pro forma) manifest.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 19 Customs Duties 1 2010-04-01 2010-04-01 false Incomplete (pro forma) manifest. 122.74 Section 122.74 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT OF HOMELAND SECURITY; DEPARTMENT... Aircraft Departing From the United States 122.74 Incomplete (pro forma) manifest. (a)...

  18. ProPSA Test for Detection of Prostate Cancer Validated

    Cancer.gov

    Past studies have found a form of free PSA, called proenzyme PSA (pro-PSA), to be elevated in cancerous prostate tissue. Results from a multi-center study, supported by the NCI Early Detection Research Network (EDRN), have validated proPSA as a detector o

  19. Ethical Dilemmas of Providing Pro Bono Art Therapy

    ERIC Educational Resources Information Center

    Moon, Bruce L.

    2011-01-01

    This viewpoint addresses ethical questions regarding the provision of art therapy as a pro bono service, a term from Latin roots that mean "for the public good." Approaches to ethical reasoning are discussed using the case of pro bono art therapy in a residential treatment program for adolescents.

  20. Upregulation of Circulating PD-L1/PD-1 Is Associated with Poor Post-Cryoablation Prognosis in Patients with HBV-Related Hepatocellular Carcinoma

    PubMed Central

    Zhang, Min-Na; Chen, Yan; Chang, Xiu-Juan; Lu, Yin-Ying; Bai, Wen-Lin; Qu, Jian-Hui; Wang, Chun-Ping; Wang, Hong; Lou, Min; Wang, Fu-Sheng; Lv, Ji-Yun; Yang, Yong-Ping

    2011-01-01

    Background The programmed cell death-1 receptor/programmed cell death-1 ligand (PD-1/PD-L1) pathway plays a crucial role in tumor evasion from host immunity. This study was designed to evaluate the association between circulating PD-L1/PD-1 and prognosis after cryoablation in patients with HBV-related hepatocellular carcinoma (HCC). Methodology/Principal Findings In the present study, 141 HBV-related HCC patients were enrolled and of those 109 patients received cryoablation. Circulating PD-L1/PD-1 expression was tested by flow cytometry, and 23 patients were simultaneously evaluated for intratumoral PD-L1 expression by immunohistochemical staining. Circulating PD-1/PD-L1 expression was associated with severity of diseases in patients with HCC, and the circulating PD-L1 expression was closely correlated with intratumoral PD-L1 expression. Of the clinical parameters, PD-1/PD-L1 expression was associated with tumor size, blood vessel invasion and BCLC staging. Moreover, PD-1/PD-L1 expression dropped after cryoablation while being elevated at the time of tumor recurrence. Patients with higher expression of circulating PD-L1, as well as circulating PD-1, had a significantly shorter overall survival and tumor-free survival than those with lower expression. Multivariate analysis confirmed that circulating PD-L1 could serve as an independent predictor of overall survival and tumor-recurrence survival in HCC patients after cryoablation. Conclusions/Significance Upregulation of circulating PD-L1/PD-1 is associated with poor post-cryoablation prognosis in patients with HBV-related hepatocellular carcinoma. PMID:21912640

  1. Artificial Liver Support System Improves Short- and Long-Term Outcomes of Patients With HBV-Associated Acute-on-Chronic Liver Failure

    PubMed Central

    Qin, Gang; Shao, Jian-Guo; Wang, Bin; Shen, Yi; Zheng, Jian; Liu, Xian-Jin; Zhang, You-Yi; Liu, Yan-Mei; Qin, Yan; Wang, Lu-Jun

    2014-01-01

    Abstract For patients with acute-on-chronic liver failure (ACLF), artificial liver support system (ALSS) may help prolong lifespan and function as a bridge to liver transplantation (LT), but data on its long-term benefit are lacking. We conducted this prospective, controlled study to determine the efficacy of ALSS and the predictors of mortality in patients with hepatitis B virus (HBV)-associated ACLF. From January 2003 to December 2007, a total of 234 patients with HBV-associated ACLF not eligible for LT were enrolled in our study. They were allocated to receive either plasma exchange centered ALSS plus standard medical therapy (SMT) (ALSS group, n?=?104) or SMT alone (control group, n?=?130). All the patients were followed-up for at least 5 years, or until death. At 90 days, the survival rate of ALSS group was higher than that of the control group (62/104 [60%] vs 61/130 [47%], respectively; P?HBV-associated ACLF. PMID:25526495

  2. Prevalence of National Responsiveness to HBV Vaccine After 22 Years of Iranian Expanded Program on Immunization (EPI): A Systematic Review and Meta-Analysis Study

    PubMed Central

    Rezaee, Reza; Aghcheli, Bahman; Poortahmasebi, Vahdat; Qorbani, Mostafa; Alavian, Seyed Moayed; Jazayeri, Seyed Mohammad

    2015-01-01

    Context: Hepatitis B Virus expanded program on immunization (EPI) started on 1993 in Iran. Most surveys have assessed the level of response to vaccine by measuring the titers of anti-HBs. This meta- analysis aimed to summarize the Iranian published data on the rate of vaccine-responders versus non-responders. Moreover, the impact of variables such as age, gender, type of vaccine, etc. on the levels of responsiveness was evaluated. Evidence Acquisition: All published papers on this topic in Iranian and international journals with affiliation of Iran were reviewed using standard keywords up to 2014. We included our study to healthy participants with no previous HBV infection and who had already received a complete course of HB vaccine. The estimated prevalence and 95% confidence intervals in 28 eligible articles for HBV vaccine responders (anti-HBs > 10 IU/mL) and non-responders (10 <) were analyzed by random effect method due to between-study heterogeneity. Results: The age of subjects was between 6 months and 15 years old. Overall, 5991 (51.5%) were male and 4571 (48.5%) females. Overall, 80% were responders to vaccine versus 20% nonresponders. With increase in age, the number of responders to vaccine decreased significantly (P = 0.001). There was no strong difference between responders versus nonresponders to vaccine for gender, types of vaccine, ethnicity and living area. Conclusions: The results arose from this meta-analysis highlighted the safety of vaccine and its effectiveness in stimulating immune response of vaccines, despite being different in generation, manufacturers and types. Moreover, there was no substantial difference between Iranian and other international investigations in the rate of nonresponsiveness to HBV vaccine. PMID:26045701

  3. Genomic Methylation Inhibits Expression of Hepatitis B Virus Envelope Protein in Transgenic Mice: A Non-Infectious Mouse Model to Study Silencing of HBV Surface Antigen Genes

    PubMed Central

    Graumann, Franziska; Churin, Yuri; Tschuschner, Annette; Reifenberg, Kurt; Glebe, Dieter; Roderfeld, Martin; Roeb, Elke

    2015-01-01

    Objective The Hepatitis B virus genome persists in the nucleus of virus infected hepatocytes where it serves as template for viral mRNA synthesis. Epigenetic modifications, including methylation of the CpG islands contribute to the regulation of viral gene expression. The present study investigates the effects of spontaneous age dependent loss of hepatitis B surface protein- (HBs) expression due to HBV-genome specific methylation as well as its proximate positive effects in HBs transgenic mice. Methods Liver and serum of HBs transgenic mice aged 5–33 weeks were analyzed by Western blot, immunohistochemistry, serum analysis, PCR, and qRT-PCR. Results From the third month of age hepatic loss of HBs was observed in 20% of transgenic mice. The size of HBs-free area and the relative number of animals with these effects increased with age and struck about 55% of animals aged 33 weeks. Loss of HBs-expression was strongly correlated with amelioration of serum parameters ALT and AST. In addition lower HBs-expression went on with decreased ER-stress. The loss of surface protein expression started on transcriptional level and appeared to be regulated epigenetically by DNA methylation. The amount of the HBs-expression correlated negatively with methylation of HBV DNA in the mouse genome. Conclusions Our data suggest that methylation of specific CpG sites controls gene expression even in HBs-transgenic mice with truncated HBV genome. More important, the loss of HBs expression and intracellular aggregation ameliorated cell stress and liver integrity. Thus, targeted modulation of HBs expression may offer new therapeutic approaches. Furthermore, HBs-transgenic mice depict a non-infectious mouse model to study one possible mechanism of HBs gene silencing by hypermethylation. PMID:26717563

  4. The Association between Preoperative Serum C-Reactive Protein and Hepatocellular Carcinoma Recurrence in Patients with Chronic Hepatitis B Virus (HBV) Infection—A Retrospective Study

    PubMed Central

    Zhao, Xiaoming; Luo, Jingyu; Li, Bobo; Liu, Shuguang; Li, Daotang

    2015-01-01

    The prognosis of the patients with hepatocellular carcinoma (HCC) recurrence following curative hepatectomy is usually dismal. Whether preoperative serum C-reactive protein (CRP) can predict the recurrence of HCC in patients with chronic HBV infection is not clear. Total 232 patients with chronic HBV infection were included in this retrospective study. We investigated the association between detailed preoperative serum CRP levels and early (≤ 2 year) and late (> 2 year) HCC recurrence following curative hepatectomy. After adjusting for potential confounders, we found a saturation effect for preoperative serum CRP of 2.1 mg/dl existed for early HCC recurrence (ER). The incidence of ER increased with preoperative serum CRP less than 2.1 mg/dl (OR = 3.5, 95% CI 1.6–7.6, P = 0.001), and higher preoperative serum CRP (>2.1 mg/dl) did not increase the incidence of ER (OR = 0.8, 95% CI 0.2–2.7, P = 0.703). Whereas there is a linear relationship between preoperative serum CRP and late HCC recurrence (LR) (OR = 0.2, 95% CI, 0.1- 0.4) (OR = 1.8, 95% CI, 1.2–2.5, P = 0.002). In addition, the optimal cutoff point for serum CRP level was 1.5 mg/dl, instead of 1.0 mg/dl, in predicting both ER and LR. Patients with higher preoperative serum CRP level (>1.5 mg/dl) had lower recurrence free survival rates and overall survival rates (P<0.01). These results suggest that preoperative serum CRP played different roles on ER and LR following curative hepatectomy, thus further predictingthe prognosis in patients with chronic HBV infection. PMID:25602444

  5. The association between preoperative serum C-reactive protein and hepatocellular carcinoma recurrence in patients with chronic hepatitis B virus (HBV) infection--a retrospective study.

    PubMed

    Zhao, Xiaoming; Luo, Jingyu; Li, Bobo; Liu, Shuguang; Li, Daotang

    2015-01-01

    The prognosis of the patients with hepatocellular carcinoma (HCC) recurrence following curative hepatectomy is usually dismal. Whether preoperative serum C-reactive protein (CRP) can predict the recurrence of HCC in patients with chronic HBV infection is not clear. Total 232 patients with chronic HBV infection were included in this retrospective study. We investigated the association between detailed preoperative serum CRP levels and early (≤ 2 year) and late (> 2 year) HCC recurrence following curative hepatectomy. After adjusting for potential confounders, we found a saturation effect for preoperative serum CRP of 2.1 mg/dl existed for early HCC recurrence (ER). The incidence of ER increased with preoperative serum CRP less than 2.1 mg/dl (OR = 3.5, 95% CI 1.6-7.6, P = 0.001), and higher preoperative serum CRP (>2.1 mg/dl) did not increase the incidence of ER (OR = 0.8, 95% CI 0.2-2.7, P = 0.703). Whereas there is a linear relationship between preoperative serum CRP and late HCC recurrence (LR) (OR = 0.2, 95% CI, 0.1- 0.4) (OR = 1.8, 95% CI, 1.2-2.5, P = 0.002). In addition, the optimal cutoff point for serum CRP level was 1.5 mg/dl, instead of 1.0 mg/dl, in predicting both ER and LR. Patients with higher preoperative serum CRP level (>1.5 mg/dl) had lower recurrence free survival rates and overall survival rates (P<0.01). These results suggest that preoperative serum CRP played different roles on ER and LR following curative hepatectomy, thus further predicting the prognosis in patients with chronic HBV infection. PMID:25602444

  6. HBV Perinatal Transmission

    PubMed Central

    Umar, Muhammad; Hamama-tul-Bushra; Umar, Shifa; Khan, Haider Ali

    2013-01-01

    Hepatitis B is a serious public health problem all around the world. It is a blood-borne and sexually transmitted DNA virus in adults, but mother to child transmission of hepatitis B virus also occurs in infants born to hepatitis B surface antigen positive mothers. PMID:23738081

  7. Automating Pro/Engineer Using Trail Files and External Programs

    SciTech Connect

    Chow, K.

    1996-05-21

    Keyboard macros provide shortcuts to many repetitive command sequences in Pro/Engineer. They map any number of frequently used command sequences to user-selected keyboard keys. They may be nested within each other and may also include user keyboard entry within the macro. Another powerful feature of Pro/Engineer is adding menu options. Menu options may be added to any Pro/Engineer menu and is an effective way to graphically display keyboard macros to make them more accessible. Command sequences are mapped to a single user-defined menu option added to the bottom of any Pro/Engineer window. The '{at}setbutton' command added to the 'menu{_}def.pro' file specifies the commands to associate with added menu options. Menu options may also be used to execute non-Pro/Engineer commands. The associated command is linked to a menu option within Pro/Engineer's Utilities menu (in the Misc menu) and is issued whenever the menu option is selected. Such a feature is useful for adding menu options to start the Pro/Engineer User Guide utility, start a text editor from within Pro/Engineer, or perform system level actions. The '{at}setbutton{_}exec' command is used in the 'menu{_}def.pro' file for non-Pro/Engineer commands. A more detailed description of adding menu options can be found in the Pro/Engineer Fundamentals Guide. Another useful component of Pro/Engineer is the trail file functionality. Trail files are automatically created every time a new working Pro/Engineer session begins. Although they are typically used to reconstruct a previous working session, they can also be used to automate a series of commands. By specifying all the commands in a trail file, a user can issue the commands quickly and repetitively using the command sequence 'Misc-Trail' and specifying the trail file name. All actions, including keyboard entries and mouse click locations, may be included in a trail file. Although adding menu options and using trial files provide powerful functionality in Pro/Engineer, neither the menu options functionality nor trail files allow interaction between the model and the commands to perform. The commands performed by the menu options are static and cannot depend on model features and parameters. Commands cannot query the model and perfonn different actions or calculations based on the query results; the menu options commands cannot interact with Pro/Engineer. As an example, suppose we wish to generate a feature listing for all parts and subassemblies in a model. We can add a menu option or a keyboard macro to make the feature listing command easier to execute, but we would still need to select each part and subassembly individually (either through screen selection, selection by menu, or entering the component name). The task becomes quite tedious if we have an assembly with a large number of subassembly and part components. A versatile and powerful method for automating many Pro/Engineer tasks is to combine the menu options functionality with Trail files and the infonnation files which Pro/Engineer creates during infonnation listings. The combination provides communication between Pro/Engineer and other programs and enables automation of a large variety of commands. The automation scheme is comprised of three components: (1) the infonnation files (usually with extensions 'inf' or '1st'); (2) a menu option to issue a program or command external to Pro/Engineer; and (3) a menu option to run both the external program and its associated trail file.

