WorldWideScience

Sample records for hepatitis delta antigen

  1. Delta hepatitis agent: structural and antigenic properties of the delta-associated particle.

    Science.gov (United States)

    Bonino, F; Hoyer, B; Shih, J W; Rizzetto, M; Purcell, R H; Gerin, J L

    1984-01-01

    Delta agent (delta) was serially passaged to a second and third hepatitis B surface antigen (HBsAg) carrier chimpanzee, using as inoculum the peak delta antigen (delta Ag) serum of an animal previously infected with human serum. The characteristics of serially transmitted delta Ag were similar to those described in first-passage animals. It was consistently detected before the development of anti-delta, in association with a 35- to 37-nm subpopulation of HBsAg particles and a unique low-molecular-weight (5.5 X 10(5)) RNA. RNase susceptibility of the delta-associated RNA and release of delta Ag activity upon treatment of delta-associated particles with detergent revealed that this particle is organized into a virion-like form with the RNA and delta Ag as internal components within a coat of HBsAg. Surface determinants of the delta-associated particle other than HBsAg were not detected by radioimmunoprecipitation experiments, using sera of humans and chimpanzees convalescent from delta hepatitis. The HBsAg-associated particle is the "candidate agent" of delta hepatitis. Images PMID:6698598

  2. Hepatitis delta virus: protein composition of delta antigen and its hepatitis B virus-derived envelope.

    Science.gov (United States)

    Bonino, F; Heermann, K H; Rizzetto, M; Gerlich, W H

    1986-01-01

    Hepatitis delta virus (HDV)-associated particles were purified from the serum of an experimentally infected chimpanzee by size chromatography and by density centrifugation. Hepatitis delta antigen (HDAg) was detected after mild detergent treatment at a column elution volume corresponding to 36-nm particles and banded at a density of 1.25 g/ml. The serum had an estimated titer of 10(9) to 10(10) HDV-associated particles and had only a 10-fold excess of hepatitis B surface antigen (HBsAg) not associated with HDAg. Therefore, HDV appears to be much more efficiently packed and secreted than is its helper virus, hepatitis B virus (HBV), which is usually accompanied by a 1,000-fold excess of HBsAg. The protein compositions of the HDAg-containing particles were analyzed by immunoblotting with HDAg-, HBsAg-, and hepatitis B core antigen-specific antisera and monoclonal antibodies to HBV surface gene products. The HBsAg envelope of HDAg contained approximately 95% P24/GP27s, 5% GP33/36s, and 1% P39/GP42s proteins. This protein composition was more similar to that of the 22-nm particles of HBsAg than to that of complete HBV. The significant amount of GP33/36s suggests that the HBsAg component of the HDV-associated particle carries the albumin receptor. Two proteins of 27 and 29 kilodaltons which specifically bound antibody to HDAg but not HBV-specific antibodies were detected in the interior of the 36-nm particle. Since these proteins were structural components of HDAg and were most likely coded for by HDV, they were designated P27d and P29d. Images PMID:3701932

  3. Immunofluorescence detection of new antigen-antibody system (delta/anti-delta) associated to hepatitis B virus in liver and in serum of HBsAg carriers.

    Science.gov (United States)

    Rizzetto, M; Canese, M G; Aricò, S; Crivelli, O; Trepo, C; Bonino, F; Verme, G

    1977-01-01

    A new antigen-antibody system associated with the hepatitis B virus and immunologically distinct from the HB surface, core, and e systems is reported. The new antigen, termed delta, was detected by direct immunofluorescence only in the liver cell nuclei of patients with HBsAg positive chronic liver disease. At present, the intrahepatic expression of HBcAg and delta antigen appears to be mutually exclusive. No ultrastructural aspect corresponding to the delta antigen could be identified under the electron microscope. delta antibody was found in the serum of chronic HBsAg carriers, with a higher prevalence in patients with liver damage. The nuclear fluorescence patterns of HBcAg and delta antigen were similar; it is only possible to discriminate between the two antigens by using the respective specific antisera. Images Figure PMID:75123

  4. Efficient expression of histidine-tagged large hepatitis delta antigen in baculovirus-transduced baby hamster kidney cells

    Institute of Scientific and Technical Information of China (English)

    Ying-Wei Chiang; Jaw-Chin Wu; Kuei-Chun Wang; Chia-Wei Lai; Yao-Chi Chung; Yu-Chen Hu

    2006-01-01

    AIM: To study the baculovirus/mammalian cell system for efficient expression of functional large hepatitis delta antigen (L-HDAg).METHODS: A recombinant baculovirus expressing histidine-tagged L-HDAg (L-HDAgH) was constructed to transduce baby hamster kidney (BHK) cells by a simplified transduction protocol.RESULTS: The recombinant baculovirus transduced BHK cells with efficiencies higher than 90% as determined by flow cytometry. The expression level was significantly higher than that obtained by plasmid transfection and was further enhanced 3-fold to around 19 pg/cell by the addition of 10 mmol/L sodium butyrate. Importantly,the expressed L-HDAgH was localized to the cell nucleus and correctly isoprenylated as determined by immunofluorescence labeling and confocal microscopy.Moreover, L-HDAgH interacted with hepatitis B surface antigen to form virus-like particles.CONCLUSION: The fusion with histidine tags as well as overexpression of L-HDAgH in the baculovirus-transduced BHK cells does not impair the biological functions. Taken together, the baculovirus/mammalian cell system offers an attractive alternative for high level expression of L-HDAgH or other proteins that require extensive posttranslational modifications.

  5. Hepatitis Delta Virus: A Peculiar Virus

    OpenAIRE

    Carolina Alves; Cristina Branco; Celso Cunha

    2013-01-01

    The hepatitis delta virus (HDV) is distributed worldwide and related to the most severe form of viral hepatitis. HDV is a satellite RNA virus dependent on hepatitis B surface antigens to assemble its envelope and thus form new virions and propagate infection. HDV has a small 1.7 Kb genome making it the smallest known human virus. This deceivingly simple virus has unique biological features and many aspects of its life cycle remain elusive. The present review endeavors to gather the available ...

  6. Delta agent (Hepatitis D)

    Science.gov (United States)

    Hepatitis D virus ... Hepatitis D virus (HDV) is found only in people who carry the hepatitis B virus. HDV may make liver ... B virus but who never had symptoms. Hepatitis D infects about 15 million people worldwide. It occurs ...

  7. Nuclear export signal-interacting protein forms complexes with lamin A/C-Nups to mediate the CRM1-independent nuclear export of large hepatitis delta antigen.

    Science.gov (United States)

    Huang, Cheng; Jiang, Jia-Yin; Chang, Shin C; Tsay, Yeou-Guang; Chen, Mei-Ru; Chang, Ming-Fu

    2013-02-01

    Nuclear export is an important process that not only regulates the functions of cellular factors but also facilitates the assembly of viral nucleoprotein complexes. Chromosome region maintenance 1 (CRM1) that mediates the transport of proteins bearing the classical leucine-rich nuclear export signal (NES) is the best-characterized nuclear export receptor. Recently, several CRM1-independent nuclear export pathways were also identified. The nuclear export of the large form of hepatitis delta antigen (HDAg-L), a nucleocapsid protein of hepatitis delta virus (HDV), which contains a CRM1-independent proline-rich NES, is mediated by the host NES-interacting protein (NESI). The mechanism of the NESI protein in mediating nuclear export is still unknown. In this study, NESI was characterized as a highly glycosylated membrane protein. It interacted and colocalized well in the nuclear envelope with lamin A/C and nucleoporins. Importantly, HDAg-L could be coimmunoprecipitated with lamin A/C and nucleoporins. In addition, binding of the cargo HDAg-L to the C terminus of NESI was detected for the wild-type protein but not for the nuclear export-defective HDAg-L carrying a P205A mutation [HDAg-L(P205A)]. Knockdown of lamin A/C effectively reduced the nuclear export of HDAg-L and the assembly of HDV. These data indicate that by forming complexes with lamin A/C and nucleoporins, NESI facilitates the CRM1-independent nuclear export of HDAg-L.

  8. [A study of 158 cases of acute delta hepatitis].

    Science.gov (United States)

    Castro, A; Buti, M; Esteban, R; Jardí, R; Allende, H; Roget, M; Rodríguez-Frías, F; Guardia, J

    1990-09-22

    We have prospectively studied 158 cases of acute hepatitis delta observed during the last 7 years in a general hospital. Among them 136 were male and 22 female. The mean age was 22.7 years with a range between 16 and 61 years. The epidemiologic factors were drug addiction by parenteral route in 145 cases (92%), sexual transmission in 5 (3%), post transfusional in 2 (1%) and unknown in 6 (4%). With respect to the delta type infection, 105 cases (66%) were coinfections with type B and delta, and 53 patients had a type delta superinfection (34%). The clinical course was a fulminant hepatitis in three cases (two cases of coinfection B and delta an one case of delta superinfection), and an acute benign hepatitis in 155 patients. The follow-up of 118 patients revealed that 96% of coinfections by type B and delta evolved to the chronicity showing findings of active chronic hepatitis or hepatic cirrhosis. It should be noted that in 4 cases of superinfection delta type (11%) the HBsAg was negative after several months of positivity. In these patients the level of transaminases normalized and the hepatic histology evidenced alterations of chronic active hepatitis (2 cases) and hepatic cirrhosis (2 cases) without identification of tissular delta antigen.

  9. Transmission of the hepatitis B virus-associated delta agent to the eastern woodchuck.

    Science.gov (United States)

    Ponzetto, A; Cote, P J; Popper, H; Hoyer, B H; London, W T; Ford, E C; Bonino, F; Purcell, R H; Gerin, J L

    1984-01-01

    delta agent of human origin was inoculated into four woodchucks chronically infected with woodchuck hepatitis virus (WHV). The animals developed delta infections with serologic patterns similar to those previously observed in human and chimpanzee infections. delta antigen was detected transiently in serum and liver and was followed by seroconversion to anti-delta antibody. Analogous to the chimpanzee model of delta infection, serum and hepatocyte markers of WHV were suppressed in the woodchuck during acute delta infection. The suppression of WHV DNA in serum was evident only during the time of delta-antigen positivity, while the inhibition of other WHV markers was more protracted. The delta antigen in woodchuck sera circulated as an internal component of a particle similar in size to the human delta particle (36-nm diameter) and was encapsidated by the woodchuck hepatitis virus surface antigen; delta antigen from infected woodchuck and chimpanzee livers had similar biophysical properties. Histologic analysis showed that experimental delta infection is associated with a transient acute hepatitis in woodchucks and loss of hepatocytes carrying WHV antigens. The lesions differed from the conspicuous hepatitis associated with reappearance of WHV replication. Hepatitis B-like viruses, therefore, appear to provide the requisite helper functions for delta replication and the woodchuck represents a useful model for study of the virology and pathology of the delta agent. Images PMID:6585793

  10. Immunogenicity and safety of Advax™, a novel polysaccharide adjuvant based on delta inulin, when formulated with hepatitis B surface antigen: a randomized controlled Phase 1 study.

    Science.gov (United States)

    Gordon, David; Kelley, Peter; Heinzel, Susanne; Cooper, Peter; Petrovsky, Nikolai

    2014-11-12

    There is a need for additional safe and effective human vaccine adjuvants. Advax™ is a novel adjuvant produced from semi-crystalline particles of delta inulin. In animal studies Advax enhanced humoral and cellular immunity to hepatitis B surface antigen (HBsAg) without inducing local or systemic reactogenicity. This first-in-man Phase 1 clinical trial tested the safety and tolerability of three intramuscular doses of HBsAg formulated with Advax in a group of healthy adult subjects. Advax was well tolerated with injection site pain scores not significantly different to subjects receiving HBsAg alone and no adverse events were reported in subjects that received Advax. Seroprotection and HBsAb geometric mean titers (GMT) after three immunizations were higher in the Advax 5mg (seroprotection 5/6, 83.3%, GMT 40.7, 95% CI 11.9-139.1) and 10mg (seroprotection 4/5, 80%, GMT 51.6, 95% CI 10.0-266.2) groups versus HBsAg alone (seroprotection 1/5, 20%, GMT 4.1, 95% CI 1.3-12.8). Similarly the proportion of subjects with positive CD4 T-cell responses to HBsAg was higher in the Advax 5mg (4/6, 67%) and Advax 10mg (4/5, 80%) groups versus HBsAg alone (1/5, 20%). These results confirm the safety, tolerability and immunogenicity of Advax adjuvant observed in preclinical studies. Advax may represent a suitable replacement for alum adjuvants in prophylactic human vaccines subject to confirmation of current results in larger studies. Australia and New Zealand Clinical Trial Registry: ACTRN12607000598482.

  11. Structure and replication of hepatitis delta virus

    African Journals Online (AJOL)

    STORAGESEVER

    2008-12-29

    Dec 29, 2008 ... Unidade de Biologia Molecular, Centro de Malária e outras Doenças Tropicais, Instituto de Higiene e Medicina Tropical, ... molecules of both delta antigens (Ryu et al., 1993). This ..... Glenn JS, Watson JA, Havel CM, White JO (1992). ... HDV RNA encoding the large delta antigen cannot replicate. J. Gen.

  12. High prevalence and predominance of hepatitis delta virus genotype 1 infection in Cameroon.

    Science.gov (United States)

    Foupouapouognigni, Yacouba; Noah, Dominique Noah; Sartre, Michèle Tagni; Njouom, Richard

    2011-03-01

    Antibodies to the hepatitis delta virus (HDV) were found in 17.6% of 233 hepatitis B virus surface antigen-positive subjects in Cameroon. Phylogenetic analyses showed the presence of HDV-1, HDV-5, HDV-6, and HDV-7 genotypes. These results enrich the limited data on HDV prevalence and molecular diversity in Cameroon.

  13. High Prevalence and Predominance of Hepatitis Delta Virus Genotype 1 Infection in Cameroon▿

    Science.gov (United States)

    Foupouapouognigni, Yacouba; Noah, Dominique Noah; Sartre, Michèle Tagni; Njouom, Richard

    2011-01-01

    Antibodies to the hepatitis delta virus (HDV) were found in 17.6% of 233 hepatitis B virus surface antigen-positive subjects in Cameroon. Phylogenetic analyses showed the presence of HDV-1, HDV-5, HDV-6, and HDV-7 genotypes. These results enrich the limited data on HDV prevalence and molecular diversity in Cameroon. PMID:21209162

  14. Viral hepatitis and hepatitis B antigen: recent advances

    Science.gov (United States)

    Krugman, Saul

    1974-01-01

    Recent advances in hepatitis research have shed new light on the etiology, pathogenesis, epidemiology and prevention of type B hepatitis infection. The so-called ‘Dane’ particle is probably the complete hepatitis B virion; its outer coat is the hepatitis B (Australia) antigen (HB Ag) and its inner core is an immunologically distinct particle. Subtypes of HB Ag (a, d, y, w and r) are useful indices for epidemiological surveys. Concepts of epidemiology have changed: type B hepatitis is transmissible by contact as well as by inoculation. The presence of HB Ag in blood is indicative of the presence of hepatitis B virus. Tests to detect antigen and use of voluntary blood donors have played a major role in the decreased incidence of post transfusion hepatitis. A special hepatitis B gammaglobulin preparation and a heat-inactivated hepatitis B vaccine have proved to be effective in preliminary studies. PMID:4219230

  15. [Infectious hepatitis. I. Presence of HBs antigen].

    Science.gov (United States)

    Calderón, E; Ridaura, C; Legorreta, J; Gómez, D; Ruiz, M; Kassian, A

    1975-01-01

    A prospective study in 268 patients of different pediatric ages affected with icteric hepatitis is presented, with a longitudinal follow-up of one year minimum. Different types of clinical evolution are described and related to the presence of HBs antigen. In 34 of the 268 patients HBs antigen was positive; in 20 of 28 patients with acute and long evolution, positivity of the antigen was transitory with an average of 46 days; in the remaining 8 of 28 patients it extended from 6 months to less than 2 years. The presence of HBs antigen is a risk that may be correlated with the tendency to extend the prolonged.

  16. Infection with hepatitis A, B, C, and delta viruses among patients with acute hepatitis in Mongolia.

    Science.gov (United States)

    Tsatsralt-Od, Bira; Takahashi, Masaharu; Endo, Kazunori; Buyankhuu, Osorjin; Baatarkhuu, Oidov; Nishizawa, Tsutomu; Okamoto, Hiroaki

    2006-05-01

    One hundred ten consecutive patients (60 males and 50 females; age, mean +/- standard deviation [SD], 22.6 +/- 6.4 years; range 16-48 years) who were clinically diagnosed with sporadic acute hepatitis between December 2004 and January 2005 in Ulaanbaatar, Mongolia, were studied. IgM antibodies to hepatitis A virus were detected in 18 patients (16.4%), IgM antibodies to hepatitis B core (anti-HBc IgM) in 38 patients (34.5%) including two patients with concurrent hepatitis delta virus (HDV) infection, and hepatitis C virus RNA in nine patients (8.2%). There were 30 hepatitis B virus (HBV) carriers who had detectable hepatitis B surface antigen and antibodies to HDV but were negative for anti-HBc IgM, suggesting that they acquired type D acute hepatitis due to superinfection of HDV on a background of chronic HBV infection. None had IgM antibodies to hepatitis E virus (HEV). Consequently, 16.4, 32.7, 6.4, 1.8, and 27.3% of the patients were diagnosed as having acute hepatitis of type A, B, C, type B + D (HBV/HDV coinfection), and type D (superinfection of HDV), respectively. The cause of hepatitis was not known in the remaining 17 patients (15.5%). All 18 HAV isolates were genotyped as IA, all 9 HCV isolates were genotyped as 1b, and all 32 HDV isolates were classified into genotype I. The distribution of HBV genotypes among the 67 HBV isolates was A (1.5%, n = 1) and D (98.5%, n = 66). The present study indicates that de novo infections of HAV, HBV, HCV, and HDV are prevalent among young adults in Mongolia. Copyright 2006 Wiley-Liss, Inc.

  17. 21 CFR 660.40 - Hepatitis B Surface Antigen.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 7 2010-04-01 2010-04-01 false Hepatitis B Surface Antigen. 660.40 Section 660.40...) BIOLOGICS ADDITIONAL STANDARDS FOR DIAGNOSTIC SUBSTANCES FOR LABORATORY TESTS Hepatitis B Surface Antigen § 660.40 Hepatitis B Surface Antigen. (a) Proper name and definition. The proper name of this...

  18. Prevalence of antibody to hepatitis B core antigen among hepatitis B ...

    African Journals Online (AJOL)

    Prevalence of antibody to hepatitis B core antigen among hepatitis B surface antigen-negative ... PROMOTING ACCESS TO AFRICAN RESEARCH ... donor selection criteria and screening for hepatitis B surface antigen (HBsAg). ... Rwanda (3); Senegal (6); Sierra Leone (1); South Africa (96); South Sudan (1); Sudan (3) ...

  19. Effect of hepatitis B immunisation in newborn infants of mothers positive for hepatitis B surface antigen

    DEFF Research Database (Denmark)

    Lee, Chuanfang; Gong, Yan; Brok, Jesper

    2006-01-01

    To evaluate the effects of hepatitis B vaccine and immunoglobulin in newborn infants of mothers positive for hepatitis B surface antigen.......To evaluate the effects of hepatitis B vaccine and immunoglobulin in newborn infants of mothers positive for hepatitis B surface antigen....

  20. Hepatitis B virus surface antigen (HBsAg and antibody (anti-HBs forming immune complexes in fulminant hepatitis

    Directory of Open Access Journals (Sweden)

    Soares Manoel C.P.

    1999-01-01

    Full Text Available This paper reports an unusual pattern of serological HBV markers and the presence of HBsAg/anti-HBs immune complexes in serum samples from two patients with fulminant hepatitis from the Brazilian Western Amazon Basin. The diagnosis was made by both serologic tests and demonstration of antigen/antibody complexes by transmission electron microscopy. Concurrent Delta virus superinfection is also discussed.

  1. Hepatitis B Virus e Antigen Variants

    Directory of Open Access Journals (Sweden)

    2005-01-01

    Full Text Available More than 300 million people worldwide are chronically infected with hepatitis B virus (HBV. Considering the very short generation time for a virus, and the high error rate associated with the reverse transcription step of HBV replication, decades of HBV infection are probably equivalent to million years of human evolution. The most important selective force during the natural course of HBV infection appears to be the immune response. The development of anti-HBe antibody in hepatitis B patients usually correlates with reduction of HBV viremia. As a consequence, escape mutants of anti-HBe are selected. The core promoter mutants express less HBe antigen (HBeAg through transcriptional down regulation, while precore mutants express truncated products. We recently identified additional mutations that modulate HBeAg translation initiation, proteolytic cleavage, and secondary structure maintenance through a disulfide bond. The core promoter mutants have been associated with the development of fulminant hepatitis during acute infection and liver cancer during chronic infection. Consistent with their enhanced pathogenicity, core promoter mutants were found to replicate at up to 10-fold higher levels in transfected human hepatoma cells than the wild-type virus. Moreover, some core promoter mutants are impaired in virion secretion due to missense mutations in the envelope gene. These virological properties may help explain enhanced pathogenicity of core promoter mutants in vivo.

  2. Hepatitis delta in HIV-infected individuals in Europe

    DEFF Research Database (Denmark)

    Soriano, Vincent; Grint, Daniel; Monforte, Antonellad'arminio

    2011-01-01

    BACKGROUND:: Hepatitis delta virus (HDV) infection results in the most aggressive form of chronic viral hepatitis. There is scarce information about the prevalence, epidemiology, virological profile and natural historyof hepatitis delta in HIV patients. METHODS:: From 16,597 HIV patients enrolled......-RNA was quantified using a real-time PCR method. RESULTS:: A total of 61/422 HBsAg+ carriers were anti-HDV+ (prevalence: 14.5%). Hepatitis delta predominated in intravenous drug users and for this reason in South and/or East Europe. Serum HDV-RNA was detectable in 87% of tested anti-HDV+ patients, with a median...... titer of 1.76x10¿copies/ml. Overall, delta hepatitis patients showed lower serum HBV-DNA than the rest of HBsAg+ carriers, although the inhibitory effect of HDV on HBV replication was not recognized in HBV genotype D patients.Whereas HDV was not associated with progression to AIDS, it significantly...

  3. Linearized hepatitis B surface antigen and hepatitis B core-related antigen in the natural history of chronic hepatitis B.

    Science.gov (United States)

    Seto, W-K; Wong, D K-H; Fung, J; Huang, F-Y; Liu, K S-H; Lai, C-L; Yuen, M-F

    2014-11-01

    Changes in two novel HBV serological markers, linearized hepatitis B surface antigen (HQ-HBsAg) and hepatitis B core-related antigen (HBcrAg), in the natural history of chronic hepatitis B (CHB) have not been well characterized. Serum HQ-HBsAg and HBcrAg levels of 404 Asian treatment-naïve CHB patients were analysed in a cross-sectional manner. Patients were categorized into five groups: immune tolerant (IT group, n=52), immune clearance (IC group, n=105), hepatitis B e antigen (HBeAg)-negative hepatitis (ENH group, n=97), HBeAg-negative quiescent group (ENQ group, n=95) and CHB with hepatitis B surface antigen (HBsAg) seroclearance (SC group, n=55). HQ-HBsAg and HBcrAg were measured and correlated with HBV DNA, HBsAg, HBV genotype and clinical parameters. HQ-HBsAg showed good correlation with HBsAg, especially in the ENQ group (r=0.874, pHBcrAg correlated best with HBV DNA in the ENQ group (r=0.537, pHBcrAg; this subgroup of patients, when compared with those with detectable HBcrAg, had significantly lower median HBV DNA (3.17/4.48 log IU/mL, pHBcrAg up to 42 months after HBsAg seroclearance. When comparing anti-HBs positivity and median time after HBsAg seroclearance in the SC group with and without detectable HQ-HBsAg/HBcrAg, there was no significant difference (22.7% and 36.4%, respectively, p 0.284, and 76.5 and 93.2 months, respectively, p 0.245). HQ-HBsAg and HBcrAg showed unique patterns of distribution throughout the five disease phases of CHB, including high detectability rates after HBsAg seroclearance, opening up different possibilities for their applicability.

  4. 21 CFR 660.1 - Antibody to Hepatitis B Surface Antigen.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 7 2010-04-01 2010-04-01 false Antibody to Hepatitis B Surface Antigen. 660.1... Hepatitis B Surface Antigen § 660.1 Antibody to Hepatitis B Surface Antigen. (a) Proper name and definition. The proper name of this product shall be Antibody to Hepatitis B Surface Antigen. The product...

  5. Hepatitis Delta Virus: Replication Strategy and Upcoming Therapeutic Options for a Neglected Human Pathogen

    Science.gov (United States)

    Lempp, Florian A.; Urban, Stephan

    2017-01-01

    The human Hepatitis Delta Virus (HDV) is unique among all viral pathogens. Encoding only one protein (Hepatitis Delta Antigen; HDAg) within its viroid-like self-complementary RNA, HDV constitutes the smallest known virus in the animal kingdom. To disseminate in its host, HDV depends on a helper virus, the human Hepatitis B virus (HBV), which provides the envelope proteins required for HDV assembly. HDV affects an estimated 15–20 million out of the 240 million chronic HBV-carriers and disperses unequally in disparate geographical regions of the world. The disease it causes (chronic Hepatitis D) presents as the most severe form of viral hepatitis, leading to accelerated progression of liver dysfunction including cirrhosis and hepatocellular carcinoma and a high mortality rate. The lack of approved drugs interfering with specific steps of HDV replication poses a high burden for gaining insights into the molecular biology of the virus and, consequently, the development of specific novel medications that resiliently control HDV replication or, in the best case, functionally cure HDV infection or HBV/HDV co-infection. This review summarizes our current knowledge of HBV molecular biology, presents an update on novel cell culture and animal models to study the virus and provides updates on the clinical development of the three developmental drugs Lonafarnib, REP2139-Ca and Myrcludex B. PMID:28677645

  6. Hepatitis B e Antigen-Negative Chronic Hepatitis B

    Directory of Open Access Journals (Sweden)

    Seyed-Moayed Alavian

    2006-12-01

    Full Text Available IntroductionHepatitis B virus (HBV infection is a global health problem. Current estimates are that 2 billion people have been infected worldwide, of these, 360 million suffer from chronic HBV infection resulting in over 520 000 deaths from acute hepatitis B and 470 000 from cirrhosis or liver cancer(1. The prevalence of hepatitis B carriers varies in different parts of the world, ranging from less than 1% to 15%. In the Middle East, the endemicity is intermittent, with a carrier rate of 2% to 7% (2. It is estimated that over 35% of Iranians have been exposed to the HBV and about 3% are chronic carriers, ranging from 1.7% in Fars Province to over 5% in Sistan and Balouchestan(3. To date, eight different genotypes of the HBV have been identified (A-H. The clinical spectrum of HBV infection ranges from subclinical to acute symptomatic hepatitis or, rarely, fulminant hepatitis during the acute phase and from the inactive HBV infection and chronic hepatitis of various degrees of histologic severity to cirrhosis and its complications during the chronic phase(4,5. Thirty years ago, the diagnosis of chronic hepatitis B (CHB was thought to require the presence of hepatitis B e antigen (HBeAg, as a reliable and sensitive marker of hepatitis B virus (HBV replication. Individuals positive for hepatitis B surface antigen (HBsAg but negative for HBeAg were considered to have non replicative HBV infection, and if their liver enzymes were normal or nearly normal they were referred to as asymptomatic or healthy HBsAg or HBV carriers. On the other hand, if they displayed elevated serum aminotransferases and liver histology indicative of chronic hepatitis, they were generally thought to be suffering from other superimposed or complicating conditions such as hepatitis D virus infection, alcohol-induced, metabolic, autoimmune, druginduced, or other forms of chronic liver disease(6. In the early 1980s it became apparent that HBV could replicate in the absence of HBe

  7. Quantitative hepatitis B surface antigen analysis in hepatitis B e antigen-positive nucleoside-naive patients treated with entecavir

    NARCIS (Netherlands)

    R.G. Gish; T. Chang; C.L. Lai (Chen); R.A. de Man (Robert); A. Gadano; C. Llamoso (Cyril); H. Tang (Hui)

    2013-01-01

    textabstractBackground: Entecavir is a potent nucleoside analogue for treating chronic hepatitis B (CHB). Quantitative hepatitis B surface antigen (qHBsAg) levels are predictive of response to interferon-α in CHB treatment; however, the clinical utility of qHBsAg in nucleoside/nucleotide

  8. HDVDB: a data warehouse for hepatitis delta virus.

    Science.gov (United States)

    Singh, Sarita; Gupta, Sunil Kumar; Nischal, Anuradha; Pant, Kamlesh Kumar; Seth, Prahlad Kishore

    2015-01-01

    Hepatitis Delta Virus (HDV) is an RNA virus and causes delta hepatitis in humans. Although a lot of data is available for HDV, but retrieval of information is a complicated task. Current web database 'HDVDB' provides a comprehensive web-resource for HDV. The database is basically concerned with basic information about HDV and disease caused by this virus, genome structure, pathogenesis, epidemiology, symptoms and prevention, etc. Database also supplies sequence data and bibliographic information about HDV. A tool 'siHDV Predict' to design the effective siRNA molecule to control the activity of HDV, is also integrated in database. It is a user friendly information system available at public domain and provides annotated information about HDV for research scholars, scientists, pharma industry people for further study.

  9. Long-term outcome of hepatitis B e antigen-positive patients with compensated cirrhosis treated with interferon alfa. European Concerted Action on Viral Hepatitis (EUROHEP)

    DEFF Research Database (Denmark)

    Fattovich, G; Giustina, G; Realdi, G;

    1997-01-01

    The aim of this study was to evaluate whether interferon alfa (IFN-alpha) treatment-associated virological and biochemical remission improves survival in a cohort of 90 white patients with compensated cirrhosis caused by hepatitis B (Child A) followed for a mean period of 7 years. Inclusion...... criteria were biopsy-proven cirrhosis, hepatitis B e antigen (HBeAg) positivity, abnormal serum aminotransferase levels, exclusion of hepatitis delta virus, and absence of complications of cirrhosis. Of the 40 IFN-treated patients, 27 (67%) showed sustained HBeAg loss with alanine aminotransferase (ALT...

  10. Evidence of an Exponential Decay Pattern of the Hepatitis Delta Virus Evolution Rate and Fluctuations in Quasispecies Complexity in Long-Term Studies of Chronic Delta Infection.

    Science.gov (United States)

    Homs, Maria; Rodriguez-Frias, Francisco; Gregori, Josep; Ruiz, Alicia; Reimundo, Pilar; Casillas, Rosario; Tabernero, David; Godoy, Cristina; Barakat, Salma; Quer, Josep; Riveiro-Barciela, Mar; Roggendorf, Michael; Esteban, Rafael; Buti, Maria

    2016-01-01

    Chronic HDV infection can cause a severe form of viral hepatitis for which there is no specific treatment. Characterization of the hepatitis B or C viral quasispecies has provided insight into treatment failure and disease recurrence following liver transplantation, has proven useful to understand hepatitis B e antigen seroconversion, and has helped to predict whether hepatitis C infection will resolve or become chronic. It is likely that characterization of the hepatitis delta virus (HDV) quasispecies will ultimately have similar value for the management of this infection. This study sought to determine the RNA evolution rates in serum of chronic hepatitis delta (CHD) treatment-naïve patients, using next-generation sequencing methods. The region selected for study encompassed nucleotide positions 910 to 1270 of the genome and included the amber/W codon. Amber/W is a substrate of the editing process by the ADAR1 host enzyme and is essential for encoding the 2 delta antigens (HDAg). The amber codon encodes the small (unedited) HDAg form and the W codon the large (edited) HDAg form. The evolution rate was analyzed taking into account the time elapsed between samples, the percentage of unedited and edited genomes, and the complexity of the viral population. The longitudinal studies included 29 sequential samples from CHD patients followed up for a mean of 11.5 years. In total, 121,116 sequences were analyzed. The HDV evolution rate ranged from 9.5x10-3 to 1.2x10-3 substitutions/site/year and showed a negative correlation with the time elapsed between samples (pquasispecies complexity showed no relationships with the evolution rate, but the fluctuations in the percentages of genomes and in complexity suggest continuous adaptation of HDV to the host conditions.

  11. Genomic organization of the human T-cell antigen-receptor alpha/delta locus.

    Science.gov (United States)

    Satyanarayana, K; Hata, S; Devlin, P; Roncarolo, M G; De Vries, J E; Spits, H; Strominger, J L; Krangel, M S

    1988-11-01

    Two clusters of overlapping cosmid clones comprising about 100 kilobases (kb) at the human T-cell antigen-receptor alpha/delta locus were isolated from a genomic library. The structure of the germ-line V delta 1 variable gene segment was determined. V delta 1 is located 8.5 kb downstream of the V alpha 13.1 gene segment, and both V segments are arranged in the same transcriptional orientation. The V alpha 17.1 segment is located between V delta 1 and the D delta, J delta, C delta region (containing the diversity, joining, and constant gene segments). Thus, V delta and V alpha segments are interspersed along the chromosome. The germ-line organization of the D delta 2, J delta 1, and J delta 2 segments was determined. Linkage of C delta to the J alpha region was established by identification of J alpha segments within 20 kb downstream of C delta. The organization of the locus was also analyzed by field-inversion gel electrophoresis. The unrearranged V delta 1 and D delta, J delta, C delta regions are quite distant from each other, apparently separated by a minimum of 175-180 kb.

  12. Clinical presentation and genotype of hepatitis delta in Karachi

    Institute of Scientific and Technical Information of China (English)

    Tariq Moatter; Zaigham Abbas; Sabhita Shabir; Wasim Jafri

    2007-01-01

    AIM: To assess the clinical presentation and genotypes of delta hepatitis in local population.METHODS: In this prospective study, 39 consecutive patients who were positive for HBsAg and hepatitis D virus (HDV) antibody were included. The patients were divided in two groups on the basis of presence or absence of HDV RNA and a comparative study was done. Genotype of HDV was determined in PCR positive patients.RESULTS: Overall there is male dominance, in which 34 patients out of 39 (87.2%) were male. Twenty (51%) patients were from the adjacent areas of three provinces; Sindh, Punjab and Balochistan indicating the higher prevalence of delta hepatitis in this mid region of Pakistan. Patients of all age groups were affected with delta hepatitis (median 31.5 years, range 12-75).HDV RNA was detectable in 23 patients (59%). All the HDV strains belonged to genotype Ⅰ. HBV DNA was detectable only in 3 cases who were also HBeAg and HDV RNA positive. Patients with detectable HDV RNA were younger than patients with undetectable RNA; mean age 29.7 ± 12.8 years vs 36.8 ± 15.2.There were no statistically significant differences in the clinical presentation and routine biochemical profile of patients with detectable or undetectable HDV RNA.Clinical cirrhosis was present in 19 (49%) patients; 12 with detectable RNA and 7 with undetectable HDV RNA (P = 0.748). Decompensated disease was seen in eight patients; five and three respectively from each group.Four patients with undetectable RNA and two patients with detectable RNA had normal ALT and ultrasound abdomen.CONCLUSION: HDV may infect at any age, usually young adult males. Genotype Ⅰ is prevalent. With time some of the patients become HDV RNA negative or asymptomatic carrier. Most of the patients have suppressed HBV DNA replication. Significant numbers of patients have cirrhosis.

  13. Hepatitis B e Antigen-Negative Chronic Hepatitis B

    OpenAIRE

    2006-01-01

    IntroductionHepatitis B virus (HBV) infection is a global health problem. Current estimates are that 2 billion people have been infected worldwide, of these, 360 million suffer from chronic HBV infection resulting in over 520 000 deaths from acute hepatitis B and 470 000 from cirrhosis or liver cancer(1). The prevalence of hepatitis B carriers varies in different parts of the world, ranging from less than 1% to 15%. In the Middle East, the endemicity is intermittent, with a carrier rate of 2%...

  14. Some additional bioethical questions related to hepatitis B antigen.

    Science.gov (United States)

    McCullough, L B

    1977-09-01

    Dr. Baruch S. Blumberg has recently raised important questions concerning the bioethics of prevention and cure of hepatitis. This paper extends his inquiry with a view toward examining the full range of the complexity of such issues as the restriction of the use of blood infected with hepatitis B antigen, the screening and possible isolation of health care personnel found to be carriers, and the like. It pointed out that for issues like these, there is not only a conflict between personal liberties and the public interest but also a potential conflict of individual rights, a theme not treated fully by Blumberg. The complex issues that emerge when these two themes are considered together are examined in light of the work of the contemporary American philosopher, John Rawls. His theory permits one to consider these two ethical themes together in analyzing moral problems. In this light, a new strategy is proposed for addressing bioethical questions concerning hepatitis B antigen.

  15. Immunological Properties of Hepatitis B Core Antigen Fusion Proteins

    Science.gov (United States)

    Francis, Michael J.; Hastings, Gillian Z.; Brown, Alan L.; Grace, Ken G.; Rowlands, David J.; Brown, Fred; Clarke, Berwyn E.

    1990-04-01

    The immunogenicity of a 19 amino acid peptide from foot-and-mouth disease virus has previously been shown to approach that of the inactivated virus from which it was derived after multimeric particulate presentation as an N-terminal fusion with hepatitis B core antigen. In this report we demonstrate that rhinovirus peptide-hepatitis B core antigen fusion proteins are 10-fold more immunogenic than peptide coupled to keyhole limpet hemocyanin and 100-fold more immunogenic than uncoupled peptide with an added helper T-cell epitope. The fusion proteins can be readily administered without adjuvant or with adjuvants acceptable for human and veterinary application and can elicit a response after nasal or oral dosing. The fusion proteins can also act as T-cell-independent antigens. These properties provide further support for their suitability as presentation systems for "foreign" epitopes in the development of vaccines.

  16. Serum anti-hepatitis B surface antigen in hemodialysis patients

    Directory of Open Access Journals (Sweden)

    Rafieian-Kopaei Mahmoud

    2012-01-01

    Full Text Available To evaluate the immune response to hepatitis B vaccination in stable hemodialysis (HD patients, a retro-prospective investigation was conducted on 68 HD patients. Participants were vaccinated against hepatitis B virus with an intramuscular hepatitis B vaccination schedule, 40 micrograms at 0, 1, and 6 months. The serum antibody level against hepatitis B surface antigen (HBs in HD patients was 35±55. In this study, no significant differences of Anti-HBs antibody between diabetic and non-diabetics or male and female subjects were observed. There were not any significant correlation between antibody against HBs-Ag and serum albumin. There was not significant correlation between anti-HBs antibody and age, proportion of HD, duration of HD or dialysis efficacy. In this study, there was not significant correlation between serum antibody level against hepatitis B surface antigen and some demographic indices of HD patients, however, these findings need to re-test in other centers with more participants.

  17. Genetic variation and significance of hepatitis B surface antigen

    Directory of Open Access Journals (Sweden)

    ZHANG Zhenhua

    2013-11-01

    Full Text Available Hepatitis B virus (HBV is prone to genetic variation because there is reverse transcription in the process of HBV replication. The gene mutation of hepatitis B surface antigen may affect clinical diagnosis of HBV infection, viral replication, and vaccine effect. The current research and existing problems are discussed from the following aspects: the mechanism and biological and clinical significance of S gene mutation. Most previous studies focused on S gene alone, so S gene should be considered as part of HBV DNA in the future research on S gene mutation.

  18. Effects of the CCR5-Delta32 mutation on hepatitis C virus-specific immune responses in patients with haemophilia.

    Science.gov (United States)

    Ahlenstiel, Golo; Woitas, Rainer P; Iwan, Agathe; Nattermann, Jacob; Feldmann, Georg; Rockstroh, Jürgen K; Oldenburg, Johannes; Kupfer, Bernd; Sauerbruch, Tilman; Spengler, Ulrich

    2009-01-01

    In hepatitis C virus (HCV) infection antiviral T cells express the CC chemokine receptor 5 (CCR5). Their recruitment to the liver is an important step in the immune response. A 32 base pair deletion in the CCR5 gene leads to reduced expression and total loss of CCR5 in CCR5-Delta32 heterozygous and homozygous subjects, respectively. However, the role of this mutation for antiviral immunity remains unclear. Here, we analysed proliferation, IFN-gamma and IL-4 secretion (ELISpot) induced by the HCV antigens core, NS3, NS4, and NS5a in 21 anti-HCV-positive haemophiliac patients in relationship to their CCR5 genotypes (CCR5 wildtype n = 10, CCR5-Delta32 heterozygous n = 5 and CCR5-Delta32 homozygous n = 6). Furthermore, T cell migration in response to the CCR5 ligands CCL3, -4 and -5 was studied. Overall IFN-gamma responses to HCV proteins were only slightly greater in CCR5 wild-type patients than in CCR5-Delta32 carriers (0.6 versus 0.24 SFC/10(4) PBMC; p = 0.043). This difference was consistently seen with all tested HCV antigens. In contrast, neither T cell migration, nor PBMC proliferation, nor IL-4 production differed between CCR5 genotypes. Interruption of the CCR5 signalling pathway due to CCR5-Delta32 may potentially result in subtle reduction of HCV specific IFN-gamma responses in anti-HCV-positive haemophiliac patients.

  19. An outbreak of fulminant hepatitis delta in the Waorani, an indigenous people of the Amazon basin of Ecuador.

    Science.gov (United States)

    Manock, S R; Kelley, P M; Hyams, K C; Douce, R; Smalligan, R D; Watts, D M; Sharp, T W; Casey, J L; Gerin, J L; Engle, R; Alava-Alprecht, A; Martínez, C M; Bravo, N B; Guevara, A G; Russell, K L; Mendoza, W; Vimos, C

    2000-01-01

    An outbreak of delta hepatitis occurred during 1998 among the Waorani of the Amazon basin of Ecuador. Among 58 people identified with jaundice, 79% lived in four of 22 Waorani communities. Serum hepatitis B surface antigen (HBsAg) was found in the sera of 54% of the jaundiced persons, and 14% of asymptomatic persons. Ninety-five percent of 105 asymptomatic Waorani had hepatitis B core (HBc) IgG antibody, versus 98% of 51 with jaundice. These data confirm that hepatitis B virus (HBV) infection is highly endemic among the Waorani. Sixteen of 23 (70%) HBsAg carriers identified at the onset of the epidemic had serologic markers for hepatitis D virus (HDV) infection. All 16 were jaundiced, where as only two of seven (29%) with negative HDV serology were jaundiced (P = .0006). The delta cases clustered in families, 69% were children and most involved superinfection of people chronically infected with HBV. The data suggest that HDV spread rapidly by a horizontal mode of transmission other than by the sexual route.

  20. Antigenic properties of avian hepatitis E virus capsid protein.

    Science.gov (United States)

    Zhao, Qin; Syed, Shahid Faraz; Zhou, En-Min

    2015-10-22

    Avian hepatitis E virus (HEV) is the main causative agent of big liver and spleen disease and hepatitis-splenomegaly syndrome in chickens, and is genetically and antigenically related to mammalian HEVs. HEV capsid protein contains immunodominant epitopes and induces a protective humoral immune response. A better understanding of the antigenic composition of this protein is critically important for the development of effective vaccine and sensitive and specific serological assays. To date, six linear antigenic domains (I-VI) have been characterized in avian HEV capsid protein and analyzed for their applications in the serological diagnosis and vaccine design. Domains I and V induce strong immune response in chickens and are common to avian, human, and swine HEVs, indicating that the shared epitopes hampering differential diagnosis of avian HEV infection. Domains III and IV are not immunodominant and elicit a weak immune response. Domain VI, located in the N-terminal region of the capsid protein, can also trigger an intense immune response, but the anti-domain VI antibodies are transient. The protection analysis showed that the truncated capsid protein containing the C-terminal 268 amino acid residues expressed by the bacterial system can provide protective immunity against avian HEV infection in chickens. However, the synthetic peptides incorporating the different linear antigenic domains (I-VI) and epitopes are non-protective. The antigenic composition of avian HEV capsid protein is altogether complex. To develop an effective vaccine and accurate serological diagnostic methods, more conformational antigenic domains or epitopes are to be characterized in detail.

  1. Fulminant hepatitis B virus : recurrence after liver transplantation in two patients also infected with hepatitis delta virus

    NARCIS (Netherlands)

    Marsman, W A; Wiesner, R H; Batts, K P; Poterucha, J J; Porayko, M K; Niesters, H G; Zondervan, P E; Krom, R A

    Liver transplantation for hepatitis B virus (HBV)-related liver disease is complicated by HBV recurrence and, consequently, poor patient and graft survival. Patients transplanted for hepatitis delta virus (HDV)-related cirrhosis are reported to have a diminished incidence of HBV recurrence and

  2. Fulminant hepatitis B virus : recurrence after liver transplantation in two patients also infected with hepatitis delta virus

    NARCIS (Netherlands)

    Marsman, W A; Wiesner, R H; Batts, K P; Poterucha, J J; Porayko, M K; Niesters, H G; Zondervan, P E; Krom, R A

    1997-01-01

    Liver transplantation for hepatitis B virus (HBV)-related liver disease is complicated by HBV recurrence and, consequently, poor patient and graft survival. Patients transplanted for hepatitis delta virus (HDV)-related cirrhosis are reported to have a diminished incidence of HBV recurrence and impro

  3. Fulminant hepatitis B virus : recurrence after liver transplantation in two patients also infected with hepatitis delta virus

    NARCIS (Netherlands)

    Marsman, W A; Wiesner, R H; Batts, K P; Poterucha, J J; Porayko, M K; Niesters, H G; Zondervan, P E; Krom, R A

    1997-01-01

    Liver transplantation for hepatitis B virus (HBV)-related liver disease is complicated by HBV recurrence and, consequently, poor patient and graft survival. Patients transplanted for hepatitis delta virus (HDV)-related cirrhosis are reported to have a diminished incidence of HBV recurrence and impro

  4. Hepatitis B Virus Core-Related Antigens as Markers for Monitoring Chronic Hepatitis B Infection▿

    Science.gov (United States)

    Wong, Danny Ka-Ho; Tanaka, Yasuhito; Lai, Ching-Lung; Mizokami, Masashi; Fung, James; Yuen, Man-Fung

    2007-01-01

    A sensitive chemiluminescence enzyme immunoassay has been developed for hepatitis B virus (HBV) core-related antigen (HBcrAg) detection. We aimed to investigate the usefulness of HBcrAg measurement for monitoring chronic hepatitis B disease. HBcrAg levels were measured by a chemiluminescence enzyme immunoassay in 54 untreated patients and 39 patients treated with either entecavir or lamivudine. The HBcrAg concentration correlated positively with the levels of serum HBV DNA (r = 0.820), intrahepatic total HBV DNA (r = 0.700), and covalently closed circular DNA (cccDNA) (r = 0.664; for all, P values were HBcrAg concentration was associated with a greater proportion of hepatitis B core antigen immunostaining. Although the differences were not statistically significant, patients with higher Knodell necroinflammation and fibrosis scores tended to have higher serum HBcrAg concentration levels. In the treated patients, the logarithmic reduction in HBcrAg at week 48 correlated positively with the logarithmic reduction of serum HBV DNA, intrahepatic total HBV DNA, and cccDNA. Of the 31 patients with undetectable serum HBV DNA (HBcrAg. A greater reduction in posttreatment HBcrAg concentration was associated with histological improvement and a decrease in hepatitis B core antigen immunostaining. HBcrAg concentrations of HBcrAg levels correlated with HBV virological markers and reflected the chronic hepatitis B disease activity in the liver. PMID:17942661

  5. Hepatitis B virus core-related antigens as markers for monitoring chronic hepatitis B infection.

    Science.gov (United States)

    Wong, Danny Ka-Ho; Tanaka, Yasuhito; Lai, Ching-Lung; Mizokami, Masashi; Fung, James; Yuen, Man-Fung

    2007-12-01

    A sensitive chemiluminescence enzyme immunoassay has been developed for hepatitis B virus (HBV) core-related antigen (HBcrAg) detection. We aimed to investigate the usefulness of HBcrAg measurement for monitoring chronic hepatitis B disease. HBcrAg levels were measured by a chemiluminescence enzyme immunoassay in 54 untreated patients and 39 patients treated with either entecavir or lamivudine. The HBcrAg concentration correlated positively with the levels of serum HBV DNA (r = 0.820), intrahepatic total HBV DNA (r = 0.700), and covalently closed circular DNA (cccDNA) (r = 0.664; for all, P values were HBcrAg concentration was associated with a greater proportion of hepatitis B core antigen immunostaining. Although the differences were not statistically significant, patients with higher Knodell necroinflammation and fibrosis scores tended to have higher serum HBcrAg concentration levels. In the treated patients, the logarithmic reduction in HBcrAg at week 48 correlated positively with the logarithmic reduction of serum HBV DNA, intrahepatic total HBV DNA, and cccDNA. Of the 31 patients with undetectable serum HBV DNA (HBcrAg. A greater reduction in posttreatment HBcrAg concentration was associated with histological improvement and a decrease in hepatitis B core antigen immunostaining. HBcrAg concentrations of HBcrAg levels correlated with HBV virological markers and reflected the chronic hepatitis B disease activity in the liver.

  6. Gamma delta T cells recognize a microbial encoded B Cell antigen to initiate a rapid antigen-specific Interleukin-17 response

    Science.gov (United States)

    Gamma delta T cells contribute uniquely to host immune defense, but the way in which they do so remains an enigma. Here we show that an algae protein, phycoerythrin (PE) is recognized by gamma delta T cells from mice, bovine and humans and binds directly to specific gamma delta T cell antigen recept...

  7. Hepatitis B antigen in hepatocytes of chronic active liver disease.

    Science.gov (United States)

    Kawanishi, H

    1979-04-01

    To study the morphologic interrelation of hepatocytes with the replication of hepatitis B vius (HBV) and immunocompetent cells in chronic active liver disease(CALD), organ cultures were prepared from liver biopsy specimens. Replication of hepatitis B core antigen (HBcAg) appears to occur in the nucleus of the hepatocyte in close association with intranuclear electron-dense strands and sometimes intranucleolar matrixes (likely HBcAg genomes), and cytoplasmic maturation of the HBcAg takes place in the preautolytic condition of host hepatocytes. Immunocompetent cells became progressively autolyzed in the early period of cultures. No difference in progression of hepatocyte injury in tissues from normal subjects and from hepatitis B surface antigen (HBsAg)-positive and HBsAg-negative patients with CALD may suggest that intracellular synthesis of HBV alone is not cytopathic to host hepatocytes. This model is promising for the study of HBV replication and development, and also for testing the efficacy of new antiviral agents against the virus.

  8. Proteoglycans act as cellular hepatitis delta virus attachment receptors.

    Science.gov (United States)

    Lamas Longarela, Oscar; Schmidt, Tobias T; Schöneweis, Katrin; Romeo, Raffaella; Wedemeyer, Heiner; Urban, Stephan; Schulze, Andreas

    2013-01-01

    The hepatitis delta virus (HDV) is a small, defective RNA virus that requires the presence of the hepatitis B virus (HBV) for its life cycle. Worldwide more than 15 million people are co-infected with HBV and HDV. Although much effort has been made, the early steps of the HBV/HDV entry process, including hepatocyte attachment and receptor interaction are still not fully understood. Numerous possible cellular HBV/HDV binding partners have been described over the last years; however, so far only heparan sulfate proteoglycans have been functionally confirmed as cell-associated HBV attachment factors. Recently, it has been suggested that ionotrophic purinergic receptors (P2XR) participate as receptors in HBV/HDV entry. Using the HBV/HDV susceptible HepaRG cell line and primary human hepatocytes (PHH), we here demonstrate that HDV entry into hepatocytes depends on the interaction with the glycosaminoglycan (GAG) side chains of cellular heparan sulfate proteoglycans. We furthermore provide evidence that P2XR are not involved in HBV/HDV entry and that effects observed with inhibitors for these receptors are a consequence of their negative charge. HDV infection was abrogated by soluble GAGs and other highly sulfated compounds. Enzymatic removal of defined carbohydrate structures from the cell surface using heparinase III or the obstruction of GAG synthesis by sodium chlorate inhibited HDV infection of HepaRG cells. Highly sulfated P2XR antagonists blocked HBV/HDV infection of HepaRG cells and PHH. In contrast, no effect on HBV/HDV infection was found when uncharged P2XR antagonists or agonists were applied. In summary, HDV infection, comparable to HBV infection, requires binding to the carbohydrate side chains of hepatocyte-associated heparan sulfate proteoglycans as attachment receptors, while P2XR are not actively involved.