  8. Profiling the ‘Pro-environmental Individual’: A Personality Perspective

    PubMed Central

    Markowitz, Ezra M.; Goldberg, Lewis R.; Ashton, Michael C.; Lee, Kibeom

    2011-01-01

    There is considerable scientific interest in the psychological correlates of pro-environmental behaviors. Much research has focused on demographic and social-psychological characteristics of individuals who consistently perform such actions. Here, we report the results of two studies in which we explored relations between broad personality traits and pro-environmental actions. Using a wide variety of behavior and personality measures, we consistently found moderate positive relations between Openness to Experience and pro-environmental activities in both a community sample (Study 1: N = 778) and an undergraduate student sample (Study 2: N = 115). In Study 2 we showed that the effect of Openness on pro-environmental behaviors was fully mediated by individuals’ environmental attitudes and connection to nature. Our findings suggest that high levels of aesthetic appreciation, creativity, and inquisitiveness, but not personality traits associated with altruism, may have motivated the performance of pro-environmental actions among our respondents. Implications for intervention development are discussed. PMID:21241310

  9. Upregulation of miRNA-130a Represents Good Prognosis in Patients With HBV-Related Acute-on-Chronic Liver Failure

    PubMed Central

    Zheng, Qing-Fen; Zhang, Jing-Yun; Wu, Ju-Shan; Zhang, Ying; Liu, Mei; Bai, Li; Zhang, Jin-Yan; Zhao, Jing; Chen, Yu; Duan, Zhong-Ping; Zheng, Su-Jun

    2016-01-01

    Abstract Prompt and accurate prediction of the outcome is the key to make correct medical decision and to reduce the mortality in patients with HBV-related acute-on-chronic liver failure (ACLF). Increasing evidence have certified that small, noncoding microRNAs (miRNAs) play critically regulatory roles in the pathogenesis of liver diseases. However, it remains unclear whether and how miRNAs involve in the prognosis of ACLF. Microarray analysis was performed to characterize the miRNA expression profiles in liver tissues from 1 HBV-related ACLF patient and 1 matched healthy control. Nine miRNAs with at least 5 folds difference between these 2 persons were picked out. The present prospective study involving 39 HBV-related ACLF patients including 20 recovered and 19 nonrecovered patients, which include death (n?=?9) and liver transplantation (n?=?10). The serum expression of these miRNAs detected by quantitative real-time Polymerase Chain Reaction (qRT-RCR) was then compared between the 2 groups. Moreover, the correlation between the serum miRNAs and the prognostic indexes for ACLF was analyzed. The result of microarray analysis showed 9 miRNAs had different expression in liver tissues of ACLF patient compared with healthy control (upregulated: miRNA-130a, ?21, ?143, and ?200a; downregulated: miRNA-4865p, ?192, ?148a, ?122, and ?194). Unlike the expression profiles in liver tissue, 8 serum miRNAs except miRNA-194 were markedly upregulated in ACLF patients (P?HBV-related ACLF. PMID:26871786

  10. Test Reviews: Reynolds, C., & Voress, J. K. (2007). "Test of Memory and Learning: Second Edition." Austin, TX: PRO-ED

    ERIC Educational Resources Information Center

    Schmitt, Ara J.; Decker, Scott L.

    2009-01-01

    This article reviews the Test of Memory and Learning: Second Edition (TOMAL-2), published by PRO-ED, which constitutes a recent revision of the Test of Memory and Learning (TOMAL; Reynolds & Bigler, 1994). Advertised as the "single most comprehensive memory battery available for the entire age range of 5 years through 59 years of age", the TOMAL-2

  11. Nontreatment of Newborns with Severe Handicaps: A Survey of Attitudes of Pro-Life and Pro-Choice Advocates.

    ERIC Educational Resources Information Center

    McDaniel, Elizabeth A.

    1989-01-01

    When presented with hypothetical cases of newborns with a range of correctable and uncorrectable medical conditions, 10 pro-life respondents recommended treatment in virtually all cases, while 10 pro-choice respondents were more likely to recommend withholding nourishment and food, recommend limited or no medical treatment, and change initial

  12. The Experience of Bulimic College Students Who Use "Pro-Ana/Pro-Mia" Web Sites: A Two-Phase Mixed-Method Study

    ERIC Educational Resources Information Center

    Davis, Blair J.

    2010-01-01

    Eating disorders (EDs) are a serious problem in the U.S. due to their rise in prevalence during the 20th century and high morbidity and mortality rates. A relatively new, controversial phenomenon, "pro-Ana" (pro-anorexia) and "pro-Mia" (pro-bulimia) Web sites, came to the public's attention around 2000. These sites are created by and for people…

  13. The Experience of Bulimic College Students Who Use "Pro-Ana/Pro-Mia" Web Sites: A Two-Phase Mixed-Method Study

    ERIC Educational Resources Information Center

    Davis, Blair J.

    2010-01-01

    Eating disorders (EDs) are a serious problem in the U.S. due to their rise in prevalence during the 20th century and high morbidity and mortality rates. A relatively new, controversial phenomenon, "pro-Ana" (pro-anorexia) and "pro-Mia" (pro-bulimia) Web sites, came to the public's attention around 2000. These sites are created by and for people

  14. Is homocysteine a pro-oxidant?

    PubMed

    Zappacosta, B; Mordente, A; Persichilli, S; Minucci, A; Carlino, P; Martorana, G E; Giardina, B; De Sole, P

    2001-11-01

    High plasma homocysteine concentrations have been found to be associated with atherosclerosis and thrombosis of arteries and deep veins. The oxidative damage mediated by hydrogen peroxide production during the metal-catalyzed oxidation of homocysteine is to date considered to be one of the major pathophysiological mechanisms for this association. In this work, a very sensitive and accurate method was employed to measure the effective production of H2O2 during homocysteine oxidation. Furthermore, the interaction of homocysteine with powerful oxidizing species (hypochlorite, peroxynitrite, ferrylmyoglobin) was evaluated in order to ascertain the putative pro-oxidant role of homocysteine. Our findings indicate that homocysteine does not produce H2O2 in a significant amount (1/4000 mole/mole ratio of H2O2 to homocysteine). Moreover, homocysteine strongly inhibits the oxidation of luminol and dihydrorhodamine by hypochlorite or peroxynitrite and rapidly reduces back ferrylmyoglobin, the oxidizing species, to metmyoglobin. All these results should, in our opinion, lead to a rethinking of the commonly held view that homocysteine oxidation is one of the main causative mechanisms of cardiovascular damage. PMID:11767408

  15. ProPortal: A Database for Prochlorococcus

    DOE Data Explorer

    Huang, Katherine [Chisholm lab, MIT

    Prochlorococcus is a marine cyanobacterium that numerically dominates the mid-latitude oceans, and is the smallest known oxygenic phototroph. All isolates described thus far can be assigned to either a tightly clustered high-light (HL) adapted clade, or a more divergent low-light (LL) adapted group. They are closely related to, but distinct from, marine Synechococcus. The genomes of 12 strains have been sequenced and they range in size from 1.6 to 2.6 Mbp. They represent diverse lineages, spanning the rRNA diversity (97 to 99.93% similarity) of cultured representatives of this group. Our analyses of these genomes inform our understanding of how adaptation occurs in the oceans along gradients of light, nutrients, and other environmental factors, providing essential context for interpreting rapidly expanding metagenomic datasets. [Copied from http://proportal.mit.edu/project/prochlorococcus/] ProPortal allows users to browse and search genome date for not only Prochlorococcus, but Cyanophage and Synechococcus. Microarray data, environmental cell concentration data, and metagenome information are also available.

  16. Pro-angiogenic properties of orosomucoid (ORM)

    SciTech Connect

    Irmak, Ster; Oliveira-Ferrer, Leticia; Erguen, Sueleyman; Tilki, Derya

    2009-11-01

    The acute phase protein orosomucoid (ORM), also known as alpha1-acid glycoprotein (AGP), is found to be increased in infection, inflammation and cancer. Recently, we demonstrated that ORM is produced by endothelial cells and detectable in urine samples of patients with bladder cancer. However, it was not clarified yet whether ORM plays a role in new vessel formation. To this aim we performed overexpression and gene silencing for ORM in human microvascular endothelial cells (HDMECs). ORM purified from human plasma was used individually or in combination with VEGF-A in endothelial tube formation, migration and proliferation assay. The in vivo effect of ORM in angiogenesis was studied using the chicken chorionallantois membrane (CAM) with subsequent counting of blood vessels on histological sections from the stimulated areas of CAM tissue. Our data show that ORM alone enhances migration but not proliferation of HDMECs. ORM alone does not induce endothelial tubes in vitro but simultaneous application of ORM with VEGF-A increases the number and the network of VEGF-A-induced endothelial tubes. Remarkably, ORM alone induces new vessel formation in vivo using CAM assay and supports the VEGF-A-induced new vessel formation in this assay. Taken together, our results let assume that ORM has pro-angiogenic properties and supports the angiogenic effect of VEGF-A. Thus, ORM seems to be involved in the regulation of angiogenesis.

  17. ProCon - PROteomics CONversion tool.

    PubMed

    Mayer, Gerhard; Stephan, Christian; Meyer, Helmut E; Kohl, Michael; Marcus, Katrin; Eisenacher, Martin

    2015-11-01

    With the growing amount of experimental data produced in proteomics experiments and the requirements/recommendations of journals in the proteomics field to publicly make available data described in papers, a need for long-term storage of proteomics data in public repositories arises. For such an upload one needs proteomics data in a standardized format. Therefore, it is desirable, that the proprietary vendor's software will integrate in the future such an export functionality using the standard formats for proteomics results defined by the HUPO-PSI group. Currently not all search engines and analysis tools support these standard formats. In the meantime there is a need to provide user-friendly free-to-use conversion tools that can convert the data into such standard formats in order to support wet-lab scientists in creating proteomics data files ready for upload into the public repositories. ProCon is such a conversion tool written in Java for conversion of proteomics identification data into standard formats mzIdentML and Pride XML. It allows the conversion of Sequest/Comet .out files, of search results from the popular and often used ProteomeDiscoverer 1.x (x=versions 1.1 to1.4) software and search results stored in the LIMS systems ProteinScape 1.3 and 2.1 into mzIdentML and PRIDE XML. This article is part of a Special Issue entitled: Computational Proteomics. PMID:26182917

  18. Pro-inflammatory genetic markers of atherosclerosis.

    PubMed

    Incalcaterra, Egle; Accardi, Giulia; Balistreri, Carmela Rita; Caimi, Gregorio; Candore, Giuseppina; Caruso, Marco; Caruso, Calogero

    2013-06-01

    Atherosclerosis (AS) is a chronic, progressive, multifactorial disease mostly affecting large and medium-sized elastic and muscular arteries. It has formerly been considered a bland lipid storage disease. Currently, multiple independent pathways of evidence suggest this pathological condition is a peculiar form of inflammation, triggered by cholesterol-rich lipoproteins and influenced both by environmental and genetic factors. The Human Genome Project opened up the opportunity to dissect complex human traits and to understand basic pathways of multifactorial diseases such as AS. Population-based association studies have emerged as powerful tools for examining genes with a role in common multifactorial diseases that have a strong environmental component. These association studies often estimate the risk of developing a certain disease in carriers and non-carriers of a particular genetic polymorphism. Dissecting out the influence of pro-inflammatory genes within the complex pathophysiology of AS and its complications will help to provide a more complete risk assessment and complement known classical cardiovascular risk factors. The detection of a risk profile will potentially allow both the early identification of individuals susceptible to disease and the possible discovery of potential targets for drug or lifestyle modification; i.e. it will open the door to personalized medicine. PMID:23591672

  19. Pro-Inflammatory Mediation of Myoblast Proliferation

    PubMed Central

    Otis, Jeffrey S.; Niccoli, Sarah; Hawdon, Nicole; Sarvas, Jessica L.; Frye, Melinda A.; Chicco, Adam J.; Lees, Simon J.

    2014-01-01

    Skeletal muscle satellite cell function is largely dictated by the surrounding environment following injury. Immune cell infiltration dominates the extracellular space in the injured area, resulting in increased cytokine concentrations. While increased pro-inflammatory cytokine expression has been previously established in the first 3 days following injury, less is known about the time course of cytokine expression and the specific mechanisms of cytokine induced myoblast function. Therefore, the expression of IL-1? and IL-6 at several time points following injury, and their effects on myoblast proliferation, were examined. In order to do this, skeletal muscle was injured using barium chloride in mice and tissue was collected 1, 5, 10, and 28 days following injury. Mechanisms of cytokine induced proliferation were determined in cell culture using both primary and C2C12 myoblasts. It was found that there is a ?20-fold increase in IL-1? (p?0.05) and IL-6 (p?=?0.06) expression 5 days following injury. IL-1? increased proliferation of both primary and C2C12 cells ?25%. IL-1? stimulation also resulted in increased NF-?B activity, likely contributing to the increased proliferation. These data demonstrate for the first time that IL-1? alone can increase the mitogenic activity of primary skeletal muscle satellite cells and offer insight into the mechanisms dictating satellite cell function following injury. PMID:24647690

  20. P5CDH affects the pathways contributing to Pro synthesis after ProDH activation by biotic and abiotic stress conditions

    PubMed Central

    Rizzi, Yanina S.; Monteoliva, Mariela I.; Fabro, Georgina; Grosso, Carola L.; Laróvere, Laura E.; Alvarez, María E.