  9. [Pathological features of hepatocellular carcinoma carrying hepatitis C virus antigen].

    Science.gov (United States)

    Liu, B; Zhu, S; Zhang, X

    1997-10-01

    To analyze the pathological features of hepatocellular carcinomas (HCCs) carrying different hepatitis virus antigens histopathologically and systematically. PAP and ABC kits were used in the immunohistochemical study, and CAS-200 System was applied in the image cytometry. As compared with HCCs carrying HBV marker(s), the HCCs carrying HCV marker showed more cases of clear cell type (7/9 vs 4/33), better differentiation of cancers, less necrosis of hepatocytes, milder lymphocyte infiltration in the hepatic sinuses or periportal areas (P < 0.01), higher incidence of bile ductule damages, and bore a close relation to the formation of lymphoid follicle in the surrounding tissues (P < 0.05). These patients were elder, with lower grade of symptoms and better prognosis after operation. HCCs carrying only HCAg have different pathological features and clinical characteristics from which carrying HBV marker(s). The results of image cytometry are in accordance with the biological behaviour of HCC.

  10. A conformational switch controls hepatitis delta virus ribozyme catalysis.

    Science.gov (United States)

    Ke, Ailong; Zhou, Kaihong; Ding, Fang; Cate, Jamie H D; Doudna, Jennifer A

    2004-05-13

    Ribozymes enhance chemical reaction rates using many of the same catalytic strategies as protein enzymes. In the hepatitis delta virus (HDV) ribozyme, site-specific self-cleavage of the viral RNA phosphodiester backbone requires both divalent cations and a cytidine nucleotide. General acid-base catalysis, substrate destabilization and global and local conformational changes have all been proposed to contribute to the ribozyme catalytic mechanism. Here we report ten crystal structures of the HDV ribozyme in its pre-cleaved state, showing that cytidine is positioned to activate the 2'-OH nucleophile in the precursor structure. This observation supports its proposed role as a general base in the reaction mechanism. Comparison of crystal structures of the ribozyme in the pre- and post-cleavage states reveals a significant conformational change in the RNA after cleavage and that a catalytically critical divalent metal ion from the active site is ejected. The HDV ribozyme has remarkable chemical similarity to protein ribonucleases and to zymogens for which conformational dynamics are integral to biological activity. This finding implies that RNA structural rearrangements control the reactivity of ribozymes and ribonucleoprotein enzymes.

  11. Liver Allograft Its Use in Chronic Active Hepatitis With Macronodular Cirrhosis, Hepatitis B Surface Antigen

    Science.gov (United States)

    Corman, Jarques L.; Putnam, Charles W.; Iwatsuki, Shunzaburo; Redeker, Allan G.; Porter, K. A.; Peters, Robert L.; Schröter, Gerhard; Starzl, Thomas E.

    2010-01-01

    A patient suffering from chronic active hepatitis with macronodular cirrhosis, positive for hepatitis B surface antigen (HB,Ag), was treated with an orthoiopic liver allograft. The HB, antigenemia, as measured with several precipltation tests and by complement fixation, became negative after transplantation and remained so for about 2½ months. During the interval, very low Iters of the antigen were detectable by, radioimmunoassay. At about three months after transplantation, she had an attack of acute hepatitis, at which time HB,Ag became detectable by all tests. She recovered, but progressive liver disease developed during the remaining 1½ years of her life. She died of disseminaled nocardiosis and candidiasis with deteriorating hepatic function. The homograft at autopsy, showed no evidence of rejection, but was the site of chronic active liver disease, although of a different pathologic pattern than that affecting her native liver. The differences in histology may reflect the influence of chronic Immunosuppression on the features of chronic active hepatitis. PMID:365134

  12. Circulating hepatitis B surface antigen particles carry hepatocellular microRNAs.

    Directory of Open Access Journals (Sweden)

    Luisa Novellino

    Full Text Available Hepatitis B virus (HBV produces high quantities of subviral surface antigen particles (HBsAg which circulate in the blood outnumbering virions of about 1\\10(3-6 times. In individuals coinfected with the defective hepatitis Delta virus (HDV the small HDV-RNA-genome and Delta antigen circulate as ribonucleoprotein complexes within HBsAg subviral particles. We addressed the question whether subviral HBsAg particles may carry in the same way cellular microRNAs (miRNAs which are released into the bloodstream within different subcellular forms such as exosomes and microvescicles. Circulating HBsAg particles were isolated from sera of 11 HBsAg carriers by selective immunoprecipitation with monoclonal anti-HBs-IgG, total RNA was extracted and human miRNAs were screened by TaqMan real-time quantitative PCR Arrays. Thirty-nine human miRNAs were found to be significantly associated with the immunoprecipitated HBsAg, as determined by both comparative DDCT analysis and non-parametric tests (Mann-Whitney, p<0.05 with respect to controls. Moreover immunoprecipitated HBsAg particles contained Ago2 protein that could be revealed in ELISA only after 0.5% NP40. HBsAg associated miRNAs were liver-specific (most frequent = miR-27a, miR-30b, miR-122, miR-126 and miR-145 as well as immune regulatory (most frequent = miR-106b and miR-223. Computationally predicted target genes of HBsAg-associated miRNAs highlighted molecular pathways dealing with host-pathogen. The finding that HBsAg particles carry selective pools of hepatocellular miRNAs opens new avenues of research to disentangle the complex interactions between host and HBV and provides a non invasive tool to study the physiopathology of liver epigenetics.

  13. Circulating hepatitis B surface antigen particles carry hepatocellular microRNAs.

    Science.gov (United States)

    Novellino, Luisa; Rossi, Riccardo L; Bonino, Ferruccio; Cavallone, Daniela; Abrignani, Sergio; Pagani, Massimiliano; Brunetto, Maurizia R

    2012-01-01

    Hepatitis B virus (HBV) produces high quantities of subviral surface antigen particles (HBsAg) which circulate in the blood outnumbering virions of about 1\\10(3-6) times. In individuals coinfected with the defective hepatitis Delta virus (HDV) the small HDV-RNA-genome and Delta antigen circulate as ribonucleoprotein complexes within HBsAg subviral particles. We addressed the question whether subviral HBsAg particles may carry in the same way cellular microRNAs (miRNAs) which are released into the bloodstream within different subcellular forms such as exosomes and microvescicles. Circulating HBsAg particles were isolated from sera of 11 HBsAg carriers by selective immunoprecipitation with monoclonal anti-HBs-IgG, total RNA was extracted and human miRNAs were screened by TaqMan real-time quantitative PCR Arrays. Thirty-nine human miRNAs were found to be significantly associated with the immunoprecipitated HBsAg, as determined by both comparative DDCT analysis and non-parametric tests (Mann-Whitney, p<0.05) with respect to controls. Moreover immunoprecipitated HBsAg particles contained Ago2 protein that could be revealed in ELISA only after 0.5% NP40. HBsAg associated miRNAs were liver-specific (most frequent = miR-27a, miR-30b, miR-122, miR-126 and miR-145) as well as immune regulatory (most frequent = miR-106b and miR-223). Computationally predicted target genes of HBsAg-associated miRNAs highlighted molecular pathways dealing with host-pathogen. The finding that HBsAg particles carry selective pools of hepatocellular miRNAs opens new avenues of research to disentangle the complex interactions between host and HBV and provides a non invasive tool to study the physiopathology of liver epigenetics.

  14. Maturation of recombinant hepatitis B virus surface antigen particles.

    Science.gov (United States)

    Zhao, Qinjian; Wang, Yang; Freed, Daniel; Fu, Tong-Ming; Gimenez, Juan A; Sitrin, Robert D; Washabaugh, Michael W

    2006-01-01

    The major surface antigen of Hepatitis B virus (HBsAg) is a cysteine-rich, lipid-bound protein with 226 amino acids. Recombinant HBsAg (rHBsAg) with associated lipids can self-assemble into 22-nm immunogenic spherical particles, which are used in licensed Hepatitis B vaccines. Little is known about the structural evolvement or maturation upon assembly beyond an elevated level of disulfide formation. In this paper, we further characterized the maturation of HBsAg particles with respect to their degree of cross-linking, morphological changes, and changes in conformational flexibility. The lipid-containing rHBsAg particles undergo KSCN- and heat-induced maturation by formation of additional intra- and inter-molecular disulfide bonds. Direct measurements with atomic force microscopy (AFM) revealed morphological changes upon maturation through KSCN-induced and heat-/storage-incurred oxidative refolding. Particle uniformity and regularity was greatly improved, and protrusions formed by the protein subunits were more prominent on the surface of the mature particles. Decreased conformational flexibility in the mature rHBsAg particles was demonstrated by millisecond-scale unfolding kinetics in the presence of an environment-sensitive conformation probe. Both the accessible hydrophobic cavities under native conditions and the changeable hydrophobic cavities upon denaturant-induced unfolding showed substantial decrease upon maturation of the rHBsAg particles. These changes in the structural properties may be critical for the antigenicity and immuno-genicity of this widely-used vaccine component.

  15. Interferon impedes an early step of hepatitis delta virus infection.

    Directory of Open Access Journals (Sweden)

    Ziying Han

    Full Text Available Hepatitis delta virus (HDV infects hepatocytes, the major cell type of the liver. Infection of the liver may be either transient or chronic. The prognosis for patients with chronic HDV infection is poor, with a high risk of cirrhosis and hepatocellular carcinoma. The best antiviral therapy is weekly administration for at least one year of high doses of interferon alpha. This efficacy of interferon therapy has been puzzling in that HDV replication in transfected cell lines is reported as insensitive to administration of interferon alpha or gamma. Similarly, this study shows that even when an interferon response was induced by transfection of poly(IC into a cell line, HDV RNA accumulation was only modestly inhibited. However, when the HDV replication was initiated by infection of primary human hepatocytes, simultaneous addition of interferons alpha or gamma at 600 units/ml, a concentration comparable to that achieved in treated patients, the subsequent HDV RNA accumulation was inhibited by at least 80%. These interferon treatments were shown to produce significant time-dependent increases of host response proteins such as for Stat-1, phosphoStat-1, Mx1/2/3 and PKR, and yet interferon pretreatment of hepatocytes did not confer an increased inhibition of HDV replication over interferon treatment at the time of (or after infection. These and other data support the interpretation that interferon action against HDV replication can occur and is largely mediated at the level of entry into primary human hepatocytes. Thus in vivo, the success of long-term interferon therapy for chronic HDV, may likewise involve blocking HDV spread by interfering with the initiation of productive infection of naïve hepatocytes.

  16. Isolated antibody to hepatitis B core antigen in patients with chronic hepatitis C virus infection

    Institute of Scientific and Technical Information of China (English)

    Ahmed Helmy; Mohammed Ibrahim Al-Sebayel

    2006-01-01

    AIM: To evaluate the prevalence of isolated anti-HBc in patients with chronic hepatitis C virus (HCV) infection,and its relation to disease severity.METHODS: We screened all patients with chronic HCV infection referred to King Faisal Specialist Hospital and Research Center for hepatitis B surface antigen (HBsAg), antibody to hepatitis B surface antigen (antiHBs), and anti-HBc. One hundred and sixty nine patients who tested negative for both HBsAg and anti-HBs were included in this study.RESULTS: Pathologically, 59 had biopsy-proven cirrhosis and 110 had chronic active hepatitis (CAH). Of these 169 patients, 85 (50.3%) tested positive for anti-HBc.Patients with CAH had significantly higher prevalence of isolated anti-HBc than patients with cirrhosis, 71 (64.5%)and 14 (23.7%) respectively (P < 0.001). Twenty-five patients were tested for HBV DNA by qualitative PCR.The test was positive in 3 of them (12%; occult HBV infection).CONCLUSION: Isolated anti-HBc alone is common in Saudi patients with chronic HCV infection, and is significantly more common in those with CAH than those with cirrhosis. Therefore, a screening strategy that only tests for HBsAg and anti-HBs in these patients will miss a large number of individuals with isolated anti-HBc, who may be potentially infectious.

  17. Expression and characterization of hepatitis C virus core protein fused to hepatitis B virus core antigen

    Institute of Scientific and Technical Information of China (English)

    杨莉; 王春林; 汪垣; 李光地

    1999-01-01

    Recombinant plasmids were constructed by fusing the gene fragments encoding the full-length (1-191aa) and the truncated (1-40aa and 1-69aa) HCV core proteins (HCc) respectively to the core gene of HBV at the position of amino acid 144 and expressed in E. coli. The products were analyzed by ELISA, Western blotting as well as the immunization of the mice. The results showed that those fusion proteins (B144C191, B144C69, B144C40) possessed the dual antigenicity and immunogenicity of both hepatitis B virus core antigen (HBcAg) and hepatitis C virus core protein (HCc). Analysis by electron microscopy and CsCl density gradient ultra-centrifugation revealed that similar to the HBcAg itself, all fusion proteins were able to form particles. Comparison of the antigenicity and immunogenicity of those fusion proteins showed that the length of HCc gene fused to HBeAg had no much effect on the antigenicity and immunogenicity of HBcAg, however, B144C69 and B144C40 induced higher titres antibodies against HCc than B14d

  18. Expression of Hepatitis B Virus Surface Antigen Gene in Cultured Cells by Using Recombinant Plasmid Vectors

    OpenAIRE

    Siddiqui, Aleem

    1983-01-01

    By using a new host-vector system, expression of the gene coding for hepatitis B surface antigen has been studied. A subgenomic fragment of cloned hepatitis B viral DNA was inserted into the plasmid vector pSV010. Transfection of COS cells with the recombinant plasmid vector containing hepatitis sequences leads to the synthesis of hepatitis B surface antigen, which is released in the culture medium in the form of 22-nm particles similar to those found in the sera of hepatitis carriers.

  19. Quantitative Measurement of Serum Hepatitis B Surface Antigen Using an Immunoradiometric Assay in Chronic Hepatitis B

    Energy Technology Data Exchange (ETDEWEB)

    Kwon, Hyun Woo; Lee, Ho Young; Kim, Seog Gyun; Kim, Won; Jung, Wong Jin; Kang, Keon Wook; Chung, June Key; Lee, Myung Chul; Lee, Dong Soo [Seoul National Univ. Seoul (Korea, Republic of)

    2011-03-15

    Measurement of serum hepatitis B virus surface antigen (HBsAg) levels is important for the management of chronic hepatitis D patients in terms of monitoring response to antiviral therapy. This study aimed to evaluate the diagnostic performance of a new diagnostic kit, which quantitatively measures serum HBsAg level using an immunoradiometric assay (IRMA) based method. Measurements were compared with those obtained using a chemiluminescent microparticle immunoassay (CMIA) based method. The blood samples of 96 patients with chronic hepatitis B were used in this study. Copy numbers of serum hepatitis B virus (HBV) DNA were determined in 23 of these samples. The correlation between and the concordance of IRMA and CMIA results were determined using Pearson's correlation coefficients. P values of 0.05 were considered to be statistically significant throughout. Laboratory diagnoses based on CMIA. Furthermors, serum HBsAg levels by IRMA were found to be highly correlated with those determined by CMIA (correlation coefficient R{sup 2=}0.838, P<0.001). Serum HBsAg level and serum HBV DNA copies were found to be linearly related by both methods (R{sup 2=}0.067, P=0.316 by IRMA, and R{sup 2=}0.101, P=0.215 by CMIA). The diagnostic performance of the investigated IRMA method of determining HBsAg levels was found to be comparable with that of a CMIA based method in chronic hepatitis B patients.

  20. Clinical and histological characteristics of chronic hepatitis B with negative hepatitis B e-antigen

    Institute of Scientific and Technical Information of China (English)

    彭劼; 骆抗先; 朱幼芙; 郭亚兵; 章廉; 侯金林

    2003-01-01

    Abstract:Objective To study the clinical and histological features of chronic hepatitis B (CHB) with negative hepatitis B e-antigen (HBeAg). Methods A tatal of 743 in-patients with chronic hepatitis B were recruited into the study and divided into two groups according to the HBeAg status. The correlation among alanine transaminase (ALT) levels, hepatitis B virus (HBV) DNA semiquantification, and the liver histopathological data were dectected.Results Of the 743 successive in-patients, 267 (35.9%) were HBeAg-negative. The HBDAG-negative group had significantly lower serologic HBV DNA levels (63.0% of100 pg/ml, while 8.2% of them had HAIinf≥9 and 12.3% had HAIfib≥3 with HBV DNA<20 pg/ml, indicating an obverse correlation between HBV DNA levels and histology scores.Conclusions As regards clinical and histological background, the chronic HBeAg-negative hepatitis B is a different subpopulation from the HBeAg-positive counterpart.

  1. Efficient inhibition of hepatitis B virus replication by hepatitis delta virus ribozymes delivered by targeting retrovirus

    Directory of Open Access Journals (Sweden)

    Chen Long-Hua

    2010-03-01

    Full Text Available Abstract Background Hepatitis delta virus (HDV ribozyme is an attractive molecular tool that can specifically recognize and catalyze the self-cleavage of the viral RNA phosphodiester backbone. However, a major obstacle in the medical application of the HDV ribozyme is the lack of specificity in the delivery of the ribozyme to defined target cells. Results The objective of this study was to determine whether retroviral vectors can deliver the HDV ribozyme into the target cells and to elucidate whether HDV ribozyme plays a role in hepatitis B virus (HBV replication. In our study, the transduction of helper-free pseudotyped retrovirus, which showed a broad host range, in human hepatoma cells was performed under 2 conditions, that is, in the presence of polymerized human serum albumin (pHSA and in the absence of pHSA. The transduction ability in the presence of pHSA was higher than in the absence of pHSA. Moreover, HBsAg and HBeAg levels after transductions with pHSA were significantly lower than those in the absence of pHSA, thus indicating that the recombinant retrovirus had HBV-specific cleavage activity and targeted HepG2215 cells. Conclusions These data suggest that this system provides a new approach for targeting hepatocytes and has a great potential in gene therapy for HBV infection.

  2. Clinical significance of hepatitis B surface antigen mutants.

    Science.gov (United States)

    Coppola, Nicola; Onorato, Lorenzo; Minichini, Carmine; Di Caprio, Giovanni; Starace, Mario; Sagnelli, Caterina; Sagnelli, Evangelista

    2015-11-28

    Hepatitis B virus (HBV) infection is a major public health problem in many countries, with nearly 300 million people worldwide carrying HBV chronic infection and over 1 million deaths per year due to cirrhosis and liver cancer. Several hepatitis B surface antigen (HBsAg) mutations have been described, most frequently due to a single amino acid substitution and seldom to a nucleotide deletion. The majority of mutations are located in the S region, but they have also been found in the pre-S1 and pre-S2 regions. Single amino acid substitutions in the major hydrophilic region of HBsAg, called the "a" determinant, have been associated with immune escape and the consequent failure of HBV vaccination and HBsAg detection, whereas deletions in the pre-S1 or pre-S2 regions have been associated with the development of hepatocellular carcinoma. This review article will focus on the HBsAg mutants and their biological and clinical implications.

  3. Clinical significance of hepatitis B surface antigen mutants

    Institute of Scientific and Technical Information of China (English)

    Nicola; Coppola; Lorenzo; Onorato; Carmine; Minichini; Giovanni; Di; Caprio; Mario; Starace; Caterina; Sagnelli; Evangelista; Sagnelli

    2015-01-01

    Hepatitis B virus(HBV) infection is a major public health problem in many countries, with nearly 300 million people worldwide carrying HBV chronic infection and over 1 million deaths per year due to cirrhosis and liver cancer. Several hepatitis B surface antigen(HBs Ag) mutations have been described, most frequently due to a single amino acid substitution and seldom to a nucleotide deletion. The majority of mutations are located in the S region, but they have also been found in the pre-S1 and pre-S2 regions. Single amino acid substitutions in the major hydrophilic region of HBs Ag, called the "a" determinant, have been associated with immune escape and the consequent failure of HBV vaccination and HBs Ag detection, whereas deletions in the pre-S1 or pre-S2 regions have been associated with the development of hepatocellular carcinoma. This review article will focus on the HBs Ag mutants and their biological and clinical implications.

  4. Liver grafts from hepatitis B surface antigen-positive donors: A review of the literature.

    Science.gov (United States)

    Loggi, Elisabetta; Conti, Fabio; Cucchetti, Alessandro; Ercolani, Giorgio; Pinna, Antonio Daniele; Andreone, Pietro

    2016-09-21

    The scarcity of available organs and the gap between supply and demand continue to be the main limitations of liver transplantation. To relieve the organ shortage, current transplant strategies have implemented extended criteria, which include the use of liver from patients with signs of past or present hepatitis B virus (HBV) infection. While the use of liver grafts from donors with evidence of past HBV infection is quite limited, some data have been collected regarding the feasibility of transplanting a liver graft from a hepatitis B surface antigen (HBsAg) positive donor. The aim of the present work was to review the literature regarding liver transplants from HBsAg-positive donors. A total of 17 studies were identified by a search in Medline. To date, HBsAg positive grafts have preferentially been allocated to HBsAg positive recipients. The large majority of these patients continue to be HBsAg positive despite the use of immunoglobulin, and infection prevention can only be guaranteed by using antiviral prophylaxis. Although serological persistence is evident, no significant HBV-related disease has been observed, except in patients coinfected with delta virus. Consistently less data are available for HBsAg negative recipients, although they are mostly promising. HBsAg-positive grafts could be an additional organ source for liver transplantation, provided that the risk of reinfection/reactivation is properly prevented.

  5. Influence of delta virus infection on the virologic status in Egyptian patients with chronic hepatitis B virus genotype D.

    Science.gov (United States)

    Fouad, Rabab; Abdo, Mahmoud; Eldeen, Hadeel Gamal; Sabry, Dina; Atef, Mira; Ahmed, Rasha; Zayed, Naglaa

    2016-05-01

    Hepatitis delta virus (HDV) usually have an unfavorable clinical outcome in chronic hepatitis B virus (HBV) patients. In Egypt, data about epidemiology, the spectrum of disease, and impact of HDV on HBV infection are rare. To assess the prevalence, clinical and virological characteristics of HDV infection among Egyptian patients with chronic HBV. Adult patients with Hepatitis B surface antigen (HBsAg)-positive were evaluated for the presence of HDV using anti HDV-IgG and HDV RNA by RT-PCR. Routine laboratory investigations, genotypes and subtypes for both HBV and HDV, abdominal sonography, and transient elastography (TE) were done. Liver biopsy was performed only in whenever indicated. One hundred and twenty-one treatment-naïve chronic HBV patients were included. Wild HBV genotype-D2 was found in 98.2% and 81.9% were HBeAg negative. Prevalence of HDV was 8.3% by anti-HDV IgG and 9.9% by RT-PCR. Wild HDV genotype-IIb was reported in 83.3%. HDV infection was more common in males, 90.9% of delta patients were HBeAg negative. Compared to the mono-infected HBV, concomitant HBV/HDV infection was not associated with more derangment in ALT nor advanced stage of fibrosis. 66.7% of HDV patients had significantly lower HBV-DNA level compared to the non-delta patients (P infection was associated with negative HBeAg status, reduction of HBV replication, but neither influenced the clinical course nor increased significant liver damage risk. © 2015 Wiley Periodicals, Inc.

  6. The Immune Response Induced by Hepatitis B Virus Principal Antigens

    Institute of Scientific and Technical Information of China (English)

    Chien-Fu Huang; Shih-Shen Lin; Yung-Chyuan Ho; Fong-Ling Chen; Chi-Chiang Yang

    2006-01-01

    Hepatitis B virus (HBV) infection occurs primarily in hepatocytes in the liver with release of infectious virions and non-infectious empty surface antigen particles into the bloodstream. HBV replication is non-cytopathic. Transient infections run a course of several months, and chronic infections are often life-long. Chronic infections can lead to liver failure with cirrhosis and hepatocellular carcinoma. It is generally accepted that neutralizing anti-HBs antibodies plays a key role in recovery from HBV infection by containing the spread of infection in the infected host and facilitating the removal and destruction of viral particles. However, the immune response initiated by the T-cell response to viral antigens is also important for viral clearance and disease pathogenesis in HBV infection.The three structural forms of the viral proteins, the HBsAg, the particulate HBcAg, and the nonparticulate HBeAg,may preferentially elicit different Th cell subsets. The different IgG subclass profiles of anti-HBs, anti-HBc, and anti-HBe in different HBV infection status were revealed. Moreover, the different IgG subclass profiles in chronic carriers did not change with different ALT and AST levels and may reflect the difference between stimulating antigens, immune response, and the stages of viral disease and provide the basis for the use of vaccines and prophylactic treatments for individuals at high risk of human HBV infection. This review elucidates the detailed understanding of the immune responses induced during transient and persistent infection, and the development of immunotherapy and immunodiagnosis in patients with HBV infection, and possible means of reducing the liver damage.

  7. Hepatosplenic Gamma/DeltaT-Cell Lymphoma Masquerading as Alcoholic Hepatitis and Methadone Withdrawal

    Directory of Open Access Journals (Sweden)

    H.A. Lopez Morra

    2007-09-01

    Full Text Available Hepatosplenic gamma/delta T-cell lymphoma is a rare neoplasm of mature gamma/delta T-cells with sinusoidal infiltration of spleen, liver, and bone marrow. Patients are predominantly adolescent and young adult males and usually present with marked hepatosplenomegaly. Pancytopenia is another common finding. Despite an initial response to treatment, patients have a median survival of one to two years. In this report, we document a case of alcoholic hepatitis and methadone withdrawal masquerading unsuspected, hepatosplenic gamma/delta T-cell lymphoma with unusual CD20 positivity.

  8. Artificial neural network accurately predicts hepatitis B surface antigen seroclearance.

    Directory of Open Access Journals (Sweden)

    Ming-Hua Zheng

    Full Text Available BACKGROUND & AIMS: Hepatitis B surface antigen (HBsAg seroclearance and seroconversion are regarded as favorable outcomes of chronic hepatitis B (CHB. This study aimed to develop artificial neural networks (ANNs that could accurately predict HBsAg seroclearance or seroconversion on the basis of available serum variables. METHODS: Data from 203 untreated, HBeAg-negative CHB patients with spontaneous HBsAg seroclearance (63 with HBsAg seroconversion, and 203 age- and sex-matched HBeAg-negative controls were analyzed. ANNs and logistic regression models (LRMs were built and tested according to HBsAg seroclearance and seroconversion. Predictive accuracy was assessed with area under the receiver operating characteristic curve (AUROC. RESULTS: Serum quantitative HBsAg (qHBsAg and HBV DNA levels, qHBsAg and HBV DNA reduction were related to HBsAg seroclearance (P<0.001 and were used for ANN/LRM-HBsAg seroclearance building, whereas, qHBsAg reduction was not associated with ANN-HBsAg seroconversion (P = 0.197 and LRM-HBsAg seroconversion was solely based on qHBsAg (P = 0.01. For HBsAg seroclearance, AUROCs of ANN were 0.96, 0.93 and 0.95 for the training, testing and genotype B subgroups respectively. They were significantly higher than those of LRM, qHBsAg and HBV DNA (all P<0.05. Although the performance of ANN-HBsAg seroconversion (AUROC 0.757 was inferior to that for HBsAg seroclearance, it tended to be better than those of LRM, qHBsAg and HBV DNA. CONCLUSIONS: ANN identifies spontaneous HBsAg seroclearance in HBeAg-negative CHB patients with better accuracy, on the basis of easily available serum data. More useful predictors for HBsAg seroconversion are still needed to be explored in the future.

  9. Docking of B-cell epitope antigen to specific hepatitis B antibody

    Indian Academy of Sciences (India)

    R Rajkannan; E J Padma Malar

    2007-09-01

    The interaction of pres1 region of hepatitis B virus B-cell epitope antigen with specific hepatitis B neutralizing monoclonal antibody was examined by docking study. We modelled the 3D complex structure of B-cell epitope antigen residues CTTPAQGNSMFPSCCCTKPTDGNCY by homology modelling and docked it with the crystal structure of monoclonal antibody specific for the pres1 region of the hepatitis B virus. At the optimized docked conformation, the interactions between the amino acids of antigen and antibody were examined. It is found that the docked complex is stabilized by 59.3 kcal/mol. The stability of the docked antigen-antibody complex is due to hydrogen bonding and van der Waals interactions. The amino acids of the antigen and antibody responsible for the interaction were identified.

  10. Structure, sequence and expression of the hepatitis delta (δ) viral genome

    Science.gov (United States)

    Wang, Kang-Sheng; Choo, Qui-Lim; Weiner, Amy J.; Ou, Jing-Hsiung; Najarian, Richard C.; Thayer, Richard M.; Mullenbach, Guy T.; Denniston, Katherine J.; Gerin, John L.; Houghton, Michael

    1986-10-01

    Biochemical and electron microscopic data indicate that the human hepatitis δ viral agent contains a covalently closed circular and single-stranded RNA genome that has certain similarities with viroid-like agents from plants. The sequence of the viral genome (1,678 nucleotides) has been determined and an open reading frame within the complementary strand has been shown to encode an antigen that binds specifically to antisera from patients with chronic hepatitis δ viral infections.

  11. Antigenicity and immunogenicity of novel chimeric hepatitis B surface antigen particles with exposed hepatitis C virus epitopes.

    Science.gov (United States)

    Netter, H J; Macnaughton, T B; Woo, W P; Tindle, R; Gowans, E J

    2001-03-01

    The small envelope protein of hepatitis B virus (HBsAg-S) can self-assemble into highly organized virus like particles (VLPs) and induce an effective immune response. In this study, a restriction enzyme site was engineered into the cDNA of HBsAg-S at a position corresponding to the exposed site within the hydrophilic a determinant region (amino acid [aa] 127-128) to create a novel HBsAg vaccine vector allowing surface orientation of the inserted sequence. We inserted sequences of various lengths from hypervariable region 1 (HVR1) of the hepatitis C virus (HCV) E2 protein containing immunodominant epitopes and demonstrated secretion of the recombinant HBsAg VLPs from transfected mammalian cells. A number of different recombinant proteins were synthesized, and HBsAg VLPs containing inserts up to 36 aa were secreted with an efficiency similar to that of wild-type HBsAg. The HVR1 region exposed on the particles retained an antigenic structure similar to that recognized immunologically during natural infection. VLPs containing epitopes from either HCV-1a or -1b strains were produced that induced strain-specific antibody responses in immunized mice. Injection of a combination of these VLPs induced antibodies against both HVR1 epitopes that resulted in higher titers than were achieved by vaccination with the individual VLPs, suggesting a synergistic effect. This may lead to the development of recombinant particles which are able to induce a broad anti-HCV immune response against the HCV quasispecies or other quasispecies-like infectious agents.

  12. Antigenicity and Immunogenicity of Novel Chimeric Hepatitis B Surface Antigen Particles with Exposed Hepatitis C Virus Epitopes†

    Science.gov (United States)

    Netter, Hans J.; Macnaughton, Thomas B.; Woo, Wai-Ping; Tindle, Robert; Gowans, Eric J.

    2001-01-01

    The small envelope protein of hepatitis B virus (HBsAg-S) can self-assemble into highly organized virus like particles (VLPs) and induce an effective immune response. In this study, a restriction enzyme site was engineered into the cDNA of HBsAg-S at a position corresponding to the exposed site within the hydrophilic a determinant region (amino acid [aa] 127–128) to create a novel HBsAg vaccine vector allowing surface orientation of the inserted sequence. We inserted sequences of various lengths from hypervariable region 1 (HVR1) of the hepatitis C virus (HCV) E2 protein containing immunodominant epitopes and demonstrated secretion of the recombinant HBsAg VLPs from transfected mammalian cells. A number of different recombinant proteins were synthesized, and HBsAg VLPs containing inserts up to 36 aa were secreted with an efficiency similar to that of wild-type HBsAg. The HVR1 region exposed on the particles retained an antigenic structure similar to that recognized immunologically during natural infection. VLPs containing epitopes from either HCV-1a or -1b strains were produced that induced strain-specific antibody responses in immunized mice. Injection of a combination of these VLPs induced antibodies against both HVR1 epitopes that resulted in higher titers than were achieved by vaccination with the individual VLPs, suggesting a synergistic effect. This may lead to the development of recombinant particles which are able to induce a broad anti-HCV immune response against the HCV quasispecies or other quasispecies-like infectious agents. PMID:11160717

  13. Hepatitis B virus e antigen induces activation of rat hepatic stellate cells

    Energy Technology Data Exchange (ETDEWEB)

    Zan, Yanlu [Center for Molecular Virology, CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101 (China); University of Chinese Academy of Sciences, Beijing 100049 (China); Zhang, Yuxia, E-mail: yzhang@wehi.edu.au [Center for Molecular Virology, CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101 (China); Tien, Po, E-mail: tienpo@sun.im.ac.cn [Center for Molecular Virology, CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101 (China)

    2013-06-07

    Highlights: •HBeAg expression in HSCs induced production of ECM protein and liver fibrotic markers. •The activation and proliferation of HSCs were mediated by TGF-β. •HBeAg protein purified from cell medium directly activated HSCs. -- Abstract: Chronic hepatitis B virus infection is a major cause of hepatic fibrosis, leading to liver cirrhosis and hepatocellular carcinoma. Hepatitis B virus e antigen (HBeAg) is an accessory protein of HBV, not required for viral replication but important for natural infection in vivo. Hepatic stellate cells (HSCs) are the major producers of excessive extracellular matrix during liver fibrogenesis. Therefore, we examined the influence of HBeAg on HSCs. The rat HSC line HSC-T6 was transfected with HBeAg plasmids, and expression of α-smooth muscle actin, collagen I, transforming growth factor-β1 (TGF-β), and tissue inhibitors of metalloproteinase 1 (TIMP-1) was investigated by quantitative real-time PCR. The proliferation of HSCs was determined by MTS analysis. HBeAg transduction induced up-regulation of these fibrogenic genes and proliferation of HSCs. We found that HBeAg induced TGF-β secretion in HSCs, and the activation of HSCs was prevented by a neutralizing anti-TGF-β antibody. Depletion and addition of HBeAg protein in conditioned medium from HSC-T6 cells transduced with HBeAg indicated that HBeAg directly induced the activation and proliferation of rat primary HSCs. Taken together, HBeAg induces the activation and proliferation of HSCs, mainly mediated by TGF-β, and HBeAg protein purified from cell medium can directly activate HSCs.

  14. Infectious vaccinia virus recombinants that express hepatitis B virus surface antigen

    Science.gov (United States)

    Smith, Geoffrey L.; Mackett, Michael; Moss, Bernard

    1983-04-01

    Potential live vaccines against hepatitis B virus have been produced. The coding sequence for hepatitis B virus surface antigen (HBsAg) has been inserted into the vaccinia virus genome under control of vaccinia virus early promoters. Cells infected with these vaccinia virus recombinants synthesize and excrete HBsAg and vaccinated rabbits rapidly produce antibodies to HBsAg.

  15. Cellular Nuclear Export Factors TAP and Aly Are Required for HDAg-L-mediated Assembly of Hepatitis Delta Virus.

    Science.gov (United States)

    Huang, Hsiu-Chen; Lee, Chung-Pei; Liu, Hui-Kang; Chang, Ming-Fu; Lai, Yu-Heng; Lee, Yu-Ching; Huang, Cheng

    2016-12-09

    Hepatitis delta virus (HDV) is a satellite virus of hepatitis B virus (HBV). HDV genome encodes two forms of hepatitis delta antigen (HDAg), small HDAg (HDAg-S), which is required for viral replication, and large HDAg (HDAg-L), which is essential for viral assembly. HDAg-L is identical to HDAg-S except that it bears a 19-amino acid extension at the C terminus. Both HDAgs contain a nuclear localization signal (NLS), but only HDAg-L contains a CRM1-independent nuclear export signal at its C terminus. The nuclear export activity of HDAg-L is important for HDV particle formation. However, the mechanisms of HDAg-L-mediated nuclear export of HDV ribonucleoprotein are not clear. In this study, the host cellular RNA export complex TAP-Aly was found to form a complex with HDAg-L, but not with an export-defective HDAg-L mutant, in which Pro(205) was replaced by Ala. HDAg-L was found to colocalize with TAP and Aly in the nucleus. The C-terminal domain of HDAg-L was shown to directly interact with the N terminus of TAP, whereas an HDAg-L mutant lacking the NLS failed to interact with full-length TAP. In addition, small hairpin RNA-mediated down-regulation of TAP or Aly reduced nuclear export of HDAg-L and assembly of HDV virions. Furthermore, a peptide, TAT-HDAg-L(198-210), containing the 10-amino acid TAT peptide and HDAg-L(198-210), inhibited the interaction between HDAg-L and TAP and blocked HDV virion assembly and secretion. These data demonstrate that formation and release of HDV particles are mediated by TAP and Aly. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  16. Early predictive efficacy of core antigen on antiviral outcomes in genotype 1 hepatitis C virus infected patients

    Directory of Open Access Journals (Sweden)

    Bo Feng

    Full Text Available Response-guided therapy is of limited use in developing countries because hepatitis C virus RNA detection by sensitive molecular methods is time- and labor-consuming and expen- sive. We evaluated early predictive efficacy of serum hepatitis C virus core antigen kinetics on sustained virologic response in patients with genotype 1 hepatitis C virus during pegylated interferon plus ribavirin treatment. For 478 patients recruited, hepatitis C virus RNAs were detected at baseline, and at weeks 4, 12, 24, 48, and 72 using Cobas TaqMan. Architect hepatitis C virus core antigen was performed at baseline, and weeks 4 and 12. Predictive values of hepatitis C virus core antigen on sustained virologic response were compared to hepatitis C virus RNA. In the first 12 weeks after treatment initiation the dynamic patterns of serum hepatitis C virus core antigen and hepatitis C virus RNA levels were similar in sustained virologic response, relapse, and null response patients groups. Although areas under the receiver operating characteristics curves of hepatitis C virus core antigen were lower than those of hepatitis C virus RNA at the same time points, modeling analysis showed that undetectable hepatitis C virus core antigen (rapid virological response based on hepatitis C virus core antigen had similar positive predictive value on sustained virologic response to hepatitis C virus RNA at week 4 (90.4% vs 93.3%, and hepatitis C virus core antigen decrease greater than 1 log10 IU/mL (early virological response based on hepatitis C virus core antigen had similar negative predictive value to hepatitis C virus RNA at week 12 (94.1% vs 95.Z%. Analysis on the validation group demonstrated a positive predictivevalue of 97.5% in rapid virological response based on hepatitis C virus core antigen and a negative predictive value of 100% in early virological response based on hepatitis C virus core antigen. In conclusion, hepatitis C virus core antigen is comparable to

  17. Hepatitis B immunisation for newborn infants of hepatitis B surface antigen-positive mothers

    DEFF Research Database (Denmark)

    Lee, C; Gong, Yanzhang; Brok, J

    2006-01-01

    Hepatitis B vaccine and hepatitis B immunoglobulin are considered for newborn infants of HBsAg-positive mothers to prevent hepatitis B infection.......Hepatitis B vaccine and hepatitis B immunoglobulin are considered for newborn infants of HBsAg-positive mothers to prevent hepatitis B infection....

  18. Comparable quality attributes of hepatitis E vaccine antigen with and without adjuvant adsorption-dissolution treatment.

    Science.gov (United States)

    Zhang, Yue; Li, Min; Yang, Fan; Li, Yufang; Zheng, Zizheng; Zhang, Xiao; Lin, Qingshan; Wang, Ying; Li, Shaowei; Xia, Ningshao; Zhang, Jun; Zhao, Qinjian

    2015-01-01

    Most vaccines require adjuvants for antigen stabilization and immune potentiation. Aluminum-based adjuvants are the most widely used adjuvants for human vaccines. Previous reports demonstrated the preservation of antigen conformation and other antigen characteristics after recovery from adjuvanted Hepatitis B and human papillomavirus vaccines. In this study, we used a combination of various physiochemical and immunochemical methods to analyze hepatitis E vaccine antigen quality attributes after recovery from adjuvants. All biochemical and biophysical methods showed similar characteristics of the p239 protein after recovery from adjuvanted vaccine formulation compared to the antigen in solution which never experienced adsorption/desorption process. Most importantly, we demonstrated full preservation of key antigen epitopes post-recovery from adjuvanted vaccine using a panel of murine monoclonal antibodies as exquisite probes. Antigenicity of p239 was probed with a panel of 9 mAbs using competition/blocking ELISA, surface plasmon resonance and sandwich ELISA methods. These multifaceted analyses demonstrated the preservation of antigen key epitopes and comparable protein thermal stability when adsorbed on adjuvants or of the recovered antigen post-dissolution treatment. A better understanding of the antigen conformation in adjuvanted vaccine will enhanced our knowledge of antigen-adjuvant interactions and facilitate an improved process control and development of stable vaccine formulation.

  19. OCCULT HEPATITIS B VIRUS INFECTION AMONG BLOOD DONORS WITH ANTIBODIES TO HEPATITIS B CORE ANTIGEN

    Directory of Open Access Journals (Sweden)

    A. Jafarzadeh

    2008-04-01

    Full Text Available Diagnosis of hepatitis B is routinely based on of serological assay of hepatitis B surface antigen (HBsAg. Occult hepatitis B virus (HBV infection is generally defined as the detection of HBV -DNA in the serum or tissues of subjects who have negative test for HBsAg. Transmission of HBV infection has been documented from HBsAg negative, anti-HBc positive blood and organ donors. The aim of this study was to determine the rate of occult HBV infection among HBsAg negative and anti-HBc positive blood donors of Rafsanjan blood transfusion center. ‎ Sera from 270 healthy blood donors who were negative for both HBsAg and anti-HCV, were tested for anti-HBc antibodies by use of ELISA technique. The samples that were negative for HBsAg but positive for anti-HBc markers also examined for the presence of HBV-DNA by polymerase chain reaction (PCR. ‎ Out of 270 HBsAg negative blood samples, 14 samples (5.18% were positive for anti-HBc antibodies. HBV-DNA was detected in 4/14 (28.57% of HBsAg negative and anti-HBc positive samples. Moreover, anti-HBs antibody was detected in 2/4 (50% of HBV-DNA positive samples. ‎ These results indicated that HBV-DNA found in the majority of HBsAg negative and anti-HBc-positive donors. In addition, the present study recommend the incorporation of routine anti-HBc screening of blood as a surrogate marker of occult HBV infection to prevent some transfusion-transmitted HBV infections.

  20. Kinetics of Hepatitis B Surface Antigen Level in Chronic Hepatitis B Patients who Achieved Hepatitis B Surface Antigen Loss during Pegylated Interferon Alpha-2a Treatment

    Science.gov (United States)

    Li, Ming-Hui; Zhang, Lu; Qu, Xiao-Jing; Lu, Yao; Shen, Ge; Wu, Shu-Ling; Chang, Min; Liu, Ru-Yu; Hu, Lei-Ping; Li, Zhen-Zhen; Hua, Wen-Hao; Song, Shu-Jing; Xie, Yao

    2017-01-01

    Background: Hepatitis B surface antigen (HBsAg) loss/seroconversion is considered to be the ideal endpoint of antiviral therapy and the ultimate treatment goal in chronic hepatitis B (CHB). This study aimed to assess the patterns of HBsAg kinetics in CHB patients who achieved HBsAg loss during the treatment of pegylated interferon (PEG-IFN) α-2a. Methods: A total of 150 patients were enrolled, composing of 83 hepatitis B envelope antigen (HBeAg)-positive and 67 HBeAg-negative patients. Patients were treated with PEG-IFN α-2a180 μg/week until HBsAg loss/seroconversion was achieved, which occurred within 96 weeks. Serum hepatitis B virus deoxyribonucleic acid and serological indicators (HBsAg, anti-HBs, HBeAg, and anti-HBe) were determined before and every 3 months during PEG-IFN α-2a treatment. Biochemical markers and peripheral blood neutrophil and platelet counts were tested every 1–3 months. Results: Baseline HBsAg levels were 2.5 ± 1.3 log IU/ml, and decreased rapidly at 12 and 24 weeks by 48.3% and 88.3%, respectively. The mean time to HBsAg loss was 54.2 ± 30.4 weeks, though most patients needed extended treatment and 30.0% of HBsAg loss occurred during 72–96 weeks. Baseline HBsAg levels were significantly higher in HBeAg-positive patients (2.9 ± 1.1 log IU/ml) compared with HBeAg-negative patients (2.0 ± 1.3 log IU/ml; t = 4.733, P < 0.001), but the HBsAg kinetics were similar. Patients who achieved HBsAg loss within 48 weeks had significantly lower baseline HBsAg levels and had more rapid decline of HBsAg at 12 weeks compared to patients who needed extended treatment to achieve HBsAg loss. Conclusions: Patients with lower baseline HBsAg levels and more rapid decline during early treatment with PEG-IFN are more likely to achieve HBsAg loss during 96 weeks of treatment, and extended therapy longer than 48 weeks may be required to achieve HBsAg loss. PMID:28229987

  1. Hepatitis D Virus Infection Among Hepatitis B Surface Antigen Carriers and in “Isolated anti-HBc” Antibodies Profile in Central Tunisia

    Science.gov (United States)

    Mhalla, Salma; Kadri, Yosr; Alibi, Sana; Letaief, Amel; Boukadida, Jalel; Hannachi, Naila

    2016-01-01

    Background: Hepatitis D Virus (HDV) causes accelerated liver diseases in patients with Hepatitis B Virus (HBV) infection. There is lack of data about its prevalence, related risk factors and interaction with HBV carriers in our country. Objectives: The aim of this study was to estimate the prevalence of hepatitis delta and associated risk factors among Hepatitis B surface antigen (HBsAg) and “isolated anti-HBc” profile carriers in central Tunisia. Patients and Methods: In this cross-sectional study, 540 patients with positive HBsAg and 109 “isolated anti-HBc” profile receiving care in a teaching hospital were tested for the presence of HDV serum-markers using commercially available enzyme immunoassay kit. HBV-DNA was detected by nested PCR in “isolated anti-HBc” profile group. Results: Prevalence of HDV was 8.1% in HBsAg carriers group, but it was significantly higher in active than inactive hepatitis (30.2% and 4.5%, respectively, OR = 9, 95% CI: [4.48-18.58]). There was no significant association between studied risk factors and HDV infection. In the “isolated anti-HBc” profile group, prevalence of HDV was 4.6% and HBV-DNA had negative result in all patients with positive results for HDV. Conclusions: Although HDV had low prevalence in our area, it is vital to plan preventive strategies for HDV spread as well as HBV prevention. It is particularly important to suspect HDV infection in active HBV carriers to manage a particularly severe dual infection. HDV infection should be suspected even in negative HBsAg patients having “isolated anti-HBc” profile. PMID:27110257

  2. Expression, biosynthesis and release of preadipocyte factor-1/ delta-like protein/fetal antigen-1 in pancreatic -cells

    DEFF Research Database (Denmark)

    Friedrichsen, B N; Carlsson, C; Møldrup, A

    2003-01-01

    Preadipocyte factor-1 (Pref-1)/delta-like protein/fetal antigen-1 (FA1) is a member of the epidermal growth factor-like family. It is widely expressed in embryonic tissues, whereas in adults it is confined to the adrenal gland, the anterior pituitary, the endocrine pancreas, the testis and the ov......Preadipocyte factor-1 (Pref-1)/delta-like protein/fetal antigen-1 (FA1) is a member of the epidermal growth factor-like family. It is widely expressed in embryonic tissues, whereas in adults it is confined to the adrenal gland, the anterior pituitary, the endocrine pancreas, the testis...

  3. Complement fixing hepatitis B core antigen immune complexes in the liver of patients with HBs antigen positive chronic disease.

    Science.gov (United States)

    Rizzetto, M; Bonino, F; Crivelli, O; Canese, M G; Verme, G

    1976-01-01

    One hundred and fifty-two biopsies from serologically HBsAg positive and negative patients with liver disease were studied in immunofluorescence: for the presence of the surface (HBs) and the core (HBc) antigenic determinants foeterminants of the hepatitis B virus, of immunoglobulins and complement (C) deposits, and for the capacity to fix human C. Circumstantial evidence is presented suggesting that HBc immune-complexes are a relevant feature in the establishment and progression of chronic HBSAg liver disease. C fixation by liver cells was shown in all HBC positive patients with chronic hepatitis; an active form was present in every case, except two with a persistent hepatitis, an inverse ratio of HBc to C binding fluorescence being noted between active chronic hepatitis and cirrhotic patients. HBc without C fixation was observed in only three patients in the incubation phase of infectious hepatitis. IgG deposits were often found in HBc containing, C fixing nuclei. No C binding or IgG deposits were observed in acute self-limited type B hepatitis, in serologically positive patients with normal liver or minimal histological lesions, with and without HBs cytoplasmic fluorescence in their biopsy, or in serologically negative individuals. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 PMID:1001973

  4. Purinergic receptor functionality is necessary for infection of human hepatocytes by hepatitis delta virus and hepatitis B virus.

    Directory of Open Access Journals (Sweden)

    John M Taylor

    Full Text Available Hepatitis B virus (HBV and hepatitis delta virus (HDV are major sources of acute and chronic hepatitis. HDV requires the envelope proteins of HBV for the processes of assembly and infection of new cells. Both viruses are able to infect hepatocytes though previous studies have failed to determine the mechanism of entry into such cells. This study began with evidence that suramin, a symmetrical hexasulfated napthylurea, could block HDV entry into primary human hepatocytes (PHH and was then extrapolated to incorporate findings of others that suramin is one of many compounds that can block activation of purinergic receptors. Thus other inhibitors, pyridoxal-phosphate-6-azophenyl-2',4'-disulfonate (PPADS and brilliant blue G (BBG, both structurally unrelated to suramin, were tested and found to inhibit HDV and HBV infections of PHH. BBG, unlike suramin and PPADS, is known to be more specific for just one purinergic receptor, P2X7. These studies provide the first evidence that purinergic receptor functionality is necessary for virus entry. Furthermore, since P2X7 activation is known to be a major component of inflammatory responses, it is proposed that HDV and HBV attachment to susceptible cells, might also contribute to inflammation in the liver, that is, hepatitis.

  5. Detection of hepatitis C virus core antigen for early diagnosis of hepatitis C virus infection in plasma donor in China

    Institute of Scientific and Technical Information of China (English)

    He-Qiu Zhang; Shao-Bo Li; Guo-Hua Wang; Kun Chen; Xiao-Guo Song; Xiao-Yan Feng

    2007-01-01

    AIM: To evaluate the efficacy of a new hepatitis C virus (HCV) core antigen assay developed in China.METHODS: After the determination of HCV infection, 49 serial samples were selected from 11 regular plasma donors in 5 different plasma stations. To compare the performance of HCV core antigen detection and HCV PCR, these samples were genotyped, and each specimen was analyzed by ELISA for the detection of HCV core antigen and by qualitative HCV PCR.RESULTS: Among all of the sequential samples, the original 13 specimens were HCV RNA-negative, and 36 samples were HCV RNA-positive. Twenty-seven samples (75%) were HCV core antigen-positive from these HCV RNA-positive specimens. Conversely, 27 samples (93.1%) were found HCV RNA-positive in HCV core antigen-positive samples. Intervals between HCV RNA and HCV core antigen-positive, as well as between HCV core antigen-positive and HCV antibody-positive were 36.0 and 32.8 d, respectively.CONCLUSION: This HCV core antigen assay, developed in China, is able to detect much of anti-HCV-negative, HCV RNA-positive preseroconversion window period (PWP) plasma donations.

  6. Human CD4+ T-cell response to hepatitis delta virus: identification of multiple epitopes and characterization of T-helper cytokine profiles.

    Science.gov (United States)

    Nisini, R; Paroli, M; Accapezzato, D; Bonino, F; Rosina, F; Santantonio, T; Sallusto, F; Amoroso, A; Houghton, M; Barnaba, V

    1997-01-01

    The T-cell-mediated immune response plays a crucial role in defense against hepatotropic viruses as well as in the pathogenesis of viral chronic hepatitides. However, very little is known about the role of specific T cells during hepatitis delta virus (HDV) infection in humans. In this study, the T-cell response to HDV in chronic hepatitis B virus (HBV) carriers with HDV superinfection was investigated at different levels. Analysis of peripheral blood mononuclear cell (PBMC) proliferation in response to a recombinant form of large hepatitis delta antigen (HDAg) revealed that 8 of 30 patients studied (27%) specifically responded to HDAg. By employing synthetic peptides spanning the entire HDAg sequence, we found that T-cell recognition was directed against different antigenic determinants, with patient-to-patient variation in the pattern of response to peptides. Interestingly, all responders had signs of inactive HDV-induced disease, while none of the patients with active disease and none of the control subjects showed any significant proliferation. More accurate information about the specific T-cell response was obtained at the clonal level. A panel of HDAg-specific CD4+ T-cell clones from three HDV-infected individuals and fine-specificity analysis revealed that the clones tested individually recognized four epitopes corresponding to amino acids (aa) 26 to 41, 50 to 65, 66 to 81, or 106 to 121 of HDAg sequence. The study of human leukocyte antigen (HLA) restriction revealed that peptides 50 to 65 and 106 to 121 were presented to specific T cells in association with multiple class II molecules. In addition, peptide 26 to 41 was efficiently generated after processing of HDAg through the endogenous processing pathway. Cytokine secretion analysis showed that all the CD4+ T-cell clones assayed were able to produce high levels of gamma interferon (IFN-gamma), belonging either to T helper-1 (Th1) or Th0 subsets and that some of them were cytotoxic in a specific assay

  7. Prevalence of hepatitis B surface antigen (HBsAg) in blood donors from Bombay.

    Science.gov (United States)

    Satoskar, A; Ray, V

    1992-01-01

    Analysis of serum samples from 3104 blood donors from Bombay screened for hepatitis B surface antigen (HBsAg) by ELISA. HBsAg was detected in 4.7% of the subjects. Relatives showed a significantly higher prevalence of HBsAg than volunteer donors. There was no significant association between HBsAg positivity and a particular blood group.

  8. Lamivudinbehandling af en hepatitis Bs- antigen-positiv patient med reaktiv artritis

    DEFF Research Database (Denmark)

    Borup, Christian; Siboni, Anders

    2008-01-01

    . After one year and nine months lamivudine was discontinued, resulting in a flare of the hepatitis after 56 days: HBV-DNA rose to 40 million copies per ml and HBe antigen became positive. Lamivudine was reinstituted, resulting in normalization of ALAT and lowering of HBV-DNA under detection level...

  9. 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.

    Science.gov (United States)

    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 HBcrAg assays.

  10. Detection of Hepatitis B Virus Antigens in Paraffin-embedded Liver Specimens from the Amazon Region, Brazil

    Directory of Open Access Journals (Sweden)

    Simonetti SRR

    2002-01-01

    Full Text Available Hepatic viscerotomy of paraffin-preserved old specimens, collected in the period from 1934 to 1967, were analyzed by immunohistochemical assays to detect hepatitis B, hepatitis D, dengue and yellow fever virus antigens. The material belongs to the Yellow Fever Collection, Department of Pathology, Instituto Oswaldo Cruz, Rio de Janeiro, Brazil and the cases were diagnosed at that time according to clinical aspects and histopathological findings reporting viral hepatitis, yellow fever, focal necrosis and hepatic atrophy. From the 79 specimens, 69 were collected at the Labrea Region and the other 10 in different other localities in the Amazon Region. The five micra thick histological slices were analyzed for the presence of hepatitis B surface antigen (HBsAg and hepatitis B core antigen (HBcAg by immunoperoxidase technique. An immunofluorescence assay was applied to the detection of hepatitis D, yellow fever and dengue virus antigens. Nine (11.4% histological samples were HBsAg reactive and 5 (6.3% were HBcAg reactive. The oldest reactive sample was from 1934. Viral antigens related to the other pathologies were not detected in this study. Our results confirm that the methodology described may be used to elucidate the aetiology of hepatitis diseases even after a long time of conservation of the specimens.

  11. Complexes of hepatitis B surface antigen and immunoglobulin M in the sera of patients with hepatitis B virus infection.

    Science.gov (United States)

    Palla, M; Rizzi, R; Toti, M; Almi, P; Rizzetto, M; Bonino, F; Purcell, R

    1983-01-01

    Hepatitis B surface antigen (HBsAg) bound to immunoglobulin M (IgM) was detected in sera of HBsAg carriers by a radioimmunoassay based on selective absorption of the immunoglobulin on a solid phase coated with antiserum to human IgM. Isopycnic banding and rate-zonal sedimentation have shown that the reaction is related to particulate forms of the HBsAg complexed with IgM. The binding of IgM possibly occurred because of a selective affinity of these molecules to the surface of HBsAg particles. HBsAg/IgM was found transiently in 24 of 25 (96%) patients with acute self-limited hepatitis B and persistently in 6 of 25 patients whose acute hepatitis B progressed to chronicity. It was also found in 20 of 39 (51%) chronic HBsAg carriers with inactive and asymptomatic infection. The HBsAg/IgM phenomenon is not dependent on replication of hepatitis B virions; its persistence in patients with acute hepatitis B may provide complementary evidence of transition of the infection to chronicity. PMID:6309673

  12. Development of hepatitis C virus vaccine using hepatitis B core antigen as immuno-carrier

    Institute of Scientific and Technical Information of China (English)

    Jia-Yu Chen; Fan Li

    2006-01-01

    AIM: To develop hepatitis C virus (HCV) vaccine using HBcAg as the immuno-carrier to express HCV T epitope and to investigate its immunogenicity in mice.METHODS: We constructed the plasmid pTrc-coreNheI using gene engineering technique, constructed the pcDNA3.1-coreNheI-GFP plasmid with GFP as the reporter gene, and transfected them into Hela cells.The expression of GFP was observed under confocal microscopy and the feasibility of using HBcAg as an immuno-carrier vaccine was studied. pTrc-core gene with a synthetic T epitope antigen gene of HCV (35-44aa) was fused and expressed in the plasmid pTrccore-HCV (T). For the fusion of the HBcAg-T protein,sucrose, density gradient centrifugation was used, and its molecular weight and purity were analyzed by SDSPAGE. Then balb/c mice were immunized by the plasmid with the HBcAg (expressed by pTrc-core) protein as control. The tumor regression potential was investigated in mice and evaluated at appropriate time. After three times of immunization, the peripheral blood and spleen of vaccinated mice were collected. HBcAb was detected by ELISA, and nonspecific T lymphocyte proliferation and response of splenocytes were respectively examined by MTT assay. T cell subset of blood and spleen were detected by FACS.RESULTS: GFP was successfully expressed. Tumor regression trial showed that no tumor formation was found in the group receiving immunization, while tumor xenograft progression was not changed in the control group. Strong nonspecific lymphocyte proliferation response was induced. FACS also showed that the ratio of CD8+T cells in the experimental group was higher than the controls, but the serum HBcAb in experimental group was similar to the control.CONCLUSION: HBcAg can be used as an immunocarrier of vaccine, the fusion of HBcAg-T protein could induce stronger cellular immune responses and it might be a candidate for therapeutic vaccines specific for HCV.

  13. Cytotoxic T-lymphocyte antigen 4 gene polymorphisms and susceptibility to chronic hepatitis B

    Institute of Scientific and Technical Information of China (English)

    Amir Houshang Mohammad Alizadeh; Mehrdad Hajilooi; Mitra Ranjbar; Farahnaz Fallahian; Seyed Mohsen Mousavi

    2006-01-01

    AIM: To assess the three polymorphism regions within cytotoxic T-lymphocyte antigen 4 (CTLA-4) gene, a C/T base exchange in the promoter region-318 (CTLA-4 -318C/T), an A/G substitution in the exon 1 position 49 (CTLA-4 49A/G), a T/C substitution in 1172 (CTLA-4 -1172T/C) in patients with chronic hepatitis B.METHODS: Fifty-one patients with chronic hepatitis B virus infection and 150 healthy subjects were recruited sequentially as they presented to the hepatic clinic. Classification of chronic hepatitis B virus (HBV)-infected patients was as asymptomatic carrier state (26 patients) and chronic hepatitis B (25 patients). Genomic DNA was isolated from anti-coagulated peripheral blood Buffy coat using Miller's salting-out method. The presence of the CTLA-4 gene polymorphisms was determined using polymerase chain reaction amplification refractory mutation system (ARMS).RESULTS: We observed a significant association between -318 genotypes frequency (T+C-, T+C+, T-C+) and susceptibility to chronic hepatitis B (P=0.012,OR=0.49, 95%CI: 0.206-1.162). However, we did not observe a significant association for +49 genotype frequency (T+C+, T+C- T-C+) and -1172 genotype frequency (C+T+, T+C- C+T-) and state of disease.CONCLUSION: Our results suggest that CTLA-4 gene polymorphisms may partially be involved in the susceptibility to chronic hepatitis B.

  14. Limited benefit of hepatitis B immunoglobulin prophylaxis in children of hepatitis B e antigen-negative mothers

    Science.gov (United States)

    Lee, Le Ye; Aw, Marion M; Saw, Sharon; Rauff, Mary; Tong, Pearl YS; Lee, Guan Huei

    2016-01-01

    INTRODUCTION In 2006, Singapore adopted the universal hepatitis B immunoglobulin (HBIg) policy. Since then, all infants of hepatitis B surface antigen (HBsAg)-positive mothers receive HBIg, irrespective of maternal hepatitis B e antigen (HBeAg) status. However, the benefits of HBIg for infants of HBeAg-negative mothers are unclear. We compared the vertical transmission rates among children of HBeAg-negative mothers who were given HBIg versus a retrospective cohort who were not given HBIg, to determine its protective effect. METHODS This observational study involved pregnant HBsAg-positive women seen at National University Hospital, Singapore, between June 2009 and December 2013. If the infants of these mothers completed the recommended vaccination schedule, they were recruited into the study, along with their older siblings. Serological testing for the children was performed three months after completion of the last dose of vaccine, and hepatitis B virus (HBV) surface gene sequencing was carried out if HBV DNA was detected. RESULTS A total of 111 infants and 47 siblings were recruited. 2 (1.5%) children were found to have vertical transmission despite receiving HBIg, while no incidences of vertical transmission were found among the historical controls who did not receive HBIg (p = 1.00). CONCLUSION The overall effectiveness of the hepatitis B vaccination programme for children of HBsAg-positive mothers was high, regardless of HBIg administration. The addition of HBIg did not appear to confer additional benefits, in terms of vertical transmission rate, among infants born to HBeAg-negative mothers. PMID:26778725

  15. Efficient Hepatitis Delta Virus RNA Replication in Avian Cells Requires a Permissive Factor(s) from Mammalian Cells

    OpenAIRE

    Liu, Yu-Tsueng; Brazas, Rob; Ganem, Don

    2001-01-01

    Hepatitis delta virus (HDV) is a highly pathogenic human RNA virus whose genome is structurally related to those of plant viroids. Although its spread from cell to cell requires helper functions supplied by hepatitis B virus (HBV), intracellular HDV RNA replication can proceed in the absence of HBV proteins. As HDV encodes no RNA-dependent RNA polymerase, the identity of the (presumably cellular) enzyme responsible for this reaction remains unknown. Here we show that, in contrast to mammalian...

  16. Hepatitis B core-related antigen levels are associated with response to entecavir and peginterferon add-on therapy in hepatitis B e antigen-positive chronic hepatitis B patients.

    Science.gov (United States)

    van Campenhout, M J H; Brouwer, W P; van Oord, G W; Xie, Q; Zhang, Q; Zhang, N; Guo, S; Tabak, F; Streinu-Cercel, A; Wang, J; Pas, S D; Sonneveld, M J; de Knegt, R J; Boonstra, A; Hansen, B E; Janssen, H L A

    2016-06-01

    Hepatitis B core-related antigen (HBcrAg), a new serum marker, may be useful in monitoring chronic hepatitis B infection. HBcrAg was measured in 175 hepatitis B e antigen-positive patients treated with entecavir (ETV) with or without peginterferon (PEG-IFN) add-on therapy. Decline in HBcrAg was stronger in patients with vs. without combined response (ETV: -3.22 vs. -1.71 log U/mL, p HBcrAg was associated with combined response (adjusted odds ratio 0.3, 95% confidence interval 0.2-0.5, p <0.001), but was not superior to quantitative HBsAg (qHBsAg).

  17. Epidemiological and molecular features of hepatitis B and hepatitis delta virus transmission in a remote rural community in central Africa.

    Science.gov (United States)

    François-Souquière, Sandrine; Makuwa, Maria; Bisvigou, Ulrich; Kazanji, Mirdad

    2016-04-01

    Hepatitis B virus (HBV) and hepatitis delta virus (HDV) occur worldwide and are prevalent in both urban and remote rural communities. In a remote village in Gabon, central Africa, we observed a high prevalence of HBsAg carriage and HDV infection, particularly in children and adolescents. The prevalence of HBsAg differed significantly by gender and age, females being more likely than males to carry the HBsAg during the first 10 years of life, while the prevalence was higher among males than females aged 11-20 years. We also characterised HBV and HDV strains circulating in the village. The principal HBV strains belonged to genotype HBV-E and subgenotype QS-A3. Complete genome analysis revealed for the first time the presence of the HBV-D genotype in Gabon, in the form of an HBV-D/E recombinant. Molecular analysis of HDV strains and their complete genomic characterisation revealed two distinct groups within the dominant HDV clade 8. Molecular analysis of HBV and HDV strains did not reveal vertical transmission within the families studied but rather horizontal, intrafamilial transmission among children aged 0-10 years. Our findings indicate that HBV is transmitted in early childhood by body fluids rather than by sexual contact. Health education adapted to the different age groups might therefore help to reduce HBV transmission. Young children should be vaccinated to control HBV infection in areas of extremely high prevalence.

  18. Hepatitis C Virus Core Antigen Test in Monitoring of Dialysis Patients

    Directory of Open Access Journals (Sweden)

    Gioacchino Li Cavoli

    2012-01-01

    Full Text Available Hepatitis C virus infection is a persistent worldwide public health concern. The prevalence of HCV infection is much higher in patients on chronic haemodialysis (HD than in the general population. HCV infection can detrimentally affect patients throughout the spectrum of chronic kidney disease. Despite the control of blood products, hepatitis C virus transmission is still being observed among patients undergoing dialysis. Detection systems for serum HCV antibodies are insensitive in the acute phase because of the long serological window. Direct detection of HCV depends on PCR test but this test is not suitable for routine screening. Recent studies have highlighted the importance of HCV core antigen detection as an alternative to PCR. Few studies exist about the efficacy of HCV core antigen test in dialysis population. We studied the utility of HCV core antigen test in routine monitoring of virological status of dialysis patients. We screened 92 patients on long-term dialysis both by PCR HCV-RNA and HCV core antigen test. The sensitivity of HCVcAg test was 90%, the specificity 100%, the positive predictive power 100%, the negative predictive power 97%, and the accuracy 97%. We think serological detection of HCV core antigen may be an alternative to NAT techniques for routine monitoring of patients on chronic dialysis.

  19. Hepatitis B surface antigen quantity positively correlates with plasma levels of microRNAs differentially expressed in immunological phases of chronic hepatitis B in children

    DEFF Research Database (Denmark)

    Winther, Thilde Nordmann; Heiberg, Ida Louise; Bang-Berthelsen, Claus Heiner

    2013-01-01

    Children with chronic hepatitis B (CHB) are at high risk of progressive liver disease. It is suggested that a newly-identified panel of 16 microRNAs is important in the pathogenesis of CHB in children. Subviral hepatitis B surface antigen (HBsAg) particles are produced in large excess over...

  20. A mimotope of Pre-S2 region of surface antigen of viral hepatitis Bscreened by phage display

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    To acquire the phage-displayed mimotopes which mimic the specificity of hepatitis B virus surface antigen (HBsAg), a random peptide library expressing linear peptide with 12 amino acids in length were used to screen with the serum from a hepatitis B virus infected patient in the recovery phase. After 3 rounds of biopanning, the positive phages were confirmed by competitive ELISA using HBsAg/P33. Two phagotopes were identified and one of them was confirmed as mimotope by competition experiment. Based on the mimotpe, a multiple antigenic peptide with four branches was synthesized by solid phase peptide synthesis. The antiginicity and specificity of the synthesized antigen was tested in BALB/c mice compared with the native epitope-based antigen. The results showed that the mimotope-based antigen could evoke higher titer of antibodies with the same specificity of the epitope-based antigen. Those findings indicate mimotopes can be used in antigen and vaccine design.

  1. The effect of non-alcoholic fatty liver disease on virologic response in patients with hepatitis B e antigen-positive chronic hepatitis B treated with nucleoside analogues

    Institute of Scientific and Technical Information of China (English)

    陈梅琴

    2014-01-01

    Objective To investigate the effect of non-alcoholic fatty liver disease(NAFLD)on virologic response in chronic hepatitis B patients treated with nucleoside analogues.Methods Three hundred and thirty-two treatment-naive patients with hepatitis B e antigen(HBeAg)-positive chronic hepatitis B(CHB)who visited clinic or hospitalized in the First Affiliated Hospital of Wenzhou Medical College from January 2007 to December 2009

  2. Hepatitis C virus and ethanol alter antigen presentation in liver cells

    Institute of Scientific and Technical Information of China (English)

    Natalia A Osna

    2009-01-01

    Alcoholic patients have a high incidence of hepatitis Cvirus (HCV) infection. Alcohol consumption enhances the severity of the HCV disease course and worsens the outcome of chronic hepatitis C. The accumulation of virally infected cells in the liver is related to the HCVinduced inability of the immune system to recognizeinfected cells and to develop the immune responses. This review covers the effects of HCV proteins and ethanol on major histocompatibility complex (MHC) classⅠ- and class Ⅱ-restricted antigen presentation. Here, we discuss the liver which functions as an immune privilege organ; factors, which affect cleavage and loading of antigenic peptides onto MHC classⅠand class Ⅱ in hepatocytes and dendritic cells, and the modulating effects of ethanol and HCV on antigen presentation by liver cells. Altered antigen presentation in the liver limits the ability of the immune system to clear HCV and infected cells and contributes to disease progression. HCV by itself affects dendritic cell function, switching their cytokine profile to the suppressive phenotype of interleukin-10 (IL-10) and transforming growth factor beta (TGFβ) predominance,preventing cell maturation and allostimulation capacity.The synergistic action of ethanol with HCV results in the suppression of MHC class Ⅱ-restricted antigen presentation. In addition, ethanol metabolism and HCV proteins reduce proteasome function and interferon signaling, thereby suppressing the generation of peptides for MHC classⅠ-restricted antigen presentation.Collectively, ethanol exposure further impairs antigen presentation in HCV-infected liver cells, which may provide a partial explanation for exacerbations and the poor outcome of HCV infection in alcoholics.

  3. Evaluation of hepatitis B surface antigen and hepatitis B virus-DNA results in postmortem plasma specimens

    Directory of Open Access Journals (Sweden)

    Nihan Ziyade

    2015-03-01

    Full Text Available Objective: To assess the presence of hepatitis B surface antigen, one of the serologic markers of hepatitis B virus (HBV infection, in postmortem blood samples from autopsy cases using ELISA, and to compare the results with those obtained by PCR, which is the gold standard method in assessing HBV infection. Methods: The HBV test results of the blood samples from 880 autopsy cases determined in our laboratory, were retrospectively studied. Results: When compared with the gold standard method PCR, the sensitivity and specificity of postmortem ELISA were 100% and 84.1%, respectively. Conclusions: The increasingly used molecular diagnostic methods, such as PCR, should be used in cases where serological tests remain insufficient.We think that prospective studies on the comparison of ELISA and PCR assessment of postmortem blood samples with larger material should be carried out.

  4. Evaluation of hepatitis B surface antigen and hepatitis B virus-DNA results in postmortem plasma specimens

    Institute of Scientific and Technical Information of China (English)

    Nihan Ziyade; Sermet Koc; Fatih Abali

    2015-01-01

    Objective:To assess the presence of hepatitis B surface antigen, one of the serologic markers of hepatitis B virus (HBV) infection, in postmortem blood samples from autopsy cases using ELISA, and to compare the results with those obtained byPCR, which is the gold standard method in assessingHBV infection. Methods: TheHBV test results of the blood samples from 880 autopsy cases determined in our laboratory, were retrospectively studied. Results:When compared with the gold standard methodPCR, the sensitivity and specificity of postmortemELISA were 100% and 84.1%, respectively. Conclusions: The increasingly used molecular diagnostic methods, such asPCR, should be used in cases where serological tests remain insufficient.We think that prospective studies on the comparison ofELISA andPCR assessment of postmortem blood samples with larger material should be carried out.

  5. Recombinant hepatitis B surface antigen production in Aspergillus niger: evaluating the strategy of gene fusion to native glucoamylase

    CSIR Research Space (South Africa)

    James, ER

    2012-10-01

    Full Text Available Microbiology and Biotechnology October 2012/ Vol. 96, No.2 Recombinant hepatitis B surface antigen production in Aspergillus niger: evaluating the strategy of gene fusion to native glucoamylase ER James a,c & WH van Zyl b & PJ van Zyl c & JF Görgens..., Pretoria 0001, South Africa Abstract This study demonstrates the potential of Aspergillus niger as a candidate expression system for virus- like particle production using gene fusion. Hepatitis B surface antigen (HBsAg) production, targeted...

  6. [Quantification of the hepatitis B surface antigen in the characterization and follow-up].

    Science.gov (United States)

    Rodríguez, Manuel; González-Diéguez, María Luisa

    2014-07-01

    The recent availability of commercial techniques for the quantification of the hepatitis B surface antigen (HBsAg) has revived interest in this antigen. In recent years, the antigen's potential as a biomarker of the natural history of the disease and its response to antiviral treatment has been assessed. HBsAg serum values reflect the transcriptional activity of cccDNA; reading these values could therefore complement the reading of hepatitis B virus (HBV) DNA in the categorization of the various phases of chronic HBV infection. During its natural history, HBsAg values progressively decrease from the immune-tolerant phase to the inactive carrier phase. For patients who are HBeAg-negative, the combined reading of HBV DNA and HBsAg can be useful for differentiating inactive carriers from patients with chronic HBeAg-negative hepatitis, for stratifying the risk of developing hepatocarcinoma and for predicting HBsAg clearance. Copyright © 2014 Elsevier España, S.L. All rights reserved.

  7. Chronic Hepatitis B Virus Infection: The Relation between Hepatitis B Antigen Expression, Telomere Length, Senescence, Inflammation and Fibrosis.

    Directory of Open Access Journals (Sweden)

    Phaedra M Tachtatzis

    Full Text Available Chronic Hepatitis B virus (HBV infection can lead to the development of chronic hepatitis, cirrhosis and hepatocellular carcinoma. We hypothesized that HBV might accelerate hepatocyte ageing and investigated the effect of HBV on hepatocyte cell cycle state and biological age. We also investigated the relation between inflammation, fibrosis and cell cycle phase.Liver samples from patients with chronic HBV (n = 91, normal liver (n = 55 and regenerating liver (n = 15 were studied. Immunohistochemistry for cell cycle phase markers and HBV antigens was used to determine host cell cycle phase. Hepatocyte-specific telomere length was evaluated by quantitative fluorescent in-situ hybridization (Q-FISH in conjunction with hepatocyte nuclear area and HBV antigen expression. The effects of induced cell cycle arrest and induced cellular senescence on HBV production were assessed in vitro.13.7% hepatocytes in chronic HBV had entered cell cycle, but expression of markers for S, G2 and M phase was low compared with regenerating liver. Hepatocyte p21 expression was increased (10.9% in chronic HBV and correlated with liver fibrosis. Mean telomere length was reduced in chronic HBV compared to normal. However, within HBV-affected livers, hepatocytes expressing HBV antigens had longer telomeres. Telomere length declined and hepatocyte nuclear size increased as HBV core antigen (HBcAg expression shifted from the nucleus to cytoplasm. Nuclear co-expression of HBcAg and p21 was not observed. Cell cycle arrest induced in vitro was associated with increased HBV production, in contrast to in vitro induction of cellular senescence, which had no effect.Chronic HBV infection was associated with hepatocyte G1 cell cycle arrest and accelerated hepatocyte ageing, implying that HBV induced cellular senescence. However, HBV replication was confined to biologically younger hepatocytes. Changes in the cellular location of HBcAg may be related to the onset of cellular senescence.

  8. Human leukocyte antigen-DRB1*1101 correlates with less severe hepatitis in Taiwanese male carriers of hepatitis B virus.

    Science.gov (United States)

    Huang, Yi-Wen; Hu, Chung-Yi; Chen, Chi-Lin; Liao, Ya-Tang; Liu, Chun-Jen; Lai, Ming-Yang; Chen, Pei-Jer; Yang, Sien-Sing; Hu, Jui-Ting; Chen, Ding-Shinn; Kao, Jia-Horng

    2009-04-01

    Human leukocyte antigen (HLA) class II molecules are associated with host immune responses against hepatitis B virus infection. Male gender is the apparent host factor when someone encounters with the severity of hepatitis. The aim of this study was to investigate the association of the most polymorphic HLA class II allele, human leukocyte antigen-DRB1, with the severity of hepatitis in male carriers of hepatitis B virus. In this prospective cohort study, a total of 204 carriers of hepatitis B virus (131 men and 73 women) who have been followed-up for more than 1 year at the outpatient clinic of a university hospital were collected consecutively. Fifty carriers of hepatitis B virus (group I) with alanine aminotransferase /=2x upper limit of normal (mean follow-up 81.3 months). Alleles of HLA-DRB1 were typed by the polymerase chain reaction-sequence specific oligonucleotide probe hybridization and genotypes of hepatitis B virus by melting curve analysis. HLA-DRB1*1101 was found in 18% of group I versus 8% of group II in male carriers (OR 0.23, P = 0.020, after adjustment for age) and 4% versus 9.4% in female carriers (P = 0.094). In male carriers harboring DRB1*1101, the distribution of hepatitis B viral genotype was comparable between the two groups. HLA-DRB1*1101 correlates with less severe hepatitis in Taiwanese male carriers of hepatitis B virus.

  9. Hepatitis delta virus:Making the point from virus isolation up to 2014

    Institute of Scientific and Technical Information of China (English)

    Raffaella; Romeo; Riccardo; Perbellini

    2015-01-01

    Chronic infection with hepatitis delta virus(HDV) has lately regained clinical importance because of the recent evidence of increasing prevalence in several European countries,due to immigration from highly endemic areas. HDV requires the mandatory presence ofhepatitis B virus(HBV) for propagation to hepatocytes. It is transmitted by the same routes of HBV and it can be acquired either by co-infection(simultaneous transmission of the two viruses) or super-infection(acquisition of HDV by an already chronic carrier of HBV). As a consequence,every HBV carrier is potentially at risk for HDV superinfection. Since the clinical course of superinfection can be severe,early diagnosis of HDV infection is necessary.

  10. Immuno disc assay for screening duck hepatitis B surface antigen in serum, liver tissue and cultured hepatocytes

    NARCIS (Netherlands)

    G.A. de Wilde (G.); R.A. Heijtink

    1993-01-01

    textabstractAn immuno disc assay (IDA) for semi-quantitative analysis of the surface antigen (DHBsAg) of duck hepatitis B virus (DHBV) is described. Unpurified antigen preparations were adsorbed onto punched-out nitrocellulose membrane discs. Rabbit antiserum raised against serum-derived

  11. New antiviral targets for innovative treatment concepts for hepatitis B virus and hepatitis delta virus.

    Science.gov (United States)

    Durantel, David; Zoulim, Fabien

    2016-04-01

    Current therapies of chronic hepatitis B (CHB) remain limited to pegylated-interferon-alpha (PegIFN-α) or any of the five approved nucleos(t)ide analogues (NUC) treatments. While viral suppression can be achieved in the majority of patients with the high-barrier-to-resistance new-generation of NUC, i.e. entecavir and tenofovir, HBsAg loss is achieved by PegIFN-α and/or NUC in only 10% of patients, after a 5-year follow-up. Attempts to improve the response by administering two different NUC or a combination of NUC and PegIFN-α have not provided a dramatic increase in the rate of functional cure. Because of this and the need of long-term NUC administration, there is a renewed interest regarding the understanding of various steps of the HBV replication cycle, as well as specific virus-host cell interactions, in order to define new targets and develop new antiviral drugs. This includes a direct inhibition of viral replication with entry inhibitors, drugs targeting cccDNA, siRNA targeting viral transcripts, capsid assembly modulators, and approaches targeting the secretion of viral envelope proteins. Restoration of immune responses is a complementary approach. The restoration of innate immunity against HBV can be achieved, with TLR agonists or specific antiviral cytokine delivery. Restoration of adaptive immunity may be achieved with inhibitors of negative checkpoint regulators, therapeutic vaccines, or autologous transfer of engineered HBV-specific T cells. Novel targets and compounds will readily be evaluated using both relevant and novel in vitro and in vivo models of HBV infection. The addition of one or several new drugs to current therapies should offer the prospect of a markedly improved response to treatments and an increased rate of functional cure. This should lead to a reduced risk of antiviral drug resistance, and to a decreased incidence of cirrhosis and hepatocellular carcinoma (HCC).

  12. Association of Human Leukocyte Antigen Class I Polymorphism with Spontaneous Clearance of Hepatitis B Surface Antigen in Qidong Han Population

    Directory of Open Access Journals (Sweden)

    Fengqin Miao

    2013-01-01

    Full Text Available Aim. To investigate whether HLA class I polymorphisms could influence the clearance of hepatitis B surface antigen (HBsAg in Qidong Han population. Methods. We genotyped HLA-A, -B, and -C loci of 448 individuals with HBV persistent infection and 140 persons with spontaneous clearance of HBsAg by polymerase chain reaction with sequencing based typing (PCR/SBT. All the individuals were unrelated males enrolled from Qidong Han population and were followed up for 10 years. Results. The frequency of HLA-A*33:03:01G was increased in persistent HBV infection group (P value is 0.028, while frequency of HLA-B*13:01:01G was increased in HBsAg clearance group (P value is 0.0004. Conclusion. These findings suggested that the host HLA class I polymorphism is an important factor in determining the outcomes of HBV infection.

  13. Gamma delta T-lymphocytes in hepatitis C and chronic liver disease

    Directory of Open Access Journals (Sweden)

    neil erajoriya

    2014-08-01

    Full Text Available Discovered thirty years ago, gamma delta (γδ T-lymphocytes remain an intriguing and enigmatic T-cell subset. Although in humans they comprise a small fraction of the total circulating T-lymphocyte pool, they represent an important T-cell subset in tissues such as the liver, with roles bridging the innate and adaptive immune systems. The associations of γδ T-lymphocytes with chronic liver disease have been explored - however there remain conflicting data as to whether these T-cells are pathogenic or protective. In patients with some forms of liver disease, their expansion in the periphery and especially in the liver may indeed help pathogen clearance, while in other conditions their presence may, in contrast, contribute to disease progression. Gamma-delta T cells can also express CD161, a C-type lectin, and such cells have been found to be involved in the pathogenesis of inflammatory disease. CD161+ T-cells of diverse subsets are known to be enriched in the livers of patients with chronic hepatitis C. This article serves to provide a review of the γδ T-cell population and its role in chronic liver disease, and also to explore a potential role of the CD161+ γδ T-cells in liver disease.

  14. The prevalence of hepatitis B virus E antigen among Ghanaian blood donors

    Science.gov (United States)

    Rufai, Tanko; Mutocheluh, Mohamed; Kwarteng, Kwaku; Dogbe, Elliot

    2014-01-01

    Hepatitis B viral infection is an important clinical problem due to its worldwide distribution and potential of adverse sequelae, including hepatocellular carcinoma (HCC). We studied the prevalence of hepatitis B virus ‘e’ antigen (HBeAg) among individuals determined to be hepatitis B virus (HBV) surface antigen-positive and analyzed the gender/age category associated with more active HBV infection and whether alteration in the levels of alanine aminotransferase could be associated with HBeAg positivity. A total of 150 prospective blood donors who tested positive for hepatitis B surface antigen (HBsAg) at the blood transfusion center of the Komfo Anokye Teaching Hosptital (KATH), Kumasi were randomly selected for the study. The serum samples were further tested for HBsAg and HBeAg using a lateral flow immunochromatographic assay. Twenty (20) individuals were found to be HBeAg-positive giving an overall prevalence of 13.3%, of which 18 (15.5%) were males and 2 (5.9%) were females. Our results also revealed that the prevalence of HBeAg was higher in patients between the age group of 10-20 years and appeared to decrease with increase in age. There was no statistical difference between the HBeAg positive and negative individuals with respect to alanine aminotransferase (ALT) levels. We show for the first time that approximately 1/10 of HBV-infected individuals are HBeAg positive in the Ashanti Region of Ghana, suggestive of active viral replication and liver-cell infectivity thereby contributing to an increased HBV-transmission pool within the Ghanaian population. PMID:25018803

  15. Liver transplantation in bearers of hepatitis B associated or not with delta hepatitis in the age of the new antiviral drugs: is hyperimmune globulin still necessary?

    Science.gov (United States)

    Genzini, T; Dos Santos, R G; Pedrosa, C; Curvelo, L A; Noujaim, H M; Crescentini, F; Mota, L T; Guirro, T G; Ferreira, F Y; Salomão, P; Pereira, J R B; de Miranda, M P

    2010-03-01

    Hepatitis B (HBV) is a public health problem worldwide; one-third of the population has already been in contact with HBV, and 350 million people are chronic carriers of virus. The appearance of hyperimmune gamma globulin and antiviral drugs has allowed that group to undergone hepatic transplantation, achieving satisfactory results to prevent a relapse. But the use of hyperimmune gamma globulin has an extremely high cost, and combined therapies with new antiviral drugs seem to be a therapeutic alternative. We analyzed 21 patients with hepatitis B associated or not with Delta hepatitis over a mean follow-up period of 19.5 months, concluding that use of only nucleotide analogues has sufficient to achieve satisfactory results. Copyright (c) 2010 Elsevier Inc. All rights reserved.

  16. Hepatitis B Vaccination Coverage and Prevalence of Hepatitis B Surface Antigen Among Children in French Polynesia, 2014.

    Science.gov (United States)

    Patel, Minal K; Le Calvez, Evelyne; Wannemuehler, Kathleen; Ségalin, Jean-Marc

    2016-06-01

    French Polynesia is considered to be moderately endemic for chronic hepatitis B virus infection, with an estimated 3% of the population having hepatitis B surface antigen (HBsAg). From 1990 to 1992, a 3-dose hepatitis B vaccination series was introduced into the routine infant immunization schedule in French Polynesia, including a birth dose (BD). In 2014, a nationally representative 2-stage cluster survey was undertaken to evaluate the impact of the vaccination program on HBsAg prevalence among school children (∼6 years of age) in Cours Préparatoire (CP). Documented vaccination data were reviewed for all eligible children; children with consent were tested for HBsAg with a rapid point-of-care test. In total, 1,660 students were identified; 1,567 (94%) had vaccination data for review and 1,196 (72%) participated in the serosurvey. Three-dose vaccination coverage was 98%, while timely BD coverage, defined as a dose administered within 24 hours of life, was 89%. Receipt of the second and third doses was often delayed, with 75% and 55% receiving a second and third dose within 1 month of the recommended age, respectively. No children tested positive for HBsAg. French Polynesia's vaccination program has achieved high coverage and an HBsAg seroprevalence of 0% (0-0.5%) among CP school children, but timeliness of vaccination could be improved.

  17. Early hepatitis B surface antigen decline predicts treatment response to entecavir in patients with chronic hepatitis B

    Science.gov (United States)

    Peng, Cheng-Yuan; Lai, Hsueh-Chou; Su, Wen-Pang; Lin, Chia-Hsin; Chuang, Po-Heng; Chen, Sheng-Hung; Chen, Ching-Hsiang

    2017-01-01

    Early declines in serum hepatitis B surface (HBsAg) levels, their optimal cutoffs, and association with therapeutic endpoints in chronic hepatitis B (CHB) patients receiving entecavir treatment remain unclear. We prospectively enrolled 529 patients (195 hepatitis B e antigen [HBeAg]-positive and 334 HBeAg-negative) with a median treatment duration of 49.2 months. Median HBsAg levels declined significantly in both groups at Month 3, but only at Months 6–12 in the HBeAg-negative group. Both groups exhibited a significant HBsAg decline with each successive year of treatment. An HBsAg decline of ≥75% from baseline, assessed at Months 3 and 12 of treatment in the HBeAg-positive and -negative patients, respectively, independently predicted a virological response and HBeAg seroconversion in the HBeAg-positive patients, an HBsAg level of B-infected or C-infected CHB patients receiving entecavir therapy. PMID:28220833

  18. Hepatitis fulminante en la Sierra Nevada: Una forma de superinfección del virus delta con el virus de la hepatitis B.

    Directory of Open Access Journals (Sweden)

    Alvaro Villanueva

    1992-06-01

    Full Text Available Durante septiembre de 1980 a octubre de 1983, se realizó un estudio seroepidemiológico para hepatitis A y B, en 258 personas en una ciudad (Santa Marta población de 250.000 y tres pequeños municipios (Santa Rosalía, Julio Zawady y Aracataca, poblaciones de 768, 800 y 5.000 habitantes respectivamente. La presencia de hepatitis A se encontró en un 77 a 93% (IgG Hepatitis A. Hbs Ag o Anti-Hbs Ag en 30.5% de la población en dos municipios (Santa Rosalía y Julio Zawady, en 2.5% en el municipio de Aracataca y 48.5% en la ciudad de Santa Marta. La presencia del Agente Delta (Anti-delta en el suero se determinó también en estas mismas poblaciones, encontrándose ausente en la ciudad y uno de los municipios (Aracataca, en contraste con una prevalencia de 13.7% y 22% en Julio Zawady y Santa Rosalía (P: 0.0001. Se excluyeron por historia clínica, antecedentes de drogadicción, transfusiones, o prácticas homosexuales, como mecanismos de transmisión de los virus B y delta. En veinte pacientes con diagnóstico histopalógico de hepatitis fulminante y en quienes se descartaron otras etiologías se demostró la presencia serológica de los virus de la hepatitis By Delta. De estos veinte, diez provenían de Julio Zawady y los otros diez de Santa Rosalía. La evolución clínica de esta enfermedad fue indistinguible de otras causas de falla hepática aguda. La mortalidad de estas formas fulminantes de hepatitis alcanzaron hasta un 65%. Los corticoides no modificaron el curso de esta enfermedad. La población joven mostró mayor compromiso y peor diagnóstico (P:0.033. La hepatitis fulminante de la Sierra Nevada de Santa Marta es el resultado de la superinfección con el virus Delta sobre la infección virus B. La aparición simultánea de casos intrafamiliares sugiere una relación importante entre los grupos comprometidos, aunque la forma exacta de transmisión permanece aún desconocida.

  19. Postvaccination seroconversion against the surface antigen of Hepatitis B virus, in nursing students

    Directory of Open Access Journals (Sweden)

    Gladys Amanda Mera-Urbano

    2013-09-01

    Full Text Available Objective: To determine the status of seroconversion after vaccination against the surface antigen of hepatitis B virus in nursing students, University of Cauca. Methods: Cross sectional study in students of V and VI semester. The sample was taken from 37 students, 15 of V and 22 of VI semester. The instrument used was a survey that included 11 questions of multiple selections. Records for weight, height and laboratory results were collected; blood samples for antibody titers were performed with informed consent. The data were tabulated and analyzed using SPSS, version 17.0. Results: 89.2% of students had levels of antibodies to the surface antigen. This value was greater than 10 mUI/ml, considered by the scientific community as a protector value of Hepatitis B. 10.8% of had lesser values. Regarding vaccination scheme, 24% had a dose, 19% two, 48% three and 8% had a one dose. The population with 3 doses and reinforcement seroconverted by 100%. Conclusion: This study demonstrated failings in the scheme of vaccination of the students of nursing and that 10.8 % presented lower values than 10 mIU/ml. It is necessary to apply the institutional rules with more strength as a preventive measure for hepatitis B.

  20. Identification of hepatitis A virus mimotopes by phage display, antigenicity and immunogenicity.

    Science.gov (United States)

    Larralde, Osmany G; Martinez, Raiza; Camacho, Frank; Amin, Nevis; Aguilar, Alicia; Talavera, Arturo; Stott, David I; Perez, Ela M

    2007-03-01

    A phage-displayed peptide approach was used to identify ligands mimicking antigenic determinants of hepatitis A virus (HAV) for the first time. Bacteriophages displaying HAV mimotopes were isolated from a phage-display peptide library by affinity selection on serum antibodies from hepatitis A patients. Selected phage-peptides were screened for reactivity with sera from HAV infected patients and healthy controls. Four cloned peptides with different sequences were identified as mimotopes of HAV; three of them showed similarity in their amino acid sequences with at least one of the VP3 and VP1 antigenic proteins of HAV. One clone was recognised by 92% of the positive sera. The phagotopes competed effectively with HAV for absorption of anti-HAV-specific antibodies in human sera, as determined by ELISA. The four phage clones induced neutralising anti-HAV antibodies in immunised mice. These results demonstrate the potential of this method to elucidate the disease related epitopes of HAV and to use these mimotopes in diagnostic applications or in the development of a mimotope-based hepatitis A vaccine without the necessity of manipulation of the virus.

  1. The prevalence and impact of brucellosis in patients with hepatitis delta virus infection: inside the Brucella outbreak with cirrhosis

    Science.gov (United States)

    Dulger, Ahmet Cumhur; Suvak, Ozlem; Yesilyurt, Aysun Özel; Gultepe, Bilge; Guducuoglu, Huseyin

    2017-01-01

    Introduction Hepatitis D virus (HDV) infection is a serious health problem leading to cirrhosis and hepatocellular carcinoma (HCC). Despite evidence that zoonotic infections are associated with end-stage liver disease, brucellosis in patients with delta hepatitis related to liver disease has not been well characterized. So, we examined this relationship using recent hospital-based data. Material and methods We analyzed data from 96 delta hepatitis patients (mean age: 52.5 ±12.8 years; 50 male; 52 cirrhotics) and 117 (mean age: 50.4 ±7 years; 60 male) control subjects who were selected from patients with splenomegaly. The Brucella Wright test in connection with blood culture was used to detect active Brucella infection. Demographic features, laboratory data, results of ultrasonographic examination of the abdomen and Wright agglutination titers were compared between groups. Results There were 9 (9%) patients with active brucellosis in delta hepatitis patients. Compared to the control group, there was a statistically significant difference between groups in terms of having active brucellosis (9 vs. 2 patients; p brucellosis requiring hospitalization. Higher Wright titers among patients with more advanced liver disease may reflect a unique phenomenon that requires further investigation to determine underlying causative factors. PMID:28261291

  2. Detection of liver HBc antigen and its antibody in sera from viral hepatitis by the immunofluorescent complement technique

    Directory of Open Access Journals (Sweden)

    Tsuji,Takao

    1976-02-01

    Full Text Available Hepatitis B core antigen (HBc Ag and hepatitis B surface antigen (HBs Ag were detected in the liver tissue of a patient with chronic aggressive hepatitis by the immunofluorescent complement technique. The presence of anti-HBc was examined by the same method in 67 human sera previously tested for HBs Ag, anti-HBs and s-GPT levels. HBc Ag was localized mainly in the nucleus and sometimes in the cytoplasm of the hepatic cells. HBs Ag was found only in the cytoplasm. The focal area of HBc Ag positive hepatic cells seemed to correspond to the HBs Ag positive cells. Double staining demonstrated the simultaneous presence of HBs Ag and HBc Ag in individual cells. Anti-HBc positive serum was found in 46 (68.7% cases. Forty-eight (71.6% indicated a combination of HBs Ag and anti-HBc.

  3. Poly-ϵ-caprolactone/chitosan nanoparticles provide strong adjuvant effect for hepatitis B antigen.

    Science.gov (United States)

    Jesus, Sandra; Soares, Edna; Borchard, Gerrit; Borges, Olga

    2017-10-01

    This work aims to investigate the adjuvant effect of poly-ϵ-caprolactone/chitosan nanoparticles (NPs) for hepatitis B surface antigen (HBsAg) and the plasmid DNA encoding HBsAg (pRC/CMV-HBs). Both antigens were adsorbed onto preformed NPs. Vaccination studies were performed in C57BL/6 mice. Transfection efficiency was investigated in A549 cell line. HBsAg-adsorbed NPs generated strong anti-HBsAg IgG titers, mainly of IgG1 isotype, and induced antigen-specific IFN-γ and IL-17 secretion by spleen cells. The addition of pRC/CMV-HBs to the HBsAg-adsorbed NPs inhibited IL-17 secretion but had minor effect on IFN-γ levels. Lastly, pRC/CMV-HBs-loaded NPs generated a weak serum antibody response. Poly-ϵ-caprolactone/chitosan NPs provide a strong humoral adjuvant effect for HBsAg and induce a Th1/Th17-mediated cellular immune responses worth explore for hepatitis B virus vaccination.

  4. T cell responses to hepatitis B surface antigen are detectable in non-vaccinated individuals

    Institute of Scientific and Technical Information of China (English)

    Martin R Weihrauch; Michael von Bergwelt-Baildon; Milos Kandic; Martin Weskott; Winfried Klamp; Joachim R(o)sier; Joachim L Schultze

    2008-01-01

    AIM: To evaluate, whether humoral hepatitis-B-vaccine non-responders also fail to mount a T cell response and to compare these results to normal vaccinees.METHODS: Fourty-seven health care employees were enrolled in this study including all available nonresponders (n = 13) with an anti-HBsAg titer 1000 kU/L as controls.PBMC from all subjects were analyzed by IFN-γ and IL-4 ELISPOT assays for the presence of hepatitis B surface antigen (HBsAg) reactive T cells.RESULTS: Non-responders and low-responders had no or only very limited T cell responses, respectively.Individuals responding to vaccination with the induction of a high anti-HBsAg titer showed a strong T cell response after the third vaccination.Surprisingly, these individuals showed response even before the first vaccination.T cell response to control antigens and mitogens was similar in all groups.CONCLUSION: Our data suggest that there is no general immune deficiency in non-/low-responders.Thus,we hypothesize that the induction of anti-HBsAg responses by vaccination is significantly dependent on the pre-existing T cell repertoire against the specific antigen rather than the presence of a general T cell defect.

  5. Should antibody to hepatitis B core antigen be tested in routine screening of donor corneas for transplant?

    Science.gov (United States)

    Mattern, R M; Cavanagh, H D

    1997-03-01

    A review of the literature on transfusion-transmitted infectious diseases shows that antibody to hepatitis B core antigen (anti-HBc) is not presently viewed as helpful for hepatitis C or hepatitis non-ABC screening of blood donors. Its utility as a screen for hepatitis B or human immunodeficiency virus-1 (HIV-1) is controversial among experts. We compare relevant aspects of the screening of blood donations and the screening of cornea transplant donors to assess implications for the screening of donor corneas. We conclude that there is not sufficient evidence to warrant introducing anti-HBc as a routine screening test for cornea donors.

  6. Effects of entecavir on hepatitis B virus covalently closed circular DNA in hepatitis B e antigen-positive patients with hepatitis B.

    Directory of Open Access Journals (Sweden)

    Ming Shi

    Full Text Available The aim of this study was to assess the effect of 48-week entecavir therapy on serum and intrahepatic hepatitis B virus, covalently closed circular DNA (HBV cccDNA levels in hepatitis B e antigen (HBeAg-positive patients. A total of 120 patients with HBeAg-positive chronic hepatitis were treated with entecavir for 48 weeks. Serum HBV markers, total HBV DNA, and HBV cccDNA levels were measured at baseline and week 48. Biopsies from 20 patients were available for both intrahepatic total HBV DNA and cccDNA testing at these timepoints. HBV cccDNA levels were decreased from a median level of 5.1×106 copies/mL at baseline to a median level of 2.4×103 copies/mL at week 48. Reduction magnitudes of HBV cccDNA in patients with normalized alanine aminotransferase levels and those undergoing HBeAg seroconversion were significantly greater than those in alanine aminotransferase-abnormal and HBeAg positive patients. Intrahepatic HBV cccDNA was decreased significantly after 48 weeks of treatment, but could not be eradicated. In conclusion, treatment of HBeAg-positive hepatitis B patients with entecavir for 48 weeks decreased serum and intrahepatic HBV cccDNA significantly, and the magnitude of HBV cccDNA reduction was related to total HBV DNA decrease, alanine aminotransferase normalization, and HBeAg seroconversion.

  7. A prophylactic approach for bone marrow transplantation from a hepatitis B surface antigen-positive donor

    Institute of Scientific and Technical Information of China (English)

    Abhasnee Sobhonslidsuk; Artit Ungkanont

    2007-01-01

    It has been accepted that bone marrow transplantation (BMT)is the only curative therapeutic option for certain hematologic malignancies.The southeast Asia region is an endemic area of hepatitis B virus(HBV)infection;thus,BMT using a hepatitis B surface antigen(HBsAg)-positive donor is occasionally unavoidable.Organ transplantation using a HBsAg-positive donor can lead to post-transplantation de novo HBV infection and severe HBV-related hepatitis if no effective prophylactic measures are taken prior to and after transplantation.In this report,a four-level approach was designed for a patient with chronic myeloid leukemia,beginning with a booster HBV vaccination before performing BMT with a HBsAg-positive donor.Prior to BMT,the HBV viral load of the donor was reduced to an undetectable level by antiviral therapy.After BMT,hepatitis B immunoglobulin was administered intramuscularly for 1 wk together with a long-term antiviral drug,lamivudine.One year after discontinuation of lamivudine,the patient is still free of HBV infection.

  8. Clinical application and analysis of hepatitis C virus NS3 antigen detection by ELISA in human serum

    Institute of Scientific and Technical Information of China (English)

    XIE Li; WU Xiao-dong; HUANG De-zhuang; CHEN Hai-lun; HE Li-xiang; WANG Jian; HAN Da-kang

    2007-01-01

    Background Hepatitis C virus (HCV) core antigen assays have been produced to exclude infectious donations collected during the preseroconversion window phase (PWP). For the same purpose, we evaluated the specificity and sensitivity of a novel hepatitis C virus NS3 antigen detection immunoassay and the application of this assay in clinical diagnosis.Methods Samples from 77 healthy subjects, 173 anti-HCV positive patients and 3708 hepatitis patients other than HCV positive were tested with the HCV NS3 antigen assay. Some HCV NS3 antigen positive samples were further validated with HCV-RNA, neutralization and immunodot assays. Twenty-five sequential samples from 11 HCV NS3 antigen positive patients were subjected to kinetic study.Results Only 48 (1.3%) of 3708 anti-HCV negative samples were positive for HCV NS3 antigen. Among them, 44 of 3030 samples from patients only infected with HBV were HCV NS3 antigen positive, 4 of the 445 samples from patients infected with other type hepatitis were HCV NS3 antigen positive. In addition, 42 (24.3%) of 173 anti-HCV positive samples were HCV NS3 antigen positive and all 77 samples from healthy subjects were negative to HCV NS3 antigen assay. Of the 15 HCV NS3 antigen positive samples, 9 (60%) were HCV-RNA positive. The neutralization and positive percentage of immunodot assay for 23 HCV NS3 antigen positive sera were 87.0% (20/23) and 69.6% (16/23)respectively. Of the 25 sequential samples from 11 HCV NS3 antigen positive patients, there was a negative correlation between the OD values and the duration of test (r=-0.989, P<0.05), and there were correlations among their HCV NS3 antigen, HCV-RNA and anti-HCV titres. The anti-HCV antibodies of two sera were detected while their OD values of HCV NS3 antigen decreased gradually.Conclusions The HCV NS3 antigen detection assay showed perfect specificity and high sensitivity. Thus, it would be useful and economical as a routine test in laboratories for early diagnosis of HCV infection

  9. Biotin avidin amplified magnetic immunoassay for hepatitis B surface antigen detection using GoldMag nanoparticles

    Science.gov (United States)

    Yu, An; Geng, Tingting; Fu, Qiang; Chen, Chao; Cui, Yali

    2007-04-01

    Using GoldMag (Fe3O4/Au) nanoparticles as a carrier, a biotin-avidin amplified ELISA was developed to detect hepatitis B surface antigen (HBsAg). A specific antibody was labeled with biotin and then used to detect the antigen with an antibody coated on GoldMag nanoparticles by a sandwich ELISA assay. The results showed that 5 mol of biotin were surface bound per mole of antibody. The biotin-avidin amplified ELISA assay has a higher sensitivity than that of the direct ELISA assay. There is 5-fold difference between HBsAg positive and negative serum even at dilution of 1:10000, and the relative standard deviation of the parallel positive serum at dilution of 1:4000 is 5.98% (n=11).