    2015-01-01

    Plants facing adverse conditions usually alter proline (Pro) metabolism, generating changes that help restore the cellular homeostasis. These organisms synthesize Pro from glutamate (Glu) or ornithine (Orn) by two-step reactions that share Δ1 pyrroline-5-carboxylate (P5C) as intermediate. In the catabolic process, Pro is converted back to Glu using a different pathway that involves Pro dehydrogenase (ProDH), P5C dehydrogenase (P5CDH), and P5C as intermediate. Little is known about the coordination of the catabolic and biosynthetic routes under stress. To address this issue, we analyzed how P5CDH affects the activation of Pro synthesis, in Arabidopsis tissues that increase ProDH activity by transient exposure to exogenous Pro, or infection with Pseudomonas syringae pv. tomato. Wild-type (Col-0) and p5cdh mutant plants subjected to these treatments were used to monitor the Pro, Glu, and Orn levels, as well as the expression of genes from Pro metabolism. Col-0 and p5cdh tissues consecutively activated ProDH and Pro biosynthetic genes under both conditions. However, they manifested a different coordination between these routes. When external Pro supply was interrupted, wild-type leaves degraded Pro to basal levels at which point Pro synthesis, mainly via Glu, became activated. Under the same condition, p5cdh leaves sustained ProDH induction without reducing the Pro content but rather increasing it, apparently by stimulating the Orn pathway. In response to pathogen infection, both genotypes showed similar trends. While Col-0 plants seemed to induce both Pro biosynthetic routes, p5cdh mutant plants may primarily activate the Orn route. Our study contributes to the functional characterization of P5CDH in biotic and abiotic stress conditions, by revealing its capacity to modulate the fate of P5C, and prevalence of Orn or Glu as Pro precursors in tissues that initially consumed Pro. PMID:26284090

  1. HBV preS2 promotes the expression of TAZ via miRNA-338-3p to enhance the tumorigenesis of hepatocellular carcinoma

    PubMed Central

    Liu, Peng; Zhang, Hualin; Liang, Xiaohong; Ma, Hongxin; Luan, Fang; Wang, Bo; Bai, Fuxiang; Gao, Lifen; Ma, Chunhong

    2015-01-01

    Transactivators encoded by HBV, including HBx and preS2, play critical role in hepatocellular carcinoma (HCC). YAP, a downstream effector of the Hippo pathway, is involved in hepatocarcinogenesis mediated by HBx. Here, we investigated whether preS2, another transactivator encoded by HBV, regulates the Hippo pathway to promote HCC. We found that preS2 overexpression upregulated TAZ, a downstream effector of the Hippo pathway, at protein level but not at mRNA level. preS2 suppressed miRNA-338-3p expression in HCC cell lines. miRNA-338-3p mimics downregulated TAZ, while miRNA-338-3p inhibitor restored the expression of TAZ, suggesting that TAZ is a direct target of miRNA-338-3p. TAZ overexpression stimulated growth of HCC cell lines. Knockdown of TAZ dampened preS2-promoted HCC proliferation and migration. Thus, preS2 upregulates TAZ expression by repressing miRNA-338-3p. TAZ is necessary for preS2-promoted HCC proliferation and migration PMID:26315112

  2. Aspartate aminotransferase-lymphocyte ratio index and systemic immune-inflammation index predict overall survival in HBV-related hepatocellular carcinoma patients after transcatheter arterial chemoembolization.

    PubMed

    Yang, Zongguo; Zhang, Jianliang; Lu, Yunfei; Xu, Qingnian; Tang, Bozong; Wang, Qiang; Zhang, Wensi; Chen, Shishi; Lu, Lingqing; Chen, Xiaorong

    2015-12-15

    It has been suggested that lymphocytes play central roles in host antitumor immune responses and control cancer outcome. We reviewed the clinical parameters of 189 hepatocellular carcinoma (HCC) patients and investigated the prognostic significance of lymphocyte-related scores in HCC patients following transcatheter arterial chemoembolization (TACE). Survival analysis revealed that an elevated aspartate aminotransferase-lymphocyte ratio index (ALRI) > 57 and a systemic immune-inflammation index (SII) > 300 were negatively associated with overall survival in HBV-related HCC (HR = 2.181, P = 0.003 and HR = 2.453, P = 0.003; respectively). Spearman chi-square analysis showed that ALRI had a specificity of 82.4% and that SII index had a sensitivity of 71.9% for HCC overall survival. ALRI and SII had negative predictive values of 74.6% and 80%, respectively for HCC overall survival. Additionally, Barcelona Clinic Liver Cancer (BCLC) stage C patients had significantly higher ALRI and SII scores (both P < 0.0001) and poorer overall survival (HR = 3.618, P < 0.001). Additionally, HCC patients with portal vein tumor thrombosis (PVTT) had higher ALRI and SII scores (P < 0.0001 and P = 0.0059, respectively). In conclusion, as noninvasive, low cost, easily assessable and reproducible parameters, elevated ALRI and SII should be used as negative predictive factors for overall survival in HBV-related HCC in clinical practice. PMID:26506519

  3. Relatively Small Contribution of Methylation and Genomic Copy Number Aberration to the Aberrant Expression of Inflammation-Related Genes in HBV-Related Hepatocellular Carcinoma

    PubMed Central

    Huang, Xudong; Wu, Chen; Tan, Wen; Qiao, Yan; Chang, Jiang; Zhao, Hong; Bi, Xinyu; Cai, Jianqiang; Li, Yun; Lin, Dongxin

    2015-01-01

    Background It is well known that chronic inflammation plays a pivotal role in the development of hepatitis B virus (HBV) related hepatocellular carcinoma (HCC). However, the causes behind aberrant expression of inflammation-related genes occurred in HCC remain unclear. Methods We performed array-based analyses to comprehensively investigate the contributions of DNA methylation and somatic copy number aberration (SCNA) to the aberrant expression of 1,027 inflammation-related genes in 30 HCCs and paired non-tumor tissues. The results were validated in public datasets and an additional sample set of 47 paired HCCs and non-tumor tissues. Results We identified 252 differentially expressed, 125 aberrantly methylated and 287 copy number changed inflammation-related genes. Despite reasonable statistical power, among them, only 11 genes and 56 genes whose aberrant expression was associated with DNA methylation or SCNA, respectively. DNA methylation and SCNA together contributed to less than 30% aberrant expression of inflammation-related genes. Conclusion These results suggest that molecular mechanisms other than DNA methylation and SCNA might play major role in the regulation of aberrant expression of inflammation-related gene in HBV-related HCCs. PMID:25965583

  4. Aspartate aminotransferase-lymphocyte ratio index and systemic immune-inflammation index predict overall survival in HBV-related hepatocellular carcinoma patients after transcatheter arterial chemoembolization

    PubMed Central

    Yang, Zongguo; Zhang, Jianliang; Lu, Yunfei; Xu, Qingnian; Tang, Bozong; Wang, Qiang; Zhang, Wensi; Chen, Shishi; Lu, Lingqing; Chen, Xiaorong

    2015-01-01

    It has been suggested that lymphocytes play central roles in host antitumor immune responses and control cancer outcome. We reviewed the clinical parameters of 189 hepatocellular carcinoma (HCC) patients and investigated the prognostic significance of lymphocyte-related scores in HCC patients following transcatheter arterial chemoembolization (TACE). Survival analysis revealed that an elevated aspartate aminotransferase-lymphocyte ratio index (ALRI) > 57 and a systemic immune-inflammation index (SII) > 300 were negatively associated with overall survival in HBV-related HCC (HR = 2.181, P = 0.003 and HR = 2.453, P = 0.003; respectively). Spearman chi-square analysis showed that ALRI had a specificity of 82.4% and that SII index had a sensitivity of 71.9% for HCC overall survival. ALRI and SII had negative predictive values of 74.6% and 80%, respectively for HCC overall survival. Additionally, Barcelona Clinic Liver Cancer (BCLC) stage C patients had significantly higher ALRI and SII scores (both P < 0.0001) and poorer overall survival (HR = 3.618, P < 0.001). Additionally, HCC patients with portal vein tumor thrombosis (PVTT) had higher ALRI and SII scores (P < 0.0001 and P = 0.0059, respectively). In conclusion, as noninvasive, low cost, easily assessable and reproducible parameters, elevated ALRI and SII should be used as negative predictive factors for overall survival in HBV-related HCC in clinical practice. PMID:26506519

  5. One-year vaccination against hepatitis B virus with a MPL-vaccine in liver transplant patients for HBV-related cirrhosis.

    PubMed

    Di Paolo, Daniele; Lenci, Ilaria; Cerocchi, Carlo; Tariciotti, Laura; Monaco, Andrea; Brega, Arianna; Lotti, Laura; Tisone, Giuseppe; Angelico, Mario

    2010-11-01

    Conflicting results have been reported on vaccination against hepatitis B virus (HBV) as a prophylaxis against viral recurrence after liver transplantation. We investigated the efficacy of 1-year, monthly vaccination using an adjuvant 3-deacylated monophosphoryl-lipid-A (MPL) recombinant S vaccine initially administered together with hepatitis B immunoglobulins (HBIg) in 18 patients transplanted for HBV-related cirrhosis. All received 12 vaccine doses (HBsAg, 20 mcg plus MPL, 50 mcg): the initial six doses (phase I) were administered within 7days after intravenous HBIg (2000IU), while the last 6 (phase II) following HBIg withdrawal. All patients received lamivudine during the study. Anti-HBs titers were determined before each dose and then for 1year after vaccination. After phase I anti-HBs titers were greater than 100IU/l in all patients and in three (16.6%) were greater than 500IU/l. After phase II 10 patients (55.5%) achieved anti-HBs titers greater than 100IU/l and five (27.7%) greater than 500IU/l. One year after vaccination eight patients (44.4%) maintained anti-HBs titers greater than 100IU/l, with a median titer of 234IU/l (102-1205), and 2 (11.1%) greater than 500IU/l. One-year extended monthly vaccination with a MPL-adjuvant recombinant vaccine induces a sustained protective anti-HBs response in approximately half of transplant recipients. PMID:20492620

  6. The Pro-Apoptotic and Pro-Inflammatory Effects of Calprotectin on Human Periodontal Ligament Cells

    PubMed Central

    Peng, Lei; Zhang, Xin; Jia, Lingfei; Wang, Xian'e; Wei, Shicheng; Meng, Huanxin

    2014-01-01

    Calprotectin, a heterodimer of S100A8 and S100A9 subunits, is associated with inflammatory disorders such as rheumatoid arthritis and cystic fibrosis. Although calprotectin levels are increased significantly in the gingival crevicular fluid (GCF) of periodontitis patients, its effects on periodontal ligament cells (PDLCs) remain largely unknown. The aim of this study was to evaluate calprotectin levels in the GCF of generalized aggressive periodontitis (AgP) patients and to investigate the effects of recombinant human calprotectin (rhS100A8/A9) and its subunits (rhS100A8 and rhS100A9) in PDLCs. Both the concentration and amount of crevicular calprotectin were significantly higher in the AgP group compared with healthy controls. In addition, the GCF calprotectin levels were correlated positively with clinical periodontal parameters including bleeding index, probing depth, and clinical attachment loss. rhS100A8/A9 promoted cell apoptosis, whereas rhS100A8 and rhS100A9 individually exerted little effect on apoptosis in PDLCs. rhS100A9 and rhS100A8/A9 increased the activation of nuclear factor-κB (NF-κB) by promoting the nuclear translocation of p65 in PDLCs, subsequently inducing expression of the pro-inflammatory cytokines IL-6, IL-8, TNFα, and COX2. Treatment with an NF-κB inhibitor partially reversed the rhS100A9- and rhS100A8/A9-induced upregulation of the pro-inflammatory cytokines. rhS100A9, and not rhS100A8, was mainly responsible for the pro-inflammatory role of calprotectin. Collectively, our results suggest that calprotectin promotes apoptosis and the inflammatory response in PDLCs via rhS100A9. These findings might help identify novel treatments for periodontitis. PMID:25338166

  7. A hepatitis A, B, C and HIV prevalence and risk factor study in ever injecting and non-injecting drug users in Luxembourg associated with HAV and HBV immunisations

    PubMed Central

    2011-01-01

    Background In Luxembourg, viral hepatitis and HIV infection data in problem drug users (PDUs) are primarily based on self-reporting. Our study aimed to determine the prevalence of HAV, HBV, HCV and HIV infections in ever injecting (IDUs) and non-injecting drug users (nIDUs) including inherent risk factors analysis for IDUs. Secondary objectives were immunisation against HAV and HBV, referral to care and treatment facilities as well as reduction in risk behaviour. Methods A nationwide, cross-sectional multi-site survey, involving 5 in-, 8 out-treatment and 2 prison centres, included both an assisted questionnaire (n = 368) and serological detection of HIV and Hepatitis A, B, C (n = 334). A response rate of 31% resulted in the participation of 310 IDUs and 58 nIDUs. Risk factors such as drug use, sexual behaviour, imprisonment, protection and health knowledge (HAV, HBV status and immunisations, HCV, HIV), piercing/tattoo and use of social and medical services were studied by means of chi2 and logistic models. Results Seroprevalence results for IDUs were 81.3% (218/268, 95%CI=[76.6; 86.0]) for HCV, 29.1% (74/254, 95%CI=[25.5;34.7 ]) for HBV (acute/chronic infection or past cured infection), 2.5% (5/202, 95%CI=[0.3; 4.6]) for HIV-1 and 57.1% (108/189, 95%CI=[50.0; 64.1]) for HAV (cured infections or past vaccinations). Seroprevalence results for nIDUs were 19.1% (9/47, 95%CI=[7.9;30.3]) for HCV, 8.9% (4/45, 95%CI=[0.6;17.2]) for HBV (acute/chronic infection or past cured infection), 4.8% (2/42, 95%CI=[-1.7;11.3]) for HIV-1 and 65.9% (27/41, 95%CI=[51.4;80.4]) for HAV. Prisoners showed the highest rates for all infections. Age, imprisonment and setting of recruitment were statistically associated with HCV seropositivity. Age, speedball career and nationality were significantly associated with HBV seropositivity. Only 56% of the participants in outpatient centres collected their serology results and 43 doses of vaccine against HAV and/or HBV were administered. Conclusions Despite the existing national risk-reduction strategies implemented since 1993, high prevalence of HCV and HBV infections in injecting drug users is observed. Our study showed that implementing risk-prevention strategies, including immunisation remains difficult with PDUs. Improvement should be looked for by the provision of field healthcare structures providing tests with immediate results, advice, immunisation or treatment if appropriate. PMID:21595969