  10. Is Hepatitis C Virus Core Antigen an Adequate Marker for Community Screening?

    OpenAIRE

    Kuo, Yuan-Hung; Chang, Kuo-Chin; Wang, Jing-Houng; Tsai, Pei-Shan; Hung, Shu-Feng; Hung, Chao-Hung; Chen, Chien-Hung; Lu, Sheng-Nan

    2012-01-01

    A new hepatitis C virus (HCV) core antigen (HCV Ag) assay was thought to have a good correlation with HCV RNA. The aim was to elucidate the usefulness of this HCV Ag assay in community screening. In a township where HCV is endemic, 405 residents aged 58 years or older responded to a follow-up community screening. All subjects were tested for anti-HCV (AxSYM, version 3.0; Abbott Diagnostics) and HCV Ag (Architect HCV Ag test; Abbott Diagnostics). For subjects with anti-HCV signal-to-cutoff rat...

  11. Enhancement of antibody production to hepatitis B surface antigen by anti-idiotypic antibody.

    OpenAIRE

    Kakumu, S; Murase, K.; A Tsubouchi; Yoshioka, K.; Sakamoto, N.

    1986-01-01

    Studies were undertaken to determine whether anti-idiotypic antibody (anti-Id) against antibody to hepatitis B surface antigen (anti-HBs) could modulate in vitro anti-HBs production by human peripheral blood mononuclear cells stimulated with pokeweed mitogen. Peripheral blood mononuclear cells from patients positive for serum anti-HBs produced significantly increased amounts of anti-HBs by the addition of IgG fraction of anti-anti-HBs as well as purified HBsAg in a soluble form when compared ...

  12. Enteric trimethyl chitosan nanoparticles containing hepatitis B surface antigen for oral delivery.

    Science.gov (United States)

    Farhadian, Asma; Dounighi, Naser Mohammadpour; Avadi, Mohammadreza

    2015-01-01

    Oral vaccination is the preferred route of immunization. However, the degradative condition of the gastrointestinal tract and the higher molecular size of peptides pose major challenges in developing an effective oral vaccination system. One of the most excellent methods used in the development of oral vaccine delivery system relies on the entrapment of the antigen in polymeric nanoparticles. In this work, trimethyl chitosan (TMC) nanoparticles were fabricated using ionic gelation teqnique by interaction hydroxypropyl methylcellulose phthalate (HPMCP), a pH-sensitive polymer, with TMC and the utility of the particles in the oral delivery of hepatitis B surface antigen (HBsAg) was evaluated employing solutions that simulated gastric and intestinal conditions. The particle size, morphology, zeta potential, loading capacity, loading efficiency, in vitro release behavior, structure, and morphology of nanoparticles were evaluated, and the activity of the loaded antigen was assessed. Size of the optimized TMC/HPMCP nanoparticles and that of the antigen-loaded nanoparticles were 85 nm and 158 nm, respectively. Optimum loading capacity (76.75%) and loading efficiency (86.29%) were achieved at 300 µg/mL concentration of the antigen. SEM images revealed a spherical shape as well as a smooth and near-homogenous surface of nanoparticles. Results of the in vitro release studies showed that formulation with HPMCP improved the acid stability of the TMC nanoparticles as well as their capability to preserve the loaded HBsAg from gastric destruction. The antigen showed good activity both before and after loading. The results suggest that TMC/HPMCP nanoparticles could be used in the oral delivery of HBsAg vaccine.

  13. Characterization of antigenic variants of hepatitis C virus in immune evasion

    Directory of Open Access Journals (Sweden)

    Hershow Ronald

    2011-07-01

    Full Text Available Abstract Background Antigenic variation is an effective way by which viruses evade host immune defense leading to viral persistence. Little is known about the inhibitory mechanisms of viral variants on CD4 T cell functions. Results Using sythetic peptides of a HLA-DRB1*15-restricted CD4 epitope derived from the non-structural (NS 3 protein of hepatitis C virus (HCV and its antigenic variants and the peripheral blood mononuclear cells (PBMC from six HLA-DRB1*15-positive patients chronically infected with HCV and 3 healthy subjects, the in vitro immune responses and the phenotypes of CD4+CD25+ cells of chronic HCV infection were investigated. The variants resulting from single or double amino acid substitutions at the center of the core region of the Th1 peptide not only induce failed T cell activation but also simultaneously up-regulate inhibitory IL-10, CD25-TGF-β+ Th3 and CD4+IL-10+ Tr1 cells. In contrast, other variants promote differentiation of CD25+TGF-β+ Th3 suppressors that attenuate T cell proliferation. Conclusions Naturally occuring HCV antigenic mutants of a CD4 epitope can shift a protective peripheral Th1 immune response into an inhibitory Th3 and/or Tr1 response. The modulation of antigenic variants on CD4 response is efficient and extensive, and is likely critical in viral persistence in HCV infection.

  14. Virological and epidemiological features of hepatitis delta infection among blood donors in Nouakchott, Mauritania.

    Science.gov (United States)

    Mansour, Wael; Bollahi, Mohamed-Abdellahi; Hamed, Cheikh-Tijani; Brichler, Ségolène; Le Gal, Frédéric; Ducancelle, Alexandra; Lô, Baidy; Gordien, Emmanuel; Rosenheim, Michel; Lunel, Françoise

    2012-09-01

    In Mauritania, some authors have described a possible high prevalence of hepatitis delta virus (HDV) infection in the 1990s in studies of small-size samples. The aims of our study were to assess the prevalence of HDV in HBsAg positive blood donors in Mauritania, to identify the main risk factors for HDV transmission and to analyze genetic diversity of HDV strains. From October 2008 to December 2009, 11,100 consecutive blood donors were considered in this study. Among them, 1700 (15.3%) were HBsAg positive and 455 accepted to participate in this study. Demographic, epidemiological, ethnical, clinical and biological data were recorded. HDV screening, i.e., antibodies (HDVAb) and RNA (HDV-RNA) detection, was performed for all of them as well as HDV and HBV genotyping. Ninety/455 (19.78%) donors were HDVAb positive and HDV-RNA was detectable in 56 (62.2%) of them. HDV infection was significantly associated with older age, number of marriages, military profession, residence in the desert and a history of hospitalization. The HDV genotypes of the circulating strains were HDV-1 (89.3%) and HDV-5 (10.7%). HDV is highly endemic in Mauritanian blood donors indicating that a high number of them will develop chronic hepatitis, cirrhosis or hepatocellular carcinoma. Associated risk factors support nosocomial transmission of HDV. These data underline the need to reinforce HBV vaccination in newborns and in blood donors without HBV markers, together with screening for HDV in HBV-infected individuals. Copyright © 2012 Elsevier B.V. All rights reserved.

  15. Hepatitis B virus genotype has no impact on hepatitis B e antigen seroconversion after lamivudine treatment

    Institute of Scientific and Technical Information of China (English)

    Henry Lik-Yuen Chan; May-Ling Wong; Alex Yui Hui; Angel Mei-Ling Chim; Ada Mei-Ling Tse; Lawrence Cheung-Tsui Hung; Francis Ka-Leung Chan; Joseph Jao-Yiu Sung

    2003-01-01

    AIM: To investigate the association of hepatitis B virus (HBV) genotype and HBeAg seroconversion after nucleotide analogue treatment.METHODS: Chronic hepatitis B patients receiving lamivudine followed up for at least 6 months post-treatment were studied. Consecutive treatment-naive patients who were prospectively followed up in the clinic for at least 18 months were studied as controls. HBeAg seroconversion was defined as loss of HBeAg, appearance of anti-HBe and normalization of alanine aminotransferase for at least 6 months.RESULTS: Thirty-five patients on lamivudine and 96 control patients followed up for 39 (18-49) months were studied.Lamivudine was given for 12 (10-18) months, and patients were followed up for 15 (6-34) months after drug cessation.Genotype B and C HBV were found in 43 and 88 patients and HBeAg seroconversion occurred in 12 (28 %) and 16(18 %) patients, respectively (P=0.30). There was no difference in HBeAg seroconversion between patients infected by genotype B and C HBV in the control (35 % vs 21%, P=0.25) and lamivudine-treated (14 % vs 10 %,P=1.00) groups.CONCLUSION: HBeAg seroconversion after treatment by lamivudine was not influenced by the HBV genotype.

  16. Predictive value of interferon-gamma inducible protein 10 kD for hepatitis B e antigen clearance and hepatitis B surface antigen decline during pegylated interferon alpha therapy in chronic hepatitis B patients.

    Science.gov (United States)

    Wang, Yadong; Zhao, Caiyan; Zhang, Li; Yu, Weiyan; Shen, Chuan; Wang, Wei; Zhen, Zhen; Zhou, Junying

    2014-03-01

    Chronic hepatitis B (CHB) is an immune-mediated infectious disease caused by the hepatitis B virus (HBV). No ideal immunological markers are available at present. In this study, the expression level of interferon-gamma inducible protein 10 kD (IP-10) in chronic asymptomatic HBV carriers (AsC), patients with CHB, and patients with HBV-related acute-on-chronic liver failure (ACLF) was detected. Serum IP-10 level changes were evaluated during the pre-, on- and post-treatment periods for CHB patients receiving Peg IFN-α therapy. The correlation between the IP-10 level and the inflammation activity (IA) score, alanine aminotransferase (ALT) level, HBV DNA load, and hepatitis B surface antigen (HBsAg) quantification were also evaluated. The IP-10 expression gradually increased from AsC to patients with CHB and was highest in patients with ACLF. Serum IP-10 levels were positively correlated with the hepatic IA score and ALT level, but negatively with the HBV DNA load and HBsAg quantification. The CHB patients achieved hepatitis B e antigen (HBeAg) clearance or HBsAg decline >1 log10 IU/ml had higher pre-treatment IP-10 levels and more obvious on-treatment reduction of the IP-10 level than did patients with HBeAg persistent-positive or HBsAg decline <1 log10 IU/ml. Multivariate logistic-regression analysis revealed that the serum IP-10 level was an independent predictor of HBeAg clearance and HBsAg decline. In conclusion, IP-10 expression distinctly varies at different clinical stages of HBV infection. Higher pre-treatment serum IP-10 expression and dynamic down-regulation might be associated with an increased probability of HBeAg clearance and HBsAg decline in CHB patients during Peg IFN-α therapy.

  17. Serological and Molecular Diagnosis of Hepatitis Delta Virus Infection: Results of a French National Quality Control Study

    Science.gov (United States)

    Brichler, Ségolène; Le Gal, Frédéric; Neri-Pinto, Fernando; Mansour, Wael; Roulot, Dominique; Laperche, Syria

    2014-01-01

    A French national quality control study for the serological and molecular diagnosis of hepatitis delta virus (HDV) was organized. Total HDV antibodies were properly detected by all laboratories; 8/14 laboratories failed to detect low titers of IgM, and 6/11 failed to quantify and/or underestimated the RNA viral load in several samples. These discrepancies are likely related to the molecular diversity of HDV. PMID:24523467

  18. Early hepatitis B surface antigen decline predicts treatment response to entecavir in patients with chronic hepatitis B.

    Science.gov (United States)

    Peng, Cheng-Yuan; Lai, Hsueh-Chou; Su, Wen-Pang; Lin, Chia-Hsin; Chuang, Po-Heng; Chen, Sheng-Hung; Chen, Ching-Hsiang

    2017-02-21

    Early declines in serum hepatitis B surface (HBsAg) levels, their optimal cutoffs, and association with therapeutic endpoints in chronic hepatitis B (CHB) patients receiving entecavir treatment remain unclear. We prospectively enrolled 529 patients (195 hepatitis B e antigen [HBeAg]-positive and 334 HBeAg-negative) with a median treatment duration of 49.2 months. Median HBsAg levels declined significantly in both groups at Month 3, but only at Months 6-12 in the HBeAg-negative group. Both groups exhibited a significant HBsAg decline with each successive year of treatment. An HBsAg decline of ≥75% from baseline, assessed at Months 3 and 12 of treatment in the HBeAg-positive and -negative patients, respectively, independently predicted a virological response and HBeAg seroconversion in the HBeAg-positive patients, an HBsAg level of <100 IU/mL in the HBeAg-negative patients, and HBsAg loss in all the patients during treatment. HBsAg levels of <3,000 IU/mL at baseline combined with an HBsAg decline of ≥75% from baseline provided a predictive algorithm for HBsAg loss (positive and negative predictive values: 70% and 100%, respectively) during 5 years of treatment. The proposed cutoffs for defining an HBsAg decline may assist clinicians in early assessments of treatment responses in genotype B-infected or C-infected CHB patients receiving entecavir therapy.

  19. Lichen Planus Induced by Pegylated Interferon Alfa-2a Therapy in a Patient Monitored for Delta Hepatitis

    Directory of Open Access Journals (Sweden)

    Safak Kaya

    2015-01-01

    Full Text Available Interferons are used for treatment of chronic hepatitis B. They can induce or exacerbate some skin disorders, such as lichen planus. In this study, as we know, we presented the first case developing lichen planus while receiving interferon treatment due to delta hepatitis. A 31-year-old male patient presented to our outpatient clinic with HBsAg positivity. With his analyses, HBV DNA was negative, anti-delta total was positive, ALT was 72 U/L (upper limit 41 U/L, and platelet was 119 000/mm3. He was therefore started on subcutaneous pegylated interferon alfa-2a therapy at 180 mcg/week for delta hepatitis. At month 4 of therapy, the patient developed diffuse eroded lace-like lesions in oral mucosa, white plaques on lips, and itchy papular lesions in the hands and feet. Lichen planus was considered by the dermatology clinic and topical treatment (mometasone furoate was given. The lesions persisted at month 5 of therapy and biopsy samples were obtained from oral mucosal lesions and interferon dose was reduced to 135 mcg/week. Biopsy demonstrated nonkeratinized stratified squamous epithelium; epithelial acanthosis, spongiosis, and apoptotic bodies were observed in the epidermis and therefore lichen planus was considered. At month 6 of therapy, lesions did not improve and even progressed and interferon treatment was therefore discontinued.

  20. Biliary carcinoembryonic antigen levels in diagnosis of occult hepatic metastases from colorectal carcinoma

    Institute of Scientific and Technical Information of China (English)

    Jaques Waisberg; Rog(e)rio T. Palma; Lu(i)s Contim Neto; Lourdes C. Martins; Maur(i)cio S. L. Oliveira; Carlos A. Nagashima; Antonio C. Godoy; Fabio S. Goffi

    2003-01-01

    AIM: To prospectively explore the role of carcinoembryonic antigen (CEA) in gallbladder bile in patients with colorectal carcinoma and the morphological and clinical features of neoplasia and the occurrence of hepatic metastases.METHODS: CEA levels in the gallbladder and peripheral blood were studied in 44 patients with colorectal carcinoma and 10 patients with uncomplicated cholelithiasis. CEA samples were collected from the gallbladder bile and peripheral blood during the operation, immediately before extirpating the colorectal neoplasia or cholecystectomy.Values of up to 5 ng/ml were considered normal for bile and serum CEA.RESULTS: In the 44 patients with colorectal carcinoma who underwent operation with curative intent, the average level of serum CEA was 8.5 ng/ml (range: 0.1 to 111.0 ng/ml) and for bile CEA it was 74.5 ng/ml (range: 0.2 to 571.0ng/ml). In the patients with uncomplicated cholelithiasis who underwent cholecystectomy, the average level of serum CEA was 1.9 ng/ml (range: 1.0 to 3.5 ng/ml) and for bile CEA it was 1.2 ng/ml (range: 0.3 to 2.9 ng/ml).The average duration of follow-up time was 16.5 months (range: 6 to 48 months). Four patients who underwent extirpation of the colorectal carcinoma without evidence of hepatic metastasis and with an average bile CEA value of 213.2 ng/ml presented hepatic metastases between three and seventeen months after removal of the primary colorectal neoplasia. Three of them successfully underwent extirpation of the hepatic lesions.CONCLUSION: High CEA levels in gallbladders of patients undergoing curative operation for colorectal carcinoma may indicate the presence of hepatic metastases. Such patients must be followed up with special attention to the diagnosis of such lesions.

  1. Cations and hydration in catalytic RNA: molecular dynamics of the hepatitis delta virus ribozyme.

    Science.gov (United States)

    Krasovska, Maryna V; Sefcikova, Jana; Réblová, Kamila; Schneider, Bohdan; Walter, Nils G; Sponer, Jirí

    2006-07-15

    The hepatitis delta virus (HDV) ribozyme is an RNA enzyme from the human pathogenic HDV. Cations play a crucial role in self-cleavage of the HDV ribozyme, by promoting both folding and chemistry. Experimental studies have revealed limited but intriguing details on the location and structural and catalytic functions of metal ions. Here, we analyze a total of approximately 200 ns of explicit-solvent molecular dynamics simulations to provide a complementary atomistic view of the binding of monovalent and divalent cations as well as water molecules to reaction precursor and product forms of the HDV ribozyme. Our simulations find that an Mg2+ cation binds stably, by both inner- and outer-sphere contacts, to the electronegative catalytic pocket of the reaction precursor, in a position to potentially support chemistry. In contrast, protonation of the catalytically involved C75 in the precursor or artificial placement of this Mg2+ into the product structure result in its swift expulsion from the active site. These findings are consistent with a concerted reaction mechanism in which C75 and hydrated Mg2+ act as general base and acid, respectively. Monovalent cations bind to the active site and elsewhere assisted by structurally bridging long-residency water molecules, but are generally delocalized.

  2. Genetic association of autoimmune hepatitis and human leucocyte antigen in German patients

    Institute of Scientific and Technical Information of China (English)

    Andreas Teufel; Markus W(o)rns; Arndt Weinmann; Catherine Centner; Anja Piendl; Ansgar W Lohse; Peter R Galle; Stephan Kanzler

    2006-01-01

    AIM: To report on our large German collective and updated data of 142 patients with autoimmune hepatitis (AIH) type 1.METHODS: Key investigations performed were liver biopsy, serum autoantibodies as well as serum markers such as IgG and elevated transaminases.Antinuclear antigen (ANA) and smooth muscle antigen (SMA) autoantibodies characterized type 1 AIH. Type 3 (AIH) was solely characterized by the occurrence of soluble liver antigen/liver-pancreas antigen (SLA/LP)autoantibodies either with or without ANA or SMA autoantibodies.RESULTS: Most prevalent HLAs were A2 (68 patients, 48%), B8 (63 patients, 44%), C7 (90 patients, 63%), DR3 (49 patients, 38%), DR4 (49 patients, 38%) and DQ2 (42 patients, 30%). Compared to the Italian and North American patients, we found fewer patients with a DQ2 subtype. Furthermore, the B8-DR3-DQ2human leucocyte antigen (HLA) was also less prominent compared to the North American patients. However, prevalences of B8, DR3, DR4, DR7, DR11 and DR13 were comparable to the Italian and North American patients. Furthermore, we report on an additional subgroup of patients with SLA/LP positive AIH. Generally, in this subgroup of patients the same HLA subtypes were favoured as the AIH type 1. CONCLUSION: Although HLA subtypes were comparable between these three collectives, the German patients were distinct from the Italian and North American patients with respect to DQ2 and from the North American patients with respect to B8-DR3-DQ2HLA. A clinical correlation, e.g. difference in severity or treatability of AIH type 1, has yet to be determined.

  3. Prevalence of Hepatitis B Surface Antigen in US-Born and Foreign-Born Asian/Pacific Islander College Students

    Science.gov (United States)

    Quang, Yen N.; Vu, Joanne; Yuk, Jihey; Li, Chin-Shang; Chen, Moon; Bowlus, Christopher L.

    2010-01-01

    The prevalence of chronic hepatitis B (HBV) among college-age US-born Asian and Pacific Islanders (A/PI) is not well known. Objectives: To compare the prevalence of hepatitis B surface antigen (HBsAg) seropositivity in US-born to A/PI-born students at a public university. Participants: Undergraduate who self-identified themselves as A/PI. Results:…

  4. Prevalence of Hepatitis B Surface Antigen in US-Born and Foreign-Born Asian/Pacific Islander College Students

    Science.gov (United States)

    Quang, Yen N.; Vu, Joanne; Yuk, Jihey; Li, Chin-Shang; Chen, Moon; Bowlus, Christopher L.

    2010-01-01

    The prevalence of chronic hepatitis B (HBV) among college-age US-born Asian and Pacific Islanders (A/PI) is not well known. Objectives: To compare the prevalence of hepatitis B surface antigen (HBsAg) seropositivity in US-born to A/PI-born students at a public university. Participants: Undergraduate who self-identified themselves as A/PI. Results:…

  5. Expression, biosynthesis and release of preadipocyte factor-1/ delta-like protein/fetal antigen-1 in pancreatic beta-cells

    DEFF Research Database (Denmark)

    Friedrichsen, B N; Carlsson, C; Møldrup, Annette

    2003-01-01

    Preadipocyte factor-1 (Pref-1)/delta-like protein/fetal antigen-1 (FA1) is a member of the epidermal growth factor-like family. It is widely expressed in embryonic tissues, whereas in adults it is confined to the adrenal gland, the anterior pituitary, the endocrine pancreas, the testis and the ov......Preadipocyte factor-1 (Pref-1)/delta-like protein/fetal antigen-1 (FA1) is a member of the epidermal growth factor-like family. It is widely expressed in embryonic tissues, whereas in adults it is confined to the adrenal gland, the anterior pituitary, the endocrine pancreas, the testis...

  6. Clinical significance of hepatitis B e antigen level measurement during long-term lamivudine therapy in chronic hepatitis B patients with e antigen positive

    Institute of Scientific and Technical Information of China (English)

    Jung Woo Shin; Neung Hwa Park; Seok Won Jung; Byung Chul Kim; Sung Ho Kwon; Jae Serk Park; In Du Jeong; Sung-Jo Bang; Do Ha Kim

    2006-01-01

    AIM: To determine the changes of quantitative hepatitis B e antigen (HBeAg) that predicts early detection of nonresponse or breakthrough to long-term lamivudine (LAM)therapy.METHODS: Among HBeAg positive chronic hepatitis B patients who failed to achieve HBeAg seroconversion within 12 mo, we retrospectively analyzed 220 patients who had received LAM more than 24 mo.RESULTS: The mean duration of LAM therapy was 36(range, 24-72) mo. HBeAg seroconversion after the first 12 mo of LAM therapy was achieved in 53 (24.1%)patients. Viral breakthrough was observed in 105 (47.7%)patients. To find out whether the changing patterns of HBeAg levels can predict the outcome of LAM therapy,we analyzed the reduction rates of HBeAg levels during LAM therapy. Using the decrease more than 90% of pretreatment HBeAg levels, the sensitivity and specificity of response were 96.2% and 70.1%, respectively.Patients were divided into 3 groups according to the reduction patterns of the decrease of quantitative HBeAg: decrescendo, decrescendo-crescendo, no change or fluctuating groups. The optimal time to predict nonresponse or breakthrough was the first 9 mo of therapy.At 9 mo of therapy, 49 (92.5%) of 53 patients who had achieved HBeAg seroconversion were included in the decrescendo group. On the contrary, in the no change or fluctuating group, only four (7.5%) had achieved HBeAg seroconversion. Among patients who did not show the continuous decrease of HBeAg levels at 9 mo, 95.2%(negative predictive value) failed to achieve HBeAg seroconversion.CONCLUSION: Almost all patients who failed to show a continuous decrease of HBeAg levels at 9 mo of LAM therapy were non-response or breakthrough. Therefore,monitoring changes of HBeAg levels during LAM therapy in HBeAg positive chronic hepatitis B may be valuable for identifying patients who are at high risk of non-response or breakthrough.

  7. Intrahepatic distribution of hepatitis B virus antigens in patients with and without hepatocellular carcinoma

    Science.gov (United States)

    Safaie, Parham; Poongkunran, Mugilan; Kuang, Ping-Ping; Javaid, Asad; Jacobs, Carl; Pohlmann, Rebecca; Nasser, Imad; Lau, Daryl TY

    2016-01-01

    AIM: To study the intrahepatic expression of hepatitis B surface antigen (HBsAg) and hepatitis B core antigen (HBcAg) in chronic hepatitis B patients with and without hepatocellular carcinoma. METHODS: A total of 33 chronic hepatitis B patients (mean age of 40.3 ± 2.5 years), comprising of 14 HBeAg positive and 19 HBeAg negative patients; and 13 patients with hepatitis B virus related hepatocellular carcinoma (mean age of 49.6 ± 4.7 years), were included in our study. Immunohistochemical staining for HBcAg and HBsAg was done using standard streptavidin-biotin-immunoperoxidase technique on paraffin-embedded liver biopsies. The HBcAg and HBsAg staining distributions and patterns were described according to a modified classification system. RESULTS: Compared to the HBeAg negative patients, the HBeAg positive patients were younger, had higher mean HBV DNA and alanine transaminases levels. All the HBeAg positive patients had intrahepatic HBcAg staining; predominantly with “diffuse” distribution (79%) and “mixed cytoplasmic/nuclear” pattern (79%). In comparison, only 5% of the HBeAg-negative patients had intrahepatic HBcAg staining. However, the intrahepatic HBsAg staining has wider distribution among the HBeAg negative patients, namely; majority of the HBeAg negative cases had “patchy” HBsAg distribution compared to “rare” distribution among the HBeAg positive cases. All but one patient with HCC were HBeAg negative with either undetectable HBV DNA or very low level of viremia. Intrahepatic HBcAg and HBsAg were seen in 13 (100%) and 10 (77%) of the HCC patients respectively. Interestingly, among the 9 HCC patients on anti-viral therapy with suppressed HBV DNA, HBcAg and HBsAg were detected in tumor tissues but not the adjacent liver in 4 (44%) and 1 (11%) patient respectively. CONCLUSION: Isolated intrahepatic HBcAg and HBsAg can be present in tumors of patients with suppressed HBV DNA on antiviral therapy; that may predispose them to cancer development

  8. Reduced Hepatic Carcinoembryonic Antigen-Related Cell Adhesion Molecule 1 Level in Obesity

    Science.gov (United States)

    Heinrich, Garrett; Muturi, Harrison T.; Rezaei, Khadijeh; Al-Share, Qusai Y.; DeAngelis, Anthony M.; Bowman, Thomas A.; Ghadieh, Hilda E.; Ghanem, Simona S.; Zhang, Deqiang; Garofalo, Robert S.; Yin, Lei; Najjar, Sonia M.

    2017-01-01

    Impairment of insulin clearance is being increasingly recognized as a critical step in the development of insulin resistance and metabolic disease. The carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) promotes insulin clearance. Null deletion or liver-specific inactivation of Ceacam1 in mice causes a defect in insulin clearance, insulin resistance, steatohepatitis, and visceral obesity. Immunohistological analysis revealed reduction of hepatic CEACAM1 in obese subjects with fatty liver disease. Thus, we aimed to determine whether this occurs at the hepatocyte level in response to systemic extrahepatic factors and whether this holds across species. Northern and Western blot analyses demonstrate that CEACAM1 mRNA and protein levels are reduced in liver tissues of obese individuals compared to their lean age-matched counterparts. Furthermore, Western analysis reveals a comparable reduction of CEACAM1 protein in primary hepatocytes derived from the same obese subjects. Similar to humans, Ceacam1 mRNA level, assessed by quantitative RT-PCR analysis, is significantly reduced in the livers of obese Zucker (fa/fa, ZDF) and Koletsky (f/f) rats relative to their age-matched lean counterparts. These studies demonstrate that the reduction of hepatic CEACAM1 in obesity occurs at the level of hepatocytes and identify the reduction of hepatic CEACAM1 as a common denominator of obesity across multiple species. PMID:28396653

  9. Benefit of Hepatitis C Virus Core Antigen Assay in Prediction of Therapeutic Response to Interferon and Ribavirin Combination Therapy

    OpenAIRE

    Takahashi, Masahiko; Saito, Hidetsugu; Higashimoto, Makiko; Atsukawa, Kazuhiro; Ishii, Hiromasa

    2005-01-01

    A highly sensitive second-generation hepatitis C virus (HCV) core antigen assay has recently been developed. We compared viral disappearance and first-phase kinetics between commercially available core antigen (Ag) assays, Lumipulse Ortho HCV Ag (Lumipulse-Ag), and a quantitative HCV RNA PCR assay, Cobas Amplicor HCV Monitor test, version 2 (Amplicor M), to estimate the predictive benefit of a sustained viral response (SVR) and non-SVR in 44 genotype 1b patients treated with interferon (IFN) ...

  10. An immunodominant HLA-A*1101-restricted CD8+ T-cell response targeting hepatitis B surface antigen in chronic hepatitis B patients.

    Science.gov (United States)

    Chen, Xiaoling; Wang, Wenbo; Wang, Shufeng; Meng, Gang; Zhang, Mengjun; Ni, Bing; Wu, Yuzhang; Wang, Li

    2013-12-01

    Hepatitis B virus (HBV) infection is a worldwide public health problem. HBV-specific CD8(+) CTLs are vital for viral clearance. Identification of immunodominant CTL epitopes from HBV-associated antigens is necessary for therapeutic vaccine development. We showed that the HLA-A*1101 allele is one of the most common alleles in both healthy individuals and chronic hepatitis B (CHB) patients in the Chongqing area, China. However, less than 10% of epitopes of HBV-associated antigens have been identified in an HLA-A*1101 context. Here, we describe an immunodominant CD8(+) T-cell response targeting a hepatitis B surface antigen determinant (HBs(295-304)) restricted by HLA-A*1101 in both healthy individuals and CHB patients. Moreover, HBs(295-304) is more immunogenic for CTL induction than a known naturally HLA-A*1101-processed epitope from hepatitis B core antigen (HBc(88-96)). Therefore, the newly identified epitope, HBs(295-304), will benefit the development of immunotherapeutic approaches for HBV infection.

  11. Quantification of hepatitis B surface antigen: a new concept for the management of chronic hepatitis B.

    Science.gov (United States)

    Moucari, Rami; Marcellin, Patrick

    2011-01-01

    HBsAg is a very important clinical test that might not only indicate active hepatitis B virus (HBV) infection but might also be used to predict clinical and treatment outcome. Clearance of HBsAg in patients with chronic HBV infection is associated with a much better clinical outcome, although surveillance for early detection of hepatocellular carcinoma (HCC) should continue. HBV DNA quantification is currently used for selecting candidates for therapy, monitoring response to therapy and detecting the emergence of drug resistance. Assays for HBsAg quantification are less expensive than HBV DNA and fully automated with a high throughput capacity. HBsAg titering may be a useful tool to manage patients with chronic HBV, to more clearly define which patients may, and more importantly, may not, benefit from treatment. Baseline and on-treatment HBsAg quantification may help to refine future treatment algorithms for both immune-modulator therapy and nucleos(t)ide analogues. Both HBV markers provide complementary information on the status of HBV infection. However, the relevance of serum HBsAg levels and its use as a reliable replacement for both covalently closed circular DNA and HBV DNA remain unclear.

  12. Systemic and mucosal immune response induced by transcutaneous immunization using Hepatitis B surface antigen-loaded modified liposomes.

    Science.gov (United States)

    Mishra, Dinesh; Mishra, Pradyumna Kumar; Dubey, Vaibhav; Nahar, Manoj; Dabadghao, Sunil; Jain, N K

    2008-04-23

    We have evaluated the efficiency of novel modified liposomes (ethosomes) for transcutaneous immunization (TCI) against Hepatitis B. Antigen-loaded ethosomes were prepared and characterized for shape, lamellarity, fluidity, size distribution, and entrapment efficiency. Spectral bio-imaging and flow cytometric studies showed efficient uptake of Hepatitis B surface antigen (HBsAg)-loaded ethosomes by murine dendritic cells (DCs) in vitro, reaching a peak by 180 min. Transcutaneous delivery potential of the antigen-loaded system using human cadaver skin demonstrated a much higher skin permeation of the antigen in comparison to conventional liposomes and soluble antigen preparation. Topically applied HBsAg-loaded ethosomes in experimental mice showed a robust systemic and mucosal humoral immune response compared to intramuscularly administered alum-adsorbed HBsAg suspension, topically applied plain HBsAg solution and hydroethanolic (25%) HBsAg solution. The ability of the antigen-pulsed DCs to stimulate autologous peripheral blood lymphocytes was demonstrated by BrdU assay and a predominantly TH1 type of immune response was observed by multiplex cytometric bead array analysis. HBsAg-loaded ethosomes are able to generate a protective immune response and their ability to traverse and target the immunological milieu of the skin may find a potential application in the development of a transcutaneous vaccine against Hepatitis B virus (HBV).

  13. Association Between Serum Level of Hepatitis B Surface Antigen at End of Entecavir Therapy and Risk of Relapse in E Antigen-Negative Patients.

    Science.gov (United States)

    Hsu, Yao-Chun; Mo, Lein-Ray; Chang, Chi-Yang; Wu, Ming-Shiang; Kao, Jia-Horng; Wang, Wen-Lun; Yang, Tzeng-Huey; Wang, Chaur-Shine; Chiang, Ming-Feng; Chen, Chieh-Chang; Fang, Yu-Jen; Hung, Hsu-Wei; Wu, Chun-Ying; Lin, Jaw-Town

    2016-10-01

    This study investigated whether serum level of hepatitis B surface antigen (HBsAg) at the end of entecavir treatment was associated with risk of relapse. We performed a prospective multicenter study of 161 consecutive patients with chronic hepatitis B in whom the hepatitis B virus was no longer detected after 3 years or more of entecavir therapy. Treatment ended between July 1, 2011 and July 1, 2015. Patients were monitored for clinical relapse (hepatitis B virus DNA >2000 IU/mL and level of alanine aminotransferase more than 2-fold the upper limit of normal) and virologic relapse (hepatitis B virus DNA >2000 IU/mL). Outcomes were calculated using the Kaplan-Meier method and risk factors were identified by Cox proportional hazards modeling. Two years after therapy ended, 49.2% of patients in the entire cohort had a clinical relapse (95% confidence interval [CI], 40.9%-58.1%) and 81.7% had a virologic relapse (95% CI, 74.3%-88.0%). Among patients who were hepatitis B e antigen-negative at the end of therapy, 39.2% had a clinical relapse (95% CI, 30.3%-49.6%) and 77.4% had a virologic relapse (95% CI, 68.6%-85.2%). Serum level of HBsAg was associated with relapse in the hepatitis B e antigen-negative patients (Ptrend = .006 for clinical relapse; Ptrend = .0001 for virologic relapse). In multivariate Cox regression analysis, the hazard ratio (per log IU/mL increment) for clinical relapse was 2.47 (95% CI, 1.45-4.23) and for virologic relapse was 1.80 (95% CI, 1.33-2.45). The 11 (9%) patients with levels of HBsAg <10 IU/mL did not relapse. Serum level of HBsAg is associated with risk of relapse in patients who are hepatitis B e antigen-negative after treatment with entecavir. A low titer of HBsAg might be used to identify patients at low risk for relapse after treatment. Copyright © 2016 AGA Institute. Published by Elsevier Inc. All rights reserved.

  14. Seroprevalence of hepatitis B e antigen (HBe antigen and B core antibodies (IgG anti-HBcore and IgM anti-HBcore among hepatitis B surface antigen positive blood donors at a Tertiary Centre in Nigeria

    Directory of Open Access Journals (Sweden)

    Akinbami Akinsegun A

    2012-03-01

    Full Text Available Abstract Background Hepatitis B virus (HBV is a common cause of liver disease throughout the world. HBV is transmitted through blood and other body fluids, including semen and saliva. Chronic replication of HBV virons is characterized by persistence circulation of HBsAg, HBeAg and HBV DNA; usually with anti-HBc and occasionally with anti-HBs. Aim: To determine the prevalence of HBeAg, IgG anti-HBcore and IgM anti-HBcore amongst HBsAg positive blood donors. These parameters are reflective of transmissibility and active hepatitis B infection. A cross sectional study was carried out at the blood donor clinics of Lagos State University Teaching Hospital Ikeja and Lagos University Teaching Hospital Idiaraba. A total of 267 donors were recruited to determine HBe antigen, IgG and IgM anti-HBcore antibodies amongst hepatitis BsAg positive donors. Five milliliters of blood was collected from those who tested positive to HBsAg screen during donation. The sera were subjected to enzyme linked immunosorbent assay (ELISA. Pearson chi-squared test was used for the analytical assessment. Findings A total number of 267 HBsAg positive blood donors were studied. A seroprevalence of 8.2% (22 of 267 HBeAg was obtained, 4 of 267 (1.5% were indeterminate while 241 (90.3% tested negative. Only 27 out of 267 donors (10.1% tested positive to IgM anti-HBcore, 234(87.6% tested negative, while 6(2.2% were indeterminate. A higher percentage of 60.7% (162 of 267 tested positive to IgG anti-HBcore, while 39.3% (105 of 267 tested negative. Conclusion There is a low seroprevalence rate of HBeAg-positive chronic hepatitis and relatively high IgG anti-HBcore and IgM anti-HBcore rates in South West Nigeria.

  15. Yeast expressing hepatitis B virus surface antigen determinants on its surface: Implications for a possible oral vaccine

    NARCIS (Netherlands)

    Schreuder, M.P.; Deen, C.; Boersma, W.J.A.; Pouwels, P.H.; Klis, F.M.

    1996-01-01

    The two major hydrophilic regions of the hepatitis B virus surface antigen (HBsAg) have been expressed in the outer mannoprotein layer of the cell wall of 'Bakers Yeast', Saccharomyces cerevisiae, by fusing them between the yeast invertase signal sequence and the yeast α-agglutinin carboxyterminal c

  16. The Expression of Sperm Membrane Peptide-Hepatitis B Surface Antigen Fusion Protein with Recombinant Vaccinia Virus

    Institute of Scientific and Technical Information of China (English)

    杨晓鸣; 赵峰; 严缘昌; 李光地; 汪垣

    1998-01-01

    A synthetic oligonucleotide, HSD-2a, encoding a peptide segment of the extracellular domain of a human sperm membrane protein, YWK-Ⅱ, was fused with hepatitis B surface antigen gene (HBs gene). The fused gene was then cloned to pUC18 plasmid.

  17. [Study on expression of Fas/FasL and HBV antigens in liver tissue of patients with hepatitis B].

    Science.gov (United States)

    Wang, H; Hu, J; Zhu, K

    2001-03-01

    To evaluate the role of apoptosis mediated by Fas/FasL in the liver of hepatitis B and the expression status of Fas, FasL, and HBV antigens. We studied the expression of Fas antigen, Fas-ligand (FasL) and hepatitis B virus(HBV) antigens(HBsAg and HBcAg) in the livers of 62 patients with hepatitis B using immunohistochemistry ABC method. Six normal liver samples were used as control. Hepatocytes in normal liver had no Fas/FasL expression, but in the cases of hepatitis B, Fas was expressed mainly in the cytoplasm in 58 cases(93.5%); FasL was observed in infiltrating mononuclear cells and in the cytoplasm of hepatocytes in 37 cases (59.7%). The expressions of Fas/FasL were closely related to the liver histological inflammation degrees. The apoptosis mediated by Fas/FasL may play an important role in the hepatocellular injury in hepatitis B. No correlation was found between the degrees of Fas/FasL expression and the presence of HBsAg and HBcAg in the liver.

  18. Delta-like 1/fetal antigen 1(DLK1/FA1) inhibits BMP2 induced osteoblast differentiation through modulation of NFκB signaling pathway

    DEFF Research Database (Denmark)

    Qiu, Weimin; Abdallah, Basem; Kassem, Moustapha

    DLK1/FA1 (delta-like 1/fetal antigen-1) is a negative regulator of bone mass that acts to inhibit osteoblast differentiation and stimulate osteoclast differentiation. However, the molecular mechanisms underlying these effects are not known. Thus, we studied the effect of DLK1/FA1 on different...

  19. Fermentation study for the production of hepatitis B virus pre-S2 antigen by the methylotrophic yeast Hansenula polymorpha.

    Science.gov (United States)

    de Roubin, M R; Bastien, L; Shen, S H; Groleau, D

    1991-10-01

    Various physico-chemical parameters have been studied in order to improve the production of hepatitis B virus pre-S2 antigen (middle surface antigen) by the methylotrophic yeast Hansenula polymorpha. Antigen production was done in two steps: first, production of cells on glycerol (Phase 1), followed by induction of antigen expression with methanol (Phase 2). Dense cultures of H. polymorpha, equivalent to 35-40 g/l (dry weight), were readily obtained in small fermenters using minimal medium containing glycerol as carbon source. Antigen expression in this minimal medium, after induction with methanol, was however, low and never exceeded 1.6 mg/l of culture. Antigen production was greatly enhanced by adding complex organic nitrogen sources along with methanol at induction time; yeast extract was the best of all the sources tested. In shake flasks, antigen production was proportional to yeast extract concentration up to 7% (w/v) yeast extract, it became clear the the nutritional conditions for good antigen expression were different from those for good biomass production. The effects of yeast extract were reproduced in small fermenters: antigen levels reached 8-9 mg/l in medium containing 6% (w/v) yeast extract during induction with methanol. The mechanisms of yeast extract's effects are still unknown but are probably nutritional. The recombinant H. polymorpha strain produced both periplasmic and intracellular antigen. The periplasmic antigen was shown to be present as 20-22-nm particles and was therefore immunogenic. Immunoblotting indicated that part of the pre-S2 antigen was present as a 24-kDa degradation product. These studies have led to a 140-fold increase in volumetric productivity of antigen and to a 4.6-fold increase in specific production.

  20. Expression of hepatitis B surface antigen gene (HBsAg) in Laminaria japonica (Laminariales, Phaeophyta)

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    A transformation model for Laminaria japonica was established from 1993 to 1998, on the basis of which the transgenic kelp with heterologous gene encoding hepatitis B surface antigen (HBsAg) was obtained by using the micro- particle bombardment transformation method. Results of quantitative ELISA showed that HBsAg in transgenic kelp was 0.529 μg/mg soluble proteins on average and the highest value was 2.497 μg/mg, implying that recombinant HBsAg had natural epitope. Further support for the integration of HBsAg gene into kelp genome was obtained by PCR- Southern and total DNA hybridization. Prospect of kelp bioreactor producing high value materials such as edible HBV vaccine was discussed as well.

  1. Expression of Human Hepatitis B Virus Surface Antigen Gene in Transgenic Tobacco

    Institute of Scientific and Technical Information of China (English)

    刘玉乐; 王晋芳; 邱并生; 赵淑珍; 田波

    1994-01-01

    Expression of Human hepatitis B virus surface antigen (HBsAg) gene in plant was reported for the first time. The recombinant plasmid pRoKⅡ-HBsAg was constructed by inserting HBsAg gene into the downstream of CaMV 35S promoter of binary vector pRoKⅡ and then introduced into Agrobacterium tumefaciens LBA4404. The kanamycin-resistant plants were obtained by Agrobacterium-mediated transformation system. It was shown that HBsAg gene was expressed in transgenic tobacco plants and their progenies by ELISA. The spherical particles of ψ 22 nm in the leaf extract of trangenic tobacco were observed by immunosorbent electron microscopy.

  2. Biodegradable polylactide microspheres enhance specific immune response induced by Hepatitis B surface antigen.

    Science.gov (United States)

    Qiu, Shaohui; Wei, Qiang; Liang, Zhenglun; Ma, Guanghui; Wang, Lianyan; An, Wenqi; Ma, Xiaowei; Fang, Xin; He, Peng; Li, Hemin; Hu, Zhongyu

    2014-01-01

    Hepatitis B (HB) infection caused by Hepatitis B virus (HBV) is the most common liver disease in the world. HB vaccine, when administered in conjunction with alum adjuvants, induces Th2 immunity that confers protection against HBV. However, currently available vaccine formulations and adjuvants do not elicit adequate Th1 and CTL responses that are important for prevention of maternal transmission of the virus. Microspheres synthesized from poly (D, L-lactide-co-glycolide) (PLGA) or poly (D, L-lactide) (PLA) polymers have been considered as promising tools for in vivo delivery of antigens and drugs. Here we describe PLA microspheres synthesized by premix membrane emulsification method and their application in formulating a new microsphere based HB vaccine. To evaluate the immunogenicity of this microsphere vaccine, BALB/c mice were immunized with microsphere vaccine and a series of immunological assays were conducted. Results of Enzyme-linked ImmunoSpot (ELISPOT) assays revealed that the number of interferon-gamma (IFN-γ)-producing splenocytes and CD8(+) T cells increased significantly in the microsphere vaccine group. Microsphere vaccine group showed enhanced specific cell lysis when compared with HB surface antigen (HBsAg) only group in (51)Cr cytotoxicity assays. Moreover, microsphere vaccine elicited a comparable level of antibody production as that of HB vaccine administered with alum adjuvant. We show that phagocytosis of HBsAg by dendritic cells is more pronounced in microsphere vaccine group when compared with other control groups. These results clearly demonstrate the potential of using PLA microspheres as effective HB vaccine adjuvants for an enhanced Th1 immune response.

  3. Sensitive enzyme immunoassay for hepatitis B virus core-related antigens and their correlation to virus load.

    Science.gov (United States)

    Kimura, Tatsuji; Rokuhara, Akinori; Sakamoto, Yoko; Yagi, Shintaro; Tanaka, Eiji; Kiyosawa, Kendo; Maki, Noboru

    2002-02-01

    A sensitive enzyme immunoassay (EIA) specific for hepatitis B virus core antigen (HBcAg) and hepatitis B e antigen (HBeAg) was developed. We designated the precore/core gene products as hepatitis B virus (HBV) core-related antigens (HBcrAg). In order to detect HBcrAg even in anti-HBc/e antibody-positive specimens, the specimens were pretreated in detergents. The antibodies are inactivated by this pretreatment and, simultaneously, the antigens are released and the epitopes are exposed. The assay demonstrated 71 to 112% recovery using HBcrAg-positive sera. We observed no interference from the tested anticoagulants or blood components. When the cutoff value was tentatively set at 10(3) U/ml, all healthy control (HBsAg/HBV-DNA negative; n = 108) and anti-HCV antibody-positive (n = 59) sera were identified as negative. The assay showed a detection limit of 4 x 10(2) U/ml using recombinant antigen. Detection limits were compared in four serially diluted HBV high-titer sera. The HBcrAg assay demonstrated higher sensitivity than HBV-DNA transcription-mediated amplification (TMA) or HBeAg radio immunoassay (RIA) in the dilution test. HBcrAg concentrations correlated well with HBV-DNA TMA (r = 0.91, n = 29) and in-house real-time detection-PCR (r = 0.93, n = 47) in hepatitis B patients. On HBeAg/anti-HBe antibody seroconversion panels, the HBcrAg concentration changed in accordance with HBV-DNA levels. HBcrAg concentration provides a reflection of HBV virus load equivalent to HBV-DNA level, and the assay therefore offers a simple method for monitoring hepatitis B patients.

  4. An inducible transgenic mouse model for immune mediated hepatitis showing clearance of antigen expressing hepatocytes by CD8+ T cells.

    Directory of Open Access Journals (Sweden)

    Marcin Cebula

    Full Text Available The liver has the ability to prime immune responses against neo antigens provided upon infections. However, T cell immunity in liver is uniquely modulated by the complex tolerogenic property of this organ that has to also cope with foreign agents such as endotoxins or food antigens. In this respect, the nature of intrahepatic T cell responses remains to be fully characterized. To gain deeper insight into the mechanisms that regulate the CD8+ T cell responses in the liver, we established a novel OVA_X_CreER(T2 mouse model. Upon tamoxifen administration OVA antigen expression is observed in a fraction of hepatocytes, resulting in a mosaic expression pattern. To elucidate the cross-talk of CD8+ T cells with antigen-expressing hepatocytes, we adoptively transferred K(b/OVA257-264-specific OT-I T cells to OVA_X_CreER(T2 mice or generated triple transgenic OVA_X CreER(T2_X_OT-I mice. OT-I T cells become activated in OVA_X_CreER(T2 mice and induce an acute and transient hepatitis accompanied by liver damage. In OVA_X_CreER(T2_X_OT-I mice, OVA induction triggers an OT-I T cell mediated, fulminant hepatitis resulting in 50% mortality. Surviving mice manifest a long lasting hepatitis, and recover after 9 weeks. In these experimental settings, recovery from hepatitis correlates with a complete loss of OVA expression indicating efficient clearance of the antigen-expressing hepatocytes. Moreover, a relapse of hepatitis can be induced upon re-induction of cured OVA_X_CreER(T2_X_OT-I mice indicating absence of tolerogenic mechanisms. This pathogen-free, conditional mouse model has the advantage of tamoxifen inducible tissue specific antigen expression that reflects the heterogeneity of viral antigen expression and enables the study of intrahepatic immune responses to both de novo and persistent antigen. It allows following the course of intrahepatic immune responses: initiation, the acute phase and antigen clearance.

  5. Determination of hepatitis B surface antigen using magnetic immunoassays in a thin channel.

    Science.gov (United States)

    Tsai, H Y; Chan, J R; Li, Y C; Cheng, F C; Fuh, C Bor

    2010-08-15

    We report novel methods for detection of hepatitis B surface antigen (HBsAg) based on competitive and sandwiched magnetic immunoassays using functional magnetic nanoparticles in a thin channel. Magnetic nanoparticles labeled with hepatitis B antibody are flowed through a thin channel to form a predeposition layer for capturing HBsAg. Competitive and sandwiched magnetic immunoassays were studied and detection limit, linear range, and sample selectivity were compared. The detection limits of competitive and sandwiched magnetic immunoassays were found to be 0.26 and 0.25 pg/ml, respectively. The linear range of HBsAg concentration was 0.26 pg/ml-2.6 ng/ml for competitive magnetic immunoassay and was 0.89 pg/ml-8.9 ng/ml for sandwiched magnetic immunoassay. The advantages of these methods over ELISA and other methods for HBsAg detection are lower detection limits and wider linear ranges. The running time was less than 30 min. Competitive magnetic immunoassay was faster than sandwiched magnetic immunoassay for detection of HBsAg. The measurements of HBsAg in serum samples from these methods differed by about 10% from those of ELISA. These methods can provide simple, fast, and sensitive detections of biomarkers and other immunoassay-related samples.