  8. Pro-oxidative action of polyphenols as action mechanism for their pro-apoptotic activity.

    PubMed

    Lecci, Raffaella Marina; Logrieco, Antonio; Leone, Antonella

    2014-01-01

    Polyphenols, secondary metabolites widely present in plant kingdom, are known for their positive effects on human health, such as treatments of degenerative disease and cancer. Many dietary polyphenols show anti-inflammatory, immunomodulatory and antioxidant properties and they are proposed as chemopreventive agents for many skin disorders and cancer. Exposure to solar UV radiation is widely considered to cause skin cancer and a consistent carcinogenic dose derived from UVA causes several skin disorders as a consequence of free radicals generation and DNA damages. In this study, verbascoside, isoverbascoside and tyrosol were investigated for their effects on HEKa (Human Epidermal Keratinocytes adult) cell cultures challenged from UVA-rays. Non-toxic doses of each polyphenol were assayed on HEKa before, during and after the exposure to a damaging dose of UVA. Treatment with polyphenols before and after the UVA-irradiation exerted a pro-oxidant effect, while the simultaneous treatment caused a weak decrease of ROS production. The increasing of ROS levels was associated with a proapoptotic effect on HEKa, detected by AnnexinV/Propidiun Iodide, mainly evident in surviving cells treated with the polyphenols after the UVA-irradiation. The pro-apoptotic effect was confirmed by the immunodetection of significant changes in the Bax and Bcl-xL protein levels, leading to apoptotic events. The hypothesis that these polyphenols could trigger the apoptosis pathway mainly in UVA-damaged cells, via ROS increase, is here proposed as action mechanism behind their protective effect. PMID:25244914

  9. Intensity modulated radiotherapy induces pro-inflammatory and pro-survival responses in prostate cancer patients

    PubMed Central

    EL-SAGHIRE, HOUSSEIN; VANDEVOORDE, CHARLOT; OST, PIET; MONSIEURS, PIETER; MICHAUX, ARLETTE; DE MEERLEER, GERT; BAATOUT, SARAH; THIERENS, HUBERT

    2014-01-01

    Intensity modulated radiotherapy (IMRT) is one of the modern conformal radiotherapies that is widely used within the context of cancer patient treatment. It uses multiple radiation beams targeted to the tumor, however, large volumes of the body receive low doses of irradiation. Using γ-H2AX and global genome expression analysis, we studied the biological responses induced by low doses of ionizing radiation in prostate cancer patients following IMRT. By means of different bioinformatics analyses, we report that IMRT induced an inflammatory response via the induction of viral, adaptive, and innate immune signaling. In response to growth factors and immune-stimulatory signaling, positive regulation in the progression of cell cycle and DNA replication were induced. This denotes pro-inflammatory and pro-survival responses. Furthermore, double strand DNA breaks were induced in every patient 30 min after the treatment and remaining DNA repair and damage signaling continued after 18–24 h. Nine genes belonging to inflammatory responses (TLR3, SH2D1A and IL18), cell cycle progression (ORC4, SMC2 and CCDC99) and DNA damage and repair (RAD17, SMC6 and MRE11A) were confirmed by quantitative RT-PCR. This study emphasizes that the risk assessment of health effects from the out-of-field low doses during IMRT should be of concern, as these may increase the risk of secondary cancers and/or systemic inflammation. PMID:24435511

  10. Intensity modulated radiotherapy induces pro-inflammatory and pro-survival responses in prostate cancer patients.

    PubMed

    El-Saghire, Houssein; Vandevoorde, Charlot; Ost, Piet; Monsieurs, Pieter; Michaux, Arlette; De Meerleer, Gert; Baatout, Sarah; Thierens, Hubert

    2014-04-01

    Intensity modulated radiotherapy (IMRT) is one of the modern conformal radiotherapies that is widely used within the context of cancer patient treatment. It uses multiple radiation beams targeted to the tumor, however, large volumes of the body receive low doses of irradiation. Using γ-H2AX and global genome expression analysis, we studied the biological responses induced by low doses of ionizing radiation in prostate cancer patients following IMRT. By means of different bioinformatics analyses, we report that IMRT induced an inflammatory response via the induction of viral, adaptive, and innate immune signaling. In response to growth factors and immune-stimulatory signaling, positive regulation in the progression of cell cycle and DNA replication were induced. This denotes pro-inflammatory and pro-survival responses. Furthermore, double strand DNA breaks were induced in every patient 30 min after the treatment and remaining DNA repair and damage signaling continued after 18-24 h. Nine genes belonging to inflammatory responses (TLR3, SH2D1A and IL18), cell cycle progression (ORC4, SMC2 and CCDC99) and DNA damage and repair (RAD17, SMC6 and MRE11A) were confirmed by quantitative RT-PCR. This study emphasizes that the risk assessment of health effects from the out-of-field low doses during IMRT should be of concern, as these may increase the risk of secondary cancers and/or systemic inflammation. PMID:24435511

  11. 25 CFR 273.32 - Pro rata requirement.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR INDIAN SELF-DETERMINATION AND EDUCATION ASSISTANCE ACT PROGRAM EDUCATION CONTRACTS UNDER JOHNSON-O'MALLEY ACT Funding Provisions § 273.32 Pro rata... Education Committee....

  12. Robotics Vision for a Scouting Rover - PRoViScout

    NASA Astrophysics Data System (ADS)

    Paar, G.; Woods, M.; Pullan, D.; Proviscout Team

    2011-10-01

    The FP7-SPACE Project ProViScout (Planetary Robotics Vision Scout, scheduled from April 2010 to September 2012) aims to demonstrate the feasibility of vision-based autonomous sample identification & selection in combination with vision-based navigation for a long range scouting/exploration mission on a terrestrial planet along with the robotic elements required. The paper gives an overview of the PRoViScout technical and scientific objectives, envisaged solutions and achievements so far.

  13. The survival of the pro-choice movement.

    PubMed

    Staggenborg, S

    1995-01-01

    In the US, the pro-choice movement has not only survived but grown stronger in the 25 years since the legalization of abortion provided its greatest victory. This longevity is explained through an examination of the internal organizational changes which have taken place in the movement as well as the external changes which have taken place in the political environment surrounding the movement. After providing a theoretical basis for this investigation, the history of the pro-choice movement in the US is traced in light of these elements. In the pre-1973 era, the movement lacked formal organization but was bolstered by external political factors provided by the protest cycle of the 1960s. During 1973-76, the actions of anti-abortion groups forced pro-choice groups to develop the more formalized organizational structures which helped the pro-choice movement survive its initial success and the decline of the era of protests. In the period 1976-83, the anti-abortion movement achieved passage of the Hyde Amendment banning federal funding of abortions. This victory by the opposition led to an expansion in the pro-choice movement which included the formation of many local reproductive rights organizations. Many of these organizations failed to create formalized structures and, therefore, failed to maintain their impetus to survive. However, NARAL (the National Association for Repeal of Abortion Laws) had adopted a more formalized structure and professional leadership following the Hyde legislation and developed strong, formal connections with its state affiliates while continuing to strengthen grassroots actions. The visible threats to abortion laws mounted by the anti-abortion groups added to NARAL's strength. During 1983-89, the pro-choice movement gained some key victories which threatened its survival. Continued activity on the part of the anti-abortion groups (such as release of the movie "The Silent Scream") generated enough pro-choice support, however, to weather this period. The activities of Operation Rescue also stimulated pro-choice reactions. In the period 1989-92, the Supreme Court gave pro-choice groups a victory in its Webster vs. Reproductive Health decision. Thus, NARAL's membership grew to an unprecedented 400,000 in 1990 and allowed the group to pump money into local grassroots activities. By the time the Court issued its Casey decision in 1992, neither group was willing to claim victory, although the ruling was a great victory for pro-choice forces because although the Court allowed states to impose new restrictions to abortion, it refused to overturn Roe vs. Wade. 1992 also saw the election of a pro-choice President who was able to appoint a pro-choice Justice to the Supreme Court in 1993. The ability of the pro-choice movement to survive victory (the creation of a favorable political opportunity structure) will be decided by the critical battles surrounding attempts to limit access to abortion providers as well as the accessibility of drug-induced abortion. State legislatures will remain major battlefields because of the Court-allowed restrictions. The pro-choice movement will also have to resolve conflicts over strategy such as whether to appeal to mainstream Americans or use the favorable climate to push for rights. The pro-choice movement will likely survive because the anti-abortion groups continue to pose threats and because formal organizations with professional leadership will keep the issues before the membership. PMID:12346343

  14. Updated U.S. Public Health Service Guidelines for the Management of Occupational Exposures to HBV, HCV, and HIV and Recommendations for Postexposure Prophylaxis.

    PubMed

    2001-06-29

    This report updates and consolidates all previous U.S. Public Health Service recommendations for the management of health-care personnel (HCP) who have occupational exposure to blood and other body fluids that might contain hepatitis B virus (HBV), hepatitis C virus (HCV), or human immunodeficiency virus (HIV). Recommendations for HBV postexposure management include initiation of the hepatitis B vaccine series to any susceptible, unvaccinated person who sustains an occupational blood or body fluid exposure. Postexposure prophylaxis (PEP) with hepatitis B immune globulin (HBIG) and/or hepatitis B vaccine series should be considered for occupational exposures after evaluation of the hepatitis B surface antigen status of the source and the vaccination and vaccine-response status of the exposed person. Guidance is provided to clinicians and exposed HCP for selecting the appropriate HBV PEP. Immune globulin and antiviral agents (e.g., interferon with or without ribavirin) are not recommended for PEP of hepatitis C. For HCV postexposure management, the HCV status of the source and the exposed person should be determined, and for HCP exposed to an HCV positive source, follow-up HCV testing should be performed to determine if infection develops. Recommendations for HIV PEP include a basic 4-week regimen of two drugs (zidovudine [ZDV] and lamivudine [3TC]; 3TC and stavudine [d4T]; or didanosine [ddI] and d4T) for most HIV exposures and an expanded regimen that includes the addition of a third drug for HIV exposures that pose an increased risk for transmission. When the source person's virus is known or suspected to be resistant to one or more of the drugs considered for the PEP regimen, the selection of drugs to which the source person's virus is unlikely to be resistant is recommended. In addition, this report outlines several special circumstances (e.g., delayed exposure report, unknown source person, pregnancy in the exposed person, resistance of the source virus to antiretroviral agents, or toxicity of the PEP regimen) when consultation with local experts and/or the National Clinicians' Post-Exposure Prophylaxis Hotline ([PEPline] 1-888-448-4911) is advised. Occupational exposures should be considered urgent medical concerns to ensure timely postexposure management and administration of HBIG, hepatitis B vaccine, and/or HIV PEP. PMID:11442229

  15. Frequency and genotypic distribution of GB virus C (GBV-C) among Colombian population with Hepatitis B (HBV) or Hepatitis C (HCV) infection

    PubMed Central

    2011-01-01

    Background GB virus C (GBV-C) is an enveloped positive-sense ssRNA virus belonging to the Flaviviridae family. Studies on the genetic variability of the GBV-C reveals the existence of six genotypes: genotype 1 predominates in West Africa, genotype 2 in Europe and America, genotype 3 in Asia, genotype 4 in Southwest Asia, genotype 5 in South Africa and genotype 6 in Indonesia. The aim of this study was to determine the frequency and genotypic distribution of GBV-C in the Colombian population. Methods Two groups were analyzed: i) 408 Colombian blood donors infected with HCV (n = 250) and HBV (n = 158) from Bogot and ii) 99 indigenous people with HBV infection from Leticia, Amazonas. A fragment of 344 bp from the 5' untranslated region (5' UTR) was amplified by nested RT PCR. Viral sequences were genotyped by phylogenetic analysis using reference sequences from each genotype obtained from GenBank (n = 160). Bayesian phylogenetic analyses were conducted using Markov chain Monte Carlo (MCMC) approach to obtain the MCC tree using BEAST v.1.5.3. Results Among blood donors, from 158 HBsAg positive samples, eight 5.06% (n = 8) were positive for GBV-C and from 250 anti-HCV positive samples, 3.2%(n = 8) were positive for GBV-C. Also, 7.7% (n = 7) GBV-C positive samples were found among indigenous people from Leticia. A phylogenetic analysis revealed the presence of the following GBV-C genotypes among blood donors: 2a (41.6%), 1 (33.3%), 3 (16.6%) and 2b (8.3%). All genotype 1 sequences were found in co-infection with HBV and 4/5 sequences genotype 2a were found in co-infection with HCV. All sequences from indigenous people from Leticia were classified as genotype 3. The presence of GBV-C infection was not correlated with the sex (p = 0.43), age (p = 0.38) or origin (p = 0.17). Conclusions It was found a high frequency of GBV-C genotype 1 and 2 in blood donors. The presence of genotype 3 in indigenous population was previously reported from Santa Marta region in Colombia and in native people from Venezuela and Bolivia. This fact may be correlated to the ancient movements of Asian people to South America a long time ago. PMID:21745373

  16. Safety and immunogenicity of fully liquid DTaP?-IPV-Hib pediatric combination vaccine (Pediacel) compared to DTaP?-HBV-IPV/Hib (Infanrix Hexa) when coadministered with heptavalent pneumococcal conjugate vaccine (PCV7) as a booster at 11-18 months of age: a phase III, modified double-blind, randomized, controlled, multicenter study.

    PubMed

    Berner, Reinhard; Boisnard, Florence; Thomas, Stphane; Mwawasi, Grace; Reynolds, Donna

    2012-07-27

    This study compared the safety and immunogenicity of DTaP?-IPV-Hib vaccine (followed by monovalent hepatitis B vaccine [HBV]) and DTaP?-HBV-IPV/Hib vaccines, both coadministered with PCV7, as a fourth-dose booster in toddlers 11-18 months who had a hexavalent vaccine primary series. The fever rate within 4 days of DTaP?-IPV-Hib was noninferior to DTaP?-HBV-IPV/Hib. DTaP?-IPV-Hib induced a marked immune response and had a similar safety and immunogenicity profile compared with DTaP?-HBV-IPV/Hib. Fully liquid DTaP?-IPV-Hib can be used as a booster after a hexavalent vaccine primary series; where required, a fourth dose of monovalent HBV can be administered after DTaP?-IPV-Hib (NCT ID: NCT00355654). PMID:22691430

  17. Zebrafish ProVEGF-C Expression, Proteolytic Processing and Inhibitory Effect of Unprocessed ProVEGF-C during Fin Regeneration

    PubMed Central

    Khatib, Abdel-Majid; Lahlil, Rachid; Scamuffa, Nathalie; Akimenko, Marie-Andre; Ernest, Sylvain; Lomri, Abdderahim; Lalou, Claude; Seidah, Nabil G.; Villoutreix, Bruno O.; Calvo, Fabien; Siegfried, Geraldine

    2010-01-01

    Background In zebrafish, vascular endothelial growth factor-C precursor (proVEGF-C) processing occurs within the dibasic motif HSIIRR214 suggesting the involvement of one or more basic amino acid-specific proprotein convertases (PCs) in this process. In the present study, we examined zebrafish proVEGF-C expression and processing and the effect of unprocessed proVEGF-C on caudal fin regeneration. Methodology/Principal Findings Cell transfection assays revealed that the cleavage of proVEGF-C, mainly mediated by the proprotein convertases Furin and PC5 and to a less degree by PACE4 and PC7, is abolished by PCs inhibitors or by mutation of its cleavage site (HSIIRR214 into HSIISS214). In vitro, unprocessed proVEGF-C failed to activate its signaling proteins Akt and ERK and to induce cell proliferation. In vivo, following caudal fin amputation, the induction of VEGF-C, Furin and PC5 expression occurs as early as 2 days post-amputation (dpa) with a maximum levels at 47 dpa. Using immunofluorescence staining we localized high expression of VEGF-C and the convertases Furin and PC5 surrounding the apical growth zone of the regenerating fin. While expression of wild-type proVEGF-C in this area had no effect, unprocessed proVEGF-C inhibited fin regeneration. Conclusions/Significances Taken together, these data indicate that zebrafish fin regeneration is associated with up-regulation of VEGF-C and the convertases Furin and PC5 and highlight the inhibitory effect of unprocessed proVEGF-C on fin regeneration. PMID:20625388

  18. The InterPro BioMart: federated query and web service access to the InterPro Resource.

    PubMed

    Jones, Philip; Binns, David; McMenamin, Conor; McAnulla, Craig; Hunter, Sarah

    2011-01-01

    The InterPro BioMart provides users with query-optimized access to predictions of family classification, protein domains and functional sites, based on a broad spectrum of integrated computational models ('signatures') that are generated by the InterPro member databases: Gene3D, HAMAP, PANTHER, Pfam, PIRSF, PRINTS, ProDom, PROSITE, SMART, SUPERFAMILY and TIGRFAMs. These predictions are provided for all protein sequences from both the UniProt Knowledge Base and the UniParc protein sequence archive. The InterPro BioMart is supplementary to the primary InterPro web interface (http://www.ebi.ac.uk/interpro), providing a web service and the ability to build complex, custom queries that can efficiently return thousands of rows of data in a variety of formats. This article describes the information available from the InterPro BioMart and illustrates its utility with examples of how to build queries that return useful biological information. Database URL: http://www.ebi.ac.uk/interpro/biomart/martview. PMID:21785143

  19. [Cholesterol-lowering effect of the regulatory peptide Pro-Gly-Pro-Leu].

    PubMed

    Miasoedov, N F; Shubina, T A; Obergan, T Iu; Grigor'eva, M E; Andreeva, L A; Liapina, L A

    2013-01-01

    In the present paper anticoagulant-fibrinolytic effects of the peptide Pro-Gly-Pro-Leu in rats (370-500 g body weight) who consumed fatty foods with excess of saturated fatty acids (wheat flour and bread--35%, sugar--10%, margarine hydrogenated fats, mayonnaise, cheese--35% and offals--10%, cholesterol--1%, dry food--9%) has been established. The duration of the animals on the diet was 15 days. The experimental animals intranasally obtained peptide (200 microg/kg body weight per volume of 0.02 ml per 200 g body weight) 11 times (daily except weekends). Animals from the control group intranasally received instead of peptide its vehicle (0.85% solution of NaCl) at the same time and in the same amount. It has been shown that daily nasal administration of the regulatory tetrapeptide under fatty food intake for the entire period of the experiment has a positive effect on lipid metabolism. It warned the development of alimentary hypercholesterolemia, an increase in body weight, normalized disturbed lipid profile, blood cholesterol level. In addition, its administration also restored functional status of anticoagulation system and decreased elevated degree of blood coagulation to normal values. Possible mechanism of hypocholesterolemic activity of peptide can be explained by its ability to interact with receptors of blood or brain cells, and through a series of reactions mediated to reduce blood cholesterol levels. Thanks to the anti-platelet activity glyprolines effectively improves endothelial function and reduces the risk of blood clots in the blood vessels, providing improved rheological properties of blood and preventing the formation of atherosclerotic plaques in the arterial wall. PMID:24640158

  20. Enhanced Activity of Meprin-?, a Pro-Migratory and Pro-Angiogenic Protease, in Colorectal Cancer

    PubMed Central

    Nol, Agns; Blacher, Silvia; Huguenin, Maya; Nievergelt, Alexandra; Niggli, Verena; Kern, Alexander; Mller, Stefan; Seibold, Frank; Friess, Helmut; Becker-Pauly, Christoph; Stcker, Walter; Sterchi, Erwin E.

    2011-01-01

    Meprin-? is a metalloprotease overexpressed in cancer cells, leading to the accumulation of this protease in a subset of colorectal tumors. The impact of increased meprin-? levels on tumor progression is not known. We investigated the effect of this protease on cell migration and angiogenesis in vitro and studied the expression of meprin-? mRNA, protein and proteolytic activity in primary tumors at progressive stages and in liver metastases of patients with colorectal cancer, as well as inhibitory activity towards meprin-? in sera of cancer patient as compared to healthy controls. We found that the hepatocyte growth factor (HGF)- induced migratory response of meprin-transfected epithelial cells was increased compared to wild-type cells in the presence of plasminogen, and that the angiogenic response in organ-cultured rat aortic explants was enhanced in the presence of exogenous human meprin-?. In patients, meprin-? mRNA was expressed in colonic adenomas, primary tumors UICC (International Union Against Cancer) stage I, II, III and IV, as well as in liver metastases. In contrast, the corresponding protein accumulated only in primary tumors and liver metastases, but not in adenomas. However, liver metastases lacked meprin-? activity despite increased expression of the corresponding protein, which correlated with inefficient zymogen activation. Sera from cancer patients exhibited reduced meprin-? inhibition compared to healthy controls. In conclusion, meprin-? activity is regulated differently in primary tumors and metastases, leading to high proteolytic activity in primary tumors and low activity in liver metastases. By virtue of its pro-migratory and pro-angiogenic activity, meprin-? may promote tumor progression in colorectal cancer. PMID:22096485

  1. NT-proBNP concentrations in mountain marathoners.

    PubMed

    Banfi, Giuseppe; Lippi, Giuseppe; Susta, Daniele; Barassi, Alessandra; D'Eril, Gianvico Melzi; Dogliotti, Giada; Corsi, Massimiliano M

    2010-05-01

    The 76 amino acid N-terminal proB-type natriuretic peptide (NT-proBNP) is proposed for evaluating and monitoring heart pathologies characterized by myocardial wall stress. Strenuous exercise might generate transitory ischemia, myocardial stress, and diastolic left ventricular dysfunction, possibly inducing an increase of some biochemical parameter concentrations. An alert has been claimed owing to biochemical and instrumental signs of heart dysfunction in recreational athletes during marathon races. We studied the behaviour of NT-proBNP in 15 mountain marathoners before and after a race. The concentrations of the parameter were lower than that observed in controls at rest and were similar to that observed in professional soccer and rugby players. The concentrations significantly increased after the race. NT-proBNP is low at rest in professional athletes, and the increase after physical exercise is physiological. The marathoners, even when performing races in a high-altitude environment, show NT-proBNP concentrations similar to those of athletes from other sports disciplines, characterized by low levels of effort and by a mix of aerobic and anaerobic metabolism. The increase of NT-proBNP is linked to strenuous physical exercise and to heavy heart effort, testified also by an increase of troponin I. However, the role of the NT-proBNP could be important to screen recreational and professional marathoners to avoid possible heart problems and sudden cardiac death in subjects with occult heart disease. The results of the present study are relevant to the design and evaluation of training programs for improving strength and function of professional marathoners. PMID:20393354

  2. Failure recovery of circulating NKG2D+CD56dimNK cells in HBV-associated hepatocellular carcinoma after hepatectomy predicts early recurrence

    PubMed Central

    Gao, Jian; Duan, Zhaojun; Zhang, Ling; Huang, Xiangbo; Long, Lu; Tu, Jing; Liang, Hua; Zhang, Yu; Shen, Tao; Lu, Fengmin

    2016-01-01

    Dysfunction of natural killer (NK) cells has been implicated in the failure of antitumor immune responses in hepatocellular carcinoma (HCC) patients. However, the changes of NK profile in peripheral blood after surgery and tumor tissues of HCC patients, as well as the underlying reason and the significance are vague. Here, we observed that the frequencies of circulating NKG2D+CD56dimNK cells decreased significantly in HBV-related HCC and were negatively correlated with the levels of serum TGF-? and soluble MICA (sMICA). In vitro experiments confirmed that the TGF-? and sMICA in tumor tissue homogenates, as well as sMICA in HCC cells culture supernatants could reduce the frequency of NKG2D+CD56dimNK cells. In addition, in HCC patients the lower frequency of circulating NKG2D+CD56dimNK cells was associated with larger tumor size and/or higher serum GGT. Noticeably, the frequency of NKG2D+CD56dimNK cells at one month after surgery usually failed to restore in early recurrent patients, and that frequency was negatively associated with early recurrence and shorter overall survival. These results suggest that declined frequency of NKG2D+CD56dimNK cells in HCC was associated with higher TGF-? and sMICA production, and low frequency of circulating NKG2D+CD56dimNK cells at one month after surgery may predict poor prognosis of HBV-related HCC patients accepting hepatectomy. PMID:26942056

  3. Safety and reactogenicity of DTPa-HBV-IPV/Hib and DTPa-IPV/I-Hib vaccines in a post-marketing surveillance setting.

    PubMed

    Lim, Fong Seng; Phua, Kong Boo; Lee, Bee Wah; Quak, Seng Hock; Teoh, Yee Leong; Ramakrishnan, Gunasekaran; Han, Htay-Htay; Van Der Meeren, Olivier; Jacquets, Jeanne-Marie; Bock, Hans L

    2011-01-01

    Combination vaccines have been shown to improve the timeliness of vaccination and vaccine coverage. Safety and reactogenicity of combined diphtheria-tetanus-acellular pertussis-inactivated poliovirus and Haemophilus influenzae type b vaccine (DTPa-IPV/Hib, Infanrix IPV+Hib, GlaxoSmithKline Biologicals) was assessed in two clinical studies. In Study A, 2,590 subjects received DTPa-IPV/Hib at 3, 4 and 5 months of age with a booster at 18 months. In Study B, 702 subjects received the same schedule but with DTPa-hepatitis B-IPV/Hib (DTPa-HBV-IPV/Hib, Infanrix hexa, GlaxoSmithKline Biologicals) vaccine administered at 5 months of age. Reactogenicity was assessed for four days after each dose using diary cards. Serious adverse events (SAEs) were assessed until 24 months of age. The vaccines were well tolerated. After primary vaccination, irritability was the most frequently reported grade 3 general symptom (0.8% of doses in both studies). Fever (axillary) > 39 degrees C was infrequent (0.3% of doses in Study A; 0.5% of doses in Study B). After the booster dose, the most frequently reported grade 3 symptom was redness (5%) in Study A and pain (0.5%) in Study B. An axillary temperature > 39 degrees C was reported in 1.1% of subjects. Throughout the study period, 646 SAEs were reported, of which 6 SAEs were considered to be vaccination-related. The reactogenicity and safety profile of the combined DTPa-IPV/Hib vaccine was good when used for primary and booster vaccinations in over 3,000 Singaporean infants. Substitution of DTPa-IPV/Hib with DTPa-HBV-IPV/Hib at Month 5 reduced the number of injections required at this age by one. PMID:21323176

  4. The Levels of Ghrelin, Leptin, TNF-?, and IL-6 in Liver Cirrhosis and Hepatocellular Carcinoma due to HBV and HDV Infection

    PubMed Central

    Ataseven, Huseyin; Bahcecioglu, Ibrahim Halil; Kuzu, Nalan; Yalniz, Mehmet; Celebi, Selman; Erensoy, Ahmet; Ustundag, Bilal

    2006-01-01

    Background/Aim. Malnutrition, a common problem in liver cirrhosis and HCC, may readily deteriorate the clinical functions with resultant poor prognosis. Beside the hyper catabolic state frequently encountered in chronic liver disease and HCC, anorexia and reduced food intake also worsen the malnutrition. The recently discovered peptide hormone ghrelin acts as a counterpart of leptin in regulation of food intake and fat utilization. The aim of the present study was to investigate the ghrelin and leptin levels in cirrhosis and HCC due to hepatitis B and D viruses, and the association of ghrelin and leptin with TNF-?, IL-6 and the severity of the disease. Materials and methods. We measured serum ghrelin, leptin, TNF-?, and IL-6 levels using specific immunoassay in 45 patients (23 cirrhosis, 22 HCC) with HBV and/or HDV and in 25 control subjects. Results. In comparison to controls, serum ghrelin, TNF-?, and IL-6 levels were significantly higher in cirrhosis and HCC (P < .05), whereas serum leptin levels were found decreased (P < .05). There was a positive correlation between ghrelin and TNF-?, and a negative correlation between leptin and TNF-? (P < .05). Conclusion. In cirrhosis and HCC due to HBV or HDV, serum ghrelin levels were increased with a corresponding decrease in serum leptin concentrations, acting as a physiological counterpart of ghrelin. The increasing of ghrelin is more prominent in Child C cirrhosis and the level was correlated with TNF-?. The presence of nutritional and metabolic abnormalities, including malnutrition, in cirrhosis and HCC may, at least partly, elucidate high ghrelin and low leptin levels. PMID:17047295

  5. Detection and genotyping of torque teno virus (TTV) in healthy blood donors and patients infected with HBV or HCV in Qatar.