  6. High affinity mouse-human chimeric Fab against Hepatitis B surface antigen

    Institute of Scientific and Technical Information of China (English)

    Biplab Bose; Navin Khanna; Subrat K Acharya; Subrata Sinha

    2005-01-01

    AIM: Passive immunotherapy using antibody against hepatitis B surface antigen (HBsAg) has been advocated in certain cases of Hepatitis B infection. We had earlier reported on the cloning and expression of a high affinity scFv derived from a mouse monoclonal (5S) against HBsAg. However this mouse antibody cannot be used for therapeutic purposes as it may elicit anti-mouse immune responses. Chimerization by replacing mouse constant domains with human ones can reduce the immunogenicity of this antibody.METHODS: We cloned the VH and VL genes of this mouse antibody; and fused them with CH1 domain of human IgG1 and CL domain of human kappa chain respectively. These chimeric genes were cloned into a phagemid vector. After initial screening using the phage display system, the chimeric Fab was expressed in soluble form in E. Coli.RESULTS: The chimeric Fab was purified from the bacterial periplasmic extract. We characterized the chimeric Fab using several in vitro techniques and it was observed that the chimeric molecule retained the high affinity and specificity of the original mouse monoclonal.This chimeric antibody fragment was further expressed in different strains of E> coli to increase the yield.CONCLUSION: We have generated a mouse-human chimeric Fab against HBsAg without any significant loss in binding and epitope specificity. This chimeric Fab fragment can be further modified to generate a fulllength chimeric antibody for therapeutic uses.

  7. [Validation of a ultramicroELISA for detecting antibodies against hepatitis B surface antigen].

    Science.gov (United States)

    Rodríguez, L; Balmaseda, A; Bravo, J; Trujillo, J; Martínez, L; Ochoa, R; Díaz, M; Laferté, J; Ramos, F

    1996-01-01

    The results of a validation study of the ultramicroanalitical assay for the detection of antibodies against the hepatitis B surface antigen (UMELISA anti-HBsAg), which was carried out by comparing the results obtained with the Hepanostika anti-HBsAg, commercial diagnosis kit are presented. For this purpose, sera from the clinical assays of the Cuban recombinant vaccine against hepatitis B were used. With the first sera group (n = 30) it was obtained, 93.1% of sensitivity, 98.5% of specificity and a concordance of 94.3%. The correlation coefficient showed a similar trend of the results (p 0.05). With the second group (n = 100), whose assays were carried out at the "Pedro Kouri" Institute of Tropical Medicine (PKI) and at the Immunoassay Center (IAC) simultaneously, it was observed a sensitivity of 96.25% in both centers, a specificity of 75% at the PKI and of 90% at the IAC, and a coincidence of 92% and 95%, respectively. The correlation coefficient presented similar values and there were no significant differences between the TPG obtained by the two methods (p > 0.05). The results attained show in general the validity of the new assay and the feasibility to put it into practice either for following up the infection, or for carrying out clinical assays of vaccine evaluations.

  8. Multicenter Evaluation of the Elecsys Hepatitis B Surface Antigen Quantitative Assay ▿

    Science.gov (United States)

    Zacher, B. J.; Moriconi, F.; Bowden, S.; Hammond, R.; Louisirirotchanakul, S.; Phisalprapa, P.; Tanwandee, T.; Wursthorn, K.; Brunetto, M. R.; Wedemeyer, H.; Bonino, F.

    2011-01-01

    The Elecsys hepatitis B surface antigen (HBsAg) II quantitative assay is a new quantitative electrochemiluminescence immunoassay which uses onboard dilution and a simple algorithm to determine HBsAg levels expressed in international units (IU)/ml (standardized against the World Health Organization [WHO] Second International Standard). This study evaluated its performance using routine serum samples from a wide range of HBsAg carriers and patients with chronic hepatitis B (CHB). HBsAg levels were measured in serum samples collected independently by five centers in Europe, Australia, and Asia. Serial dilution analyses were performed to assess the recommended dilution algorithm and determine the assay range free of hook effect. Assay precision was also established. Following assessment of serial dilutions (1:100 to 1:1,000,000) of the 611 samples analyzed, 70.0% and 85.6% of samples tested with analyzers incorporating 1:100 (Elecsys 2010 and cobas e 411) and 1:400 (Modular Analytics E170) onboard dilution, respectively, fell within the linear range of the assay, providing a final result on the first test. No high-dose hook effect was seen up to the maximum HBsAg serum level tested (870,000 IU/ml) using the dilution algorithm. HBsAg levels were reliably determined across all hepatitis B virus (HBV) genotypes, phases of HBV infection, and stages of disease tested. Precision was high across all analyzers (% coefficient of variation [CV], 1.4 to 9.6; HBsAg concentrations, 0.1 to 37,300 IU/ml). The Elecsys HBsAg II quantitative assay accurately and reliably quantifies HBsAg in routine clinical samples. Onboard dilution minimizes retesting and reduces the potential for error. PMID:21880853

  9. Multicenter evaluation of the Elecsys hepatitis B surface antigen quantitative assay.

    Science.gov (United States)

    Zacher, B J; Moriconi, F; Bowden, S; Hammond, R; Louisirirotchanakul, S; Phisalprapa, P; Tanwandee, T; Wursthorn, K; Brunetto, M R; Wedemeyer, H; Bonino, F

    2011-11-01

    The Elecsys hepatitis B surface antigen (HBsAg) II quantitative assay is a new quantitative electrochemiluminescence immunoassay which uses onboard dilution and a simple algorithm to determine HBsAg levels expressed in international units (IU)/ml (standardized against the World Health Organization [WHO] Second International Standard). This study evaluated its performance using routine serum samples from a wide range of HBsAg carriers and patients with chronic hepatitis B (CHB). HBsAg levels were measured in serum samples collected independently by five centers in Europe, Australia, and Asia. Serial dilution analyses were performed to assess the recommended dilution algorithm and determine the assay range free of hook effect. Assay precision was also established. Following assessment of serial dilutions (1:100 to 1:1,000,000) of the 611 samples analyzed, 70.0% and 85.6% of samples tested with analyzers incorporating 1:100 (Elecsys 2010 and cobas e 411) and 1:400 (Modular Analytics E170) onboard dilution, respectively, fell within the linear range of the assay, providing a final result on the first test. No high-dose hook effect was seen up to the maximum HBsAg serum level tested (870,000 IU/ml) using the dilution algorithm. HBsAg levels were reliably determined across all hepatitis B virus (HBV) genotypes, phases of HBV infection, and stages of disease tested. Precision was high across all analyzers (% coefficient of variation [CV], 1.4 to 9.6; HBsAg concentrations, 0.1 to 37,300 IU/ml). The Elecsys HBsAg II quantitative assay accurately and reliably quantifies HBsAg in routine clinical samples. Onboard dilution minimizes retesting and reduces the potential for error.

  10. Maternal ABO and rhesus blood group phenotypes and hepatitis B surface antigen carriage.

    Science.gov (United States)

    Lao, T T; Sahota, D S; Chung, M-K; Cheung, T K W; Cheng, Y K Y; Leung, T Y

    2014-11-01

    In view of a persistently high prevalence of hepatitis B surface antigen (HBsAg) carriage in our obstetric population, we examined the association between HBsAg carriage with maternal ABO and rhesus (Rh) blood group phenotypes determined at routine antenatal screening. In a retrospective study, the antenatal screening results of women booked for confinement between 1998 and 2011 in our hospital were examined for the relationship between HBsAg carriage with the ABO and rhesus blood groups, taking into account also the effects of advanced maternal age (≥ 35 years) and parity status (nulliparous or multiparous), and year of birth before or following the availability of the hepatitis B vaccine (1984). HBsAg carriage was found in 9.9%, 9.6%, 9.1% and 10.2% (P = 0.037) for group-A (n = 20 581 or 26.1%), -B (n = 20 744 or 26.4%), -AB (n = 5138 or 6.5%) and -O (n = 32 242 or 41.0%) among the 78705 women in the study cohort. Rhesus negativity was found in 0.6%, and HBsAg carriage was 12.3% and 9.8%, respectively, for the Rh-negative and Rh-positive women (P = 0.071). Carriage rate between group-O and non-O was influenced by nulliparity, age ≥ 35 years and Rh-positive status. Regression analysis indicated that group-B (P = 0.044, aOR = 1.062, 95% CI 1.002-1.127) and group-AB (P = 0.016, aOR = 1.134, 95% CI 1.024-1.256) were associated with HBsAg carriage. Blood groups-B and -AB are associated with increased hepatitis B virus (HBV) infection in our population, and further studies are warranted to elucidate the implications of this on the sequelae of HBV infection.

  11. Vaccine adjuvant ginsenoside Rg1 enhances immune responses against hepatitis B surface antigen in mice.

    Science.gov (United States)

    Yuan, Ding; Yuan, Qin; Cui, Qianqian; Liu, Chaoqi; Zhou, Zhiyong; Zhao, Haixia; Dun, Yaoyan; Wang, Ting; Zhang, Changcheng

    2016-06-01

    The adjuvant effect of ginsenoside Rg1 on immune responses against hepatitis B surface antigen (HBsAg) in mice was investigated. Female BALB/c mice were subcutaneously injected with saline or HBsAg antigen with or without Rg1 on days 7 and 21. Samples were collected 2 weeks after the boosting for the detection of anti-HBsAg immunoglobulin G (IgG) isotypes in sera and gamma interferon (IFN-γ) and interleukin-4 (IL-4) produced in splenocytes. The innate and adaptive immune responses were measured in mice immunized as described above. The results showed that ginsenoside Rg1 had adjuvant properties in stimulating IgG, splenocyte proliferation, and mRNA expression of cytokines IFN-γ and IL-4, as well as the expression of cell surface marker TLR4 in the HBsAg-immunized mice. These results indicate that Rg1 enhances both Th1 (IgG2b and IFN-γ) and Th2 (IgG1 and IL-4) responses. In addition, the TLR4 signaling pathway is involved in the adjuvant activities of ginsenoside Rg1.

  12. Generation of Hepatitis B virus PreS2-S antigen in Hansenula polymorpha

    Institute of Scientific and Technical Information of China (English)

    Xiaowei; Xu; Sulin; Ren; Xiaoxiao; Chen; Jun; Ge; Zhenxing; Xu; Hongying; Huang; Honglin; Sun; Yue; Gu; Tong; Zhou; Jianqiang; Li; Hanmei; Xu

    2014-01-01

    Despite the long availability of a traditional prophylactic vaccine containing the HBV surface antigen(HBsA g) and aluminum adjuvant, nearly 10% of the population remains unable to generate an effective immune response. Previous studies have indicated that hepatitis B virus(HBV) PreS 2-S is abundant in T/B cell epitopes, which induces a stronger immune response than HBsA g, particularly in terms of cytotoxic T lymphocyte(CTL) reaction. In the current study, the HBV PreS 2-S gene encoding an extra26 amino acids(PreS 2 C-terminus) located at the N-terminus of HBsA g was cloned into the pV CH1300 expression vector. Pre S2-S expressed in the methylotrophic yeast, Hansenula polymorpha, was produced at a yield of up to 250 mg/L. Subsequent purification steps involved hydrophobic adsorption to colloidal silica, ion-exchange chromatography and density ultracentrifugation. The final product was obtained with a total yield of ~15% and purity of ~99%. In keeping with previous studies, ~22 nm viruslike particles were detected using electron microscopy. The generated PreS 2-S antigen will be further studied for efficacy and safty in animals.

  13. Hepatitis virales B y Delta: epidemiología y prevención en el Perú

    OpenAIRE

    César Cabezas Sánchez

    2002-01-01

    Se describe la epidemiología de las hepatitis virales B (HVB) y Delta (HVD) en el Perú, destacando su disímil prevalencia según áreas geográficas que, sin embargo, tienden a ser cada vez más similares debido a la intensa migración interna. Igualmente, se mencionan mecanismos de transmisión diferentes a los clásicamente reportados en la literatura, así como las consecuencias de la infección crónica, traducidas en cirrosis hepática y hepatocarcinoma. Finalmente, se describen las intervenciones ...

  14. A one step real time PCR method for the quantification of hepatitis delta virus RNA using an external armored RNA standard and intrinsic internal control.

    Science.gov (United States)

    Karataylı, Ersin; Altunoğlu, Yasemin Çelik; Karataylı, Senem Ceren; Alagöz, S Gökçe K; Cınar, Kubilay; Yalçın, Kendal; Idilman, Ramazan; Yurdaydın, Cihan; Bozdayı, A Mithat

    2014-05-01

    Hepatitis delta virus (HDV) RNA viral load measurement is critical in diagnosis and monitoring the response to antiviral treatment. Our aim is to design a real time PCR method for accurate quantitation of HDV RNA in clinical specimens using an armored RNA as external standard, and an intrinsic internal control. A plasmid bearing delta antigen region of genotype I HDV genome was used to develop an armored RNA. Serial dilutions of the armored HDV RNA standard with 10(12)copy/mL were used as standards for quantitation. A primer-probe set derived from HDAg region was used in one step EZ RT PCR kit chemistry which uses rTth enzyme allowing reverse transcription and polymerization in the same tube. The kit also uses the advantage of uracil-N-glycosylase (UNG) enzyme treatment to prevent PCR contamination. The established assay has a dynamic range of 10(2)-10(11)copy/mL with a PCR efficiency of 96.9%. Detection limit was 858±32copy/mL with 95% confidence interval. Intra- and inter-assay variabilities were low for high, medium and low levels of viremia. Incorporation of freely circulating GAPDH in serum into the assay as an intrinsic internal control prevented false negative results and failures in PCR amplifications due to inhibitors, inefficient extraction procedures or enzymatic reactions. In conclusion, this study defines a novel assay for sensitive and reliable quantification of HDV RNA using an armored HDV RNA as a standard and GAPDH in plasma or serum as an intrinsic internal control in a single tube. Copyright © 2014 Elsevier B.V. All rights reserved.

  15. Hepatitis B virus (HBV) and dual HBV-hepatitis delta virus (HDV) infection in apparently healthy persons.

    Science.gov (United States)

    Brehar-Cioflec, D; Claici, C; Roşiu, N; Negrea, D A; Moldovan, R; Coşniţă, M

    1998-01-01

    The main aims of the present study were to evaluate the transfusional risk concerning HBV and HBV-HDV infections and the prevalence of viral serum markers in apparently healthy persons. Our study included 226 apparently healthy persons in whom we performed tests for HBV (HBsAg, HBsAb, HBcAb) and HDV (Delta Ab) serum markers, using the enzyme immunoassay. In 45 (19.9%) subjects we detected serum HBsAg. In the 181 HBsAg-negative apparently healthy persons, our tests detected HBsAb (31 subjects) and HBcAb (49 subjects). Thus, 125 (55.3%) of the 226 apparently healthy persons had serologic evidence of past HBV infections. Delta Ab were detected in 3 (1.3%) of our subjects. We must state that one of the three Delta Ab-positive apparently healthy persons tested negative for both HBsAg and HBcAb.

  16. Impact of hepatitis B and delta virus co-infection on liver disease in Mauritania: a cross sectional study.

    Science.gov (United States)

    Lunel-Fabiani, Françoise; Mansour, Wael; Amar, Abdellahi Ould; Aye, Mohamed; Le Gal, Frédéric; Malick, F-Zahra Fall; Baïdy, Lô; Brichler, Ségolène; Veillon, Pascal; Ducancelle, Alexandra; Gordien, Emmanuel; Rosenheim, Michel

    2013-11-01

    Mauritania is a highly endemic region for hepatitis B (HBV) and delta (HDV) viruses. No data are available on HDV's impact on the severity of liver disease in consecutive HBV-infected patients in Africa. This study evaluated the degree of liver fibrosis in a cohort of chronic HBV carriers. Three-hundred consecutive HBV-infected Mauritanian patients were checked for HDV infection via the detection of anti-HDV antibodies (Ab) and viral RNA. HBV- vs. HBV/HDV-infected patients were compared by physical examination, biological analyses, and the APRI (aspartate aminotransferase to platelet ratio index) and FibroMeter tests for determination of liver fibrosis. More than 30% of the patients had anti-HDVAb. Among these, 62.2% were HDV-RNA positive. Co-infected patients were older (>8-years) than HBV-mono-infected patients. They had more liver tests abnormalities and clinical or ultrasound signs of liver fibrosis. APRI and FibroMeter scores were also significantly increased in these patients. In multivariate analysis, beyond HDVAb, male gender and HBV-VL >3.7 log IU/mL were the only markers linked to significant liver fibrosis. In Mauritania, HDV co-infection worsens liver disease, both clinically and biologically, as confirmed by the APRI and FibroMeter tests. These tests may be useful for the management of delta hepatitis, which is a major health problem in Mauritania. Copyright © 2013 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

  17. The anti-HBsAg (human type B hepatitis, surface antigen) and anti-HBeAg (human type B hepatitis, e antigen) C18 dibenzocyclooctadiene lignans from Kadsura matsudai and Schizandra arisanensis.

    Science.gov (United States)

    Wu, Ming-Der; Huang, Ray-Ling; Kuo, Li-Ming Yang; Hung, Chia-Cheng; Ong, Chi-Wi; Kuo, Yao-Haur

    2003-11-01

    The C(18) dibenzocyclooctadiene lignans including three novel schizanrin F (1), G (2), H (3), along with the known kadsurarin (4), were isolated from Kadsura matsudai. A new C(19) homolignan named schiarisanrin E (5), together with the known C(18) lignans, gomisin B (6), G (7) and (+)-gomisin K(3) (8) were obtained from Schizandra arisanensis. Gomisin B, G and (+)-gomisin K(3) showed moderate to strong activity for antihepatitis in anti-HBsAg (human type B hepatitis, surface antigen) and/or anti-HBeAg (human type B hepatitis, e antigen) tests. The structural elucidations of new compounds 1-3 and 5 were based on two-dimensional (2D) NMR techniques including COSY, HMQC, HMBC, NOESY and CD spectra. Preliminary structure-activity relationship studies for these isolated lignans are also discussed.

  18. Characterization of antigenic domains and epitopes in the ORF3 protein of a Chinese isolate of avian hepatitis E virus.

    Science.gov (United States)

    Zhao, Qin; Sun, Ya-ni; Hu, Shou-bin; Wang, Xin-jie; Xiao, Yi-hong; Hsu, Walter H; Xiao, Shu-qi; Wang, Cheng-bao; Mu, Yang; Hiscox, Julian A; Zhou, En-Min

    2013-12-27

    Avian hepatitis E virus (HEV) is an emerging virus associated with the big liver and spleen disease or hepatitis-splenomegaly syndrome in chickens and subclinical infections by the virus are also common. The complete genome of avian HEV contains three open-reading frames (ORFs) in which ORF2 protein is part of virus particles and thus contains primary epitopes. Antigenic epitopes of avian HEV ORF2 protein have been described but those associated with the ORF3 have not. To analyze the antigenic domains and epitopes in the ORF3 protein of a Chinese isolate of avian HEV (CaHEV), we generated a series of antigens comprised of the complete ORF3 and also five truncated overlapping ORF3 peptides. The antibodies used in this study were mouse antisera and monoclonal antibodies against ORF3, positive chicken sera from Specific Pathogen Free chickens experimentally infected with CaHEV and clinical chicken sera. Using these antigens and antibodies, we identified three antigenic domains at amino acids (aa) 1-28, 55-74 and 75-88 in which aa 75-88 was a dominant domain. The dominant domain contained at least two major epitopes since field chickens infected with avian HEV produced antibodies against the domain and epitopes. These results provide useful information for future development of immunoassays for the diagnosis of avian HEV infection.

  19. Liver Cancer and Hepatitis B

    Science.gov (United States)

    ... Our Accomplishments Annual Reports Our Videos What Is Hepatitis B? What Is Hepatitis B? The ABCs of Viral Hepatitis Liver Cancer and Hepatitis B Hepatitis Delta Coinfection Hepatitis C Coinfection HIV/AIDS ...

  20. Detection of hepatitis B surface antigen subtype adr in an epidemic of papular acrodermatitis of childhood (Gianotti's disease.

    Directory of Open Access Journals (Sweden)

    Kanzaki,Susumu

    1981-12-01

    Full Text Available Papular acrodermatitis of childhood (PAC has recently been reported to be associated with hepatitis B surface antigen (HBsAg subtype ayw. Between September, 1978, and June, 1979, we saw 14 patients with PAC in a small epidemic occurring in Iwakuni City, Japan. HBsAg was detected in sera from all patients. Subtyping of HBsAg in 11 patients showed that 8 had a determinant adr and 3 had no detectable determinant because of low antigen titers. The result suggests that factors other than the specific HBsAg subtype contribute to the development of PAC.

  1. Detection of hepatitis B surface antigen subtype adr in an epidemic of papular acrodermatitis of childhood (Gianotti's disease).

    Science.gov (United States)

    Kanzaki, S; Kanda, S; Terada, K; Nohno, S; Kumano, K; Narahara, K; Hayashi, H; Kimoto, H

    1981-12-01

    Papular acrodermatitis of childhood (PAC) has recently been reported to be associated with hepatitis B surface antigen (HBsAg) subtype ayw. Between September, 1978, and June, 1979, we saw 14 patients with PAC in a small epidemic occurring in Iwakuni City, Japan. HBsAg was detected in sera from all patients. Subtyping of HBsAg in 11 patients showed that 8 had a determinant adr and 3 had no detectable determinant because of low antigen titers. The result suggests that factors other than the specific HBsAg subtype contribute to the development of PAC.

  2. Small-angle neutron scattering study of recombinant yeast-derived human hepatitis B virus surface antigen vaccine particle

    Science.gov (United States)

    Sato, M.; Ito, Y.; Kameyama, K.; Imai, M.; Ishikawa, N.; Takagi, T.

    1995-02-01

    The overall and internal structure of recombinant yeast-derived human hepatitis B virus surface antigen vaccine particles was investigated by small-angle neutron scattering using the contrast variation method. The vaccine is a nearly spherical particle, and its contrast-matching point was determined to be at about 24% D 2O content, indicating that a large part of the vaccine particle is occupied by lipids and carbohydrates from the yeast. The Stuhrmann plot suggests that the surface antigens exist predominantly in the peripheral region of the particle, which is favorable to the induction of anti-virus antibodies.

  3. Epidemiology of acute and chronic hepatitis B and delta over the last 5 decades in Italy

    National Research Council Canada - National Science Library

    Evangelista Sagnelli Caterina Sagnelli Mariantonietta Pisaturo Margherita Macera Nicola Coppola

    2014-01-01

    The spread of hepatitis B virus(HBV)infection has gradually decreased in Italy in the last 5 decades as shown by the steady reduction in the incidence rates of acute hepatitis B,from 10/100000 inhabitants in1984...

  4. PRISM hepatitis B surface antigen detection of hepatits B virus minipool nucleic acid testing yield samples.

    Science.gov (United States)

    Linauts, Sandy; Saldanha, John; Strong, D Michael

    2008-07-01

    Hepatitis B virus (HBV) residual risk has been estimated at 1:63,000-1:205,000 and introduction of more sensitive serological tests and nucleic acid testing (NAT) would reduce that risk. Sensitivity of the recently licensed Abbott PRISM hepatitis B surface antigen (HBsAg) CLIA and minipool (MP) HBV NAT has been described as comparable and thus the need for HBV NAT has not been compelling. In this study, eight samples identified as yield samples with MP HBV NAT were tested using the PRISM test. Seven samples were identified using the Roche COBAS AmpliScreen HBV test and one additional sample was obtained from the clinical trial for the Roche cobas TaqScreen MPX test. Each of these samples was reactive by MP HBV NAT and nonreactive for HBsAg using one of three licensed enzyme immunoassay (EIA) tests. After licensure of the PRISM HBsAg, aliquots were tested with this assay, and DNA quantitation and genotyping were repeated where sample volume permitted. Three samples (2000, 2300, and 61,000 copies/mL) produced reactive results with PRISM. Four samples with viral loads less than 300 copies per mL produced nonreactive results. One sample, originally quantitated at 37,000 copies per mL (but 3850 copies/mL in repeat testing) was also nonreactive by PRISM. Genotyping of this sample indicated a type C genotype with no mutations. Adding serological sensitivity of PRISM CLIA reduced the NAT yield from the original 1: 385,555 to 1:610,488. However, MP HBV NAT still provides additional sensitivity over CLIA, even for a donation with a viral load of almost 4000 copies per mL.

  5. [Fundamental and clinical evaluation of hepatitis B virus core-related antigen assay by LUMIPULSE f].

    Science.gov (United States)

    Tanaka, Yasuhito; Takagi, Kazumi; Hiramatsu, Kumiko; Naganuma, Hatsue; Iida, Takayasu; Takasaka, Yoshimitsu; Mizokami, Masashi

    2006-07-01

    A sensitive chemiluminescence enzyme immunoassay (CLEIA) has been developed for hepatitis B virus (HBV) core-related antigens (HBcrAg) detection. The HBcrAg is designated as the precore/core gene products including HBeAg. The aim of this study is to evaluate reproducibility of HBcrAg and correlation with HBV-DNA in serum using the automatic LUMIPULSE f to estimate an assay suitable for general laboratory use. In this study, we demonstrated that HBcrAg assay had highly intra-assay reproducible [coefficients of variation(CVs); 2.8-5.2%] and inter-assay reproducible [CVs; 3.9-9.1%]. When the cutoff value was tentatively set at 1 kU/ml, all healthy controls (HBsAg/HBV-DNA negative; n=100) and anti-HCV antibody-positive (n=50) sera were identified as negative. The assay showed a detection limit of 0.5 kU/ml using four serially diluted HBV high-titer sera, indicating higher sensitivity than HBV-DNA (transcription-mediated amplification). The HBcrAg concentration correlated positively with serum HBV-DNA (n=125, r = 0.860, p HBcrAg levels were higher in HBeAg-positive group than in HBeAg-negative group. In the natural course of HBV infection, the HBcrAg concentration usually changed in accordance with HBV-DNA levels, however during lamivudine therapy the change of HBcrAg was more gradual than that of HBV-DNA. In conclusion, HBcrAg concentration provides a reflection of HBV virus load equivalent to HBV-DNA level, and the assay therefore offers a simple method for monitoring hepatitis B patients.

  6. Prevalence of hepatitis B surface antigen among refugees entering the United States between 2006 and 2008.

    Science.gov (United States)

    Rein, David B; Lesesne, Sarah B; O'Fallon, Ann; Weinbaum, Cindy M

    2010-02-01

    The Centers for Disease Control and Prevention recommends hepatitis B surface antigen (HBsAg) testing to identify chronic hepatitis B virus infection for foreign-born persons from countries or regions with HBsAg prevalence of >or=2%. However, limited data exist to indicate which countries meet this definition. To address this data gap, we estimated the HBsAg prevalence among refugees entering the United States between 2006 and 2008. We contacted state refugee health coordinators and asked them to report the number of refugees, country of origin, and HBsAg prevalence among refugees screened in their jurisdiction during the most recently available 12-month period prior to August 2008. We pooled data across jurisdictions and calculated the prevalence for any country with more than 30 refugees entering the United States, and where this level of data was not available by country, continents were considered. Of the 47 jurisdictions contacted, we received basic information from 31, with nine jurisdictions reporting HBsAg prevalence by country of origin applicable to 31,980 refugees (approximately 42% of refugees entering the United States during the observation period). We estimated an HBsAg prevalence of 2.8% (95% confidence interval 2.6%-3.0%) for refugees overall. Of the 37 countries with 30 or more refugees entering the United States, 25 had a prevalence of >or=2%. Prevalence was highest among refugees from Africa and Southeast Asia, and lowest among refugees from the Middle East and South/Central America. In the eight countries for which we had comparison data, six had lower HBsAg prevalence than in 1991.

  7. Hepatitis B surface antigen variants in voluntary blood donors in Nanjing, China

    Science.gov (United States)

    2012-01-01

    Background Hepatitis B virus (HBV) is still one of the serious infectious risks for the blood transfusion safety in China. One plausible reason is the emergence of the variants in the major antigenic alpha determinant within the major hydrophilic region (MHR) of hepatitis B surface antigen (HBsAg), which have been assumed to evade the immune surveillance and pose a challenge to the disease diagnosis. It is well documented that some commercial ELISA kits could detect the wild-type but not the mutant viruses. The high prevalence of HBV in China also impaired the application of nucleic acid testing (NAT) in the improvement of blood security. Molecular epidemiological study of HBsAg variations in China is still limited. This study was designed to identify the prevalence of mutations in the HBsAg in voluntary blood donors in Nanjing, China. Methods A total of 20,326 blood units were enrolled in this study, 39 donors were positive for HBV S gene in the nested-PCR. Mutations in the major hydrophilic region (MHR; aa 99-169) were identified by direct sequencing of S region. Results Among of 20,326 blood units in the Red Cross Transfusion Center of Nanjing from October 2008 to April 2009, 296 samples (1.46%, 296/20,326) were HBsAg positive in the 2 successive rounds of the ELISA test. In these HBsAg positive units, HBV S gene could be successfully amplified from 39 donors (13.18%, 39/296) in the nested-PCR. Sequence analysis revealed that 32 strains (82.1%, 32/39) belong to genotype B, 7 strains (17.9%, 7/39) to genotype C. Besides well known G145R, widely dispersed variations in the MHR of S region, were observed in 20 samples of all the strains sequenced. Conclusions HBV/B and HBV/C are dominant in Nanjing, China. The mutations in the MHR of HBsAg associated with disease diagnosis are common. PMID:22500577

  8. Hepatitis B surface antigen variants in voluntary blood donors in Nanjing, China

    Directory of Open Access Journals (Sweden)

    Yong-lin Yang

    2012-04-01

    Full Text Available Abstract Background Hepatitis B virus (HBV is still one of the serious infectious risks for the blood transfusion safety in China. One plausible reason is the emergence of the variants in the major antigenic alpha determinant within the major hydrophilic region (MHR of hepatitis B surface antigen (HBsAg, which have been assumed to evade the immune surveillance and pose a challenge to the disease diagnosis. It is well documented that some commercial ELISA kits could detect the wild-type but not the mutant viruses. The high prevalence of HBV in China also impaired the application of nucleic acid testing (NAT in the improvement of blood security. Molecular epidemiological study of HBsAg variations in China is still limited. This study was designed to identify the prevalence of mutations in the HBsAg in voluntary blood donors in Nanjing, China. Methods A total of 20,326 blood units were enrolled in this study, 39 donors were positive for HBV S gene in the nested-PCR. Mutations in the major hydrophilic region (MHR; aa 99-169 were identified by direct sequencing of S region. Results Among of 20,326 blood units in the Red Cross Transfusion Center of Nanjing from October 2008 to April 2009, 296 samples (1.46%, 296/20,326 were HBsAg positive in the 2 successive rounds of the ELISA test. In these HBsAg positive units, HBV S gene could be successfully amplified from 39 donors (13.18%, 39/296 in the nested-PCR. Sequence analysis revealed that 32 strains (82.1%, 32/39 belong to genotype B, 7 strains (17.9%, 7/39 to genotype C. Besides well known G145R, widely dispersed variations in the MHR of S region, were observed in 20 samples of all the strains sequenced. Conclusions HBV/B and HBV/C are dominant in Nanjing, China. The mutations in the MHR of HBsAg associated with disease diagnosis are common.

  9. Preparation and testing of a Haemophilus influenzae Type b/Hepatitis B surface antigen conjugate vaccine.

    Science.gov (United States)

    An, So Jung; Woo, Joo Sung; Chae, Myung Hwa; Kothari, Sudeep; Carbis, Rodney

    2015-03-24

    The majority of conjugate vaccines focus on inducing an antibody response to the polysaccharide antigen and the carrier protein is present primarily to induce a T-cell dependent response. In this study conjugates consisting of poly(ribosylribitolphosphate) (PRP) purified from Haemophilus influenzae Type b bound to Hepatitis B virus surface antigen (HBsAg) virus like particles were prepared with the aim of inducing an antibody response to not only the PRP but also the HBsAg. A conjugate consisting of PRP bound to HBsAg via an adipic acid dihydrazide (ADH) spacer induced strong IgG antibodies to both the PRP and HBsAg. When conjugation was performed without the ADH spacer the induction of an anti-PRP response was equivalent to that seen by conjugate with the ADH spacer, however, a negligible anti-HBsAg response was induced. For comparison, PRP was conjugated to diphtheria toxoid (DT) and Vi polysaccharide purified from Salmonella Typhi conjugated to HBsAg both using an ADH spacer. The PRPAH-DT conjugate induced strong anti-PRP and anti-DT responses, the Vi-AHHBsAg conjugate induced a good anti-HBsAg response but not as strong as that induced by the PRPAH-HBsAg conjugate. This study demonstrated that in mice it was possible to induce robust antibody responses to both polysaccharide and carrier protein provided the conjugate has certain physico-chemical properties. A PRPAH-HBsAg conjugate with the capacity to induce anti-PRP and anti-HBsAg responses could be incorporated into a multivalent pediatric vaccine and simplify formulation of such a vaccine.

  10. Characterization of Fetal Antigen 1/Delta-Like 1 Homologue Expressing Cells in the Rat Nigrostriatal System

    DEFF Research Database (Denmark)

    Liechti, Rémy; Ducray, Angélique D; Jensen, Pia;

    2015-01-01

    Fetal antigen 1/delta-like 1 homologue (FA1/dlk1) belongs to the epidermal growth factor superfamily and is considered to be a non-canonical ligand for the Notch receptor. Interactions between Notch and its ligands are crucial for the development of various tissues. Moreover, FA1/dlk1 has been su...... adult rats. FA1/dlk1-ir cells were predominantly distributed in the substantia nigra (SN) pars compacta (SNc) and in the ventral tegmental area. Interestingly, the expression of FA1/dlk1 significantly increased in tyrosine hydroxylase (TH)-ir cells during early postnatal development. Co......-localization and tracing studies demonstrated that FA1/dlk1-ir cells in the SNc were nigrostriatal dopaminergic neurons, and unilateral 6-OHDA lesions resulted in loss of both FA1/dlk1-ir and TH-ir cells in the SNc. Surprisingly, increased numbers of FA1/dlk1-ir cells (by 70%) were detected in dopamine-depleted striata...... as compared to unlesioned controls. The higher number of FA1/dlk1-ir cells was likely not due to neurogenesis as colocalization studies for proliferation markers were negative. This suggests that FA1/dlk1 was up-regulated in intrinsic cells in response to the 6-OHDA-mediated loss of FA1/dlk1-expressing SNc...

  11. Natural killer cells contribute to hepatic injury and help in viral persistence during progression of hepatitis B e-antigen-negative chronic hepatitis B virus infection.

    Science.gov (United States)

    Ghosh, S; Nandi, M; Pal, S; Mukhopadhyay, D; Chakraborty, B C; Khatun, M; Bhowmick, D; Mondal, R K; Das, S; Das, K; Ghosh, R; Banerjee, S; Santra, A; Chatterjee, M; Chowdhury, A; Datta, S

    2016-08-01

    Hepatitis B e-antigen negative (e(-)) chronic HBV infection (CHI) encompasses a heterogeneous clinical spectrum ranging from inactive carrier (IC) state to e(-) chronic hepatitis B (CHB), cirrhosis and hepatic decompensation. In the backdrop of dysfunctional virus-specific T cells, natural killer (NK) cells are emerging as innate effectors in CHI. We characterized CD3(-) CD56(+) NK cells in clinically well-defined, treatment-naive e(-) patients in IC, e(-)CHB or decompensated liver cirrhosis (LC) phase to appraise their role in disease progression. The NK cell frequencies increased progressively with disease severity (IC 8.2%, e(-)CHB 13.2% and LC 14.4%). Higher proportion of NK cells from LC/e(-)CHB expressed CD69, NKp46, NKp44, TRAIL and perforin, the last two being prominent features of CD56(bright) and CD56(dim) NK subsets, respectively. The frequencies of CD3(-) CD56(+) NK cells together with TRAIL(+) CD56(bright) and Perforin(+) CD56(dim) NK cells correlated positively with serum alanine transaminase levels in e(-)CHB/LC. K562 cell-stimulated NK cells from e(-)CHB/LC exhibited significantly greater degranulation but diminished interferon-γ production than IC. Further, Perforin(+) NK cell frequency inversely correlated with autologous CD4(+) T-cell count in e(-) patients and ligands of NK receptors were over-expressed in CD4(+) T cells from e(-)CHB/LC relative to IC. Co-culture of sorted CD56(dim) NK cells and CD4(+) T cells from e(-)CHB showed enhanced CD4(+) T-cell apoptosis, which was reduced by perforin inhibitor, concanamycin A, suggesting a possible perforin-dependent NK cell-mediated CD4(+) T-cell depletion. Moreover, greater incidence of perforin-expressing NK cells and decline in CD4(+) T cells were noticed intrahepatically in e(-)CHB than IC. Collectively, NK cells contribute to the progression of e(-)CHI by enhanced TRAIL- and perforin-dependent cytolytic activity and by restraining anti-viral immunity through reduced interferon-γ secretion and

  12. Hepatitis B and Delta Virus: Advances on Studies about Interactions between the Two Viruses and the Infected Hepatocyte

    Science.gov (United States)

    Giersch, Katja; Dandri, Maura

    2015-01-01

    The mechanisms determining persistence of hepatitis B virus (HBV) infection and long-term pathogenesis of HBV-associated liver disease appear to be multifactorial. Although viral replication can be efficiently suppressed by the antiviral treatments currently available, viral clearance is generally not achieved since HBV has developed unique replication strategies, enabling persistence of its genome within the infected hepatocytes. Moreover, no direct antiviral therapy exists for the more than 15 million people worldwide that are also coinfected with the hepatitis delta virus (HDV), a defective virus that needs the HBV envelope proteins for propagation. The limited availability of robust HBV and HDV infection systems has hindered the understanding of the complex network of virus-virus and virus-host interactions that are established in the course of infection and slowed down progress in drug development. Since chronic HBV/HDV coinfection leads to the most severe form of chronic viral hepatitis, elucidation of the molecular mechanisms regulating virus-host interplay and pathogenesis are urgently needed. This article summarizes the current knowledge regarding the interactions among HBV, HDV, and the infected target cell and discusses the dependence of HDV on HBV activity and possible future therapeutic approaches. PMID:26623269

  13. Preclinical evaluation of multi antigenic HCV DNA vaccine for the prevention of Hepatitis C virus infection.

    Science.gov (United States)

    Lee, Hyojin; Jeong, Moonsup; Oh, Jooyeon; Cho, Youngran; Shen, Xuefei; Stone, John; Yan, Jian; Rothkopf, Zachary; Khan, Amir S; Cho, Byung Mun; Park, Young K; Weiner, David B; Son, Woo-Chan; Maslow, Joel N

    2017-03-07

    Direct-acting antiviral treatment for hepatitis C virus (HCV) infection is costly and does not protect from re-infection. For human and chimpanzees, recovery from acute HCV infection correlates with host CD4+ and CD8+ T cell responses. DNA plasmids targeting the HCV non-structural antigens NS3, NS4, and NS5, were previously reported to induce robust and sustained T cell responses in mice and primates. These plasmids were combined with a plasmid encoding cytokine IL-28B, together named as VGX-6150. The dose-dependent T cell response and safety of VGX-6150 administered intramuscularly and followed by electroporation was assessed in mice. Immune responses plateaued at 20 μg/dose with IL-28B demonstrating significant immunoadjuvant activity. Mice administered VGX-6150 at 40, 400, and 800 μg given either as a single injection or as 14 injections given bi-weekly over 26 weeks showed no vaccine related changes in any clinical parameter compared to placebo recipients. There was no evidence of VGX-6150 accumulation at the injection site or in any organ 1 month following the 14(th) vaccination. Based on these studies, the approximate lethal dose (ALD) exceeds 800 μg/dose and the NOAEL was 800 μg/dose in mouse. In conclusion, VGX-6150 appears safe and a promising preventive vaccine candidate for HCV infection.

  14. Persistence of hepatitis C virus in a white population: associations with human leukocyte antigen class 1.

    LENUS (Irish Health Repository)

    Fanning, Liam J

    2012-02-03

    The aim of this study was to define novel associations between human leukocyte antigen (HLA) class 1 alleles and persistence or clearance of the hepatitis C virus (HCV) in a white population. All individuals in the study were seropositive for anti-HCV antibodies. Viral status was determined by the Roche HCV Amplicor test. HLA-A, -B, -C allelic group profile was molecularly defined by reverse line probe hybridization. The strongest individual allelic group associations with persistent HCV infection were HLA A*11 (p = 0.044) and Cw*04 (p = 0.006). However, only the HLA C*04 association survived correction for multiple comparisons. Further analysis of alleles in linkage with HLA Cw*04 revealed that the haplotype HLA A*11, Cw*04 was present in 11 individuals, 10 of whom were viremic (p = 0.05). No gene dosage effect was observed. No association between HLA class 1 allelic groups and aviremia and virus load was evident in this white population. HLA B*44 is associated with low virus load in human immunodeficiency virus disease, but this association was not evident in this HCV-infected population. Novel HLA class 1 alleles associated with persistence of HCV have been identified.

  15. Measurement of Hepatitis B Surface Antigen Concentrations Using a Piezoelectric Microcantilever as a Mass Sensor

    Directory of Open Access Journals (Sweden)

    Sangkyu Lee

    2012-01-01

    Full Text Available Hepatitis B surface antigen (HBsAg concentrations were measured using a piezoelectric microcantilever sensor (PEMS developed by the authors. The developed PEMS is label-free and detects the sensing signal electrically. It was designed to measure the mass of biomolecules attached to it using an accurate mass-microbalancing technique; its probe area is confined to the end of the cantilever, and its equivalent spring constant is relatively high to minimize the effect of changes in the surface stress when the biomolecules are attached to it. The “dip- and-dry” technique was used to enable the probe area of the sensor to react with reagents in controlled environmental conditions. HBsAg was detected by an immunoreaction whereas the reaction time, antibody density, and its area on the probe were kept at a constant level. The mass of the detected HBsAg was measured in the range of 0.1–100 ng/mL.

  16. Structural and Antigenic Definition of Hepatitis C Virus E2 Glycoprotein Epitopes Targeted by Monoclonal Antibodies

    Directory of Open Access Journals (Sweden)

    Giuseppe Sautto

    2013-01-01

    Full Text Available Hepatitis C virus (HCV is the major cause of chronic liver disease as well as the major indication for liver transplantation worldwide. Current standard of care is not completely effective, not administrable in grafted patients, and burdened by several side effects. This incomplete effectiveness is mainly due to the high propensity of the virus to continually mutate under the selective pressure exerted by the host immune response as well as currently administered antiviral drugs. The E2 envelope surface glycoprotein of HCV (HCV/E2 is the main target of the host humoral immune response and for this reason one of the major variable viral proteins. However, broadly cross-neutralizing monoclonal antibodies (mAbs directed against HCV/E2 represent a promising tool for the study of virus-host interplay as well as for the development of effective prophylactic and therapeutic approaches. In the last few years many anti-HCV/E2 mAbs have been evaluated in preclinical and clinical trials as possible candidate antivirals, particularly for administration in pre- and post-transplant settings. In this review we summarize the antigenic and structural characteristics of HCV/E2 determined through the use of anti-HCV/E2 mAbs, which, given the absence of a crystal structure of this glycoprotein, represent currently the best tool available.

  17. Preclinical evaluation of multi antigenic HCV DNA vaccine for the prevention of Hepatitis C virus infection

    Science.gov (United States)

    Lee, Hyojin; Jeong, Moonsup; Oh, Jooyeon; Cho, Youngran; Shen, Xuefei; Stone, John; Yan, Jian; Rothkopf, Zachary; Khan, Amir S.; Cho, Byung Mun; Park, Young K.; Weiner, David B.; Son, Woo-Chan; Maslow, Joel N.

    2017-01-01

    Direct-acting antiviral treatment for hepatitis C virus (HCV) infection is costly and does not protect from re-infection. For human and chimpanzees, recovery from acute HCV infection correlates with host CD4+ and CD8+ T cell responses. DNA plasmids targeting the HCV non-structural antigens NS3, NS4, and NS5, were previously reported to induce robust and sustained T cell responses in mice and primates. These plasmids were combined with a plasmid encoding cytokine IL-28B, together named as VGX-6150. The dose-dependent T cell response and safety of VGX-6150 administered intramuscularly and followed by electroporation was assessed in mice. Immune responses plateaued at 20 μg/dose with IL-28B demonstrating significant immunoadjuvant activity. Mice administered VGX-6150 at 40, 400, and 800 μg given either as a single injection or as 14 injections given bi-weekly over 26 weeks showed no vaccine related changes in any clinical parameter compared to placebo recipients. There was no evidence of VGX-6150 accumulation at the injection site or in any organ 1 month following the 14th vaccination. Based on these studies, the approximate lethal dose (ALD) exceeds 800 μg/dose and the NOAEL was 800 μg/dose in mouse. In conclusion, VGX-6150 appears safe and a promising preventive vaccine candidate for HCV infection. PMID:28266565

  18. Upregulated Expression of a Unique Gene by Hepatitis B x Antigen Promotes Hepatocellular Growth and Tumorigenesis

    Directory of Open Access Journals (Sweden)

    Zhaorui Lian

    2003-05-01

    Full Text Available Hepatitis B x antigen (HBxAg is a trans-activating protein that may be involved in hepatocarcinogenesis, although few natural effectors of HBxAg that participate in this process have been identified. To identify additional effectors, whole cell RNA isolated from HBxAg-positive and HBxAg-negative HepG2 cells were compared by polymerase chain reaction select cDNA subtraction, and one clone, upregulated gene, clone 11 (URG11, was chosen for further characterization. Elevated levels of URG11 mRNA and protein were observed in HBxAg-positive compared to HBxAg-negative HepG2 cells. Costaining was observed in infected liver (P<.01. URG11 stimulated cell growth in culture (P<.01, anchorage-independent growth in soft agar (P<.001, and accelerated tumor formation (P<.01, and yielded larger tumors (P<.02 in SCID mice injected subcutaneously with HepG2 cells. These data suggest that URG11 is a natural effector of HBxAg that may promote the development of hepatocellular carcinoma.

  19. Total Hepatitis B Core Antigen Antibody, a Quantitative Non-Invasive Marker of Hepatitis B Virus Induced Liver Disease.

    Directory of Open Access Journals (Sweden)

    Quan Yuan

    Full Text Available Non invasive immunologic markers of virus-induced liver disease are unmet needs. We tested the clinical significance of quantitative total and IgM-anti-HBc in well characterized chronic-HBsAg-carriers. Sera (212 were obtained from 111 HBsAg-carriers followed-up for 52 months (28-216 during different phases of chronic-HBV-genotype-D-infection: 10 HBeAg-positive, 25 inactive-carriers (HBV-DNA≤2000IU/ml, ALT<30U/L, 66 HBeAg-negative-CHB-patients and 10 with HDV-super-infection. In 35 patients treated with Peg-IFN±nucleos(tide-analogues (NUCs sera were obtained at baseline, end-of-therapy and week-24-off-therapy and in 22 treated with NUCs (for 60 months, 42-134m at baseline and end-of-follow-up. HBsAg and IgM-anti-HBc were measured by Architect-assays (Abbott, USA; total-anti-HBc by double-antigen-sandwich-immune-assay (Wantai, China; HBV-DNA by COBAS-TaqMan (Roche, Germany. Total-anti-HBc were detectable in all sera with lower levels in HBsAg-carriers without CHB (immune-tolerant, inactive and HDV-superinfected, median 3.26, range 2.26-4.49 Log10 IU/ml versus untreated-CHB (median 4.68, range 2.76-5.54 Log10 IU/ml, p<0.0001. IgM-anti-HBc positive using the chronic-hepatitis-cut-off" (0.130-S/CO were positive in 102 of 212 sera (48.1%. Overall total-anti-HBc and IgM-anti-HBc correlated significantly (p<0.001, r=0.417. Total-anti-HBc declined significantly in CHB patients with response to Peg-IFN (p<0.001 and in NUC-treated patients (p<0.001; the lowest levels (median 2.68, range 2.12-3.08 Log10 IU/ml were found in long-term responders who cleared HBsAg subsequently. During spontaneous and therapy-induced fluctuations of CHB (remissions and reactivations total- and IgM-anti-HBc correlated with ALT (p<0.001, r=0.351 and p=0.008, r=0.185 respectively. Total-anti-HBc qualifies as a useful marker of HBV-induced-liver-disease that might help to discriminate major phases of chronic HBV infection and to predict sustained response to antivirals.

  20. Hepatitis B virus prevention strategies for antibody to hepatitis B core antigen-positive liver donation: a survey of North American, European, and Asian-Pacific transplant programs.

    Science.gov (United States)

    Perrillo, Robert

    2009-02-01

    Prophylactic therapy is generally used to prevent reactivated hepatitis B after transplantation of an antibody to hepatitis B core antigen (anti-HBc)-positive liver. To gain insight into current practice, a questionnaire was e-mailed to 89 liver transplant physicians in the United States, Europe, and Asia/Australia and 4 hepatitis B experts. Addressees were asked if they prefer lamivudine or other nucleoside analogs and whether these drugs are used indefinitely. They were also questioned about the use of hepatitis B immune globulin (HBIg), the preferred duration of its administration, and whether treatment strategies differ according to the knowledge of the serologic status of the recipient. Responses were obtained from 78 physicians. All transplant physicians reported the use of nucleoside analog therapy, and 65% prefer lamivudine (58% versus 81% for US and non-US physicians, P = 0.05). Sixty-one percent use HBIg (38% always, 23% sometimes). HBIg was used more frequently in the United States than other parts of the world (69% versus 46%, P = 0.03). Eighty-one percent of transplant physicians use nucleoside analog therapy for an indefinite period, but the duration of HBIg treatment varies widely. Although some centers omit nucleoside analog or HBIg therapy in antibody to hepatitis B surface antigen-positive recipients, 90% will not omit these agents if the recipient is positive for anti-HBc alone. In conclusion, nucleoside analog therapy is nearly always used for anti-HBc-positive livers, and most transplant physicians treat for an indefinite period. Lamivudine continues to be preferred as first-line therapy. Many programs also use HBIg, but there is wide variation in the way this is administered. Further study is needed to determine the most cost-beneficial regimen. (c) 2009 AASLD.

  1. Seroprevalence of hepatitis B surface antigen in pregnant women attending antenatal clinic in Honiara Solomon Islands, 2015

    Science.gov (United States)

    Getahun, Aneley; Baekalia, Margaret; Panda, Nixon; Lee, Alice; Puiahi, Elliot; Khan, Sabiha; Tahani, Donald; Manongi, Doris

    2016-01-01

    AIM To determine the seroprevalence of hepatitis B surface antigen (HBsAg) among pregnant women attending antenatal clinic in Honiara, Solomon Islands. METHODS This descriptive cross-sectional study was carried out in seven area health centers in Honiara. From March to June 2015, identification of eligible pregnant women in each site was conducted using systematic random sampling technique. A total of 243 pregnant women who gave written informed consent were enrolled. Standardized tool was used to record demographics, obstetric history and serology results. HBsAg and hepatitis B e antigen (HBeAg) were tested using point-of-care rapid diagnostic test. All HBsAg positive samples were verified using enzyme-linked immunosorbent assay. RESULTS The mean age of participants was 26 ± 6 years. The overall hepatitis HBsAg prevalence was 13.8% with higher rate (22%) reported in women between 30-34 years of age. Majority of HBsAg positive participants were Melanesians (29 out for 33). None of the pregnant women in the 15-19 years and ≥ 40 years tested positive for HBsAg. There was no statistically significant difference in HBsAg prevalence by age, ethnicity, education and residential location. The overall HBeAg seroprevalence was 36.7%. Women between 20-24 years of age had the highest rate of 54.5%. Low level of knowledge about hepatitis B vaccination was reputed. Overall, 54.6% of participants were not aware of their hepatitis B vaccination status and only 65.2% of mothers reported their child had been vaccinated. CONCLUSION Hepatitis B is a disease of public health importance in Solomon Islands and emphasize the need for integrated preventative interventions for its control. PMID:28008343

  2. Prevalence of Hepatitis B surface antigen (HBsAg among visitors of Shashemene General Hospital voluntary counseling and testing center

    Directory of Open Access Journals (Sweden)

    Medhin Girmay

    2011-02-01

    Full Text Available Abstract Background Hepatitis B virus (HBV infection is significant health problem, as it can lead to chronic hepatitis, liver cirrhosis, and hepatic carcinoma. Due to shared routes of transmission, HBV and human immunodeficiency virus (HIV co-infection is common and is an emerging concern in the clinical management of patients because of increased mortality, accelerated hepatic disease progression, and the frequent hepatotoxicity caused by anti-retroviral therapy. The aim of this study was to determine the prevalence of Hepatitis B surface antigen (HBsAg and its risk factors, among individuals visiting Shashemene General Hospital VCT center. Findings Institution based cross-sectional study was performed from November 3, 2008 to December 29, 2008 and 384 voluntary counseling and testing (VCT clients were investigated. Data on socio demographic and HBV risk factors was collected using structured questionnaires. Blood samples were collected and screened for hepatitis B surface antigen (HBsAg and HIV by commercially available rapid test kits. The prevalence of HBsAg in this study group was 5.7%. Fourteen percent of HIV positive subjects (8/57 and 4.3% (14/327 of HIV negative subjects were positive for HBsAg. Significantly high prevalence of HBsAg was observed among individuals who had history of invasive procedures, like tooth extraction, abortion and ear piercing; history of hospital admission, history of unsafe inject and HIV positives. Conclusions Although HBsAg prevalence is much higher among subjects who are HIV positive (14.0% versus 4.3%, the prevalence of HBsAg in HIV negative subjects is high enough to warrant a recommendation to screen all clients at VCT centers irrespective of HIV status.