    PubMed

    AbuOdeh, Raed; Al-Mawlawi, Naema; Al-Qahtani, Ahmed A; Bohol, Marie Fe F; Al-Ahdal, Mohammed N; Hasan, Haydar A; AbuOdeh, Lamees; Nasrallah, Gheyath K

    2015-07-01

    Torque Teno virus (TTV) has been associated with non A-G hepatitis. The goal of this study was to estimate the infection rates and genotypic characteristics of TTV in the State of Qatar. A total of 644 blood samples representing different nationalities: (i) Qatari (118) and (ii) non-Qatari (526) nationals (mostly from Arab and South Eeast Asia countries) were tested for the presence of TTV DNA by nested PCR. The majority (573) of the blood samples belonged to healthy blood donors, whereas 54 and 53 of the blood samples belonged to patients infected with hepatitis B virus (HBV) and hepatitis C virus (HCV), respectively. The results obtained showed that the TTV infection rates in the healthy blood donors, and those infected with HBV or HCV patients were 81.4, 90.75 and 84.9%, respectively. Significant association between TTV viremia and age, or nationality was observed. Sequence analysis of PCR fragments amplified from the 5'-untranslated region (5'-UTR) of all (531) TTV positive samples showed that 65.5% (348/531) of the PCR fragment sequences were classified into main genogroup 3, followed by main genogroups 5 (24%), 2 (5.8%), and 1 (4.7%). Genogroup 4 was not detected among the our studied subjects. Phylogenetic and pairwise analyses using sequences from TTV viremic samples also showed an overall close similarity to the main genogroup 3. In conclusion, there was no significant difference in the rates of TTV detection among Qataris and non-Qataris and several genotypes, mainly genotype 3, were isolated. PMID:25676255

  6. Potent killing of HBV-related hepatocellular carcinoma by a chimeric protein of anti-HBsAg single-chain antibody and truncated Bid.

    PubMed

    Yan, Bo; Ouyang, Qing; Zhao, Zhining; Cao, Feng; Wang, Tao; Jia, Xiaofei; Meng, Yanling; Jiang, Shuai; Liu, Jiayun; Chen, Rui; Jia, Lintao; Zhang, Rui; Wen, Weihong; Jin, Boquan; Chen, Siyi; Zhao, Jing; Yang, Angang

    2013-07-01

    Targeted therapy is needed for hepatitis B virus (HBV)-mediated hepatocellular carcinoma (HCC) which shows overexpression of HBV surface antigen (HBsAg). We previously developed scFv15, a human single-chain antibody against HBsAg. Here we tested the strategic feasibility of scFv15-mediated delivery of apoptotic effectors for HBsAg-targeted HCC therapy and application of HA2 motif of influenza hemagglutinin to enhance endosome escape and antitumor effect. A class of HBsAg-targeted immunoproapoptotic molecule was generated by sequentially fusing scFv15, the furin-cleavable motif from diphtheria toxin (Fdt), HA2 and a truncated apoptotic protein Bid (tBid). The resulting scFv15-Fdt-HA2-tBid was prokaryotically expressed and functionally characterized for HBsAg-binding capacity, endosome escape activity and antitumor effect as compared with scFv15-Fdt-tBid. Both scFv15-Fdt-HA2-tBid and scFv15-Fdt-tBid retained affinity and specificity for HBsAg, and bound and selectively killed HBsAg-positive HCC cells via apoptosis. Notably, the IC50 of scFv15-Fdt-HA2-tBid in HBsAg-positive PLC/PRF/5 cells was 10 times lower than that of scFv15-Fdt-tBid. In vivo imaging of antitumor activity demonstrated 95% growth inhibition of orthotopic HCC by scFv15-Fdt-HA2-tBid compared with 75% suppression by scFv15-Fdt-tBid. This study represents an extended application of the immunoproapoptotic strategy in the treatment of HBsAg-positive HCC and shows significant potential of HA2 as a functional enhancer for endosome-encapsulated antibody-conjugates. PMID:23562050

  7. Immunohistochemical expression of the PRO2268 protein in psoriasis vulgaris skin.

    PubMed

    Douroudis, Konstantinos; Sirotkina, Meeli; Kingo, Külli; Mössner, Rotraut; Kõks, Sulev

    2011-06-01

    The PRO2268 gene encodes for the PRO2268 molecule and maps to a chromosomal region (12q14), which clusters genes with a key role in immune signaling. Although the PRO2268 protein is as yet of unknown function, we should not exclude the possibility that the PRO2268 gene, because of its location, might have a distinct role in autoimmunity and inflammation. The aim of the present study was to investigate the expression pattern of the PRO2268 protein in psoriasis skin. Formalin-fixed paraffin-embedded sections from normal and psoriasis skin tissue were studied immunohistochemically using custom-ordered antibodies (anti-PRO2268#1 and anti-PRO2268#2) against the PRO2268. The present study revealed an expression of the anti-PRO2268#2 in the inflammatory infiltrate, and suggesting a possible role for the PRO2268 molecule in pathophysiology of psoriasis, which needs further investigation. PMID:21414369

  8. GeoPro: Technology to Enable Scientific Modeling

    SciTech Connect

    C. Juan

    2004-02-09

    Development of the ground-water flow model for the Death Valley Regional Groundwater Flow System (DVRFS) required integration of numerous supporting hydrogeologic investigations. The results from recharge, discharge, hydraulic properties, water level, pumping, model boundaries, and geologic studies were integrated to develop the required conceptual and 3-D framework models, and the flow model itself. To support the complex modeling process and the needs of the multidisciplinary DVRFS team, a hardware and software system called GeoPro (Geoscience Knowledge Integration Protocol) was developed. A primary function of GeoPro is to manage the large volume of disparate data compiled for the 100,000-square-kilometer area of southern Nevada and California. The data are primarily from previous investigations and regional flow models developed for the Nevada Test Site and Yucca Mountain projects. GeoPro utilizes relational database technology (Microsoft SQL Server{trademark}) to store and manage these tabular point data, groundwater flow model ASCII data, 3-D hydrogeologic framework data, 2-D and 2.5-D GIS data, and text documents. Data management consists of versioning, tracking, and reporting data changes as multiple users access the centralized database. GeoPro also supports the modeling process by automating the routine data transformations required to integrate project software. This automation is also crucial to streamlining pre- and post-processing of model data during model calibration. Another function of GeoPro is to facilitate the dissemination and use of the model data and results through web-based documents by linking and allowing access to the underlying database and analysis tools. The intent is to convey to end-users the complex flow model product in a manner that is simple, flexible, and relevant to their needs. GeoPro is evolving from a prototype system to a production-level product. Currently the DVRFS pre- and post-processing modeling tools are being re-engineered to improve their versatility, ease-of-deployment, and integration with GeoPro and current GIS technology. For instance, a Microsoft Access application used to analyze and develop model head observations from water-level data is being re-engineered to use SQL Server{trademark} and ArcMap. At present, GeoPro improves the modeling process by (1) reducing data discovery time, (2) automating routine data manipulations, and (3) integrating and sharing analysis and visualization tools. When fully developed, it is envisioned that GeoPro will also (1) provide consistency between reports, databases, models, and archives, and (2) provide a means to develop and share best work practices with future projects.

  9. [Requirement of standardizing anti-HBs assay methods in Japan for HBV infection-preventing strategy--discrepancy of anti-HBs measurements among three different kits widely used in Japan].

    PubMed

    Ogata, Norio

    2006-09-01

    The strategy to eliminate hepatitis B virus (HBV) infection by administrating an HB vaccine is changing worldwide; however, this is not the case in Japan. An important concern about the HBV infection-preventing strategy in Japan may be that the assay methods for the antibody to hepatitis B surface antigen (anti-HBs) are not standardized. The minimum protective anti-HBs titer against HBV infection has been established as 10 mIU/ml by World Health Organization (WHO) -standardized assay methods worldwide, but that is still determined as a "positive" test result by the passive hemagglutination (PHA) method in Japan. We compared anti-HBs measurements in given samples among PHA(Mycell II, Institute of Immunology), chemiluminescent enzyme immunoassay (CLEIA) (Lumipulse, Fujirebio), and chemiluminescent immunoassay (CLIA) (Architect, Abbott), all of which are currently in wide use in Japan. First, anti-HBs measurements in serum from individuals who received a yeast-derived recombinant HB vaccine composed of the major surface protein of either subtype adr or subtype ayw were compared. The results clearly showed that in subtype adr-vaccinees CLIA underestimated the anti-HBs amount compared with CLEIA and PHA, but in ayw-vaccinees, the discordance in the measurements among the three kits was not prominent. Second, anti-HBs measurements in standard or calibration solutions of each assay kit were compared. Surprisingly, CLEIA showed higher measurements in all three kit-associated standard or calibration solutions than CLIA. Thus, the anti-HBs titer of 10 mIU/ml is difficult to introduce in Japan as the minimum protective level against HBV infection. Efforts to standardize anti-HBs assay methods are expected to share international evidence about the HBV infection-preventing strategy. PMID:17063878

  10. Development of the Flight Tether for ProSEDS

    NASA Technical Reports Server (NTRS)

    Curtis, Leslie; Vaughn, Jason; Welzyn, Ken; Carroll, Joe; Brown, Norman S. (Technical Monitor)

    2002-01-01

    The Propulsive Small Expendable Deployer System (ProSEDS) space experiment will demonstrate the use of an electrodynamic tether propulsion system to generate thrust in space by decreasing the orbital altitude of a Delta 11 Expendable Launch Vehicle second stage. ProSEDS will use the flight-proven Small Expendable Deployer System to deploy a newly designed and developed tether which will provide tether generated drag thrust of approx. 0.4 N. The development and production of very long tethers with specific properties for performance and survivability will be required to enable future tether missions. The ProSEDS tether design and the development process may provide some lessons learned for these future missions. The ProSEDS system requirements drove the design of the tether to have three different sections of tether each serving a specialized purpose. The tether is a total of 15 kilometers long: 10 kilometers of a non-conductive Dyneema lead tether; 5 km of CCOR conductive coated wire; and 220 meters of insulated wire with a protective Kevlar overbraid. Production and joining of long tether lengths involved many development efforts. Extensive testing of tether materials including ground deployment of the full-length ProSEDS tether was conducted to validate the tether design and performance before flight.

  11. Development of the flight tether for ProSEDS

    NASA Astrophysics Data System (ADS)

    Curtis, Leslie; Vaughn, Jason; Welzyn, Ken; Carroll, Joe

    2002-01-01

    The Propulsive Small Expendable Deployer System (ProSEDS) space experiment will demonstrate the use of an electrodynamic tether propulsion system to generate thrust in space by decreasing the orbital altitude of a Delta II Expendable Launch Vehicle second stage. ProSEDS will use the flight-proven Small Expendable Deployer System to deploy a newly designed and developed tether which will provide tether generated drag thrust of ~0.4 N. The development and production of very long tethers with specific properties for performance and survivability will be required to enable future tether missions. The ProSEDS tether design and the development process may provide some lessons learned for these future missions. The ProSEDS system requirements drove the design of the tether to have three different sections of tether each serving a specialized purpose. The tether is a total of 15 kilometers long: 10 kilometers of a non-conductive Dyneema lead tether; 5 km of CCOR conductive coated wire; and 220 meters of insulated wire with a protective Kevlar overbraid. Production and joining of long tether lengths involved many development efforts. Extensive testing of tether materials including ground deployment of the full-length ProSEDS tether was conducted to validate the tether design and performance before flight. .

  12. Propulsive Small Expendable Deployer System (ProSEDS)

    NASA Astrophysics Data System (ADS)

    Ballance, Judy; Johnson, Les

    2001-02-01

    The Propulsive Small Expendable Deployer System (ProSEDS) space experiment will demonstrate the use of an electrodynamic tether propulsion system to generate thrust in space by decreasing the orbital altitude of a Delta II expendable launch vehicle (ELV) second stage. ProSEDS, which is planned to fly in 2001, will use the flight-proven Small Expendable Deployer System (SEDS) to deploy a tether (5-km bare wire plus 10-km spectra or dyneema) from a Delta II second stage to achieve ~0.4 N drag thrust, ProSEDS will utilize the tether-generated current to provide limited spacecraft power. The ProSEDS instrumentation includes a Langmuir probe and differential ion flux probe, which will determine the characteristics of the ambient ionospheric plasma. Two global positioning system (GPS) receivers will be used (one on the Delta and one on the endmass) to help determine tether dynamics and to limit transmitter operations to occasions when the spacecraft is over selected ground stations. The flight experiment is a precursor to the more ambitious electrodynamic tether upperstage demonstration mission, which will be capable of orbit raising, lowering, and inclination changes-all using electrodynamic thrust. An immediate application of ProSEDS technology is for the deorbit of spent satellites for orbital debris mitigation. In addition to the use of this technology to provide orbit transfer and debris mitigation, it may also be an attractive option for future missions to Jupiter and any other planetary body with a magnetosphere. .

  13. Propulsive Small Expendable Deployer System (ProSEDS)

    NASA Technical Reports Server (NTRS)

    Ballance, Judy; Johnson, Les; Rogacki, John R. (Technical Monitor)

    2000-01-01

    The Propulsive Small Expendable Deployer System (ProSEDS) space experiment will demonstrate the use of an electrodynamic tether propulsion system to generate thrust in space by decreasing the orbital altitude of a Delta II Expendable Launch Vehicle (ELV) second stage. ProSEDS, which is planned to fly in 2001, will use the flight proven Small Expendable Deployer System (SEDS) to deploy a tether (5km bare wire plus 10 km spectra or dyneema) from a Delta II second stage to achieve approximately 0.4N drag thrust. ProSEDS will utilize the tether-generated current to provide limited spacecraft power. The ProSEDs instrumentation includes a Langmuir probe and Differential Ion Flux Probe, which will determine the characteristics of the ambient ionospheric plasma. Two Global Positioning System (GPS) receivers will be used (one on the Delta and one on the endmass) to help determine tether dynamics and to limit transmitter operations to occasions when the spacecraft is over selected ground stations, The flight experiment is a precursor to the more ambitious electrodynamic tether upper stage demonstration mission, which will be capable of orbit raising, lowering and inclination changes-all using electrodynamic thrust. An immediate application of ProSEDS technology is for the deorbit of spent satellites for orbital debris mitigation. In addition to the use of this technology to provide orbit transfer and debris mitigation it may also be an attractive option for future missions to Jupiter and any other planetary body with a magnetosphere.