  3. Comparison of serological tests for antibody to hepatitis A antigen, using coded specimens from individuals infected with the MS-1 strain of hepatitis A virus.

    Science.gov (United States)

    Dienstag, J L; Krugman, S; Wong, D C; Purcell, R H

    1976-01-01

    To compare serological tests for antibody to hepatitis A antigen (anti-HA), we tested 15 paired serum specimens, submitted under code, from individuals infected with the MS-1 strain of hepatitis A virus. Immune electron microscopy (IEM), immune adherence hemagglutination (IAHA), and solid-phase radioimmunoassay (RIA) tests for anti-HA were performed with hepatitis A antigen (HA Ag) derived from human stool; results were also compared with previously reported titers determined by IAHA with HA Ag derived from marmoset liver. Antibody titers (IAHA and RIA) and ratings (IEM) determined with stool-derived HA Ag compared favorably, and a seroresponse to HA Ag was detected by all three methods for every serum pair tested. Differences in titers were noted between IAHA tests with liver-derived and with stool-derived HA Ag, but the discrepancies could be accounted for by differences in test technique. The agreement found in this study among the three techniques was quite good and confirms the specificity and sensitivity of tests for anti-HA that are done with stool-derived HA-Ag. PMID:186409

  4. Mapping of Schistosoma mansoni in the Nile Delta, Egypt: Assessment of the prevalence by the circulating cathodic antigen urine assay.

    Science.gov (United States)

    Haggag, Ayat A; Rabiee, Amal; Abd Elaziz, Khaled M; Gabrielli, Albis F; Abdel Hay, Rehab; Ramzy, Reda M R

    2017-03-01

    In line with WHO recommendations on elimination of schistosomiasis, accurate identification of all areas of residual transmission is a key step to design and implement measures aimed at interrupting transmission in low-endemic settings. To this purpose, we assessed the prevalence of active S. mansoni infection in five pilot governorates in the Nile Delta of Egypt by examining schoolchildren (6-15 years) using the Urine-Circulating Cathodic Antigen (Urine-CCA) cassette test; we also carried out the standard Kato-Katz (KK) thick smear, the monitoring and evaluation tool employed by Egypt's national schistosomiasis control programme. Prevalence rates determined by the Urine-CCA test for all governorates were higher than those determined by KK (p<0.01). Of 35 districts surveyed in the five governorates, S. mansoni infection was detected in 19 districts (54.3%) using KK, and in 31 districts (88.6%) by Urine-CCA (χ2=9.94; P=0.0016). S. mansoni infections were detected by Urine-CCA, but not by KK in 12 districts (34.3%), and infection was not detected by either of the two diagnostic methods in four districts in Qalyubia governorate. Males and higher age-groups have significantly higher Urine-CCA prevalence rates. Based on the findings of the current S. mansoni mapping exercise, authorities of the Ministry of Health and Population (MoHP) adopted a new elimination strategy by readjusting thresholds for mass treatment with praziquantel and targeting all transmission areas. MoHP is now planning to remap in all other endemic governorates using Urine-CCA with the aim of identifying all areas of transmission where the elimination strategy should be applied.

  5. Treatment of surgical brain injury by immune tolerance induced by intrathymic and hepatic portal vein injection of brain antigens

    Science.gov (United States)

    Yang, Weijian; Liu, Yong; Liu, Baolong; Tan, Huajun; Lu, Hao; Wang, Hong; Yan, Hua

    2016-01-01

    Surgical brain injury (SBI) defines complications induced by intracranial surgery, such as cerebral edema and other secondary injuries. In our study, intrathymic and hepatic portal vein injection of allogeneic myelin basic protein (MBP) or autogeneic brain cell suspensions were administered to a standard SBI model. Serum pro-inflammatory IL-2, anti-inflammatory IL-4 concentrations and the CD4+T/CD8+T ratio were measured at 1, 3, 7, 14 and 21 d after surgery to verify the establishment of immune tolerance. Furthermore, we confirmed neuroprotective effects by evaluating neurological scores at 1, 3, 7, 14 and 21 d after SBI. Anti-Fas ligand (FasL) immunohistochemistry and TUNEL assays of brain sections were tested at 21 d after surgery. Intrathymic injections of MBP or autogeneic brain cell suspensions functioned by both suppressing secondary inflammatory reactions and improving prognoses, whereas hepatic portal vein injections of autogeneic brain cell suspensions exerted a better effect than MBP. Intrathymic and hepatic portal vein injections of MBP had equal effects on reducing secondary inflammation and improving prognoses. Otherwise, hepatic portal vein injections of autogeneic brain cell suspensions had better outcomes than intrathymic injections of autogeneic brain cell suspensions. Moreover, the benefit of injecting antigens into the thymus was outweighed by hepatic portal vein injections. PMID:27554621

  6. The Murine Humoral Immune Response to Hepatitis B Surface Antigen: Idiotype Network Pathways.

    Science.gov (United States)

    Schick, Michael Roy

    Recognition of a wide spectrum in disease outcomes following Hepatitis B Virus (HBV) infection has led to the suggestion that individual differences may be due to characteristics of the immune response. HBV, a hepatotropic virus, is not directly cytopathic to the host hepatocytes but the cellular damage which does not occur may be due to the host's own immune response. It is this variety in immune response capabilities following natural infection or vaccination which led to the present study in which the murine humoral immune response to hepatitis B surface antigen (HBsAg) was examined. Following immunization with purified HBsAg an anti-HBs response could be detected in 19 inbred strains of mice. The response, which varied among the strains, was linked to the major histocompatibility complex (MHC). Among high responders to HBsAg were two strains in which a poor response to a single epitope could be detected. Although quantitatively serum from these strains resembled serum from other high responders, there was a major difference in the qualitative aspects. Included within this study was the role of idotype networks within the murine anti-HBs response. By directly targeting HBsAg-specific B cells within the framework of an idiotype network by an Ab-2, it was possible to circumvent T cell-dependent regulation of an immune response. In each of five inbred strains of mice immunized with a polyclonal rabbit Ab-2 an Ab-3 population with HBsAg-specificity (Ab -1^') was induced. These mice were also immunized with HBsAg resulting in a higher anti-HBs response as compared to HBsAg immunization alone in all of the strains tested except for one. The response in this strain, normally a low responder to HBsAg, indicated that the mechanisms for genetic restriction of the anti -HBs response was still active, although it was not apparent during anti-Id immunization. The effects of an anti-Id on the murine antibody response to HBsAg may lead to insights on the presence of idiotype

  7. Detection of antibody against antigen expressed by molecularly cloned hepatitis C virus cDNA: Application to diagnosis and blood screening for posttransfusion hepatitis

    Energy Technology Data Exchange (ETDEWEB)

    Miyamura, Tatsuo; Saito, Izumu (National Institute of Health, Tokyo (Japan)); Katayama, Tohru (Tokyo National Chest Hospital (Japan)); Kikuchi, Shu; Tateda, Akira (Sendai National Hospital (Japan)); Houghton, M.; Choo, Quilim; Kuo, G. (Chiron Corporation, Emeryville, CA (USA))

    1990-02-01

    A cDNA clone has been derived from the plasma of a chimpanzee with chronic non-A, non-B viral hepatits (NANBH). The authors have assayed for antibodies reacting with the encoded antigen in sera from posttransfusion hepatitis patients (643 samples from 23 patients) and their corresponding donors collected during the past 10 years in Japan. The antibody was detected in 15 out of 17 (88.2%) posttransfusion NANBH (PT-NANBH) patients whose sera over time displayed multiple alanine aminotransferase (ALT) peaks. In general, the antibody was detected after several peaks of serum ALT elevations and, once detected, it persisted for years. Of the 15 well-defined cases of PT-NANBH that showed multiple ALT peaks and hepatitis C virus seroconversions, 11 (73.3%) were shown to be transfused with at least one unit of blood positive for the antibody. The retrospective analysis showed that all tested donor blood found to be positive for the antibody had been transfused to recipients who afterwards developed NANBH. These data strongly suggest that the cloned cDNA originated from an etiological agent of NANBH termed the hepatitis C virus. Furthermore, the present study demonstrates that had the screening been done with the anti-hepatitis C virus assay, 11 out of 17 (64.7%) cases of chronic PT-NANBH and 1 out of 6 (16.6%) acute PT-NANBH would have been prevented.

  8. Analysis of precore/core covariances associated with viral kinetics and genotypes in hepatitis B e antigen-positive chronic hepatitis B patients.

    Directory of Open Access Journals (Sweden)

    Chun-Pei Cheng

    Full Text Available Hepatitis B virus (HBV is one of the most common DNA viruses that can cause aggressive hepatitis, cirrhosis and hepatocellular carcinoma. Although many people are persistently infected with HBV, the kinetics in serum levels of viral loads and the host immune responses vary from person to person. HBV precore/core open reading frame (ORF encoding proteins, hepatitis B e antigen (HBeAg and core antigen (HBcAg, are two indicators of active viral replication. The aim of this study was to discover a variety of amino acid covariances in responses to viral kinetics, seroconversion and genotypes during the course of HBV infection. A one year follow-up study was conducted with a total number of 1,694 clones from 23 HBeAg-positive chronic hepatitis B patients. Serum alanine aminotransferase, HBV DNA and HBeAg levels were measured monthly as criteria for clustering patients into several different subgroups. Monthly derived multiple precore/core ORFs were directly sequenced and translated into amino acid sequences. For each subgroup, time-dependent covariances were identified from their time-varying sequences over the entire follow-up period. The fluctuating, wavering, HBeAg-nonseroconversion and genotype C subgroups showed greater degrees of covariances than the stationary, declining, HBeAg-seroconversion and genotype B. Referring to literature, mutation hotspots within our identified covariances were associated with the infection process. Remarkably, hotspots were predominant in genotype C. Moreover, covariances were also identified at early stage (spanning from baseline to a peak of serum HBV DNA in order to determine the intersections with aforementioned time-dependent covariances. Preserved covariances, namely representative covariances, of each subgroup are visually presented using a tree-based structure. Our results suggested that identified covariances were strongly associated with viral kinetics, seroconversion and genotypes. Moreover

  9. Surface antigen-negative hepatitis B virus infection in Dutch blood donors.

    Science.gov (United States)

    Lieshout-Krikke, R W; Molenaar-de Backer, M W A; van Swieten, P; Zaaijer, H L

    2014-01-01

    Hepatitis B virus (HBV) surface antigen (HBsAg) is a reliable marker for HBV infection, but HBsAg-negative forms of HBV infection occur. The introduction of HBV DNA screening of Dutch blood donors, which were not preselected for absence of HBV core antibodies, enabled the characterization of HBsAg-negative HBV infection in healthy persons and a comparison of the HBV genomes involved. The screening of 4.4 million Dutch blood donations identified 23 HBsAg-negative, HBV DNA-positive persons. Serological testing of the index donations, follow-up samples and archived earlier samples was performed to determine the nature of each HBV DNA-only case. Despite low viral loads HBV DNA could be sequenced in 14 out of 23 donors, allowing HBV genotyping and the analysis of mutations in the HBV surface gene. Four types of HBsAg-negative HBV infection were detected: infection in the early stage before occurrence of HBsAg; suppressed infection after vaccination; HBV genotype G infection with decreased HBsAg production; and chronic occult (HBsAg negative) HBV infection. In the donors with occult HBV genotype D infection the HBV surface gene showed multiple "escape" mutations in the HBsAg a-determinant and CTL epitopes, while in an occult genotype A case the surface gene showed no mutations. HBsAg-negative forms of HBV infection in healthy blood donors explain the ongoing transmission of HBV via blood transfusion, if donor screening is limited to HBsAg. The screening of blood donors for HBV DNA and HBV core antibodies seems to cover all stages and variants of HBV infection.

  10. Role of quantitative hepatitis B surface antigen in predicting inactive carriers and HBsAg seroclearance in HBeAg-negative chronic hepatitis B patients

    Science.gov (United States)

    Ungtrakul, Teerapat; Sriprayoon, Tassanee; Kusuman, Pattama; Chunnuan, Pitchayachuda; Soonklang, Kamonwan; Sornsamdang, Gaidganok; Auewarakul, Chirayu U.; Tanwandee, Tawesak

    2017-01-01

    Abstract To evaluate quantitative hepatitis B surface antigen (qHBsAg) as a diagnostic marker for inactive carriers (ICs) and hepatitis B surface antigen (HBsAg) seroclearance in hepatitis B e antigen (HBeAg)-negative chronic hepatitis B (CHB) patients. We retrospectively studied 300 HBeAg-negative CHB patients with initial serum hepatitis B virus (HBV) Deoxyribonucleic acid (DNA) levels <2000 IU/mL. Serum HBV DNA and alanine aminotransferase (ALT) levels were monitored every 6 months for 24 months. ICs were identified as having persistent HBV DNA levels <2000 IU/mL and normal ALT levels, whereas active carriers (ACs) were identified as having HBV DNA levels ≥2000 IU/mL, with or without elevated ALT levels. The serum qHBsAg level was defined at baseline and evaluated as a diagnostic predictor using a receiver-operating characteristic curve. The study group comprised 134 men and 166 women with a median age of 41.5 years. At baseline, 200 ICs displayed lower levels of qHBsAg (1492 IU/mL) compared with 100 ACs (2936 IU/mL) (P = 0.005). The qHBsAg level was independently associated with the IC state and HBsAg seroclearance. Baseline qHBsAg levels <1000 IU/mL and HBV DNA levels <2000 IU/mL, when detected simultaneously, allowed for identification of ICs with 41% sensitivity and 72% specificity. Fifteen patients (5%) displayed HBsAg seroclearance after 24 months. A qHBsAg cutoff value of <50 IU/mL provided 100% sensitivity and 92% specificity in predicting HBsAg seroclearance. The qHBsAg level at a single timepoint among HBeAg-negative CHB patients with low HBV DNA levels at baseline was not a predictive marker for ICs; however, it accurately predicted spontaneous HBsAg seroclearance at 24 months. PMID:28353619

  11. Prognostic Implications of Antibodies to Soluble Liver Antigen in Autoimmune Hepatitis: A PRISMA-Compliant Meta-Analysis.

    Science.gov (United States)

    Chen, Zhi-Xian; Shao, Jian-Guo; Shen, Yi; Zhang, Jian; Hua, Yu; Wang, Lu-Jun; Qin, Gang

    2015-06-01

    Prognostic evaluation is important for the management of patients with autoimmune hepatitis (AIH). Although some autoantibodies have been associated with disease activity and outcomes, the implication of antibodies to soluble liver antigen (anti-SLA) remains controversial. To conduct a meta-analysis of observational studies which addressed differences in clinical characteristics by anti-SLA status in patients with AIH. Three databases PUBMED, EMBASE, and OVID were systemically searched up to January 2015 using the terms "soluble liver antigen" or "liver-pancreas antigen" and "autoimmune hepatitis" with restriction to English-language. Studies were included if at least 50 patients with objective diagnosis of AIH were enrolled, anti-SLA detection was performed for the patients, and prognostic outcomes and/or disease severity were reported. Two investigators independently reviewed retrieved literature and evaluated eligibility. Discrepancy was resolved by discussion and a third investigator. Quality of included studies was evaluated using Newcastle-Ottawa Quality Assessment Scale (NOS). Data were pooled using fixed-effect or random-effect models. Prognostic outcomes included death from hepatic failure or requirement for liver transplantation, and responses to immunosuppressive therapy regarding remission or relapse. Results were combined on the odds ratio (OR) or standardized mean difference (SMD) scales. Eight studies were enrolled in this study, involving a total of 1297 AIH patients among whom 195 with anti-SLA. Pooled serum AST levels tended to be lower in anti-SLA seropositive patients. The presence of anti-SLA conferred 3.1-fold increased risk of hepatic death in AIH patients. The remission rates were comparable between anti-SLA seropositive and seronegative AIH patients, while anti-SLA positivity was associated with nearly 2-fold increased risk of relapse after drug withdrawal. Human leukocyte antigen (HLA) allotype DR3 was positively associated with anti

  12. New broadly reactive neutralizing antibodies against hepatitis B virus surface antigen.

    Science.gov (United States)

    Kucinskaite-Kodze, Indre; Pleckaityte, Milda; Bremer, Corinna M; Seiz, Pia L; Zilnyte, Milda; Bulavaite, Aiste; Mickiene, Gitana; Zvirblis, Gintautas; Sasnauskas, Kestutis; Glebe, Dieter; Zvirbliene, Aurelija

    2016-01-01

    Hepatitis B virus (HBV) surface antigen (HBsAg) is considered to be the most important target for the diagnosis and immune prophylaxis of HBV infection. HBsAg-specific monoclonal antibodies (MAbs) are extensively used for studying the complex structure of the HBsAg, mapping the neutralizing epitopes and development of HBV diagnostic tests. However, the efficiency of anti-HBV binding strongly depends on the epitope structure and MAb capability to recognize different HBV variants. In the current study, 9 MAbs against yeast-expressed HBsAg of ayw2 serotype were generated and 7 of them were shown to recognize a linear epitope comprising amino acid (aa) residues 119-GPCRTCT-125 within the main antigenic "a" determinant of HBsAg. One MAb of the highest affinity (clone HB1) was selected for detailed cross-reactivity studies, generation of recombinant single-chain antibody (scFv) and molecular modelling of antibody-epitope interaction. The importance of each aa residue within the identified MAb epitope was determined by alanine substitution study that revealed aa residues C(121), T(123), C(124) and T(125) as essential for binding. These aa residues are highly conserved among HBV variants. In contrast, alanine substitution of G119, P120 and R122 had no or minor influence on the reactivity with the MAb. Certain aa residues at position 122 (either R or K) define different HBV serotypes (either d or y), therefore, the affinity of the MAb HB1 for the epitope with R122K substitution was determined to evaluate its diagnostic potential. The MAb recognized both epitope variants with high affinity. Sequence alignment of the MAb epitope within different HBV strains demonstrated that the shortest peptide recognized by the MAb 121-CR(K)TCT-125 is identical among different human HBV genotypes (HBV A-F, H) and monkey HBV species (HBVCP, HBVGO, HBVGB, WMHBV). In line with these data, the MAb HB1 was cross-reactive in Western blot with a large panel of antigens derived from different HBV

  13. High serum levels of HDV RNA are predictors of cirrhosis and liver cancer in patients with chronic hepatitis delta.

    Directory of Open Access Journals (Sweden)

    Raffaella Romeo

    Full Text Available Chronic infection with the hepatitis delta virus (HDV is a risk factor for cirrhosis and hepatocellular carcinoma (HCC, but little is known whether the outcome of hepatitis is predicted by serum markers of HDV and hepatitis B virus (HBV infection. The aim of the study was to investigate these correlations in 193 patients with chronic HDV infection who had been followed up for a median of 9.5 years (4.8-19.3. HDV-RNA was first measured by qualitative in-house nested RT-PCR and quantified by in-house real-time PCR. HDV RNA levels only appeared significantly associated to HCC (univariate analysis: OR 1.32, 95% CI 1.02-1.71; p = 0.037; multivariate analysis: OR 1.42, 95% CI 1.04-1.95; p = 0.03. In non-cirrhotics at first presentation (n = 105, HDV RNA levels were associated with progression to cirrhosis (univariate analysis: OR = 1.57, 95% CI 1.20-2.05, p<0.001; multivariate analysis: OR = 1.60, 95% CI 1.20-2.12, p = 0.007 and development of HCC (univariate analysis: OR = 1.66, 95% CI 1.04-2.65, p = 0.033; multivariate analysis: OR = 1.88, 95% CI 1.11-3.19, p = 0.019. ROC analysis showed that approximately 600,000 HDV RNA copies/mL was the optimal cut-off value in our cohort of patients for discriminating the development of cirrhosis. High levels of HDV viremia in non-cirrhotic patients are associated with a considerable likelihood of progression to cirrhosis and the development of HCC. Once cirrhosis has developed, the role of HDV replication as a predictor of a negative outcome lessens.

  14. Clonorchis sinensis antigens alter hepatic macrophage polarization in vitro and in vivo.

    Directory of Open Access Journals (Sweden)

    Eun-Min Kim

    2017-05-01

    Full Text Available Clonorchis sinensis infection elicits hepatic inflammation, which can lead to cholangitis, periductal hepatic fibrosis, liver cirrhosis, and even cholangiocarcinoma. Hepatic macrophages are an intrinsic element of both innate and acquired immunity. This study was conducted to demonstrate the dynamics of hepatic macrophage polarization during C. sinensis infection in mice and to identify factors regulating this polarization. Treatment of hepatic macrophages isolated from normal mice with C. sinensis excretory/secretory products (ESPs resulted in the preferential generation of classically activated hepatic macrophages (M1 macrophages and the production of pro-inflammatory cytokines. Additionally, cells stimulated with C. sinensis ESPs exhibited changes in cellular morphology. During the early stages of C. sinensis infection, hepatic macrophages preferentially differentiated into M1 macrophages; however, during the C. sinensis mature worm stage, when eggs are released, there were significant increases in the abundance of both M1 macrophages and alternatively activated hepatic macrophages (M2 macrophages. Moreover, there was a further increase in the M2 macrophage count during the fibrotic and cirrhotic stage of infection. Notably, this fibrotic and cirrhotic stage promoted a strong increase in the proportion of Arg-1-producing macrophages (M2 phenotype, which were associated with fibrosis and tissue repair in the liver. Our results suggest that the dynamic polarization of hepatic macrophages as C. sinensis infection progresses is related to the histological lesions present in liver tissue. Hepatic macrophages thus play an important role in local immunity during C. sinensis infection.

  15. Antiviral effects of anti-HBs immunoglobulin and vaccine on HBs antigen seroclearance for chronic hepatitis B infection.

    Science.gov (United States)

    Tsuge, Masataka; Hiraga, Nobuhiko; Uchida, Takuro; Kan, Hiromi; Miyaki, Eisuke; Masaki, Keiichi; Ono, Atsushi; Nakahara, Takashi; Abe-Chayama, Hiromi; Zhang, Yizhou; Naswa, Makokha Grace; Kawaoka, Tomokazu; Miki, Daiki; Imamura, Michio; Kawakami, Yoshiiku; Aikata, Hiroshi; Ochi, Hidenori; Hayes, C Nelson; Chayama, Kazuaki

    2016-11-01

    Interferon and nucleotide/nucleoside analogues are the main treatments for chronic hepatitis B. These drugs effectively reduce serum hepatitis B virus (HBV) DNA titers but fail to sufficiently reduce hepatitis B surface antigen (HBsAg) levels. Following the recent identification of sodium taurocholate cotransporting polypeptide as a receptor for HBV entry, inhibition of HBV entry has become an attractive therapeutic target for chronic hepatitis B treatment. We therefore evaluated the antiviral effects of antibody to HBsAg (anti-HBs) immunoglobulin (HBIG), which can inhibit HBV entry, by in an vivo study and a clinical trial. In the in vivo study, HBV-infected mice were generated from human hepatocyte chimeric mice and treated with HBIG. A clinical trial evaluating HBIG therapy in patients was also performed. In the mouse study, HBV DNA titers were reduced and serum HBsAg titers decreased to undetectable levels following high-dose HBIG injection. On the basis of this result, eight chronic hepatitis B patients, who had received long-term nucleotide analogue treatment, were treated with monthly HBIG injections as an additional treatment. After 1 year of treatment, an HBsAg level reduction of more than 1 log IU/mL was observed in four patients, and three patients became anti-HBs positive. No adverse events occurred during HBIG therapy. These results suggest that monthly HBIG injection might benefit patients with chronic hepatitis B whose HBsAg titer becomes lower following long-term nucleotide/nucleoside analogue treatment.

  16. Circulating MicroRNAs in Plasma of Hepatitis B e Antigen Positive Children Reveal Liver-Specific Target Genes

    DEFF Research Database (Denmark)

    Winther, Thilde Nordmann; Jacobsen, Kari Stougaard; Mirza, Aashiq Hussain

    2014-01-01

    Background and Aim. Hepatitis B e antigen positive (HBeAg-positive) children are at high risk of severe complications such as hepatocellular carcinoma and cirrhosis. Liver damage is caused by the host immune response to infected hepatocytes, and we hypothesise that specific microRNAs play a role...... with chronic hepatitis B (CHB) and in healthy controls, candidate microRNAs with aberrant plasma expressions in HBeAg-positive children were identified. MicroRNAs targeting liver-specific genes were selected based on bioinformatics analysis and validated by qRT-PCR using plasma samples from 34 HBe...... in this complex interaction between virus and host. The study aimed to identify microRNAs with aberrant plasma expressions in HBeAg-positive children and with liver-specific target genes. Methods. By revisiting our previous screen of microRNA plasma levels in HBeAg-positive and HBeAg-negative children...

  17. Immunofluorescent Staining for the Detection of the Hepatitis B Core Antigen in Frozen Liver Sections of Human Liver Chimeric Mice.

    Science.gov (United States)

    Allweiss, Lena; Lütgehetmann, Marc; Dandri, Maura

    2017-01-01

    The hepatitis B virus (HBV) is the causative agent for chronic hepatitis B infection, which affects an estimate of 240 million people worldwide and puts them at risk of developing terminal liver disease. The life cycle of the virus and its interactions with the host immune system are still incompletely understood, and currently available treatment options rarely achieve a cure. Therefore, basic research and new drug development are needed. One parameter for measuring the intrahepatic activity of the virus is monitoring the production of the HBV core antigen (HBcAg), which not only serves as the main structural protein of its nucleocapsid but is also recruited to the covalently closed circular DNA (cccDNA), the nuclear HBV genome responsible for infection persistence. Here, we report a sensitive immunofluorescence staining method to detect HBcAg in cryopreserved liver sections. The method combines conventional immunofluorescence staining procedures with the Tyramide Signal Amplification (TSA) system.

  18. A novel hepatitis B virus mutant with A-to-G at nt551 in the surface antigen gene

    Institute of Scientific and Technical Information of China (English)

    Hua-Biao Chen; De-Xing Fang; Fa-Qing Li; Hui-Ying Jing; Wei-Guo Tan; Su-Qin Li

    2003-01-01

    AIM: Hepatitis B surface antigen (HBsAg) mutant of hepatitisB virus (HBV) is one of the important factors that result inimmune escape and cause failure of immunization. In thisstudy we reported and characterized a novel HBV mutantwith A-to-G at nt551 and intended to provide theoreticaldata for prevention of HBV infection in China.METHODS: A methodology comprising polymerase chainreaction (PCR) amplifying, M13 bacteriophage cloning andnucleotide sequencing was used to analyze the sera of thepediatric patient who was hepatitis B (HB) immune failure.Expression plasmids containing the mutant S gene and awild-type (adr) S gene were constructed respectively andthe recombinant HBsAg were expressed in COS-7 cells underthe regulation of SV40 early promoter. The recombinantproteins were investigated for their immunological reactivitywith different monoclonal antibodies (mAb) against 'a'determinant and vaccine-raised human neutralizingantibodies.RESULTS: It was found that there was a new point mutationat nt551 of the HBV (adr) genome from A to G, leading to asubstitution of methionine (Met) to valine (Val) at position133 in the 'a' determinant of HBsAg. Compared to the wild-type HBsAg, the binding activity of the muant HBsAg tomAbs (A6, A11 and S17) and to vaccine-raised human anti-hepatitis B surface antibody (anti-HBs) decreased significantly.CONCLUSION: According to the facts that the patient hasbeen immunized with HB vaccine and that the serum is anti-HBs positive and HBsAg negative, and based on thenucleotide sequence analysis of the mutant HBV S geneand its alteration of antigenicity, the HBV is considered tobe a new vaccine-induced immune escape mutant differentfrom the known ones.

  19. Evaluation of the KEMRI Hep-cell II test kit for detection of hepatitis B surface antigens in Tanzania.

    Science.gov (United States)

    Kilale, Andrew M; Range, Nyagosya S; Ngowi, Prosper H; Kahwa, Amos M; Mfinanga, Sayoki G

    2012-07-01

    Hepatitis B surface antigen (HBsAg) is one of the most important serological markers used to diagnose acute and chronic hepatitis B infection. The objective of the current evaluation was to assess the operational characteristics of the Kenya Medical Research Institute (KEMRI) Hep-cell II against an ELISA Exsym HBsAg in the detection of hepatitis B surface antigens. To evaluate the Hep-cell II test, blood samples were collected from blood donors and processed for detection of HBsAg using Hep-cell II based on the test principle and procedure outlined by the manufacturer. ELISA Axsym HBsAg test was used as golden standard. Of the 400 samples tested, 287 (71.8%) were positive by Hep-cell test and 295 (73.8%) were positive by the ELISAAxsym. Hep-cell test had a sensitivity of 98.6% and specificity of 95.96%. Similar values of sensitivity and specificity of the Hep-cell test were obtained even when Bayesian Analysis Model was applied. The positive and negative predictive values of Hep-cell test were 98.61% and 95.96%, respectively. The positive and negative diagnostic likelihood ratios of Hep-cell test were 24.4% and 0.0145, respectively. In conclusion, the Hep-cell test is useful for detecting hepatitis B virus and the high likelihood ratio observed suggests that it may be useful in blood screening. However, it may be necessary to evaluate for cost-effectiveness and robustness in field conditions before the test is recommended for use.

  20. Detection and localization of rabbit hepatitis e virus and antigen in systemic tissues from experimentally intraperitoneally infected rabbits.

    Science.gov (United States)

    Mao, Jingjing; Zhao, Yue; She, Ruiping; Cao, Binbin; Xiao, Peng; Wu, Qiaoxing; Guo, Zhaojie; Ma, Longhuan; Soomro, Majid Hussain

    2014-01-01

    Rabbit hepatitis E virus (HEV) is a novel genotype of HEV, and is considered to pose a risk of zoonotic transmission. Research into the systemic distribution of rabbit HEV in rabbits during different periods of infection has rarely been reported. To better understand this virus, we infected rabbits with second-passage rabbit HEV via an intraperitoneal route. After inoculation, the infection showed two types, temporary and constant infection. The detection of HEV RNA in the feces varied with time, and serum antigen correlated with fecal HEV RNA. Viremia only appeared 72 days after inoculation. The rabbits remained antibody negative throughout the experimental period. When HEV was localized, several organs besides the liver were HEV RNA positive. Tissue antigen was observed immunohistochemically in the different cells of various organs, especially in parts of the small intestine and the characteristic rabbit gut-associated lymphoid tissue. These data provide valuable information for future research into the pathogenesis of HEV.

  1. Delta-like 1/fetal antigen-1 (Dlk1/FA1) is a novel regulator of chondrogenic cell differentiation via inhibition of the Akt kinase-dependent pathway

    DEFF Research Database (Denmark)

    Chen, Li; Qanie, Diyako; Jafari, Abbas

    2011-01-01

    Delta-like 1 (Dlk1, also known as fetal antigen-1, FA1) is a member of Notch/Delta family that inhibits adipocyte and osteoblast differentiation; however, its role in chondrogenesis is still not clear. Thus, we overexpressed Dlk1/FA1 in mouse embryonic ATDC5 cells and tested its effects...... on chondrogenic differentiation. Dlk1/FA1 inhibited insulin-induced chondrogenic differentiation as evidenced by reduction of cartilage nodule formation and gene expression of aggrecan, collagen Type II and X. Similar effects were obtained either by using Dlk1/FA1-conditioned medium or by addition of a purified......, secreted, form of Dlk1 (FA1) directly to the induction medium. The inhibitory effects of Dlk1/FA1 were dose-dependent and occurred irrespective of the chondrogenic differentiation stage: proliferation, differentiation, maturation, or hypertrophic conversion. Overexpression or addition of the Dlk1/FA1...

  2. Transplacentally acquired maternal antibody against hepatitis B surface antigen in infants and its influence on the response to hepatitis B vaccine.

    Directory of Open Access Journals (Sweden)

    Zhiqun Wang

    Full Text Available BACKGROUND: Passively acquired maternal antibodies in infants may inhibit active immune responses to vaccines. Whether maternal antibody against hepatitis B surface antigen (anti-HBs in infants may influence the long-term immunogenicity of hepatitis B vaccine remains unknown. METHODOLOGY/PRINCIPAL FINDINGS: Totally 338 pairs of mothers and children were enrolled. All infants were routinely vaccinated against hepatitis B based on 0-, 1- and 6-month schedule. We characterized the transplacental transfer of maternal anti-HBs, and compared anti-HBs response in children of mothers with or without anti-HBs. In a prospective observation, all 63 anti-HBs positive mothers transferred anti-HBs to their infants; 84.1% of the infants had higher anti-HBs concentrations than their mothers. One and half years after vaccination with three doses of hepatitis B vaccine, the positive rate and geometric mean concentration (GMC of anti-HBs in 32 infants with maternal anti-HBs were comparable with those in 32 infants without maternal antibody (90.6% vs 87.5%, P = 0.688, and 74.5 vs 73.5 mIU/ml, P = 0.742, respectively. In a retrospective analysis, five and half years after vaccination with three doses vaccine, the positive rates of anti-HBs in 88 children of mothers with anti-HBs ≥1000 mIU/ml, 94 children of mothers with anti-HBs 10-999 mIU/ml, and 61 children of mothers with anti-HBs <10 mIU/ml were 72.7%, 69.2%, and 63.9% (P = 0.521, respectively; anti-HBs GMC in these three groups were 38.9, 43.9, and 31.7 mIU/ml (P = 0.726, respectively. CONCLUSIONS/SIGNIFICANCE: The data demonstrate that maternal anti-HBs in infants, even at high concentrations, does not inhibit the long-term immunogenicity of hepatitis B vaccine. Thus, current hepatitis B vaccination schedule for infants will be still effective in the future when most infants are positive for maternal anti-HBs due to the massive vaccination against hepatitis B.

  3. Prevalence, risk factors, and molecular epidemiology of hepatitis B and hepatitis delta virus in pregnant women and in patients in Mauritania.

    Science.gov (United States)

    Mansour, Wael; Malick, F-Zahra Fall; Sidiya, Ahmad; Ishagh, Elkhalil; Chekaraou, Mariama Abdou; Veillon, Pascal; Ducancelle, Alexandra; Brichler, Ségolène; Le Gal, Frédéric; Lo, Baidy; Gordien, Emmanuel; Lunel-Fabiani, Françoise

    2012-08-01

    No recent data are available on hepatitis B virus (HBV) and hepatitis Delta virus (HDV) prevalence in Mauritania. One thousand twenty pregnant women and 946 patients visiting for routine checkups were screened for HBV and HDV infection. Demographic, epidemiological, ethnic, clinical, and biological data were recorded. HBV and HDV genotypes were determined by sequencing and phylogenetic analyses. In the pregnant women and patients cohorts, respectively, the prevalence of HBsAg (10.7% and 18.3%) and anti-HBcAb (66.3% and 76.5%) indicated high HBV endemicity. In pregnant women, exposure to HBV was significantly associated in multivariate analysis with education level, ethnicity, blood transfusion, and occupation. HDV antibodies (HDVAb) were found in 14.7% of pregnant women. In patients, HBsAg was found less frequently in females than in males. Again in multivariate analysis, exposure to HBV was significantly correlated with gender (males), and HDVAb positivity with age and gender. The HBV DNA viral load was >3 log IU/ml in only 10.1% of pregnant women and in 17.3% of patients. HDV-RNA was detectable in 21 (67.7%) of the 31 patients positive for HDVAb, and in 11 of the 16 pregnant women positive for HDVAb (68.8%). The most frequent HBV genotypes were: HBV/D, 53%; HBV/E, 35%; and HBV/A, 12%. Sub-genotyping revealed HBV/D1,/D7, and the recently described/D8. HDV genotypes were: HDV-1, 90.3% and HDV-5, 9.7%. This study confirms the high prevalence of HBV and HDV infections in Mauritania and demonstrates the high genetic diversity of HBV in this country. Copyright © 2012 Wiley Periodicals, Inc.

  4. Prediction of Response to Immune Modifying Therapy for Patients with Chronic Hepatitis B using Hepatitis B Surface Antigen Levels

    NARCIS (Netherlands)

    V. Rijckborst (Vincent)

    2011-01-01

    textabstractThe treatment of chronic hepatitis B has greatly improved with the introduction of potent nucleos(t)ide analogues with a high barrier to resistance and peginterferon. The advantages and limitations of both treatment options should be considered when a patient has an indication to initiat

  5. Hepatitis B vaccination coverage and risk factors associated with incomplete vaccination of children born to hepatitis B surface antigen-positive mothers, Denmark, 2006 to 2010.

    Science.gov (United States)

    Kunoee, Asja; Nielsen, Jens; Cowan, Susan

    2016-01-01

    In Denmark, universal screening of pregnant women for hepatitis B has been in place since November 2005, with the first two years as a trial period with enhanced surveillance. It is unknown what the change to universal screening without enhanced surveillance has meant for vaccination coverage among children born to hepatitis B surface antigen (HBsAg)-positive mothers and what risk factors exist for incomplete vaccination. This retrospective cohort study included 699 children of mothers positive for HBsAg. Information on vaccination and risk factors was collected from central registers. In total, 93% (651/699) of the children were vaccinated within 48 hours of birth, with considerable variation between birthplaces. Only 64% (306/475) of the children had received all four vaccinations through their general practitioner (GP) at the age of two years, and 10% (47/475) of the children had received no hepatitis B vaccinations at all. Enhanced surveillance was correlated positively with coverage of birth vaccination but not with coverage at the GP. No or few prenatal examinations were a risk factor for incomplete vaccination at the GP. Maternity wards and GPs are encouraged to revise their vaccination procedures and routines for pregnant women, mothers with chronic HBV infection and their children.

  6. Expression of hepatitis B virus surface antigens induces defective gonad phenotypes in Caenorhabditis elegans

    Science.gov (United States)

    Chen, Yi-Yin; Lee, Li-Wei; Hong, Wei-Ning; Lo, Szecheng J

    2017-01-01

    AIM To test whether a simple animal, Caenorhabditis elegans (C. elegans), can be used as an alternative model to study the interaction between hepatitis B virus antigens (HBsAg) and host factors. METHODS Three plasmids that were able to express the large, middle and small forms of HBsAgs (LHBsAg, MHBsAg, and SHBsAg, respectively) driven by a ubiquitous promoter (fib-1) and three that were able to express SHBsAg driven by different tissue-specific promoters were constructed and microinjected into worms. The brood size, egg-laying rate, and gonad development of transgenic worms were analyzed using microscopy. Levels of mRNA related to endoplasmic reticulum stress, enpl-1, hsp-4, pdi-3 and xbp-1, were determined using reverse transcription polymerase reaction (RT-PCRs) in three lines of transgenic worms and dithiothreitol (DTT)-treated wild-type worms. RESULTS Severe defects in egg-laying, decreases in brood size, and gonad retardation were observed in transgenic worms expressing SHBsAg whereas moderate defects were observed in transgenic worms expressing LHBsAg and MHBsAg. RT-PCR analysis revealed that enpl-1, hsp-4 and pdi-3 transcripts were significantly elevated in worms expressing LHBsAg and MHBsAg and in wild-type worms pretreated with DTT. By contrast, only pdi-3 was increased in worms expressing SHBsAg. To further determine which tissue expressing SHBsAg could induce gonad retardation, we substituted the fib-1 promoter with three tissue-specific promoters (myo-2 for the pharynx, est-1 for the intestines and mec-7 for the neurons) and generated corresponding transgenic animals. Moderate defective phenotypes were observed in worms expressing SHBsAg in the pharynx and intestines but not in worms expressing SHBsAg in the neurons, suggesting that the secreted SHBsAg may trigger a cross-talk signal between the digestive track and the gonad resulting in defective phenotypes. CONCLUSION Ectopic expression of three forms of HBsAg that causes recognizable phenotypes in

  7. Hepatitis B Foundation Newsletter: B Informed

    Science.gov (United States)

    ... Our Accomplishments Annual Reports Our Videos What Is Hepatitis B? What Is Hepatitis B? The ABCs of Viral Hepatitis Liver Cancer and Hepatitis B Hepatitis Delta Coinfection Hepatitis C Coinfection HIV/AIDS ...

  8. STUDY ON PERIPHERAL BLOOD MONONUCLEAR CELL(PBMC) PROLIFERATIVE RESPONSES TO DIFFERENT HCV ANTIGENS IN PATIENTS WITH HEPATITIS C

    Institute of Scientific and Technical Information of China (English)

    窦骏; 刘克洲; 陈智; 沃建尔; 何南祥; 徐陈槐; 章明太; 王信子

    1999-01-01

    To explore the cellular immune function in patients with hepatitis C and study the HCV pathogenic mechanism and immune protection effect against HCV infection in host. PBMC proliferative responses in vitro to HCV synthetic peptides (Cp9, Ns4) and recombinant HCV proteins (C,E1 ,E2 ,NS3) were evaluated in 21 patients with chronic hepatitis C and 3 patients with acute hepatitis C. Phenotypic characteristics of proliferating cells in PBMC were detected by FACS after PBMC were stimulated with HCV antigens. Results showed that lymphoproliferative responses of PBMC from patients with hepatitis C to synthetic peptides (Cp9, NS4) and rccombinant proteins (C,E1 ,E2 and NS3) were detected and its stimulation index(SI) were 1.69±0.51, 1. 61±0.54, 1. 68±0.58,1. 49±0.44, 1.44±0.44 and 1. 33±0. 33 respectively. Two out of three patients with acute hepatitis C had efficient lymphoproliferative response to HCV antigens (SI≥2. 1) and their serum HCV-RNA were seroconversion and serum ALT values were returned to normal when studied. Phenotype analysis showed that phenotypic characteristics of proliferating cells was CD4+ lymphocytes and CD8+ lymphocytes proliferative responses was less than that of CD4+ lymphocytes. The results indicate that PBMC from patients with hepatitis C exist proliferative responses to different HCV antigens. CD4+ lymphocytes proliferative response is greater than that of CD8+ lymphocytes. The efficient lymphoproliferative responses to HCV antigens in patients with acute hepatitis C suggests that the patients possibly have a good clinical prognosis.%为探讨丙型肝炎(HC)病人细胞免疫功能和丙型肝炎病毒(HCV)的致病机制及机体对其免疫保护作用,收集24例HC病人(急性3例,慢性21例),用3H-TdR掺入法研究病人外周血单个核细胞(PBMC)对不同HCV抗原增殖反应,并用流式细胞仪(FACS)检测了PBMC中CD4+、CD8+淋巴细胞亚群在HCV抗原刺激后的变化.结果:HC病人PBMC对HCV合成肽CP9,NS

  9. Proteomic analysis of liver plasma membrane from hepatitis B surface antigen transgenic mice

    Institute of Scientific and Technical Information of China (English)

    贾小芳

    2012-01-01

    Objective To explore the differential liver plasma membrane( PM) proteins that may be related to the occurrence,development and reversal process of hepatitis and to understand the pathogenesis of hepatitis and the new drug targets by performing a comparative proteomics research of liver PM between

  10. Proteaselike sequence in hepatitis B virus core antigen is not required for e antigen generation and may not be part of an aspartic acid-type protease.

    Science.gov (United States)

    Nassal, M; Galle, P R; Schaller, H

    1989-01-01

    The hepatitis B virus (HBV) C gene directs the synthesis of two major gene products: HBV core antigen (HBcAg[p21c]), which forms the nucleocapsid, and HBV e antigen (HBeAg [p17e]), a secreted antigen that is produced by several processing events during its maturation. These proteins contain an amino acid sequence similar to the active-site residues of aspartic acid and retroviral proteases. On the basis of this sequence similarity, which is highly conserved among mammalian hepadnaviruses, a model has been put forward according to which processing to HBeAg is due to self-cleavage of p21c involving the proteaselike sequence. Using site-directed mutagenesis in conjunction with transient expression of HBV proteins in the human hepatoma cell line HepG2, we tested this hypothesis. Our results with HBV mutants in which one or two of the conserved amino acids have been replaced by others suggest strongly that processing to HBeAg does not depend on the presence of an intact proteaselike sequence in the core protein. Attempts to detect an influence of this sequence on the processing of HBV P gene products into enzymatically active viral polymerase also gave no conclusive evidence for the existence of an HBV protease. Mutations replacing the putatively essential aspartic acid showed little effect on polymerase activity. Additional substitution of the likewise conserved threonine residue by alanine, in contrast, almost abolished the activity of the polymerase. We conclude that an HBV protease, if it exists, is functionally different from aspartic acid and retroviral proteases. Images PMID:2657101

  11. The absence of the human platelet antigen polymorphism effect on fibrosis progression in human immunodeficiency virus-1/hepatitis C virus coinfected patients

    Directory of Open Access Journals (Sweden)

    Natália Picelli

    2015-08-01

    Full Text Available AbstractINTRODUCTION:Hepatic fibrosis progression in patients with chronic hepatitis C virus infections has been associated with viral and host factors, including genetic polymorphisms. Human platelet antigen polymorphisms are associated with the rapid development of fibrosis in HCV-monoinfected patients. This study aimed to determine whether such an association exists in human immunodeficiency virus-1/hepatitis C virus-coinfected patients.METHODS:Genomic deoxyribonucleic acid from 36 human immunodeficiency virus-1/hepatitis C virus-coinfected patients was genotyped to determine the presence of human platelet antigens-1, -3, or -5 polymorphisms. Fibrosis progression was evaluated using the Metavir scoring system, and the patients were assigned to two groups, namely, G1 that comprised patients with F1, portal fibrosis without septa, or F2, few septa (n = 23 and G2 that comprised patients with F3, numerous septa, or F4, cirrhosis (n = 13. Fisher's exact test was utilized to determine possible associations between the human platelet antigen polymorphisms and fibrosis progression.RESULTS:There were no deviations from the Hardy-Weinberg equilibrium in the human platelet antigen systems evaluated. Statistically significant differences were not observed between G1 and G2 with respect to the distributions of the allelic and genotypic frequencies of the human platelet antigen systems.CONCLUSION:The greater stimulation of hepatic stellate cells by the human immunodeficiency virus and, consequently, the increased expression of transforming growth factor beta can offset the effect of human platelet antigen polymorphism on the progression of fibrosis in patients coinfected with the human immunodeficiency virus-1 and the hepatitis C virus.

  12. Targeting the hepatitis B virus precore antigen with a novel IgNAR single variable domain intrabody.

    Science.gov (United States)

    Walsh, Renae; Nuttall, Stewart; Revill, Peter; Colledge, Danni; Cabuang, Liza; Soppe, Sally; Dolezal, Olan; Griffiths, Kate; Bartholomeusz, Angeline; Locarnini, Stephen

    2011-03-01

    The Hepatitis B virus precore protein is processed in the endoplasmic reticulum (ER) into secreted hepatitis B e antigen (HBeAg), which acts as an immune tolerogen to establish chronic infection. Downregulation of secreted HBeAg should improve clinical outcome, as patients who effectively respond to current treatments (IFN-α) have significantly lower serum HBeAg levels. Here, we describe a novel reagent, a single variable domain (V(NAR)) of the shark immunoglobulin new antigen receptor (IgNAR) antibodies. V(NAR)s possess advantages in stability, size (~14 kDa) and cryptic epitope recognition compared to conventional antibodies. The V(NAR) domain displayed biologically useful affinity for recombinant and native HBeAg, and recognised a unique conformational epitope. To assess therapeutic potential in targeting intracellular precore protein to reduce secreted HBeAg, the V(NAR) was engineered for ER-targeted in vitro delivery to function as an intracellular antibody (intrabody). In vitro data from HBV/precore hepatocyte cell lines demonstrated effective intrabody regulation of precore/HBeAg.

  13. Lamivudinbehandling af en hepatitis Bs- antigen-positiv patient med reaktiv artritis

    DEFF Research Database (Denmark)

    Borup, Christian; Siboni, Anders

    2008-01-01

    A 46-year-old man who was HBs antigen positive since childhood had painful talocrural arthritis that was considered re-active to HBs antigen. Lamivudine treatment was started and HBV-DNA disappeared from the blood, and the joint swellings disappeared. HBe antibody disappeared after eight months. ...

  14. Mimicry between the hepatitis C virus polyprotein and antigenic targets of nuclear and smooth muscle antibodies in chronic hepatitis C virus infection.

    Science.gov (United States)

    Gregorio, G V; Choudhuri, K; Ma, Y; Pensati, P; Iorio, R; Grant, P; Garson, J; Bogdanos, D P; Vegnente, A; Mieli-Vergani, G; Vergani, D

    2003-09-01

    Autoantibodies to smooth muscle (SMA) and nuclear components (ANA) arise in the natural course of chronic infection with hepatitis C virus. In view of the growing evidence for 'molecular mimicry' as a mechanism of autoimmunity we investigated whether cross-reactive immune reactions between host smooth muscle/nuclear components and HCV antigens may contribute to the formation of SMA and ANA in chronic HCV infection. Computer-assisted protein database search methods were used to identify three smooth muscle (smoothelin698-717, myosin1035-1054, vimentin69-88) and three nuclear (matrin722-741, histone H2A11-30, replication protein A133-152) host antigens with the highest local sequence similarity to the HCV polyprotein and 20-mer peptides corresponding to these regions were constructed. Sera from 51 children with chronic HCV infection [median age: 8 (2-16); 27 boys], 26 SMA positive and five ANA positive, were tested for reactivity to the synthesized HCV peptides and their human homologues by enzyme linked immunosorbent assay (ELISA). Sera from patients with HBV infection and chronic liver disease of different aetiologies were used as controls. 'Double reactivity' to HCV peptides and smooth muscle/nuclear homologues was associated strongly with HCV infection (P < 0.001 for both). Humoral cross-reactivity was established as the basis for double recognition by competition ELISA. Double-reactivity to smooth muscle and HCV peptide antigens correlated with SMA positivity by indirect immunofluouresence (P = 0.05). Of 15 patients double-reactive to myosin1035-1054 and its HCV homologue, 13 recognized whole myosin by immunoblot. These results suggest that ANA and SMA in chronic HCV infection may arise, at least in part, as a consequence of cross-reactive immune responses to HCV and host smooth muscle/nuclear antigens.

  15. Hepatitis B virus-like particles access major histocompatibility class I and II antigen presentation pathways in primary dendritic cells.

    Science.gov (United States)

    Moffat, Jessica M; Cheong, Wan-Shoo; Villadangos, José A; Mintern, Justine D; Netter, Hans J

    2013-04-26

    Virus-like particles (VLPs) represent high density displays of viral proteins that efficiently trigger immunity. VLPs composed of the small hepatitis B virus envelope protein (HBsAgS) are useful vaccine platforms that induce humoral and cellular immune responses. Notably, however, some studies suggest HBsAgS VLPs impair dendritic cell (DC) function. Here we investigated HBsAgS VLP interaction with DC subsets and antigen access to major histocompatibility complex (MHC) class I and II antigen presentation pathways in primary DCs. HBsAgS VLPs impaired plasmacytoid DC (pDC) interferon alpha (IFNα) production in response to CpG in vitro, but did not alter conventional DC (cDC) or pDC phenotype when administered in vivo. To assess cellular immune responses, HBsAgS VLPs were generated containing the ovalbumin (OVA) model epitopes OVA(257-264) and OVA(323-339) to access MHCI and MHCII antigen presentation pathways, respectively; both in vitro and following immunisation in vivo. HBsAgS VLP-OVA(257-264) elicited CTL responses in vivo that were not enhanced by inclusion of an additional MHCII helper epitope. HBsAgS VLP-OVA(257-264) administered in vivo was cross-presented by CD8(+) DCs, but not CD8(-) DCs. Therefore, HBsAgS VLPs can deliver antigen to both MHCI and MHCII antigen presentation pathways in primary DCs and promote cytotoxic and helper T cell priming despite their suppressive effect on pDCs.

  16. Characterization of monoclonal antibodies against hepatitis C virus nonstructural protein 3: different antigenic determinants from human B cells.

    Science.gov (United States)

    Ou-Yang, P; Chiang, B L; Hwang, L H; Chen, Y G; Yang, P M; Chi, W K; Chen, P J; Chen, D S

    1999-04-01

    The nonstructural (NS3) region protein of hepatitis C virus (HCV) possesses major B-cell epitopes that induce antibodies after infection. To elucidate further the characteristics of these B cells and their role in the immune regulation of HCV infection, T9 (portion of NS3 region, amino acids [a.a.] 1188-1493)-specific monoclonal antibodies were derived and mapped for B-cell antigenic determinants with recombinant proteins. A total of 10 T9-specific hybridomas were generated and tested for B-cell antigenic determinants. To analyze the B-cell antigenic determinants, eight recombinant proteins including NS3-e (a.a. 1175-1334), NS3-a' (a.a. 1175-1250), NS3-a (a.a. 1251-1334), NS3-b (a.a. 1323-1412), NS3-c (a.a. 1407-1499), NS3-a/b (a.a. 1251-1412), NS3-bc (a.a. 1323-1499), and NS3-abc (a.a. 1251-1499) encoded by NS3-region internal clones were expressed and tested for immunoblotting. The data suggested IgG hybridomas recognized NS3-a, NS3-a', or NS3-b protein by immunoblotting. By contrast, the NS3-e protein bears the major antigenic determinant recognized by human sera. Half of the hybridomas were found to react with protein NS3-a', which is not a major B-cell antigenic determinant in humans. These data suggested that conformational epitopes in vivo may be important for B-cell recognition.

  17. Long term follow-up and outcome of liver transplantation from hepatitis B surface antigen positive donors

    Science.gov (United States)

    Ballarin, Roberto; Cucchetti, Alessandro; Russo, Francesco Paolo; Magistri, Paolo; Cescon, Matteo; Cillo, Umberto; Burra, Patrizia; Pinna, Antonio Daniele; Di Benedetto, Fabrizio

    2017-01-01

    Liver transplant for hepatitis B virus (HBV) currently yields excellent outcomes: it allows to rescue patients with an HBV-related advanced liver disease, resulting in a demographical modification of the waiting list for liver transplant. In an age of patient-tailored treatments, in liver transplantation as well the aim is to offer the best suitable graft to the patient who can benefit from it, also expanding the criteria for organ acceptance and allocation. With the intent of developing strategies to increase the donor pool, we set-up a multicenter study involving 3 Liver Transplant Centers in Italy: patients undergoing liver transplantation between March 03, 2004, and May 21, 2010, were retrospectively evaluated. 1408 patients underwent liver transplantation during the study period, 28 (2%) received the graft from hepatitis B surface antigen positive (HBsAg)-positive deceased donors. The average follow-up after liver transplantation was 63.7 mo [range: 0.1-119.4; SD ± 35.8]. None Primary non-function, re-liver transplantation, early or late hepatic artery thrombosis occurred. The 1-, 3- and 5-year graft and patient survival resulted of 85.7%, 82.1%, 78.4%. Our results suggest that the use of HBsAg-positive donors liver grafts is feasible, since HBV can be controlled without affecting graft stability. However, the selection of grafts and the postoperative antiviral therapy should be managed appropriately.

  18. Rapid detection of hepatitis B virus DNA in liver tissue by in situ hybridisation and its combination with immunohistochemistry for simultaneous detection of HBV antigens.

    OpenAIRE

    Lau, J. Y.; Naoumov, N V; Alexander, G J; Williams, R

    1991-01-01

    A rapid technique using a non-radioactive receptor molecule (digoxigenin) for intrahepatic hepatitis B virus (HBV) DNA detection using in situ hybridisation was developed. It can be adapted for use in combination with standard immunohistochemistry for simultaneous detection of both HBV DNA and HBV antigens. The total time required for dual detection of HBV antigens and HBV DNA starting from paraffin wax liver sections was two working days. A good signal to background ratio for the detection o...

  19. Hepatitis virales B y delta: epidemiología y prevención en el Perú

    Directory of Open Access Journals (Sweden)

    César Cabezas Sánchez

    2002-07-01

    Full Text Available Se describe la epidemiología de las hepatitis virales B (HVB y Delta (HVD en el Perú, destacando su disímil prevalencia según áreas geográficas que, sin embargo, tienden a ser cada vez más similares debido a la intensa migración interna. Igualmente, se mencionan mecanismos de transmisión diferentes a los clásicamente reportados en la literatura, así como las consecuencias de la infección crónica, traducidas en cirrosis hepática y hepatocarcinoma. Finalmente, se describen las intervenciones para la prevención de la HVB mediante programas piloto de inmunización integradas al programa ampliado de inmunizaciones (PAI, los cuales han mostrado su impacto en la reducción de las tasas de prevalencia en áreas hiperendémica intervenidas, y que han derivado en la incorporación de la vacuna contra HVB en el PAI del Ministerio de Salud del Perú.

  20. Pegylated Interferon Alfa-2b Monotherapy and Pegylated Interferon Alfa-2b plus Lamivudine Combination Therapy for Patients with Hepatitis B Virus E Antigen-Negative Chronic Hepatitis B▿

    Science.gov (United States)

    Kaymakoglu, Sabahattin; Oguz, Dilek; Gur, Gurden; Gurel, Selim; Tankurt, Ethem; Ersöz, Galip; Ozenirler, Seren; Kalayci, Cem; Poturoglu, Sule; Cakaloglu, Yılmaz; Okten, Atilla

    2007-01-01

    Forty-eight hepatitis B virus (HBV) E antigen-negative chronic hepatitis B patients received pegylated interferon alfa-2b either alone or with lamivudine for 48 weeks and were followed for an additional 24 weeks. At the end of follow-up, virological response rates (HBV DNA levels of <400 copies/ml) were similar in the monotherapy (24%) and combination therapy (26%) groups. PMID:17517832

  1. FULL-LENGTH PEPTIDE ASSAY OF ANTIGENIC PROFILE OF ENVELOPE PROTEINS FROM SIBERIAN ISOLATES OF HEPATITIS C VIRUS

    Directory of Open Access Journals (Sweden)

    A. A. Grazhdantseva

    2010-01-01

    Full Text Available Antigenic profiles of envelope glycoproteins of hepatitis C virus presented by three genotypes 1b, 2a/2c and 3a, which are most widespread in the territory of Russia and, in particular, in Novosibirsk, were studied using a panel of overlapping synthetic peptides. It was shown that highly immunogenic peptide epitopes of Е1 and Е2 proteins common for all HCV genotypes, are located in amino acid positions 250-260, 315-325 (Е1 protein, 390-400 (hypervariable region 1, 430-440, and 680-690 (Е2 protein. The greatest inter-genotypic differences were recorded in positions 280-290, 410-430 and 520-540. A novel antigenic determinant was detected in the region of aa 280-290 of the Е1 protein which was typical only for HCV 2a/2c genotype. A broad variation in the boundaries for the most epitopes suggests a high variability of the Е1 and Е2 viral proteins; however, a similar repertoire of antibodies induced by different HCV genotypes indicates to an opportunity of designing a new generation of cross-reactive HCV vaccines based on mapping of the E1 and E2 antigenic regions.

  2. Expression of the hepatitis B surface antigen gene containing the preS2 region in Saccharomyces cerevisiae.

    Directory of Open Access Journals (Sweden)

    Yoshida,Iwao

    1991-02-01

    Full Text Available We constructed a plasmid, pBH103-ME5, in which the region encoding the 10 preS2 amino acid residues and the S domain of the hepatitis B surface antigen (HBsAg were regulated by the promoter of the yeast repressible acid phosphatase gene. Saccharomyces cerevisiae carrying pBH103-ME5 produced the HBs antigen (yHBsAg, when it was cultured in a medium containing a low concentration of phosphate. The antigen was purified to homogeneity. Its molecular weight was determined by Western blotting to be 24,000, and its amino acid composition agreed well with that deduced from the nucleotide sequence. The C-terminal amino acid sequence of yHBsAg was exactly the same as that predicted from the nucleotide sequence, while the N-terminal amino acid acetylserine, which was followed by 8 amino acid residues coded by the preS2 region. These results indicate that the recombinant yeast produced a single polypeptide consisting of the preS2 region and the subsequent S domain after being processed at the N-terminus

  3. Hepatitis B and Delta Virus Are Prevalent but Often Subclinical Co-Infections among HIV Infected Patients in Guinea-Bissau, West Africa

    DEFF Research Database (Denmark)

    Hønge, Bo Langhoff; Jespersen, Sanne; Medina, Candida

    2014-01-01

    BACKGROUND: Co-infection with human immunodeficiency virus (HIV) and hepatitis B virus (HBV) may lead to accelerated hepatic disease progression with higher rates of liver cirrhosis and liver-related mortality compared with HBV mono-infection. Co or super-infection with hepatitis Delta virus (HDV......) may worsen the liver disease and complicate treatment possibilities. METHODS: In this cross-sectional study we included HIV-infected individuals who had a routine blood analysis performed at an HIV clinic in Bissau, Guinea-Bissau between the 28th of April and 30th of September 2011. All patients were...... with lamivudine resistance. Among the HBsAg positive patients 25.0% were also positive for anti-HDV and 4/9 (44.4%) had detectable HDV RNA. CONCLUSION: HBV and HDV were frequent co-infections among HIV positive patients in Guinea-Bissau and chronic infection was associated with severe immunosuppression...

  4. Measurement of the hepatitis B core-related antigen is valuable for predicting the pathological status of liver tissues in chronic hepatitis B patients.

    Science.gov (United States)

    Zhang, Zhan-Qing; Lu, Wei; Wang, Yan-Bing; Weng, Qi-Cheng; Zhang, Zhi-Yong; Yang, Zhi-Qiang; Feng, Yan-Ling

    2016-09-01

    The objective of this study was to evaluate the validities of serum hepatitis B core-related antigen (HBcrAg) for predicting the pathological status of liver tissues of chronic hepatitis B (CHB). A total of 205 Chinese patients with CHB, including 121 HBeAg-positive and 84 HBeAg-negative patients, were enrolled in this study. In HBeAg-positive patients, AUCs of serum HBcrAg for predicting severe necro-inflammation and advanced fibrosis were greater than 0.70; using serum HBcrAgHBcrAg for predicting significant necro-inflammation and significant fibrosis were greater than 0.70; using serum HBcrAg>=1.70×10(2)kUmL(-1) and >=4.02kUmL(-1) as cutoffs, the sensitivities, specificities, accuracies for predicting significant necro-inflammation and significant fibrosis were 0.929, 0.964, 0.952 and 1.000, 1.000, 1.000, respectively. These results indicated favorable performances of serum HBcrAg for predicting severe necro-inflammation and advanced fibrosis in HBeAg-positive patients and significant necro-inflammation and significant fibrosis in negative patients.

  5. Gender disparity in distribution of the major hydrophilic region variants of hepatitis B virus genotype C according to hepatitis B e antigen serostatus.

    Science.gov (United States)

    Lee, Seoung-Ae; Cho, Yoo-Kyung; Lee, Keun-Hwa; Hwang, Eung-Soo; Kook, Yoon-Hoh; Kim, Bum-Joon

    2011-03-01

    Hepatitis B virus (HBV) e antigen (HBeAg) seroconversion during chronic HBV infection is known to play an important role in disease progression and patient response to antiviral agents. The aim of the present study was to analyze gender disparity in distribution of major hydrophilic region (MHR) variants according to HBeAg serostatus. Prevalence of MHR variants from 68 Korean patients with chronic hepatitis (31 HBeAg-positive and 37 HBeAg-negative) was examined in terms of HBeAg serostatus and sex by direct sequencing analysis of the MHR. Gender disparity was observed in the distribution of MHR variants according to HBeAg serostatus. In male patients, the prevalence of MHR variants was significantly higher in HBeAg negative patients than in HBeAg positive patients [58.8% (10/17 patients) vs. 14.3% (3/21 patients), P=0.004]. However, the same was not true in female patients [55.0% (11/20 patients) vs. 60.0% (6/10 patients), P=1.000)]. In addition, 2 mutation types (L110I and G145A) related to HBeAg serostatus were found. In conclusion, HBeAg seroconversion in male chronic patients infected with genotype C could lead to mutations of MHR, major target to host immune response, which might in turn contribute to HBV persistence and immune evasion. Copyright © 2011 Wiley-Liss, Inc.

  6. PreS deletion mutations of hepatitis B virus in chronically infected patients with simultaneous seropositivity for hepatitis-B surface antigen and anti-HBS antibodies.

    Science.gov (United States)

    Huang, Xiangyan; Qin, Yanghua; Zhang, Peng; Tang, Gusheng; Shi, Qingfen; Xu, Jun; Qi, Falian; Shen, Qian

    2010-01-01

    Hepatitis B surface antigen (HBsAg) and anti-HBs antibodies (anti-HBs) may coexist in certain chronic hepatitis B (CHB) patients. This study was designed to further explore the relationship between this coexistence and hepatitis B Virus (HBV) preS deletions. Sera of 28 patients carrying both HBsAg and anti-HBs (Group I) and those of another 28 HBsAg positive but anti-HBs negative patients (Group II) were collected from CHB patients. Direct sequencing of polymerase chain reaction products or sequencing of clones was applied to both groups to determine sequences of HBV preS and S genes. Genotyping of the S gene indicated that all sampled HBVs were either Genosubtype Ba or Genosubtype Ce. Seven samples in Group I harbored HBV preS deletion mutations. Three of the seven samples showed large deletion mutations in 3' terminus of preS1 and co-existence of the mutant type and the full-length wild type, and the remaining four samples showed deletion mutations in 5' terminus of preS2. All mutant strains were found to be genosubtype Ce. Only two samples in Group I showed G145R/A mutation. Only one sample in Group II contained preS deletion mutation. It is therefore concluded that HBV preS deletion mutations are likely to be related to the coexistence of HBsAg and anti-HBs in CHB patients (P-value = 0.024). Some immune reactions may select for the preS deletion in CHB patients with anti-HBs, the possible marker for immune selection.

  7. Overexpression of Hepatitis B Virus-binding Protein, Squamous Cell Carcinoma Antigen 1, Extends Retention of Hepatitis B Virus in Mouse Liver

    Institute of Scientific and Technical Information of China (English)

    Hong-Bin XIA; Xi-Gu CHEN

    2006-01-01

    How receptors mediate the entry of hepatitis B virus (HBV) into the target liver cells is poorly understood. Recently, human squamous cell carcinoma antigen 1 (SCCA1) has been found to mediate binding and internalization of HBV to liver-derived cell lines in vitro. In this report, we investigate if SCCA1 is able to function as an HBV receptor and mediate HBV entry into mouse liver. SCCA1 transgene under the control of Rous sarcoma virus promoter was constructed in a minicircle DNA vector that was delivered to NOD/SCID mouse liver using the hydrodynamic technique. Subsequently, HBV-positive human serum was injected intravenously. We demonstrated that approximately 30% of the mouse liver cells expressed a high level of recombined SCCA1 protein for at least 37 d. The HBV surface antigen was found to persist in mouse liver for up to 17 d. Furthermore, HBV genome also persisted in mouse liver, as determined by polymerase chain reaction, for up to 17 d, and in mouse circulation for 7 d. These results suggest that SCAA1 might serve as an HBV receptor or co-receptor and play an important role in mediating HBV entry into hepatocytes, although its role in human HBV infection remains to be determined.

  8. Combination of small interfering RNAs mediates greater inhibition of human hepatitis B virus replication and antigen expression

    Institute of Scientific and Technical Information of China (English)

    CHEN Zhe; XU Ze-feng; YE Jing-jia; YAO Hang-ping; ZHENG Shu; DING Jia-yi

    2005-01-01

    Objectives: To evaluate the inhibitory effect mediated by combination of small interfering RNAs (siRNAs) targeting different sites of hepatitis B virus (HBV) transcripts on the viral replication and antigen expression in vitro. Methods: (1) Seven siRNAs targeting surface (S), polymerase (P) or precore (PreC) region ofHBV genome were designed and chemically synthesized.(2) HBV-producing HepG2.2.15 cells were treated with or without siRNAs for 72 h. (3) HBsAg and HBeAg in the cell culture medium were detected by enzyme-linked immunoadsorbent assay. (4) Intracellular viral DNA was quantified by real-time PCR(Polymerase Chain Reaction). (5) HBV viral mRNA was reverse transcribed and quantified by real-time PCR. (6) The change of cell cycle and apoptosis was determined by flow cytometry. Results: Our data demonstrated that synthetic small interfering RNAs(siRNAs) targeting S and PreC gene could efficiently and specifically inhibit HBV replication and antigen expression. The expression of HBsAg and HBeAg and the replication of HBV could be specifically inhibited in a dose-dependent manner by siRNAs.Furthermore, our results showed that the combination of siRNAs targeting various regions could inhibit HBV replication and antigen expression in a more efficient way than the use of single siRNA at the same final concentration. No apoptotic change was observed in the cell after siRNA treatment. Conclusion: Our results demonstrated that siRNAs exerted robust and specific inhibition on HBV replication and antigen expression in a cell culture system and combination of siRNAs targeting different regions exhibited more potency.

  9. Hepatitis B core-related antigen (HBcrAg) levels in the natural history of hepatitis B virus infection in a large European cohort predominantly infected with genotypes A and D.

    Science.gov (United States)

    Maasoumy, B; Wiegand, S B; Jaroszewicz, J; Bremer, B; Lehmann, P; Deterding, K; Taranta, A; Manns, M P; Wedemeyer, H; Glebe, D; Cornberg, M

    2015-06-01

    Hepatitis B core-related antigen (HBcrAg) has been suggested as an additional marker of hepatitis B virus (HBV) infection. HBcrAg combines the antigenic reactivity resulting from denatured hepatitis B e antigen (HBeAg), HBV core antigen and an artificial core-related protein (p22cr). In Asian patients, high levels of HBcrAg have been suggested to be an independent risk factor for hepatocellular carcinoma, while low levels could guide safe cessation of treatment with nucleos(t)ide analogues. We here studied HBcrAg levels in different phases of HBV infection in a large European cohort predominantly infected with genotypes A and D: HBeAg-positive immune tolerance (n = 30), HBeAg-positive immune clearance (IC) (n = 60), HBeAg-negative hepatitis (ENH) (n = 50), HBeAg-negative inactive/quiescent carrier phase (c) (n = 109) and acute hepatitis B (n = 8). Median HBcrAg levels were high in the immune tolerance and immune clearance phases (8.41 and 8.11 log U/mL, respectively), lower in ENH subjects (4.82 log U/mL) but only 2.00 log U/mL in ENQ subjects. Correlation between HBcrAg and HBV DNA varied among the different phases of HBV infection, while HBcrAg moderately correlated with hepatitis B surface antigen in all phases. ENQ patients had HBcrAg levels infection. HBcrAg may serve as valuable marker for virus replication and reflect the transcriptional activity of intrahepatic cccDNA. In HBeAg-negative patients, HBcrAg may help to distinguish between inactive carriers (ENQ) and those with active disease (ENH). Copyright © 2015 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  10. Association between single-nucleotide polymorphisms and early spontaneous hepatitis B virus e antigen seroconversion in children.

    Science.gov (United States)

    Komatsu, Haruki; Murakami, Jun; Inui, Ayano; Tsunoda, Tomoyuki; Sogo, Tsuyoshi; Fujisawa, Tomoo

    2014-11-06

    The disease progression following hepatitis B virus (HBV) infection is associated with single-nucleotide polymorphisms (SNPs). However, the role of SNPs in chronic HBV infection in children remains unclear. Here, we investigate the association between SNPs and early spontaneous hepatitis B e antigen (HBeAg) seroconversion in children with chronic hepatitis B infection. This was a retrospective cohort study. We genotyped seven SNPs in the following genes, interleukin (IL)-10 (rs1800871 and rs1800872), human leukocyte antigen (HLA)-DPA1 (rs3077), HLA-DPB1 (rs9277535), HLA-DQB2 (rs7453920), HLA-DQB1 (rs2856718), and IL28B (rs8099917), in patients with chronic HBV infection using PCR and sequencing. These variants were analyzed for an association with early HBeAg seroconversion in children. Of 225 Japanese patients with chronic hepatitis B virus infection (male/female: 105/120, median age at initial visit: 6 years; range 0-44 years), 52 achieved spontaneous HBeAg seroconversion at the age of 10 years or younger (G1: early seroconversion group), and 57 did not achieve spontaneous HBeAg seroconversion under the age of 20 years (G2: late or no seroconversion group). Of the seven SNPs, only the HLA-DPA1 SNP displayed a low p-value (P = 0.070), but not significant, to have early HBeAg seroconversion in the dominant model and in the allele model (P = 0.073) using the chi-square test. The association study found a low p-value, but not significant, to have early HBeAg seroconversion in the dominant model for HLA-DPA1 (genotype TC + TT vs. CC, P = 0.070, odds ratio: 2.016, 95% confidence interval: 0.940-4.323) using a logistic regression model. Although the HLA-DPA1 SNP did not show a statistically significant association with early HBeAg seroconversion in this study, the HLA-DPA1 SNP might increase the likelihood of achieving early spontaneous HBeAg seroconversion in children.

  11. Predictive Value of Hepatitis B Core-Related Antigen (HBcrAg) During the Natural History of Hepatitis B Virus Infection.

    Science.gov (United States)

    Gou, Yu; Zhao, Yanhua; Rao, Chenli; Feng, Shu; Wang, Tingting; Li, Dongdong; Tao, Chuanmin

    2017-07-01

    The natural history of HBV infection includes immune tolerance (IT), immune clearance (IC), HBeAg-negative inactive/quiescent carrier (ENQ), and HBeAg-negative hepatitis (ENH) phases. As the current biomarkers for discriminating the four phases still have some weaknesses, additional serological indicators are needed. Hepatitis B core-related antigen (HBcrAg) encoded with the precore/core gene contains denatured HBeAg, HBV core antigen (HBcAg), and a 22-KDa precore protein (p22cr) and has been demonstrated to have a close association with the natural history of hepatitis B infection. However, no specific cutoff values and diagnostic parameters have been identified to evaluate the diagnostic efficacy. This study aimed to clarify the distribution of HBcrAg levels and evaluate the diagnostic performance during the natural history of HBV infection in a Western Chinese population. In this study, 294 samples were collected from treatment-naive HBV infection patients in different phases (IT = 64; IC = 72; ENQ = 100, and ENH = 58). We detected the HBcrAg values and analyzed the relationship between HBcrAg and HBV DNA. HBsAg and other clinical parameters were quantitatively detected. The HBcrAg levels of IT, IC, ENQ, and ENH were 9.30 log U/mL, 8.80 log U/mL, 3.00 log U/mL, and 5.10 log U/mL, respectively (p values of 9.25 log U/mL and 4.355 log IU/mL for distinguishing the IT phase from the IC phase were 0.704 and 0.694, with a sensitivity of 53.13% and 79.69% and specificity of 76.39% and 59.72%, respectively. AUCs of HBcrAg and quantitative HBsAg at cutoff values of 4.15 log U/mL and 2.395 log IU/mL for discriminating between the ENQ and ENH phases were 0.931 and 0.653, with a sensitivity of 87.93% and 91.38% and specificity of 84.00% and 39.00%, respectively. HBcrAg levels varied significantly among the four natural phases of HBV infection and had higher predictive performance than quantitative HBsAg for distinguishing between ENQ-patients and ENH-patients and a similar

  12. Identification of an antigenic domain in the N-terminal region of avian hepatitis E virus (HEV) capsid protein that is not common to swine and human HEVs.

    Science.gov (United States)

    Wang, Lizhen; Sun, Yani; Du, Taofeng; Wang, Chengbao; Xiao, Shuqi; Mu, Yang; Zhang, Gaiping; Liu, Lihong; Widén, Frederik; Hsu, Walter H; Zhao, Qin; Zhou, En-Min

    2014-12-01

    The antigenic domains located in the C-terminal 268 amino acid residues of avian hepatitis E virus (HEV) capsid protein have been characterized. This region shares common epitopes with swine and human HEVs. However, epitopes in the N-terminal 338 amino acid residues have never been reported. In this study, an antigenic domain located between amino acids 23 and 85 was identified by indirect ELISA using the truncated recombinant capsid proteins as coating antigens and anti-avian HEV chicken sera as primary antibodies. In addition, this domain did not react with anti-swine and human HEV sera. These results indicated that the N-terminal 338 amino acid residues of avian HEV capsid protein do not share common epitopes with swine and human HEVs. This finding is important for our understanding of the antigenicity of the avian HEV capsid protein. Furthermore, it has important implications in the selection of viral antigens for serological diagnosis.

  13. Long-term real-world entecavir therapy in treatment-naïve hepatitis B patients: base-line hepatitis B virus DNA and hepatitis B surface antigen levels predict virologic response.

    Science.gov (United States)

    Cho, Ju-Yeon; Sohn, Won; Sinn, Dong-Hyun; Gwak, Geum-Youn; Paik, Yong-Han; Choi, Moon Seok; Koh, Kwang Cheol; Paik, Seung Woon; Yoo, Byung Chul; Lee, Joon Hyeok

    2017-07-01

    Entecavir is a potent nucleoside analogue with high efficacy and barrier for resistance. We aimed to investigate the long-term efficacy and viral resistance rate of entecavir and explore the factors associated with virologic response, including quantitative hepatitis B surface antigen (qHBsAg) levels. One thousand and nine treatment-naïve chronic hepatitis B (CHB) patients were evaluated for cumulative rates of virologic response, biochemical response, and entecavir mutations. The role of baseline qHBsAg for virologic response was assessed in 271 patients with qHBsAg prior to entecavir treatment. The median duration of entecavir treatment was 26.5 months. The cumulative rate of virologic response at years 1, 3, and 5 were 79.0%, 95.6%, and 99.4%, respectively. The cumulative rate of entecavir resistance was 1.0% and 2.1% in years 3 and 5. Multivariate analysis identified baseline hepatitis B e antigen (HBeAg) negative status (p < 0.001) and lower hepatitis B virus (HBV) DNA (p < 0.001) as predictors of virologic response. Lower qHBsAg was an independent predictor of virologic response in patients with baseline qHBsAg. There were no serious adverse events during treatment. Long-term entecavir treatment of nucleos(t)ide-naïve CHB patients was associated with an excellent virologic response and a low rate of entecavir-resistant mutations at 5 years. Baseline HBV DNA load, qHBsAg levels, and HBeAg status were predictors of virologic response during entecavir treatment.

  14. A self-amplified transistor immunosensor under dual gate operation: highly sensitive detection of hepatitis B surface antigen

    Science.gov (United States)

    Lee, I.-K.; Jeun, M.; Jang, H.-J.; Cho, W.-J.; Lee, K. H.

    2015-10-01

    Ion-sensitive field-effect transistors (ISFETs), although they have attracted considerable attention as effective immunosensors, have still not been adopted for practical applications owing to several problems: (1) the poor sensitivity caused by the short Debye screening length in media with high ion concentration, (2) time-consuming preconditioning processes for achieving the highly-diluted media, and (3) the low durability caused by undesirable ions such as sodium chloride in the media. Here, we propose a highly sensitive immunosensor based on a self-amplified transistor under dual gate operation (immuno-DG ISFET) for the detection of hepatitis B surface antigen. To address the challenges in current ISFET-based immunosensors, we have enhanced the sensitivity of an immunosensor by precisely tailoring the nanostructure of the transistor. In the pH sensing test, the immuno-DG ISFET showed superior sensitivity (2085.53 mV per pH) to both standard ISFET under single gate operation (58.88 mV per pH) and DG ISFET with a non-tailored transistor (381.14 mV per pH). Moreover, concerning the detection of hepatitis B surface antigens (HBsAg) using the immuno-DG ISFET, we have successfully detected trace amounts of HBsAg (22.5 fg mL-1) in a non-diluted 1× PBS medium with a high sensitivity of 690 mV. Our results demonstrate that the proposed immuno-DG ISFET can be a biosensor platform for practical use in the diagnosis of various diseases.Ion-sensitive field-effect transistors (ISFETs), although they have attracted considerable attention as effective immunosensors, have still not been adopted for practical applications owing to several problems: (1) the poor sensitivity caused by the short Debye screening length in media with high ion concentration, (2) time-consuming preconditioning processes for achieving the highly-diluted media, and (3) the low durability caused by undesirable ions such as sodium chloride in the media. Here, we propose a highly sensitive immunosensor

  15. Electron microscopic and solution X-ray scattering observations on the structure of hepatitis B surface antigen

    Energy Technology Data Exchange (ETDEWEB)

    Aggerbeck, L.P.; Peterson, D.L.

    1985-02-01

    The structure of the small, spherical hepatitis B surface antigen was studied by negative staining, freeze-fracture and freeze-etching electron microscopy and solution X-ray scattering techniques. The protein appears to be organized at the surface into a small number of morphological subunits which display two- and threefold axes of symmetry. The mean particle size was 18.3 nm by negative staining and 19.6 nm by freeze-fracture electron microscopy. The diameter of the individual subunits was about 7.5 nm with an intersubunit distance of about 10.0 nm. The lipid is distributed more homogeneously. Some heterogeneity of the particle structure is apparent which may be due to a slightly variable lipid-protein composition or incomplete or defective particle formation.

  16. Seroprevalence of anti-HCV and hepatitis B surface antigen in HIV infected patients

    Directory of Open Access Journals (Sweden)

    Tankhiwale S

    2003-01-01

    Full Text Available Human immunodeficiency virus (HIV is known to influence the natural history of infections with certain hepatitis viruses and interactions between HIV and hepatitis viruses may potentiate HIV replication. There is high degree of epidemiological similarity between hepatitis B virus and HIV as regard to high-risk group and route of transmission. Transmission of hepatitis C virus (HCV through blood transfusion and intravenous drug abuse is well documented. Present study deals with the study of concurrent infection of HBV and HCV with HIV infection. In the study of 110 HIV seropositive patients, 34(30.4% were positive for HBV and 8(7.27% for HCV. The difference of concomitant infection was highly significant compared to controls. (p value < 0.0001. Heterosexual high risk behaviour was observed in 89(80.91% of 110 HIV positive patients, out of which 23(25.8% and 5(5.62% were HBsAg and anti-HCV positive respectively. History of transmission was unclear in remaining patients. Concomitant infection of HIV and HBV was found to be significantly more in the symptomatic group (40.68% compared to asymptomatic group (19.6%. As HIV infection is known to affect the natural history of both HBV and HCV infection, screening of their concurrent association is necessary.

  17. A self-amplified transistor immunosensor under dual gate operation: highly sensitive detection of hepatitis B surface antigen.

    Science.gov (United States)

    Lee, I-K; Jeun, M; Jang, H-J; Cho, W-J; Lee, K H

    2015-10-28

    Ion-sensitive field-effect transistors (ISFETs), although they have attracted considerable attention as effective immunosensors, have still not been adopted for practical applications owing to several problems: (1) the poor sensitivity caused by the short Debye screening length in media with high ion concentration, (2) time-consuming preconditioning processes for achieving the highly-diluted media, and (3) the low durability caused by undesirable ions such as sodium chloride in the media. Here, we propose a highly sensitive immunosensor based on a self-amplified transistor under dual gate operation (immuno-DG ISFET) for the detection of hepatitis B surface antigen. To address the challenges in current ISFET-based immunosensors, we have enhanced the sensitivity of an immunosensor by precisely tailoring the nanostructure of the transistor. In the pH sensing test, the immuno-DG ISFET showed superior sensitivity (2085.53 mV per pH) to both standard ISFET under single gate operation (58.88 mV per pH) and DG ISFET with a non-tailored transistor (381.14 mV per pH). Moreover, concerning the detection of hepatitis B surface antigens (HBsAg) using the immuno-DG ISFET, we have successfully detected trace amounts of HBsAg (22.5 fg mL(-1)) in a non-diluted 1× PBS medium with a high sensitivity of 690 mV. Our results demonstrate that the proposed immuno-DG ISFET can be a biosensor platform for practical use in the diagnosis of various diseases.

  18. M-cell targeted delivery of recombinant hepatitis B surface antigen using cholera toxin B subunit conjugated bilosomes.

    Science.gov (United States)

    Shukla, Anshuman; Katare, O P; Singh, Bhupinder; Vyas, Suresh P

    2010-01-29

    The present study aims to improve upon our earlier findings with bilosomes as potential delivery vehicle through oral route for recombinant hepatitis B surface antigen (HBsAg). The work entails the conjugation of bilosomal system with cholera toxin B subunit (CTB) to increase transmucosal uptake via M-cell specific delivery approach. The study encompasses the development and characterization of HBsAg-loaded CTB-conjugated system for percent antigen entrapment, size, shape, and stability in SGF (USP, pH 1.2), SIF (USP, pH 7.5) and in bile salt solutions. Biological activity of CTB, subsequent to conjugation, was verified by hemagglutination test. Anti-HBsAg IgG response in serum and anti-HBsAg sIgA in various body secretions were estimated using ELISA, following oral immunization with 10 microg dose-loaded CTB-conjugated bilosomes (CTB2) and 20 microg dose-loaded CTB-conjugated bilosomes (CTB1) in BALB/c mice. The results showed that CTB1 produced anti-HBsAg IgG antibody titre response comparable to that of the intramuscular (i.m.) injection of 10 microg of alum-adsorbed HBsAg. Moreover, all the bilosomal preparations elicited measurable sIgA vis-à-vis negligible response with i.m. administered HBsAg. Thus, HBsAg-loaded CTB-conjugated bilosomes provide a promising potential for targeted oral immunization against hepatitis B. 2009 Elsevier B.V. All rights reserved.

  19. Immunological evaluation of colonic delivered Hepatitis B surface antigen loaded TLR-4 agonist modified solid fat nanoparticles.

    Science.gov (United States)

    Sahu, Kantrol Kumar; Pandey, Ravi Shankar

    2016-10-01

    Hepatitis B is one of the leading liver diseases and remains a major global health problem. Currently available vaccines provide protection but often results in weaker/minimal mucosal immunity. Thus the present study is devoted to the development and in-vivo exploration of the colonically delivered biomimetic nanoparticles which capably enhance humoral as well as cellular immune response. In present work, Hepatitis B surface antigen (HBsAg) entrapped nanoparticles containing Monophosphoryl lipid A (MPLA) (HB+L-NP) were prepared by solvent evaporation method and characterized for particle size (~210nm), shape, zeta potential (-24mV±0.68), entrapment efficiency (58.45±1.68%), in-vitro release and antigen integrity. Dose escalation study was done to confirm prophylactic immune response following defined doses of prepared nanoparticulate formulations with or without MPLA. Intramuscular administered alum based marketed HBsAg (Genevac B) was used as standard (10μg) and were able to induce significant systemic (IgG) but remarkably low mucosal immune (IgA) response. Notably, HB+L-NP (0.5ml-10μg) induced strong systemic and robust mucosal immunity (510 and 470 mIU/ml respectively, p<0.001) from which mucosal was more significant due to the involvement of Common Mucosal Immune System (CMIS). Likewise, significant cellular immune response was elicited by HB+L-NP through T-cell activation (mixed Th1 and Th2) as confirmed by significantly increased cytokines level (IL-2 and Interferon-γ) in spleen homogenates. This study supports that delivery of HBsAg to the colon may open new vista in designing oral vaccines later being one of most accepted route for potential vaccines in future.

  20. Association between CISH polymorphisms and spontaneous clearance of hepatitis B virus in hepatitis B extracellular antigen-positive patients during immune active phase

    Institute of Scientific and Technical Information of China (English)

    Song Guangjun; Rao Huiying; Feng Bo; Wei Lai

    2014-01-01

    Background Some hepatitis B extracellular antigen (HBeAg)-positive chronic hepatitis B (CHB) patients in their immune active phase can clear the virus spontaneously and enter into an inactive hepatitis B virus (HBV) carrier state,indicating a benign prognosis.In this study,the association between cytokine-inducibie SRC homology 2 domain protein (C/SH) gene polymorphisms at-292 (rs414171) and the spontaneous clearance of HBV in HBeAg-positive CHB patients in immune the active phase was investigated.Methods Seventy HBeAg-positive CHB patients in the immune active phase were followed up for 76 weeks without antiviral therapy.The alanine transaminase,aspartate transaminase,HBV DNA,HBeAg and hepatitis B extracellular antibody levels were tested regularly.At week 76,27 patients were classified into group A (HBV DNA level below 2 104 IU/ml and the value of HBeAg declined below 10% of the baseline at week 76),and 43 patients were classified into group B (HBV DNA level higher than 2×104 IU/ml or the value of HBeAg did not decline substantially at week 76).CISH (rs414171) polymorphisms were also tested using the iPLEX system.Results The HBV DNA levels at week 12 were significantly greater in group B compared with group A (group A:(6.87±1.40) log10IU/ml; group B:(7.61±1.38) log10IU/ml,P=0.034) and the HBeAg values were greater in group B at week 28 compared with group A (P=0.001).The differences in HBV DNA and HBeAg values increased between the groups over time.Sixteen patients in group A and 11 in group B were genotype AA.Those with genotype AT or TT included 11 in group A and 31 in group B (AA vs.AT and TT,odds ratio 4.10 (95% confidence interval:1.462-11.491),P=0.006).Conclusion CISH gene polymorphisms at-292 (rs414171) are associated with HBV clearance in HBeAg-positive CHB patients in the immune active phase,and AA is a favorable genotype for this effect.

  1. Adenovirus tumor targeting and hepatic untargeting by a coxsackie/adenovirus receptor ectodomain anti-carcinoembryonic antigen bispecific adapter.

    Science.gov (United States)

    Li, Hua-Jung; Everts, Maaike; Pereboeva, Larisa; Komarova, Svetlana; Idan, Anat; Curiel, David T; Herschman, Harvey R

    2007-06-01

    Adenovirus vectors have a number of advantages for gene therapy. However, because of their lack of tumor tropism and their preference for liver infection following systemic administration, they cannot be used for systemic attack on metastatic disease. Many epithelial tumors (e.g., colon, lung, and breast) express carcinoembryonic antigen (CEA). To block the natural hepatic tropism of adenovirus and to "retarget" the virus to CEA-expressing tumors, we used a bispecific adapter protein (sCAR-MFE), which fuses the ectodomain of the coxsackie/adenovirus receptor (sCAR) with a single-chain anti-CEA antibody (MFE-23). sCAR-MFE untargets adenovirus-directed luciferase transgene expression in the liver by >90% following systemic vector administration. Moreover, sCAR-MFE can "retarget" adenovirus to CEA-positive epithelial tumor cells in cell culture, in s.c. tumor grafts, and in hepatic tumor grafts. The sCAR-MFE bispecific adapter should, therefore, be a powerful agent to retarget adenovirus vectors to epithelial tumor metastases.

  2. First evaluation of the serum level of anti-hepatitis B surface antigen after vaccination in Libya.

    Science.gov (United States)

    Madour, A; Alkout, A; Vanin, S

    2013-12-01

    The hepatitis B virus (HBV) vaccination schedule in Libya follows international recommendations (1st dose at birth, 2nd after 1 month and 3rd after 6 months). This research aimed to evaluate the long-term protection of the HBV immunization programme in Tripoli and to determine the best age to administer booster doses. Serum levels of hepatitis B surface antigen were determined in 277 randomly selected children aged 1-12 years. The response to HBV vaccine in 1-3-year-olds was 93.2%, but this declined with age and at 7-9 years after initial vaccination only 53.1% of children had protective titres (> or = 10 mIU/mL). No significant differences between males and females in antibody persistence or response to vaccine were observed. We recommend continuing the HBV vaccination programme and that a booster dose be given to 6-year-old children to ensure maximum protection during the period of school entry and beyond.

  3. Hepatitis Bx Antigen Stimulates Expression of a Novel Cellular Gene, URG4, that Promotes Hepatocellular Growth and Survival

    Directory of Open Access Journals (Sweden)

    N. Lale Satiroglu Tufan

    2002-01-01

    Full Text Available Hepatitis B virus encoded X antigen (HBxAg may contribute to the development of hepatocellular carcinoma (HCC by up-or downregulating the expression of cellular genes that promote cell growth and survival. To test this hypothesis, HBxAg-positive and-negative HepG2 cells were constructed, and the patterns of cellular gene expression compared by polymerase chain reaction select cDNA subtraction. The full-length clone of one of these upregulated genes (URG, URG4, encoded a protein of about 104 kDa. URG4 was strongly expressed in hepatitis 13-infected liver and in HCC cells, where it costained with HBxAg, and was weakly expressed in uninfected liver, suggesting URG4 was an effector of HBxAg in vivo. Overexpression of URG4 in HepG2 cells promoted hepatocellular growth and survival in tissue culture and in soft agar, and accelerated tumor development in nude mice. Hence, URG4 may be a natural effector of HBxAg that contributes importantly to multistep hepatocarcinogenesis.

  4. Improved cell mediated immune responses after successful re-vaccination of non-responders to the hepatitis B virus surface antigen (HBsAg) vaccine using the combined hepatitis A and B vaccine.

    Science.gov (United States)

    Nyström, Jessica; Cardell, Kristina; Björnsdottir, Thora Björg; Fryden, Aril; Hultgren, Catharina; Sällberg, Matti

    2008-11-01

    We successfully re-vaccinated hepatitis B virus (HBV) vaccine non-responders using a double dose of the combined hepatitis A virus (HAV) and HBV vaccine. The hope was to improve priming of hepatitis B surface antigen (HBsAg)-specific cell mediated immune response (CMI) by an increased antigen dose and a theoretical adjuvant-effect from the local presence of a HAV-specific CMI. A few non-responders had a detectable HBsAg-specific CMI before re-vaccination. An in vitro detectable HBsAg-specific CMI was primed equally effective in non-responders (58%) as in first time vaccine recipients (68%). After the third dose a weak, albeit significant, association was observed between the magnitude of HBsAg-specific proliferation and anti-HBs levels. This regimen improves the priming of HBsAg-specific CMIs and antibodies.

  5. Epitope-based recombinant diagnostic antigen to distinguish natural infection from vaccination with hepatitis A virus vaccines.

    Science.gov (United States)

    Su, Qiudong; Guo, Minzhuo; Jia, Zhiyuan; Qiu, Feng; Lu, Xuexin; Gao, Yan; Meng, Qingling; Tian, Ruiguang; Bi, Shengli; Yi, Yao

    2016-07-01

    Hepatitis A virus (HAV) infection can stimulate the production of antibodies to structural and non-structural proteins of the virus. However, vaccination with an inactivated or attenuated HAV vaccine produces antibodies mainly against structural proteins, whereas no or very limited antibodies are produced against the non-structural proteins. Current diagnostic assays to determine exposure to HAV, such as the Abbott HAV AB test, detect antibodies only to the structural proteins and so are not able to distinguish a natural infection from vaccination with an inactivated or attenuated virus. Here, we constructed a recombinant tandem multi-epitope diagnostic antigen (designated 'H1') based on the immune-dominant epitopes of the non-structural proteins of HAV to distinguish the two situations. H1 protein expressed in Escherichia coli and purified by affinity and anion exchange chromatography was applied in a double-antigen sandwich ELISA for the detection of anti-non-structural HAV proteins, which was confirmed to distinguish a natural infection from vaccination with an inactivated or attenuated HAV vaccine.

  6. A Retrospective Study on the Significance of Liver Biopsy and Hepatitis B Surface Antigen in Chronic Hepatitis B Infection.

    Science.gov (United States)

    Zeng, Da-Wu; Zhang, Jie-Min; Liu, Yu-Rui; Dong, Jing; Jiang, Jia-Ji; Zhu, Yue-Yong

    2016-02-01

    To investigate changes in the HBV replication level along with the natural course of chronic HBV infection and to examine the accuracy of the immune tolerant phase defined by the serological profile.A total of 390 chronic HBV-infected patients were retrospectively recruited for this study. They were classified into immune-tolerance (IT), immune-clearance (IC), low-replicative (LR), and HBeAg-negative hepatitis (ENH) phases according to serological profiles (single-standard, SS) or dual-standard (DS) with the inclusion of liver histology. Serum HBV DNA and HBsAg were quantitatively measured, and liver histology was quantitatively analyzed.The accuracy of the SS-defined IT phase was low, and active pathological changes were detected in 56 of 112 SS-defined IT patients. DS-defined IT patients had higher HBsAg levels (P = 0.0002) than the SS-defined patients. The quantitative HBsAg level can help identify SS-defined IT patients with potential liver injury. The area under the received operating characteristic curve for predicting the DS-defined IT phase was 0.831 (HBsAg 4.398 log IU/mL; sensitivity 87.5%; specificity 73.2%). HBV DNA was reduced by 4 logs, whereas HBsAg was only decreased by 2 logs with HBeAg positive to negative phase conversion.Approximately half of IT patients defined by SS may have medium or severe liver injury. Quantitative measurement of the HBsAg level can help identify SS-defined IT patients with potential liver injury.

  7. Human leukocyte antigen-DP loci are associated with the persistent infection of hepatitis B virus in Chinese population

    Institute of Scientific and Technical Information of China (English)

    LING Yun; ZHANG Dong-Hua; JIN Gen-Di; GONG Qi-Ming; ZHANG Xin-Xin; LIAO Xiang-Wei; LI Xin-Hua; HAN Yue; YANG Zhi-Tao; KONG Xiao-Fei; GU Lei-Lei; YU De-Ming; YAO Bi-Lian

    2012-01-01

    A genome-wide association study recently showed that genetic variants in human leukocyte antigen (HLA)-DP loci were strongly associated with a risk of persistent infection of hepatitis B virus (HBV) in Japanese and Thai individuals and variants in interleukin 28B (IL-28B) have been associated with responses to anti-hepatitis C virus (HCV) treatment.The aim of this study was to investigate whether the HLA-DP loci and IL-28B were associated with different outcomes of chronic HBV infection (CHB) in Chinese subjects.The rs9277535 near HLA-DPB1,rs3077 near HLA-DPA1,and rs12979860 near IL-28B were genotyped by direct sequencing in 185 CHB patients and 193 self-limited hepatitis B virus (SLHBV)-infected subjects who recovered from HBV infection.The rs9277535 near HLA-DPB1 was strongly associated with CHB ( P =0.000018 1,OR =1.905).This association was observed independent of HBV e antigen (HBeAg) status and HBV viral loads in HBeAg-positive CHB patients (P =0.0004,OR =1.956),in HBeAg-negative CHB patients (P =0.000 9,OR =1.857),and in HBeAg-negative CHB individuals without detectable levels of HBV DNA in serum ( P =0.001 1,OR =2.05).The rs3077 near HLA-DPA1 was associated with CHB (P =0.020 6,OR =0.686 5) and HBeAg-positive CHB infection status ( P =0.014 3,OR =0.604 7).Meanwhile,a genetic variation of insertion-deletion (INDEL) polymorphism (rs361527,-/ATAAATGTTGA) near HLA-DPA1 was found to be associated with CHB (P =0.030 7,OR =0.702 8)and HBeAg-positive CHB infection status (P =0.023 3,OR =0.619).However,the rs12979860 genotype near IL-28B had no correlation with CHB.This study demonstrated that in the Han Chinese populations,HLA-DP loci,but not IL-28B,were associated with persistence of infection in different outcomes of HBVinfected patients; however,the mechanism needs to be further investigated.

  8. Air sampling for hepatitis B surface antigen in a dental operatory.

    Science.gov (United States)

    Petersen, N J; Bond, W W; Favero, M S

    1979-09-01

    Forty samples of air with a mean sample volume of 104 liters were collected during the treatment of patients whose blood was positive for HBsAG: no samples contained HBsAG and occult blood. These findings suggest that, if environmentally mediated transmission of hepatitis B occurs in the dental operatory, it is more likely to occur through contact with contaminated surfaces than through the airborne route.

  9. Hepatitis B e antigen polypeptides isolated from sera of individuals infected with hepatitis B virus: comparison with HBeAg polypeptide derived from Dane particles.

    Science.gov (United States)

    Takahashi, K; Imai, M; Gotanda, T; Sano, T; Oinuma, A; Mishiro, S; Miyakawa, Y; Mayumi, M

    1980-09-01

    Hepatitis B e antigen (HBeAg) occurs in the serum of individuals infected with hepatitis B virus both free and in association with IgG. Utilizing a succession of steps involving salt precipitation, affinity chromatography, ion-exchange chromatography and isoelectrofocusing, we isolated free and IgG-bound forms of HBeAg from the sera of infected individuals with an overall gain in specific activity of 3000-fold and 540-fold, respectively. Polypeptide profiles of purified HBeAg preparations were studied by SDS-polyacrylamide gel electrophoresis in the presence of 2-mercaptoethanol. Both free and IgG-bound preparations revealed polypeptides with mol. wt. of 15500 (P15.5) and 16 500 (P16.5), and HBeAg activity was detected corresponding to their positions. The HBeAg polypeptides (P15.5/16.5) derived from sera were physicochemically different from the two polypeptides with HBeAg activity (P19 and P45) liberated from Dane particle cores by the conventional method involving incubation with Nonidet P40 and 2-mercaptoethanol. However, when core particles were prepared in the presence of a proteolytic enzyme, in addition to Nonidet P40 and 2-mercaptoethanol, they gave rise to HBeAg polypeptides with mol. wt. of 31000 (P31) and 15 500. Furthermore, P31 split into P15.5 when heated at 100 degrees C for 2 min. On the basis of these results, P15.5 may be assumed to be the essential polypeptide bearing HBeAg activity in the serum and also in Dane particles.

  10. Coexistence of hepatitis B surface antigen (HBs Ag) and anti-HBs antibodies in chronic hepatitis B virus carriers: influence of "a" determinant variants.

    Science.gov (United States)

    Lada, Olivier; Benhamou, Yves; Poynard, Thierry; Thibault, Vincent

    2006-03-01

    In chronic hepatitis B (CHB), the persistence of hepatitis B surface antigen (HBs Ag) is sometimes associated with antibodies (Ab) to HBs (anti-HBs). To assess the hypothesis of the selection of HBs Ag immune escape variants in CHB patients, the variability of the HBV S gene was determined for patients persistently carrying both HBs Ag and anti-HBs antibodies and patients solely positive for HBs Ag. We selected 14 patients who presented both markers (group I) in several consecutive samples and 12 patients positive for HBs Ag only (group II). The HBs Ag-encoding gene was amplified and cloned, and at least 15 clones per patient were sequenced and analyzed. The number of residue changes within the S protein was 2.7 times more frequent for group I than for group II patients and occurred mostly in the "a" determinant of the major hydrophilic region (MHR), with 9.52 versus 2.43 changes per 100 residues (P = 0.009), respectively. Ten patients (71%) from group I, but only three (25%) from group II, presented at least two residue changes in the MHR. The most frequent changes in group I patients were located at positions s145, s129, s126, s144, and s123, as described for immune escape variants. In CHB patients, the coexistence of HBs Ag and anti-HBs Ab is associated with an increase of "a" determinant variability, suggesting a selection of HBV immune escape mutants during chronic carriage. The consequences of this selection process with regard to vaccine efficacy, diagnosis, and clinical evolution remain partially unknown.