  14. Milk-Derived Tripeptides IPP (Ile-Pro-Pro) and VPP (Val-Pro-Pro) Promote Adipocyte Differentiation and Inhibit Inflammation in 3T3-F442A Cells

    PubMed Central

    Chakrabarti, Subhadeep; Wu, Jianping

    2015-01-01

    Milk derived tripeptides IPP (Ile-Pro-Pro) and VPP (Val-Pro-Pro) have shown promise as anti-hypertensive agents due to their inhibitory effects on angiotensin converting enzyme (ACE). Due to the key inter-related roles of hypertension, chronic inflammation and insulin resistance in the pathogenesis of metabolic syndrome, there is growing interest in investigating established anti-hypertensive agents for their effects on insulin sensitivity and inflammation. In this study, we examined the effects of IPP and VPP on 3T3-F442A murine pre-adipocytes, a widely used model for studying metabolic diseases. We found that both IPP and VPP induced beneficial adipogenic differentiation as manifested by intracellular lipid accumulation, upregulation of peroxisome proliferator-activated receptor gamma (PPAR?) and secretion of the protective lipid hormone adiponectin by these cells. The observed effects were similar to those induced by insulin, suggesting potential benefits in the presence of insulin resistance. IPP and VPP also inhibited cytokine induced pro-inflammatory changes such as reduction in adipokine levels and activation of the nuclear factor kappa B (NF-?B) pathway. Taken together, our findings suggest that IPP and VPP exert insulin-mimetic adipogenic effects and prevent inflammatory changes in adipocytes, which may offer protection against metabolic disease. PMID:25714093

  15. Presence of pro-tobacco messages on the Web.

    PubMed

    Hong, Traci; Cody, Michael J

    2002-01-01

    Ignored in the finalized Master Settlement Agreement (National Association of Attorneys General, 1998), the unmonitored, unregulated World Wide Web (Web) can operate as a major vehicle for delivering pro-tobacco messages, images, and products to millions of young consumers. A content analysis of 318 randomly sampled pro-tobacco Web sites revealed that tobacco has a pervasive presence on the Web, especially on e-commerce sites and sites featuring hobbies, recreation, and "fetishes." Products can be ordered online on nearly 50% of the sites, but only 23% of the sites included underage verification. Further, only 11% of these sites contain health warnings. Instead, pro-tobacco sites frequently associate smoking with "glamorous" and "alternative" lifestyles, and with images of young males and young (thin, attractive) females. Finally, many of the Web sites offered interactive site features that are potentially appealing to young Web users. Recommendations for future research and counterstrategies are discussed. PMID:12356288

  16. Motoneuron Programmed Cell Death in Response to proBDNF

    PubMed Central

    Taylor, AR; Gifondorwa, DJ; Robinson, MB; Strupe, JL; Prevette, D; Johnson, JE; Hempstead, BL; Oppenheim, RW; Milligan, CE

    2011-01-01

    Motoneurons (MN) as well as most neuronal populations undergo a temporally and spatially specific period of programmed cell death (PCD). Several factors have been considered to regulate the survival of MNs during this period, including availability of muscle-derived trophic support and activity. The possibility that target-derived factors may also negatively regulate MN survival has been considered, but not pursued. Neurotrophin precursors, through their interaction with p75NTR and sortilin receptors have been shown to induce cell death during development and following injury in the CNS. In this study, we find that muscle cells produce and secrete proBDNF. ProBDNF through its interaction with p75NTR and sortilin, promotes a caspase-dependent death of MNs in culture. We also provide data to suggest that proBDNF regulates MN PCD during development in vivo. PMID:21834083

  17. The neuropsychology of infants pro-social preferences

    PubMed Central

    Gredebck, Gustaf; Kaduk, Katharina; Bakker, Marta; Gottwald, Janna; Ekberg, Therese; Elsner, Claudia; Reid, Vincent; Kenward, Ben

    2015-01-01

    The current study is the first to investigate neural correlates of infants detection of pro- and antisocial agents. Differences in ERP component P400 over posterior temporal areas were found during 6-month-olds observation of helping and hindering agents (Experiment 1), but not during observation of identically moving agents that did not help or hinder (Experiment 2). The results demonstrate that the P400 component indexes activation of infants memories of previously perceived interactions between social agents. This leads to suggest that similar processes might be involved in infants processing of pro- and antisocial agents and other social perception processes (encoding gaze direction, goal directed grasping and pointing). PMID:25681955

  18. Cancer exosomes trigger mesenchymal stem cell differentiation into pro-angiogenic and pro-invasive myofibroblasts

    PubMed Central

    Gurney, Mark; Mason, Malcolm D.; Tabi, Zsuzsanna; Clayton, Aled

    2015-01-01

    Stromal fibroblasts become altered in response to solid cancers, to exhibit myofibroblastic characteristics, with disease promoting influence. Infiltrating mesenchymal stem cells (MSC) may contribute towards these changes, but the factors secreted by cancer cells that impact MSC differentiation are poorly understood. We investigated the role of nano-metre sized vesicles (exosomes), secreted by prostate cancer cells, on the differentiation of bone-marrow MSC (BM-MSC), and the subsequent functional consequences of such changes. Purified exosomes impaired classical adipogenic differentiation, skewing differentiation towards alpha-smooth muscle actin (?SMA) positive myofibroblastic cells. A single exosomes treatment generated myofibroblasts secreting high levels of VEGF-A, HGF and matrix regulating factors (MMP-1, ?3 and ?13). Differentiated MSC had pro-angiogenic functions and enhanced tumour proliferation and invasivity assessed in a 3D co-culture model. Differentiation was dependent on exosomal-TGF?, but soluble TGF? at matched dose could not generate the same phenotype. Exosomes present in the cancer cell secretome were the principal factors driving this phenotype. Prostate cancer exosomes dominantly dictate a programme of MSC differentiation generating myofibroblasts with functional properties consistent with disease promotion. PMID:25596732

  19. Two-dimensional 13C NMR study of the substance P fragment Arg?Pro?Lys?Pro

    NASA Astrophysics Data System (ADS)

    Otter, Albin; Kotovych, George

    The N-terminal Substance P fragment Arg 1?Pro 2?Lys 3?Pro 4 (SP 1-4) has been studied by means of natural abundance 13C NMR. By the combined application of various two-dimensional {13C}/{1H} correlation techniques, all 13C resonances in both isomeric forms (cis and trans about the Lys 3?Pro 4 peptide bond) including the quaternary carbons could be assigned unambiguously. The experimental details are outlined and the results are discussed in terms of the peptide conformation. From the data it can be concluded that the cis-SP 1-4 is stabilized by a charge interaction between the end group of the Lys 3 side chain and the deprotonated carboxyl group at the C-terminal end of the peptide. A ring-like interaction with the Arg 1 residue can be excluded. Some 13C? 1H long-range coupling constant have also been measured.

  20. Ionizing radiation modulates human macrophages towards a pro-inflammatory phenotype preserving their pro-invasive and pro-angiogenic capacities

    PubMed Central

    Teresa Pinto, Ana; Laranjeiro Pinto, Marta; Patrícia Cardoso, Ana; Monteiro, Cátia; Teixeira Pinto, Marta; Filipe Maia, André; Castro, Patrícia; Figueira, Rita; Monteiro, Armanda; Marques, Margarida; Mareel, Marc; dos Santos, Susana Gomes; Seruca, Raquel; Adolfo Barbosa, Mário; Rocha, Sónia; José Oliveira, Maria

    2016-01-01

    In order to improve the efficacy of conventional radiotherapy, attention has been paid to immune cells, which not only modulate cancer cell response to therapy but are also highly recruited to tumours after irradiation. Particularly, the effect of ionizing radiation on macrophages, using therapeutically relevant doses, is not well understood. To evaluate how radiotherapy affects macrophage behaviour and macrophage-mediated cancer cell activity, human monocyte derived-macrophages were subjected, for a week, to cumulative ionizing radiation doses, as used during cancer treatment (2 Gy/fraction/day). Irradiated macrophages remained viable and metabolically active, despite DNA damage. NF-kappaB transcription activation and increased Bcl-xL expression evidenced the promotion of pro-survival activity. A significant increase of pro-inflammatory macrophage markers CD80, CD86 and HLA-DR, but not CCR7, TNF and IL1B was observed after 10 Gy cumulative doses, while anti-inflammatory markers CD163, MRC1, VCAN and IL-10 expression decreased, suggesting the modulation towards a more pro-inflammatory phenotype. Moreover, ionizing radiation induced macrophage morphological alterations and increased their phagocytic rate, without affecting matrix metalloproteases (MMP)2 and MMP9 activity. Importantly, irradiated macrophages promoted cancer cell-invasion and cancer cell-induced angiogenesis. Our work highlights macrophage ability to sustain cancer cell activities as a major concern that needs to be addressed to improve radiotherapy efficacy. PMID:26735768

  1. Ionizing radiation modulates human macrophages towards a pro-inflammatory phenotype preserving their pro-invasive and pro-angiogenic capacities.

    PubMed

    Teresa Pinto, Ana; Laranjeiro Pinto, Marta; Patrcia Cardoso, Ana; Monteiro, Ctia; Teixeira Pinto, Marta; Filipe Maia, Andr; Castro, Patrcia; Figueira, Rita; Monteiro, Armanda; Marques, Margarida; Mareel, Marc; Dos Santos, Susana Gomes; Seruca, Raquel; Adolfo Barbosa, Mrio; Rocha, Snia; Jos Oliveira, Maria

    2016-01-01

    In order to improve the efficacy of conventional radiotherapy, attention has been paid to immune cells, which not only modulate cancer cell response to therapy but are also highly recruited to tumours after irradiation. Particularly, the effect of ionizing radiation on macrophages, using therapeutically relevant doses, is not well understood. To evaluate how radiotherapy affects macrophage behaviour and macrophage-mediated cancer cell activity, human monocyte derived-macrophages were subjected, for a week, to cumulative ionizing radiation doses, as used during cancer treatment (2?Gy/fraction/day). Irradiated macrophages remained viable and metabolically active, despite DNA damage. NF-kappaB transcription activation and increased Bcl-xL expression evidenced the promotion of pro-survival activity. A significant increase of pro-inflammatory macrophage markers CD80, CD86 and HLA-DR, but not CCR7, TNF and IL1B was observed after 10?Gy cumulative doses, while anti-inflammatory markers CD163, MRC1, VCAN and IL-10 expression decreased, suggesting the modulation towards a more pro-inflammatory phenotype. Moreover, ionizing radiation induced macrophage morphological alterations and increased their phagocytic rate, without affecting matrix metalloproteases (MMP)2 and MMP9 activity. Importantly, irradiated macrophages promoted cancer cell-invasion and cancer cell-induced angiogenesis. Our work highlights macrophage ability to sustain cancer cell activities as a major concern that needs to be addressed to improve radiotherapy efficacy. PMID:26735768

  2. HBpF-proBDNF: A New Tool for the Analysis of Pro-Brain Derived Neurotrophic Factor Receptor Signaling and Cell Biology.

    PubMed

    Gaub, Perrine; de Léon, Andrès; Gibon, Julien; Soubannier, Vincent; Dorval, Geneviève; Séguéla, Philippe; Barker, Philip A

    2016-01-01

    Neurotrophins activate intracellular signaling pathways necessary for neuronal survival, growth and apoptosis. The most abundant neurotrophin in the adult brain, brain-derived neurotrophic factor (BDNF), is first synthesized as a proBDNF precursor and recent studies have demonstrated that proBDNF can be secreted and that it functions as a ligand for a receptor complex containing p75NTR and sortilin. Activation of proBDNF receptors mediates growth cone collapse, reduces synaptic activity, and facilitates developmental apoptosis of motoneurons but the precise signaling cascades have been difficult to discern. To address this, we have engineered, expressed and purified HBpF-proBDNF, an expression construct containing a 6X-HIS tag, a biotin acceptor peptide (BAP) sequence, a PreScission™ Protease cleavage site and a FLAG-tag attached to the N-terminal part of murine proBDNF. Intact HBpF-proBDNF has activities indistinguishable from its wild-type counterpart and can be used to purify proBDNF signaling complexes or to monitor proBDNF endocytosis and retrograde transport. HBpF-proBDNF will be useful for characterizing proBDNF signaling complexes and for deciphering the role of proBDNF in neuronal development, synapse function and neurodegenerative disease. PMID:26950209

  3. HBpF-proBDNF: A New Tool for the Analysis of Pro-Brain Derived Neurotrophic Factor Receptor Signaling and Cell Biology

    PubMed Central

    Gaub, Perrine; de Léon, Andrès; Gibon, Julien; Soubannier, Vincent; Dorval, Geneviève; Séguéla, Philippe; Barker, Philip A.

    2016-01-01

    Neurotrophins activate intracellular signaling pathways necessary for neuronal survival, growth and apoptosis. The most abundant neurotrophin in the adult brain, brain-derived neurotrophic factor (BDNF), is first synthesized as a proBDNF precursor and recent studies have demonstrated that proBDNF can be secreted and that it functions as a ligand for a receptor complex containing p75NTR and sortilin. Activation of proBDNF receptors mediates growth cone collapse, reduces synaptic activity, and facilitates developmental apoptosis of motoneurons but the precise signaling cascades have been difficult to discern. To address this, we have engineered, expressed and purified HBpF-proBDNF, an expression construct containing a 6X-HIS tag, a biotin acceptor peptide (BAP) sequence, a PreScission™ Protease cleavage site and a FLAG-tag attached to the N-terminal part of murine proBDNF. Intact HBpF-proBDNF has activities indistinguishable from its wild-type counterpart and can be used to purify proBDNF signaling complexes or to monitor proBDNF endocytosis and retrograde transport. HBpF-proBDNF will be useful for characterizing proBDNF signaling complexes and for deciphering the role of proBDNF in neuronal development, synapse function and neurodegenerative disease. PMID:26950209

  4. Monoclonal antibodies to the carboxy-terminal Ea sequence of pro-insulin-like growth factor-IA (proIGF-IA) recognize proIGF-IA secreted by IM9 B-lymphocytes.

    PubMed

    Wilson, H E; Westwood, M; White, A; Clayton, P E

    2001-02-01

    Insulin-like growth factor-I (IGF-I) circulates in human serum as a 7 kDa peptide but analysis of IGF-I cDNAs predicts two pro-hormone precursors (proIGF-IA and proIGF-IB) with distinct C-terminal E domains. The function of these precursors, and the E peptides generated on cleavage to mature IGF-I, is unknown, largely because of a lack of tools for distinguishing precursors from constituent peptides. We used a synthetic Ea peptide to develop monoclonal antibodies (MAbs) which can recognize the carboxy-terminal sequence of proIGF-IA. These were characterized using proIGF-IA generated by transfected HEK293 cells. The anti-proIGF-IA MAbs immunoprecipitated two peptides (19--21 and 14 kDa) which were also recognized by MAbs to mature IGF-I. The proIGF-IA MAbs could also detect peptides of 9 and 4 kDa predicted to be Ea peptides. Treatment with N -glycosidase proved the 19--21 kDa and 9 kDa bands to be glycosylated proIGF-IA and Ea peptide respectively. Using these antibodies, we have identified proIGF-IA secreted from the IM9 B-lymphocyte cell line. This work paves the way for studies on proIGF-IA and Ea peptide regulation and function. PMID:11437469

  5. DNA immunization with fusion genes encoding different regions of hepatitis C virus E2 fused to the gene for hepatitis B surface antigen elicits immune responses to both HCV and HBV

    PubMed Central

    Jin, Jing; Yang, Jian-Ying; Liu, Jing; Kong, Yu-Ying; Wang, Yuan; Li, Guang-Di

    2002-01-01

    AIM: Both Hepatitis B virus (HBV) and Hepatitis C virus (HCV) are major causative agents of transfusion-associated and community-acquired hepatitis worldwide. Development of a HCV vaccine as well as more effective HBV vaccines is an urgent task. DNA immunization provides a promising approach to elicit protective humoral and cellular immune responses against viral infection. The aim of this study is to achieve immune responses against both HCV and HBV by DNA immunization with fusion constructs comprising various HCV E2 gene fragments fused to HBsAg gene of HBV. METHODS: C57BL/6 mice were immunized with plasmid DNA expressing five fragments of HCV E2 fused to the gene for HBsAg respectively. After one primary and one boosting immunizations, antibodies against HCV E2 and HBsAg were tested and subtyped in ELISA. Splenic cytokine expression of IFN-? and IL-10 was analyzed using an RT-PCR assay. Post-immune mouse antisera also were tested for their ability to capture HCV viruses in the serum of a hepatitis C patient in vitro. RESULTS: After immunization, antibodies against both HBsAg and HCV E2 were detected in mouse sera, with IgG2a being the dominant immunoglobulin sub-class. High-level expression of INF-? was detected in cultured splenic cells. Mouse antisera against three of the five fusion constructs were able to capture HCV viruses in an in vitro assay. CONCLUSION: The results indicate that these fusion constructs could efficiently elicit humoral and Th1 dominant cellular immune responses against both HBV S and HCV E2 antigens in DNA-immunized mice. They thus could serve as candidates for a bivalent vaccine against HBV and HCV infection. In addition, the capacity of mouse antisera against three of the five fusion constructs to capture HCV viruses in vitro suggested that neutralizing epitopes may be present in other regions of E2 besides the hypervariable region 1. PMID:12046080

  6. Winter Skin-Care Tips from A Pro

    MedlinePLUS

    ... FAQs Contact Us Health Topics Drugs & Supplements Videos & Tools Español You Are Here: Home → Latest Health News → Article URL of this page: https://www.nlm.nih.gov/medlineplus/news/fullstory_157386.html Winter Skin-Care Tips From a Pro Oil-based creams, ointments deliver more moisture, dermatologist ...

  7. Virtex-II Pro SEE Test Methods and Results

    NASA Technical Reports Server (NTRS)

    Petrick, David; Powell, Wesley; Howard, James W., Jr.; LaBel, Kenneth A.

    2004-01-01

    The objective of this coarse Single Event Effect (SEE) test is to determine the suitability of the commercial Virtex-II Pro family for use in spaceflight applications. To this end, this test is primarily intended to determine any Singe Event Latchup (SEL) susceptibilities for these devices. Secondly, this test is intended to measure the level of Single Event Upset (SEU) susceptibilities and in a general sense where they occur. The coarse SEE test was performed on a commercial XC2VP7 device, a relatively small single processor version of the Virtex-II Pro. As the XC2VP7 shares the same functional block design and fabrication process with the larger Virtex-II Pro devices, the results of this test should also be applicable to the larger devices. The XC2VP7 device was tested on a commercial Virtex-II Pro development board. The testing was performed at the Cyclotron laboratories at Texas A&M and Michigan State Universities using ions of varying energy levels and fluences.

  8. Variables Related to Pro-Choice Attitudes among Undergraduates.

    ERIC Educational Resources Information Center

    Wright, Loyd S.; Rogers, Robyn R.

    1987-01-01

    Used self-administered questionnaires to assess pro-choice attitudes of 840 undergraduates just prior to the 1984 presidential election. Students were asked whether they would approve or disapprove of abortion under four different circumstances. Results indicated that the majority of both males and females were in favor of allowing abortion under…

  9. Watts Up? Pro AC Power Meter for Automated Energy Recording

    PubMed Central

    Hirst, Jason M.; Miller, Jonathan R.; Kaplan, Brent A.; Reed, Derek D.

    2013-01-01

    The purpose of the present paper is to review the Watts up? Pro AC power meter. Evaluations of the meter's reliability for measuring energy consumption by consumer electronics yielded acceptable levels of reliability. Implications and limitations for the use of this product in behavior analytic research and practice are discussed.

  10. MEMS Pro Design Kit - Parts A, B, and C

    Energy Science and Technology Software Center (ESTSC)

    2006-06-15

    Part A: SUMMiT V design Kit components for use with MEMS Pro from SoftMEMS Part B: SUMMiT V remote DRC and gear generator source code for use with autocad visual basic Part C: SUMMiT V DRC rules source and test cases for Calibre DRC engine

  11. Do Null Subjects (Mis-)Trigger Pro-Drop Grammars?

    ERIC Educational Resources Information Center

    Frazier, Lyn

    2015-01-01

    Native speakers of English regularly hear sentences without overt subjects. Nevertheless, they maintain a [[superscript -]pro] grammar that requires sentences to have an overt subject. It is proposed that listeners of English recognize that speakers reduce predictable material and thus attribute null subjects to this process, rather than changing

  12. Review of the ProSEDS Electrodynamic Tether Mission Development

    NASA Technical Reports Server (NTRS)

    Vaughn, Jason A.; Curtis, Leslie; Gilchrist, Brian E.; Bilen, Sven; Lorenzini, Enrico

    2004-01-01

    The Propulsive Small Expendable Deployer System (ProSEDS) space experiment was ready to fly as a secondary payload on a Delta-II expendable launch vehicle in late March 2003. Concerns raised in February 2003 by the International Space Station resulted in the delay of the launch of ProSEDS. Issues associated with the delayed launch date and a change in starting altitude resulted in the cancellation of the mission. ProSEDS was intended to deploy a tether (5 km bare wire plus 10 km non-conducting Dyneema) from a Delta I1 second stage to achieve adequate drag thrust that would lower the orbit of the system over days as opposed to months due to atmospheric drag. It was also designed to utilize the tether-generated current to provide limited spacecraft power. Considerable effort and testing went in to developing the ProSEDS system by a dedicated team. Through this effort, important technological issues were identified and addressed and this presentation will discuss some of the important technical issues and hurdles that had to be addressed to successfully prepare for flight. It is intended that this information will be of use for future tether mission and experiment designers.

  13. Potent antioxidant dendrimers lacking pro-oxidant activity.

    PubMed

    Lee, Choon Young; Sharma, Ajit; Uzarski, Rebecca L; Cheong, Jae Eun; Xu, Hao; Held, Rich A; Upadhaya, Samik K; Nelson, Julie L

    2011-04-15

    It is well known that antioxidants have protective effects against oxidative stress. Unfortunately, in the presence of transition metals, antioxidants, including polyphenols with potent antioxidant activities, may also exhibit pro-oxidant effects, which may irreversibly damage DNA. Therefore, antioxidants with strong free radical-scavenging abilities and devoid of pro-oxidant effects would be of immense biological importance. We report two antioxidant dendrimers with a surface rich in multiple phenolic hydroxyl groups, benzylic hydrogens, and electron-donating ring substituents that contribute to their potent free radical-quenching properties. To minimize their pro-oxidant effects, the dendrimers were designed with a metal-chelating tris(2-aminoethyl)amine (TREN) core. The dendritic antioxidants were prepared by attachment of six syringaldehyde or vanillin molecules to TREN by reductive amination. They exhibited potent radical-scavenging properties: 5 times stronger than quercetin and 15 times more potent than Trolox according to the 1,1-diphenyl-2-picrylhydrazyl assay. The antioxidant dendrimers also protected low-density lipoprotein, lysozyme, and DNA against 2,2'-azobis(2-amidinopropane) dihydrochloride-induced free radical damage. More importantly, unlike quercetin and Trolox, the two TREN antioxidant dendrimers did not damage DNA via their pro-oxidant effects when incubated with physiological amounts of copper ions. The dendrimers also showed no cytotoxicity toward Chinese hamster ovary cells. PMID:20977937

  14. Language Impaired Children's Interpretation of PRO: A Longitudinal Study.

    ERIC Educational Resources Information Center

    Hsu, Jennifer R.; And Others

    The study evaluated whether specifically language impaired (SLI) children (N=6 and ages 5-8) manifested atypical or normal but delayed development in their interpretation of PRO (an empty pronomial element which has also been termed "a missing complement subject"). Language samples were taken and analyzed twice over a 9-12 month period. Among

  15. Memory for Pro-Social Intentions: When Competing Motives Collide

    ERIC Educational Resources Information Center

    Brandimonte, Maria A.; Ferrante, Donatella; Bianco, Carmela; Villani, Maria Grazia

    2010-01-01

    Memory for future actions, or "prospective memory" (PM), often involves remembering to do things "for others". The present article explores the motivational mechanisms underlying memory for pro-social intentions through the manipulation of the social relevance of goals and presence of material rewards during an activity-based PM task. Results

  16. Variables Related to Pro-Choice Attitudes among Undergraduates.

    ERIC Educational Resources Information Center

    Wright, Loyd S.; Rogers, Robyn R.

    1987-01-01

    Used self-administered questionnaires to assess pro-choice attitudes of 840 undergraduates just prior to the 1984 presidential election. Students were asked whether they would approve or disapprove of abortion under four different circumstances. Results indicated that the majority of both males and females were in favor of allowing abortion under

  17. Affordance, Learning Opportunities, and the Lesson Plan Pro Forma

    ERIC Educational Resources Information Center

    Anderson, Jason

    2015-01-01

    This article argues that the most commonly used lesson plan pro formas in language teacher education are inappropriately premised on an outcomes-based approach to teaching, one that is in conflict with what we know about how languages are learnt and how experienced teachers teach. It proposes an alternative, affordance-based approach to lesson

  18. 31 CFR 50.93 - Application of pro rata share.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 31 Money and Finance: Treasury 1 2013-07-01 2013-07-01 false Application of pro rata share. 50.93 Section 50.93 Money and Finance: Treasury Office of the Secretary of the Treasury TERRORISM RISK INSURANCE... from a subsequent act of terrorism....

  19. Affecting Community Change: Involving "Pro Bono" Professionals as Extension Volunteers

    ERIC Educational Resources Information Center

    Kelley, Diane T.; Culp, Ken, III

    2013-01-01

    "Pro bono" volunteers provide an effective means for Extension professionals to expand limited financial and human resources. Volunteers recruited from business settings can provide skills, abilities, expertise, leadership, and resources to Extension programs. Allowing professional volunteers to meet their desired leadership goals while

  20. Promoting pro-environmental action in climate change deniers

    NASA Astrophysics Data System (ADS)

    Bain, Paul G.; Hornsey, Matthew J.; Bongiorno, Renata; Jeffries, Carla

    2012-08-01

    A sizeable (and growing) proportion of the public in Western democracies deny the existence of anthropogenic climate change. It is commonly assumed that convincing deniers that climate change is real is necessary for them to act pro-environmentally. However, the likelihood of `conversion' using scientific evidence is limited because these attitudes increasingly reflect ideological positions. An alternative approach is to identify outcomes of mitigation efforts that deniers find important. People have strong interests in the welfare of their society, so deniers may act in ways supporting mitigation efforts where they believe these efforts will have positive societal effects. In Study 1, climate change deniers (N=155) intended to act more pro-environmentally where they thought climate change action would create a society where people are more considerate and caring, and where there is greater economic/technological development. Study 2 (N=347) replicated this experimentally, showing that framing climate change action as increasing consideration for others, or improving economic/technological development, led to greater pro-environmental action intentions than a frame emphasizing avoiding the risks of climate change. To motivate deniers' pro-environmental actions, communication should focus on how mitigation efforts can promote a better society, rather than focusing on the reality of climate change and averting its risks.

  1. Mexican American Adolescents' Perceptions of a Pro-College Culture

    ERIC Educational Resources Information Center

    Castillo, Linda G.; Conoley, Collie W.; Cepeda, Lisa M.; Ivy, Karen K.; Archuleta, Debra J.

    2010-01-01

    Three focus groups of ninth-grade Mexican American students explored the factors contributing to a pro-college culture. The students participated in the federal initiative program called "Gaining Early Awareness and Readiness for Undergraduate Programs." Analysis revealed specific student, family, peer, and school personnel influences toward a…

  2. The "Creation-Science" Case and Pro Bono Publico.

    ERIC Educational Resources Information Center

    Kerr, Peggy L.

    1982-01-01

    Describes contributions and efforts of New York law firm (Skadden, Arps, Slate, Meagher, Flom) personnel in developing plaintiff's case in McLean v. Arkansas 590 (balanced treatment of creationism/evolution). Discusses aspects of "Pro Bono Publico" (unpaid public interest service) endeavors in general and those related to this law firm in…

  3. The ProDom database of protein domain families: more emphasis on 3D

    PubMed Central

    Bru, Catherine; Courcelle, Emmanuel; Carrre, Sbastien; Beausse, Yoann; Dalmar, Sandrine; Kahn, Daniel

    2005-01-01