  11. Interferon and lamivudine combination therapy versus lamivudine monotherapy for hepatitis B e antigen-negative hepatitis B treatment:a meta-analysis of randomized controlled trials

    Institute of Scientific and Technical Information of China (English)

    YuShi; Yi-HuaWu; Zhe-YueShu; Wan-JunZhang; JunYang; ZhiChen

    2010-01-01

    BACKGROUND: It has been demonstrated that only a minority of patients with hepatitis B e antigen (HBeAg)-negative chronic hepatitis B (CHB) obtain a sustained response after either interferon (IFN) or nucleos(t)ide analogue monotherapy. Therefore, combination therapy of drugs with synergistic antiviral effects was proposed to have a sustained response in these patients. We compared the effect and safety of lamivudine monotherapy and its combination with IFN including conventional interferon (CON-IFN) and pegylated interferon (PEG-IFN) for HBeAg-negative CHB patients. DATA  SOURCES: A group of three independent reviewers identified 9 eligible randomized controlled trials through electronic searches (MEDLINE, OVID, EMBASE, the Cochrane Library Clinical Trials Registry, and the Chinese Medical Database), manual searches, and contact with experts. Sustained virological and biochemical responses were defined as primary efficacy measures. We performed quantitative meta-analyses to assess differences between CON-IFN plus lamivudine combination and lamivudine monotherapy groups. RESULTS: No greater sustained virological and biochemical rates were found in patients receiving CON-IFN/lamivudine combination therapy [29.1% vs. 26.7%, odds ratio (OR)=0.98, 95% confidence interval (CI) 0.65-1.50, P=0.94, and 41.8%vs. 40.3%, OR=1.13, 95% CI 0.78-1.65, P=0.51, respectively], though a reduced YMDD mutation rate was achieved in the combination group [8.39% vs. 30.0%, OR=0.16, 95% CI 0.076-0.33, P CONCLUSIONS: Addition of CON-IFN to lamivudine did not improve treatment efficacy but suppressed YMDD mutation by lamivudine. Combination of PEG-IFN and lamivudine might increase the sustained response, and further clinical trials are needed for confirmation.

  12. 丙肝抗体联合丙肝核心抗原检测在丙型肝炎早期诊断中的意义%The significance of hepatitis C antibody combined hepatitis C virus core antigen test in the early diagnosis of hepatitis C

    Institute of Scientific and Technical Information of China (English)

    杜坤; 毛元英

    2015-01-01

    目的:探讨丙肝抗体联合丙肝核心抗原检测在丙型肝炎早期诊断中的意义。方法:选取2013年1月到2014年12月在我院进行体检的人群23771例,所有体检者都进行了丙肝抗体检测,而21928例体检者进行了丙肝核心抗原检测,检测方法都为ELISA法。结果:ELISA法对于丙肝抗体与丙肝核心抗原的检测阳性率分别为0.70%和0.10%。结论:丙肝抗体联合丙肝核心抗原检测在丙型肝炎早期诊断中的应用能有效判定丙型肝炎的传染性,值得推广应用。%Objective To discuss the significance of hepatitis C antibody combined hepatitis C virus core antigen test in the early diagnosis of hepatitis C.Methods We selected 23771 cases of physical examination from January 2013 to December 2014 in our hospital, all subjects were detected for hepatitis C antibody, 21928 subjects were tested for hepatitis C core antigen, detection method is ELISA. Results ELISA method was used to detect the positive rate for hepatitis C antibody and hepatitis C core antigen were 0.70% and 0.10%. Conclusion Hepatitis C antibody combined hepatitis C virus core antigen test can determine effectively hepatitis C infectivity in the early diagnosis of hepatitis C, it is worthy of popularization and application.

  13. Effects of hepatitis B virus precore and basal core promoter mutations on the expression of viral antigens: genotype B vs C.

    Science.gov (United States)

    Liu, C-J; Cheng, H-R; Chen, C-L; Chen, T-C; Tseng, T-C; Wang, Z-L; Chen, P-J; Liu, C-H; Chen, D-S; Kao, J-H

    2011-10-01

    Hepatitis B virus (HBV) genotypes/mutants are known to affect natural outcomes. The virologic differences among HBV genotype, precore and basal core promoter (BCP) mutations were investigated. HBV strains were isolated from 18 hepatitis B e antigen (HBeAg)-positive patients (nine genotype B and nine genotype C). All had precore and BCP wild-type sequences. After cloning of full-length HBV genome, the effects of viral genotype, precore and BCP mutations singly or additively on the expression of viral DNA and antigens were investigated by mutagenesis and transfection assays in Huh7 cells. Significant findings included the following: (i) expression of intracellular core protein increased when precore or BCP mutation was introduced in genotype C strains; (ii) expression of intracellular surface protein was lower in genotype C precore wild-type strain compared with genotype B; (iii) precore mutation was associated with a lower extracellular expression level of HBV DNA; (iv) secretion of hepatitis B surface antigen in genotype C was lower than that in genotype B; and (v) secretion of HBeAg in genotype B was lower than that in genotype C. No additive effect was observed by combining precore and BCP mutations. Hence, HBV genotype and precore/BCP mutations correlate with intrahepatic expression of viral antigens in vitro.

  14. Association of oral lichen planus with hepatitis C virus, surface antigen of hepatitis B virus, and diabetes: A clinical and biochemical study

    Directory of Open Access Journals (Sweden)

    Pavani Donempudi

    2016-01-01

    Full Text Available Background: Oral lichen planus is an inflammatory mucocutaneous disease commonly encountered in the dental clinic. The etiology of oral lichen planus is still unknown. The probable factors associated with oral lichen planus include anxiety, trauma, malnutrition, infection, and autoimmunity. Objectives: The aim of the study was to evaluate the serum levels of fasting and postprandial blood sugar levels, surface antigen of hepatitis B virus (HBsAg, and hepatitis C virus (HCV autoantibodies in oral lichen planus patients and controls, and to assess the association of oral lichen planus with diabetes, HCV, and HBsAg. Study Design: The study included a total of 25 oral lichen planus patients. Twenty-five individuals who did not have the above clinical conditions were also included in the study and comprised the control group. Both the study and control groups consisted of both sexes in the age group of 20–70 years. Patients were clinically diagnosed as oral lichen planus after obtaining a detailed history and was later confirmed by histopathologic examination. Materials and Methods: Blood samples were collected from both the oral lichen planus patients and controls. Biochemical analysis of blood glucose levels, i.e., fasting and postprandial blood glucose levels, HBsAg, hepatitis C autoantibodies were done by enzyme-linked immunosorbent assay. Results: Blood glucose levels, i.e., fasting and postprandial blood glucose levels, were found to be statistically increased in oral lichen planus patients when compared with controls. There was no significant change in HCV autoantibodies and HBsAg. The results of the present study also showed a significant association of oral lichen planus with diabetes. However, there was no significant association of oral lichen planus with HCV and HBsAg in patients when compared with controls. Conclusion: There was a direct relation of oral lichen planus with diabetes whereas there was no significant association with HCV

  15. The supercritical CO₂ extract from the skin of Bufo bufo gargarizans Cantor blocks hepatitis B virus antigen secretion in HepG2.2.15 cells.

    Science.gov (United States)

    Cui, Xiaoyan; Inagaki, Yoshinori; Wang, Dongliang; Gao, Jianjun; Qi, Fanghua; Gao, Bo; Kokudo, Norihiro; Fang, Dingzhi; Tang, Wei

    2014-02-01

    The skin of Bufo bufo gargarizans Cantor has long been used for the treatment of hepatitis B in China and supercritical carbon dioxide extraction (SC-CO₂) is widely used in extracting active ingredients from natural products. The aim of present study was to assess the anti-hepatitis B virus (HBV) effect of the supercritical CO₂ extract from the skin of Bufo bufo gargarizans Cantor (SCE-BC). Cytotoxicity of SCE-BC was analyzed using an MTT [3-(4,5-dimethylthiazol-2yl)-2,5-diphenyltetrazolium bromide] assay in HepG2.2.15 cells. The hepatitis B surface antigen (HBsAg), hepatitis B e antigen (HBeAg), and hepatitis B core-related antigen (HBcrAg) concentrations in cell culture medium were determined by chemiluminescent enzyme immunoassay. HBV mRNA in cells was determined using real-time polymerase chain reaction. SCE-BC concentrations below 10(-2) μg/mL had no significant toxicity to HepG2.2.15 cells. SCE-BC at 10(-4) μg/mL effectively inhibited the secretion of HBeAg by 23.36% on day 6. It was more potent than the positive control lamivudine (100 μg/mL) in terms of the inhibition of HBeAg and HBcrAg secretion on day 6. Consistent with the HBV antigen reduction, HBV mRNA expression was markedly inhibited in comparison to the control when HepG2.2.15 cells were treated with SCE-BC. Moreover, SCE-BC had greater inhibitory activity with respect to HBeAg than to HBsAg. Since HBeAg promotes immune tolerance and persistent infection during HBV infection, the present results suggest that immune tolerance induced by HBeAg might be overcome by SCE-BC. Therefore, SCE-BC warrants further investigation.

  16. Factors associated with the decrease in hepatitis B surface antigen titers following interferon therapy in patients with chronic hepatitis B: Is interferon and adefovir combination therapy effective?

    Science.gov (United States)

    Yano, Yoshihiko; Seo, Yasushi; Hayashi, Hiroki; Hatazawa, Yuri; Hirano, Hirotaka; Minami, Akihiro; Kawano, Yuki; Saito, Masaya; Ninomiya, Toshiaki; Sugano, Masahiko; Yamada, Hajime; Kitajima, Naoto; Yoon, Seitetsu; Hayashi, Yoshitake

    2017-09-01

    The purpose of antiviral therapy in chronic hepatitis B (CHB) is generally to achieve a decrease and ultimately disappearance of HBs antigen (HBsAg). Interferon (IFN) therapy of CHB appears to be less effective in Asian countries than in European countries, and the advantage of IFN and nucleotide(s) analog (NA) combination therapy has yet to be fully investigated. The present study focused on the factors associated with a decrease in HBs antigen following IFN monotherapy or IFN + NA combination therapy. A total of 35 patients with CHB who received IFN-based therapy (mean ± standard deviation age 36.7±8.5 years; 27 males and 8 females) were enrolled in this study. Of the 35 patients, 21 patients received pegylated IFN monotherapy and 14 patients received IFN and adefovir (ADV) combination therapy. We examined the factors associated with reductions in the HBsAg titer of >1.0 log IU/ml from the initial HBsAg titer to the end of treatment and to 24 weeks after treatment. Although 13 patients (37%) had a reduction in HBsAg of >1.0 IU/ml at the end of treatment, it was only maintained to 24 weeks after treatment in 7 patients (20%). The HBV core-related antigen (HBcrAg) titer before treatment was significantly higher in patients with a decrease in HBsAg at the end of treatment than in patients without a decrease in HBsAg (6.56±0.78 vs. 5.30±1.66 log IU/ml, P2 times from baseline occurred significantly more frequently in patients with a decrease in HBsAg (62 vs. 14%, Pdecrease in HBsAg was significantly greater in patients who received IFN monotherapy than in patients who received IFN and ADV combination therapy (43 vs. 29%, Pdecrease in HBsAg titers after IFN-based therapy. The efficacy of IFN and ADV combination therapy was not apparent in terms of a reduction in the HBsAg titer.

  17. Prevalence, correlates and pattern of hepatitis B surface antigen in a low resource setting

    Directory of Open Access Journals (Sweden)

    Ezebialu Ifeanyichukwu U

    2011-01-01

    Full Text Available Abstract Background Hepatitis B virus (HBV infection in Nigeria has remained a Public Health issue. It is a major cause of mortality, especially in developing countries. Vertical transmission of hepatitis B virus infection is thought to be a major route of transmission in low resource areas. In spite of this, routine antenatal screening for hepatitis B infection is not yet practiced in many Nigerian hospitals. This paper present the findings of a study conducted among antenatal women in Nnewi, Nigeria. Methods It was a cross-sectional study carried out over a 3-month period (August - October, 2009. Recruitment of 480 women attending antenatal clinics in Nnewi, Nigeria was done by simple random sampling using computer generated random numbers. HBsAg screening was done using rapid ELISA Kits. Statistical analysis was computed using STATA 11 package. The results were subjected to analysis using cross tabulations to explore statistical relationships between variables. Chi square test was used to explore proportional relationship between groups. The level of statistical significance was set at p Results Four hundred and eighty pregnant women were recruited into the study. Of these, 40 tested positive to HBsAg, accounting for 8.3% of the sample population. The age of the subjects studied varied from 14 to 45 years (mean age - 24.3 years while the mean parity was 2.18. The HIV/HBV co-infection rate was 4.2%. The vertical transmission rate was 51.6%. There were statistically significant relationships between HBV infection and previous history of tribal marks/tattoos (χ2 = 27.39, P = 0.001, df = 1, history of contact with previously infected HBV patients (χ2 = 23.11, P = 0.001, df = 1 and occupation of the women (χ2 = 51.22, P = 0.001, df = 1. Multiple sexual partners, blood transfusion, dental manipulations, sharing of sharps/needles, and circumcision were not significant modes of transmission. There was no statistically significant relationship

  18. Prevalence of Hepatitis Delta Virus Infection in Various Groups With HBVinfection in Tehran, Imam Khomeini Hospital (2005-2006

    Directory of Open Access Journals (Sweden)

    Hadi Ghofrani

    2008-08-01

    Full Text Available Background:Hepatitis B virus infection is an important cause of liver morbidity and mortality worldwide.HDV changes the natural course of HBV.The prevalence of HDV infection wasn’t determined in the various groups of HBV infection (carriers,acute hepatitis, chronic hepatitis, cirrhosis and HCCin Iran.We aimed to research the prevalence of hepatitis D virus infection in various groups with HBV infection in Imam Khomeini Hospital, Tehran (2005-2006.   Methods: Serological markers of HBV and HDV infection [HBs Ag, Hbe Ag, Anti Hbe Ab, Anti HDVAb (IgM, IgG] were determined by ELISA test in 206 patients with HBV infection who referred to Imam Khomeini Hospital (2005-2006.These patients were categorized to asymptomatic carriers, acute hepatitis,chronic hepatitis, cirrhosis and HCC according to history, physical examination and lab findings. Result: HDV infection was detected in 12.6% ( 26/206 of HBV infected patients. It was detected in 1.6%(1/62 of asymptomatic carriers, 20% (1/5 of acute hepatitis, 5.6%(5/88of chronic hepatitis,37.2% (16/43 of cirrhosis and 37.5% (3/8 of HCC patients.HDV infection showed a five-fold increase in chronic hepatitis (P<0.05 and ~16 fold increase in cirrhosis (P< 0.001 compared to HDV infection in asymptomatic carriers. HDV infection was equally distributed between sexes. Mean ages of HDV carriers, acute hepatitis, chronic hepatitis ,cirrhosis and HCC were (28, (33,(39.521,(97.111.5, (58.69,2 year respectively. Conclusion: The prevalence of HDV infection was 12.6%. The higher prevalence of HDVinfection in more severe forms of hepatitis B virus infection suggests that HDV infection increases the severity of chronic hepatitis B.HDV infection remains a major cause of chronic liver disease in Tehran in spite of its decreasing prevalence in countries such as Italy.

  19. Hepatitis B virus surface antigen and anti-hepatitis C virus rapid tests underestimate hepatitis prevalence among HIV-infected patients

    DEFF Research Database (Denmark)

    Hønge, Bo Langhoff; Jespersen, S; Medina, C

    2014-01-01

    . RESULTS: Two rapid tests were used in Guinea-Bissau: HBsAg Strip Ref 2034 (VEDA.LAB, Alençon, France; sensitivity 62.3%; specificity 99.2%) and HEPA-SCAN (Bhat Bio-Tech, Bangalore, India; sensitivity 57.1%; specificity 99.7%). In the two tests the ability to obtain the correct outcome depended...... on the antigen and antibody concentrations, respectively. Sex, age, CD4 cell count and antiretroviral therapy status did not differ between false negative and true positive samples in either of the tests. The study is limited by a low number of anti-HCV positive samples. CONCLUSIONS: New diagnostic rapid tests...

  20. Breaking tolerance in hepatitis B surface antigen (HBsAg) transgenic mice by vaccination with cross-reactive, natural HBsAg variants

    DEFF Research Database (Denmark)

    Schirmbeck, Reinhold; Dikopoulos, Nektarios; Kwissa, Marcin;

    2003-01-01

    Processing exogenous hepatitis B surface antigen (HBsAg) of the hepatitis B virus (HBV) generates the K(b)-binding S(208-215) epitope 1; processing endogenous HBsAg generates the K(b)-binding S(190-197) epitope 2. Cross-reactive CD8(+) T cell responses were primed to epitope 1 but not epitope 2...... HBs-tg mice showed reduced antigenemia. Hence, vaccination with natural HBsAg variants from different HBV sero/genotypes can prime cross-reactive, specific CD8(+) T cell immunity that breaks tolerance to HBsAg....

  1. The Evaluation of Hepatitis C Virus Core Antigen in Immunized Balb/C Mice

    Directory of Open Access Journals (Sweden)

    Elham Torbati

    2012-06-01

    Full Text Available Background: Hepatitis infection represents one of the important causes of morbidity and mortality in developing countries, however there is not any effective vaccine against hepatitis C which is one of the significant problems in vaccine project.Objectives: The aim of the present study is to evaluate the role of HCV core protein in inducing IFN-Gamma secretion and TCL activities as a vaccine in Balb/C mice.Material and Methods: Our previous cloned plasmid (HCV Core gene into pETDuet-1 applied for protein expression in bacteria. The expressed and purified recombinant protein together with Freund’s adjuvant was injected to 15 Balb/c mice. The total IgG and IgG2a of immunized mice sera were evaluated after a week. Two weeks after booster injection, we studied the proliferation and IFNγ secretion of spleens, inguinal and popliteal lymph nodes lymphocytes by ELISA and ELISPOT.Results: The FSFC (Frequency of spot forming cells of secreting cells of immunized mice with HCV/Core protein and sera IgG2a were considerably higher than the control groups.Conclusions: The core protein together with proper adjuvant can be a candidate vaccine against of HCV infection..

  2. Construction of Recombinant Modified Vaccinia Ankara (MVA) Expressing Hepatitis B Virus Surface Antigen

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    The T lymphocyte response has been shown to be the determinant in the clearance of many viral infections.Hence, therapeutic vaccine candidates against HBV are designed to enhance this response of the immune system.Vaccinia virus vector-based vaccines have been proposed as excellent candidates to elicit long-term and strong T lymphocyte mediated immune responses. In this study, the recombinant MVA expressing HBV surface antigen has been constructed, which can elicit a potent T cell mediated response. The ELISA results for the surface protein in the medium of the recombinant MVA, strongly indicate that the recombinant virus has been successfully obtained.

  3. Cycling and Tai Chi Chuan exercises exert greater immunomodulatory effect on surface antigen expression of human hepatitis B virus

    Institute of Scientific and Technical Information of China (English)

    CHEN Yu-yawn; CHIANG Jasson; CHEN Yu-jen; CHEN Kung-tung; YANG Rong-sen; LIN Jaung-geng

    2008-01-01

    Background Both athletes with intensive exercise and aged people may have weakened immunity against virus infection.This study aimed to evaluate whether people undergoing aerobic exercises including competitive cyctists with moderate training (CMT) and middle-aged people practicing Tai Chi Chuan (TCC) exercise have higher immunity against hepatitis B virus than age-matched sedentary controls including college students (CSC) and middle-aged people (MSC).Methods Human peripheral blood mononuclear cells from competitive cyclists and sedentary controls were stimulated by phytohemagglutinin (PHA) to prepare conditioned medium (MNC-CM) for the assessment of inhibitory effects on hepatitis B surface antigen (HBsAg) expression in human hepatoma Hep3B cells.Results The inhibitory effects on the relative HBsAg expression of CMT's and TCC's MNC-CM were greater than those of the controls.The CMT's MNC-CM prepared from 5 pg/ml PHA decreased HBsAg expression to 61.5%,whereas that of CSC remained at 83.8%.Similarly,this expression by treatment of TCC group' MNC-CM was 68.4% whereas that of MSC group was 84.3%.The levels of cytokines such as interferon-y (IFN-y),tumor necrosis factor-a (TNF-α),IFN-α and interleukin-1β(1L-1β) in the MNC-CM from the CMT and TCC groups were greater than those in the controls.Antibody neutralization of CMT's MNC-CM and addition of recombinant cytokines into CSC's MNC-CM indicated that IFN-y,TNF-α and IFN-α had synergistic effects against HBsAg expression.Similar blocking effect was noted in TCC versus MSC groups.Conclusion These results suggest that the immunomodulatory response to suppress HBsAg expression in CMT and TCC with moderate aerobic exercise is greater than that in age-matched sedentary controls.

  4. Use of hepatitis B surface antigen-positive grafts in liver transplantation: a matched analysis of the US National database.

    Science.gov (United States)

    Li, Zhiwei; Hu, Zhenhua; Xiang, Jie; Zhou, Jie; Yan, Sheng; Wu, Jian; Zhou, Lin; Zheng, Shusen

    2014-01-01

    The scarcity of available donor organs is the key challenge in orthotopic liver transplantation (OLT). A viable way of expanding the donor pool is the use of liver grafts from hepatitis B surface antigen (HBsAg)-positive donors. The present study used the US Scientific Registry of Transplant Recipients database (1987-2010), and each of the 78 patients who underwent OLT with HBsAg-positive grafts was matched with 4 patients who received HBsAg-negative grafts by urgent status, donor sex, recipient sex, donor age, recipient age, transplant date, Model for End-Stage Liver Disease score, and warm ischemia time. The overall graft and patient survival rates were similar for recipients of HBsAg-positive grafts and matched controls: the 5-year graft survival rates were 66% and 64%, respectively (P = 0.95), and the 5-year patient survival rates were 71% and 71%, respectively (P = 0.87). A Cox proportional hazards regression analysis that was adjusted for other variables showed no impact of the donor HBsAg status on graft or patient survival. The use of hepatitis B immunoglobulin (HBIG) was independently associated with better posttransplant graft survival [hazard ratio (HR) = 0.23, 95% confidence interval (CI) = 0.06-0.81] and patient survival (HR = 0.16, 95% CI = 0.04-0.75) for recipients of HBsAg-positive grafts. In conclusion, the use of HBsAg-positive liver grafts did not reduce posttransplant graft or patient survival. Moreover, matching these donors to recipients treated with HBIG may improve safety.

  5. Prevalence of hepatitis B surface antigen seropositivity among HIV-infected and non-infected individuals in Nnewi, Nigeria

    Directory of Open Access Journals (Sweden)

    E C Okocha

    2012-01-01

    Full Text Available Background: Co-infection of human immunodeficiency virus (HIV and hepatitis B virus (HBV is common as both viruses share common routes of transmission. HIV significantly affects the natural history of HBV, hence the need to determine the prevalence of co-infection. Materials and Methods: This was a retrospective study between 2005 and 2009, in which is a total of 2018 subjects who reported at our University Teaching Hospital blood bank and human immunodeficiency virus clinic were studied. Hepatitis B surface antigen (HBsAg was tested for using a one step lateral flow rapid chromatographic immunoassay (Acumen labs and diagnostic centre, Bangalore, India and HIV 1/2 was tested using two kits, Determine (made by Abbot, Japan for Inverness Medical, Japan. Results: A total of 2018 subjects were studied out of which 1176 were HIV positive (964 males and 212 females and 842 (334 males and 508 females were negative. The prevalence of HBsAg positivity in the study population was 5.9%. It was 6.3% and 5.6% in the HIV-infected and un-infected population, respectively. Although the prevalence was higher in those who are HIV infected, the difference was not statistically significant ( P=0.52. Males who were HIV positive were found to be more likely to have co-infection than females (8.7% vs. 4.2%, P=0.02, OR=1.917. Conclusion: This study showed that in south-eastern Nigeria, infection with HBV is relatively common in both HIV-infected and un-infected individuals. Routine screening for HBV should be done for all HIV positive individuals.

  6. A simple and inexpensive point-of-care test for hepatitis B surface antigen detection: serological and molecular evaluation.

    Science.gov (United States)

    Gish, R G; Gutierrez, J A; Navarro-Cazarez, N; Giang, K; Adler, D; Tran, B; Locarnini, S; Hammond, R; Bowden, S

    2014-12-01

    Early identification of chronic hepatitis B is important for optimal disease management and prevention of transmission. Cost and lack of access to commercial hepatitis B surface antigen (HBsAg) immunoassays can compromise the effectiveness of HBV screening in resource-limited settings and among marginalized populations. High-quality point-of-care (POC) testing may improve HBV diagnosis in these situations. Currently available POC HBsAg assays are often limited in sensitivity. We evaluated the NanoSign(®) HBs POC chromatographic immunoassay for its ability to detect HBsAg of different genotypes and with substitutions in the 'a' determinant. Thirty-seven serum samples from patients with HBV infection, covering HBV genotypes A-G, were assessed for HBsAg titre with the Roche Elecsys HBsAg II quantification assay and with the POC assay. The POC assay reliably detected HBsAg at a concentration of at least 50 IU/mL for all genotypes, and at lower concentrations for some genotypes. Eight samples with substitutions in the HBV 'a' determinant were reliably detected after a 1/100 dilution. The POC strips were used to screen serum samples from 297 individuals at risk for HBV in local clinical settings (health fairs and outreach events) in parallel with commercial laboratory HBsAg testing (Quest Diagnostics EIA). POC testing was 73.7% sensitive and 97.8% specific for detection of HBsAg. Although the POC test demonstrated high sensitivity over a range of genotypes, false negatives were frequent in a clinical setting. Nevertheless, the POC assay offers advantages for testing in both developed and resource-limited countries due to its low cost (0.50$) and immediately available results. © 2014 John Wiley & Sons Ltd.

  7. Circulating MicroRNAs in Plasma of Hepatitis B e Antigen Positive Children Reveal Liver-Specific Target Genes

    Directory of Open Access Journals (Sweden)

    Thilde Nordmann Winther

    2014-01-01

    Full Text Available Background and Aim. Hepatitis B e antigen positive (HBeAg-positive children are at high risk of severe complications such as hepatocellular carcinoma and cirrhosis. Liver damage is caused by the host immune response to infected hepatocytes, and we hypothesise that specific microRNAs play a role in this complex interaction between virus and host. The study aimed to identify microRNAs with aberrant plasma expressions in HBeAg-positive children and with liver-specific target genes. Methods. By revisiting our previous screen of microRNA plasma levels in HBeAg-positive and HBeAg-negative children with chronic hepatitis B (CHB and in healthy controls, candidate microRNAs with aberrant plasma expressions in HBeAg-positive children were identified. MicroRNAs targeting liver-specific genes were selected based on bioinformatics analysis and validated by qRT-PCR using plasma samples from 34 HBeAg-positive, 26 HBeAg-negative, and 60 healthy control children. Results. Thirteen microRNAs showed aberrant plasma expressions in HBeAg-positive children and targeted liver-specific genes. In particular, three microRNAs were upregulated and one was downregulated in HBeAg-positive children compared to HBeAg-negative and healthy control children, which showed equal levels. Conclusion. The identified microRNAs might impact the progression of CHB in children. Functional studies are warranted, however, to elucidate the microRNAs’ role in the immunopathogenesis of childhood CHB.

  8. Expression of transforming growth factor-α and hepatitis B surface antigen in human hepatocellular carcinoma tissues and its significance

    Institute of Scientific and Technical Information of China (English)

    Jing Zhang; Wen-Liang Wang; Qing Li; Qing Qiao

    2004-01-01

    AIM: To evaluate the expression of transforming growth factor-alpha (TGF-α) and hepatitis B surface antigen (HBsAg) in human hepatocellular carcinoma (HCC) tissues and its significance. METHODS: Seventy specimens of HCC tissues were detected by immunohistochemical method. Five specimens of normal human liver tissues were used as control. RESULTS: The TGF-α positive expression rates in HCC and its surrounding tissues were 74.3%(52/70) and 88. t%(52/59), respectively. TGF-α positive granules were mainly in the cytoplasm and fewer existed on the karyotheca. The TGF-α positive expressing rate in well differentiated HCC was significantly higher than that in moderately and poorly differentiated HCC (P<0.05). The TGF-α positive expression also was observed in intrahepatic bile ducts (part of those were hyperplastic ducts). The HBsAg positive expression rates in HCC and its surrounding tissues were 21.4%(15/70) and 79.7%(47/59), respectively. HBsAg positive granules were in the cytoplasm, inclusion and on the karyotheca. There was a prominent positive correlation between TGF-α and HBsAg expression in HCC surrounding tissues (P<0.05, γ=0.34). TGF-α was usually existed with HBsAg in regenerated and/or dysplastic liver cells. In the five normal liver tissues, TGF-α and HBsAg were not detectable in hepatocytes and bile ducts.CONCLUSION: Hepatitis B virus infection is closely related with hepatocarcinogenesis. The overexpression of TGF-α in the liver seems to be associated with the regeneration of hepatocytes injured by HBsAg. The continued expression of TGF-α might lead to dysplasia of liver cells and development of HCC. Furthermore, TGF-α might play a role in morphogenesis and regeneration of intrahepatic bile ducts.

  9. Crystallization and X-ray diffraction analysis of the Trp/amber editing site of hepatitis delta virus (+)RNA: a case of rational design

    Energy Technology Data Exchange (ETDEWEB)

    MacElrevey, Celeste; Wedekind, Joseph E., E-mail: joseph-wedekind@urmc.rochester.edu [Department of Biochemistry and Biophysics, University of Rochester School of Medicine and Dentistry, Rochester, New York 14642 (United States)

    2005-12-01

    Well diffracting decamer crystals of the hepatitis delta virus RNA-editing site were prepared, but exhibited merohedral twinning and base averaging owing to duplex symmetry. A longer asymmetric construct that includes additional flanking RNA sequences has been crystallized that does not appear to exhibit these defects. RNA editing by mammalian ADAR1 (Adenosine Deaminase Acting on RNA) is required for the life cycle of the hepatitis delta virus (HDV). Editing extends the single viral open reading frame to yield two protein products of alternate length. ADARs are believed to recognize double-stranded RNA substrates via a ‘structure-based’ readout mechanism. Crystals of 10-mer duplexes representing the HDV RNA-editing site diffracted to 1.35 Å resolution, but suffered from merohedral twinning and averaging of the base registry. Expansion of the construct to include two flanking 3 × 1 internal loops yielded crystals in the primitive tetragonal space group P4{sub 1}2{sub 1}2 or P4{sub 3}2{sub 1}2. X-ray diffraction data were collected to 2.8 Å resolution, revealing a unit cell with parameters a = 62.5, c = 63.5 Å. The crystallization and X-ray analysis of multiple forms of the HDV RNA-editing substrate, encounters with common RNA crystal-growth defects and a strategy to overcome these problems are reported.

  10. Human Leukocyte Antigen Class II Alleles Are Associated with Hepatitis C Virus Natural Susceptibility in the Chinese Population

    Directory of Open Access Journals (Sweden)

    Ming Yue

    2015-07-01

    Full Text Available Human leukocyte antigen (HLA class II molecule influences host antigen presentation and anti-viral immune response. The aim of this study was to investigate whether single nucleotide polymorphisms (SNPs within HLA class II gene were associated with different clinical outcomes of hepatitis C virus (HCV infection. Three HLA class II SNPs (rs3077, rs2395309 and rs2856718 were genotyped by TaqMan assay among Chinese population, including 350 persistent HCV infection patients, 194 spontaneous viral clearance subjects and 973 HCV-uninfected control subjects. After logistic regression analysis, the results indicated that the rs2856718 TC genotype was significantly associated with the protective effect of the HCV natural susceptibility (adjusted OR: 0.712, 95% CI: 0.554–0.914 when compared with reference TT genotype, and this remained significant after false discovery rate (FDR correction (p = 0.024. Moreover, the protective effect of rs2856718 was observed in dominant genetic models (adjusted OR: 0.726, 95% CI: 0.574–0.920, and this remained significant after FDR correction (p = 0.024. In stratified analysis, a significant decreased risk was found in rs2856718C allele in the male subgroup (adjusted OR: 0.778, 95% CI: 0.627–0.966 and hemodialysis subgroup (adjusted OR: 0.713, 95% CI: 0.552–0.921. Our results indicated that the genetic variations of rs2856718 within the HLA-DQ gene are associated with the natural susceptibility to HCV infection among the Chinese population.

  11. Benefit of hepatitis C virus core antigen assay in prediction of therapeutic response to interferon and ribavirin combination therapy.

    Science.gov (United States)

    Takahashi, Masahiko; Saito, Hidetsugu; Higashimoto, Makiko; Atsukawa, Kazuhiro; Ishii, Hiromasa

    2005-01-01

    A highly sensitive second-generation hepatitis C virus (HCV) core antigen assay has recently been developed. We compared viral disappearance and first-phase kinetics between commercially available core antigen (Ag) assays, Lumipulse Ortho HCV Ag (Lumipulse-Ag), and a quantitative HCV RNA PCR assay, Cobas Amplicor HCV Monitor test, version 2 (Amplicor M), to estimate the predictive benefit of a sustained viral response (SVR) and non-SVR in 44 genotype 1b patients treated with interferon (IFN) and ribavirin. HCV core Ag negativity could predict SVR on day 1 (sensitivity = 100%, specificity = 85.0%, accuracy = 86.4%), whereas RNA negativity could predict SVR on day 7 (sensitivity = 100%, specificity = 87.2%, accuracy = 88.6%). None of the patients who had detectable serum core Ag or RNA on day 14 achieved SVR (specificity = 100%). The predictive accuracy on day 14 was higher by RNA negativity (93.2%) than that by core Ag negativity (75.0%). The combined predictive criterion of both viral load decline during the first 24 h and basal viral load was also predictive for SVR; the sensitivities of Lumipulse-Ag and Amplicor-M were 45.5 and 47.6%, respectively, and the specificity was 100%. Amplicor-M had better predictive accuracy than Lumipulse-Ag in 2-week disappearance tests because it had better sensitivity. On the other hand, estimates of kinetic parameters were similar regardless of the detection method. Although the correlations between Lumipulse-Ag and Amplicor-M were good both before and 24 h after IFN administration, HCV core Ag seemed to be relatively lower 24 h after IFN administration than before administration. Lumipulse-Ag seems to be useful for detecting the HCV concentration during IFN therapy; however, we still need to understand the characteristics of the assay.

  12. Comparative study of methods of detection of hepatitis ′B′ surface antigen (HBsAg.

    Directory of Open Access Journals (Sweden)

    Parab V

    1989-04-01

    Full Text Available The serum samples were collected from 52 patients of acute viral hepatitis and 235 hospital staff from Kasturba Hospital for Infectious Diseases. HBsAg was detected in their sera by counter-immuno-electrophoresis (CIEP, reverse passive hemogglutination (RPHA and by micro-enzyme-linked-immunosorbent assay (ELISA technique. Among the patients, HBsAg was detected in 12 cases (23% by CIEP, in 18 cases (34% by RPHA and in 23 patients (45% by ELISA. In the hospital staff, HBsAg was detected in 4 samples (1.7% by CIEP, in 8 samples (3.5% by RPHA and in 32 samples (13.5% by ELISA. Thus ELISA was found to be the most sensitive technique in detecting HBsAg.

  13. Combined hepatitis C virus (HCV) antigen-antibody detection assay does not improve diagnosis for seronegative individuals with occult HCV infection.

    Science.gov (United States)

    Quiroga, Juan A; Castillo, Inmaculada; Pardo, Margarita; Rodríguez-Iñigo, Elena; Carreño, Vicente

    2006-12-01

    A combined hepatitis C virus (HCV) antigen-antibody assay was evaluated for 115 seronegative individuals with occult HCV infection. The assay was reactive in one patient and negative to weakly reactive in three others (all four gave indeterminate results by supplemental assay) but failed to detect HCV in the remaining patients. Despite increased sensitivity the combined assay does not improve serodiagnosis of occult HCV infection.

  14. Combined Hepatitis C Virus (HCV) Antigen-Antibody Detection Assay Does Not Improve Diagnosis for Seronegative Individuals with Occult HCV Infection▿

    OpenAIRE

    Quiroga, Juan A.; Castillo, Inmaculada; Pardo, Margarita; Rodríguez-Iñigo, Elena; CARREÑO, VICENTE

    2006-01-01

    A combined hepatitis C virus (HCV) antigen-antibody assay was evaluated for 115 seronegative individuals with occult HCV infection. The assay was reactive in one patient and negative to weakly reactive in three others (all four gave indeterminate results by supplemental assay) but failed to detect HCV in the remaining patients. Despite increased sensitivity the combined assay does not improve serodiagnosis of occult HCV infection.

  15. Clinical evaluation of a new enzyme immunoassay for hepatitis B virus core-related antigen; a marker distinct from viral DNA for monitoring lamivudine treatment.

    Science.gov (United States)

    Rokuhara, A; Tanaka, E; Matsumoto, A; Kimura, T; Yamaura, T; Orii, K; Sun, X; Yagi, S; Maki, N; Kiyosawa, K

    2003-07-01

    We aimed to assess the clinical performance of a newly developed chemiluminescence enzyme immunoassay (CLEIA) for the detection of hepatitis B virus (HBV) core-related antigen (HBcrAg) in patients with chronic HBV infection. A total of 82 patients with chronic HBV infection and 167 HBV-negative controls were studied. HBcrAg was measured by CLEIA with monoclonal antibodies to hepatitis B e antigen (HBeAg) and hepatitis B core antigen (HBcAg), and HBV DNA was measured by transcription-mediated amplification assay (TMA) and in-house real-time detection polymerase chain reaction (RTD-PCR). The HBcrAg assay detected viremia in 189 of 216 samples (88%) collected from 72 patients whilst the TMA assay detected viremia in 178 of the 216 samples (82%) (P = 0.019). The HBcrAg concentration correlated linearly with the HBV DNA concentration (P HBcrAg assay was not affected by the absence of hepatitis B e antigen from the serum or the presence of precore mutations in the HBV genome. In patients without anti-viral drugs, changes in their serum HBcrAg concentration over time corresponded to their HBV DNA concentration. In six additional patients who were later treated with lamivudine, HBV DNA concentration declined more rapidly than their HBcrAg concentration. Three months after treatment commenced, the ratio of HBcrAg: HBV DNA had increased in all six patients (P = 0.031). The HBcrAg assay is a sensitive and useful test for the assessment of a patient's HBV load. When monitoring the anti-viral effect of lamivudine, HBcrAg provides a viral marker which is independent of HBV DNA.

  16. Hepatitis

    Institute of Scientific and Technical Information of China (English)

    1993-01-01

    930140 Hepatocyte stimulator peptide and itsclinical significance in viral hepatitis.ZHOUWeiping(周卫平),et al.Instit Viral Hepatitis,Chongqing Med Univ,630010.Chin J InternMed 1992;31(10):626-628.Hepatocyte stimulator peptide(HSP)is anewly developed hepatic stimulator substance.Its monoclonal antibodies have been obtained inour laboratory.In this study,HSP was deter-mined in the sera of 315 subjects including pa-

  17. Hepatitis

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    2010349 Relationships between serum hepatitis B virus load in mothers,free maternal DNA in peripheral blood of newborns and hepatitis B virus infection of newborns. WEI Junni(魏俊妮),et al. Dept Epidemiol,Shanxi Med Univ,Taiyuan 030001. Chin J Infect Dis 2010;28(5):297-300. Objective To study the relationships between serum hepatitis B virus (HBV) DNA level

  18. Hepatitis B surface antigen nanoparticles coated with chitosan and trimethyl chitosan: Impact of formulation on physicochemical and immunological characteristics.

    Science.gov (United States)

    Tafaghodi, Mohsen; Saluja, Vinay; Kersten, Gideon F A; Kraan, Heleen; Slütter, Bram; Amorij, Jean-Pierre; Jiskoot, Wim

    2012-08-03

    Mucosal immunization offers various advantages over parenteral vaccination, but typically requires potent delivery systems and/or adjuvants to result in protective immunity. Here we report on the preparation of trimethylated chitosan (TMC) and chitosan (CHT) nanoparticles (NPs) loaded with hepatitis B surface antigen (HB), by a simple and scalable method. TMC:HB and CHT:HB NPs were prepared by direct coating of antigen by polymer. The impact of buffer, pH and tonicity of the dispersion medium on NPs' polydispersity, zeta potential and association percentage of polymer with antigen was evaluated. Moreover, biological properties of both NPs were addressed in vitro by studying their effect on cell viability, transepithelial electrical resistance (TEER) and dendritic cell (DC) maturation. Finally, immunogenicity was assessed by evaluating IgG, IgG1, IgG2a, IgA titers and sIgA after both mucosal (nasal) as well intramuscular (i.m.) vaccination in a murine model. TMC:HB and CHT:HB NPs, prepared in acetate buffer pH 6.7 of three different tonicities, had comparable size, polydispersity, zeta potential and association percentage. TMC:HB NPs, but not CHT:HB NPs, had a mild negative effect on cell viability and TEER, and a considerable positive effect on DC maturation. After nasal and i.m. immunization, TMC:HB NPs in hypotonic medium and CHT:HB NPs in all media induced higher serum and nasal antibody titers compared with HB solution (P<0.001). After i.m. injection, both TMC:HB and CHT:HB NPs induced higher IgG and IgG2a titers compared with alum adsorbed HB (P<0.001). For CHT:HB NPs, the tonicity of the dispersion medium did not affect the mucosal and systemic immune responses. In conclusion, TMC NPs and CHT NPs are similarly potent mucosal immunoadjuvants for HB. Moreover, both polymers are potent immunoadjuvants for i.m. administered isotonic HB, resulting in higher IgG2a/IgG1 ratios compared with alum adjuvanted HB.

  19. The terminology of hepatitis*

    Science.gov (United States)

    1973-01-01

    It is proposed that the diseases formerly known as “infectious hepatitis” and “serum hepatitis” be referred to as viral hepatitis type A and viral hepatitis type B, respectively. It is further recommended that the “Australia” antigen be referred to as hepatitis B antigen (HB Ag) and the corresponding antibody as hepatitis B antibody (HB Ab). PMID:4544683

  20. Long-term effect of interferon plus ribavirin on hepatitis B surface antigen seroclearance in patients dually infected with hepatitis B and C viruses.

    Directory of Open Access Journals (Sweden)

    Ming-Lun Yeh

    Full Text Available BACKGROUND: Interferon-α/ribavirin combination therapy might promote hepatitis B surface antigen (HBsAg seroclearance in patients dually infected with hepatitis B and C viruses (HBV/HCV, but the long-term effect remains unclear. We aimed to investigate the rate of and the factors associated with HBsAg seroclearance during long-term follow-up after interferon-α/ribavirin combination therapy in HBV/HCV dually-infected patients. METHODOLOGY/PRINCIPAL FINDINGS: Eighty-one patients who received interferon-α/ribavirin combination therapy for 24 weeks with a follow-up period of >24 weeks were enrolled. HBV serological markers and HBV DNA were determined every 6 months. Early and late HBsAg seroclearance were defined as HBsAg loss in less or more than 6 months after end-of-treatment, respectively. Fifteen (18.5% patients had HBsAg seroclearance during a mean follow-up period of 3.4 (0.5-5.1 years. The 5-year cumulative incidence was 25.6%. Baseline cirrhosis and HBV DNA negativity 1 year after end-of-treatment were independently predictive of HBsAg seroclearance with an odds ratio (OR, 95% confidence intervals (CI of 16.6, 1.8-153 and 9.2, 1.4-62.1, respectively, by Cox regression hazard analysis. Four patients developed early and 11 developed late HBsAg seroclearance, respectively. Cox regression hazard analysis showed no factor was associated with early HBsAg seroclearance, whilst HBV DNA negativity 1 year after end-of-treatment was the only significant factor predicting late HBsAg loss (OR, 43.0; CI, 2.5-745. Five patients had HBsAg seroconversion with a 5-year cumulative incidence of 8.3%. HBV DNA negativity at baseline and one year after EOT had a trend for HBsAg seroconversion. HCV response did not correlate to HBsAg loss. CONCLUSIONS: We demonstrated that interferon-α/ribavirin had long-term effect on HBsAg seroclearance in dually HBV/HCV-infected patients. Baseline cirrhosis and seroclearance of HBV DNA 1 year after end-of-treatment were

  1. Hepatitis B surface antigen quantity positively correlates with plasma levels of microRNAs differentially expressed in immunological phases of chronic hepatitis B in children.

    Directory of Open Access Journals (Sweden)

    Thilde Nordmann Winther

    Full Text Available BACKGROUND AND AIM: Children with chronic hepatitis B (CHB are at high risk of progressive liver disease. It is suggested that a newly-identified panel of 16 microRNAs is important in the pathogenesis of CHB in children. Subviral hepatitis B surface antigen (HBsAg particles are produced in large excess over infectious virions. Interestingly, circulating HBsAg particles have been shown to carry microRNAs. A thorough characterisation of the identified microRNAs and HBsAg over time in plasma from children with CHB may provide useful information about the natural course of childhood CHB. PATIENTS AND METHODS: A cohort of 42 children with CHB was followed over time. Three to five blood samples were obtained from each child at minimum intervals of half a year; in total 180 blood samples. Plasma levels of the 16 microRNAs previously identified were analysed by quantitative real-time polymerase-chain-reaction. Plasma HBsAg was quantified using ARCHITECT® HBsAg assay. RESULTS: The presence of 14/16 plasma microRNAs in children with CHB was confirmed. All 14 microRNAs were significantly differentially expressed in different immunological phases of the disease. MicroRNA plasma levels were highest in immune-tolerant children, lower in immune-active children, and reached the lowest values in immune-inactive children, p<0.001. Plasma levels of four microRNAs decreased significantly over time in immune-tolerant and immune-active children whereas the microRNA plasma levels were stable in immune-inactive children, p<0.004. HBsAg quantity was positively correlated with plasma levels of 11/14 microRNAs, p<0.004. CONCLUSION: This is the first study to characterise plasma microRNAs and HBsAg over time in children with CHB. Our data suggest that plasma levels of selected microRNAs and HBsAg are inversely correlated with immunological control of CHB in children. Further studies are, however, needed to advance the understanding of microRNAs and HBsAg in the

  2. The prevalence of mutations in the major hydrophilic region of the surface antigen of hepatitis B virus varies with subgenotype.

    Science.gov (United States)

    Wang, X Y; Harrison, T J; He, X; Chen, Q Y; Li, G J; Liu, M H; Li, H; Yang, J Y; Fang, Z L

    2015-12-01

    Mutations in the major hydrophilic region (MHR) of the surface antigen of hepatitis B virus (HBV) may result in vaccine escape, failure of immunotherapy and antiviral resistance. These mutants may be transmitted and constitute a public health threat. We aimed to determine the prevalence of MHR mutations of HBV in areas of high endemicity in Guangxi, China. HBV surface gene was analysed from 278 HBsAg-positive asymptomatic individuals recruited from Guangxi using cluster sampling. Three genotypes, B, C and I, were identified. The overall prevalence of MHR mutations is 17·6%. The prevalence of MHR mutations in genotype B (15·1%) is not significantly different from that in genotype C (16·4%). However, the prevalence in subgenotype C5 (31·1%) is significantly higher than in subgenotype C2 (13·0%) (χ 2 = 6·997, P subgenotype C5 is significantly higher than in subgenotypes B2 and C2. In total, 7·9% of MHR mutants are escape mutations and 72·1% of MHR mutations produced amino-acid changes in the overlapping polymerase, including resistance mutations to entecavir. Our results suggest that the prevalence of MHR mutations varies with subgenotype. The prevalence of escape mutations and polymerase mutations may be associated with subgenotype.

  3. Sero-Prevalence of Hepatitis B Surface Antigen Amongst Pregnant Women Attending an Antenatal Clinic, Volta Region, Ghana

    Science.gov (United States)

    Dassah, Sylvester; Lokpo, Sylvester; Ameke, Louise; Noagbe, Mark; Adatara, Peter; Hagan, Oheneba; Binka, Fred

    2017-01-01

    Hepatitis B virus (HBV) infection remains a global challenge, although there is currently a safe and effective vaccine available. HBV prevalence in Ghana is not well documented, but vary regionally from 4.8% to 12.3% in the general population, 10.8% to 12.7% in blood donors and about 10.6% in pregnant women. This puts Ghana among the high endemic countries in Africa. The study objective was to determine the sero-prevalence of HBs antigen (Ag) and HBeAg among pregnant women in the Ho municipality. Two hundred and eigh participants (pregnant women), attending Ho Municipal antenatal clinic were enrolled into the study. This study recorded a HBsAg sero-prevalence rate of 2.4% among the pregnant women, with primigravida pregnant women recording (0.98%) and multigravida (1.42%). The prevalence of HBsAg among the pregnant women can be classified as Low Intermediate; therefore there is still the need for routine screening of pregnant women during antenatal visits. Amongst HBsAg positives, HBeAg positivity was significantly high (40% of all HBsAg positive women), which suggests high chances of carrier and vertical transmission (mother to child) state. PMID:28299162

  4. Pectinesterase Inhibitor from Jelly Fig (Ficus awkeotsang Makino Achene Inhibits Surface Antigen Expression by Human Hepatitis B Virus

    Directory of Open Access Journals (Sweden)

    Yu-Chuen Huang

    2013-01-01

    Full Text Available Pectinesterase inhibitor (PEI isolated from jelly fig (Ficus awkeotsang Makino is an edible component of a popular drink consumed in Asia. Hepatitis B virus (HBV infection is prevalent in Asia, and current treatments for HBV infection need improvement. This study aimed to evaluate the effect of PEI on the surface antigen expression by HBV (HBsAg. Human hepatoma cell lines Hep3B and Huh7 served as in vitro models for assessing the cytotoxicity and HBsAg expression. A culture of primary hepatocytes cultured from mice served as the normal counterpart. Cell viability was measured by 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide (MTT colorimetric assay. HBsAg expression was evaluated by measuring HBsAg secretion into the culture medium using an enzyme-linked immunosorbent assay. The results showed that PEI did not affect the viability of the human hepatoma cell lines or primary mouse hepatocytes. PEI inhibited the expression of HBsAg in hepatoma cell lines harboring endogenous (Hep3B and integrated (Huh7 HBV genomes in a concentration- and time-dependent manner, thus implicating a universal activity against HBV gene expression. In conclusion, it suggests that PEI from jelly fig inhibits the expression of human HBsAg in host cells without toxic effects on normal primary hepatocytes.

  5. Prevalence of hepatitis B surface antigen & its subtypes in high risk group subjects & voluntary blood donors in Bombay.

    Science.gov (United States)

    Elavia, A J; Banker, D D

    1991-09-01

    HBsAg positive subjects belonging to high risk groups and voluntary blood donors were analysed for prevalence of HBsAg among various groups of subjects for ascertaining the carrier status among the voluntary blood donors, HBsAg subtype distribution, and association of HBsAg with blood groups and caste or religion. The prevalence of HBsAg varied from 2.02 per cent in voluntary blood donors to 58.38 per cent in patients of acute viral hepatitis. 70.5 per cent subjects had subtype 'ay' while 23.9 per cent of the subjects had subtype 'ad'. We also found compound 'ady' subtype in 5.6 per cent of our subjects. HBsAg/adr, a subtype not usually prevalent in India, was found in 30 of the 90 'ad' sera. Co-occurrence of HBsAg and anti-HBs was noted in 9 subjects. Homotypic anti-HBs was found to occur together mainly in voluntary blood donors, while heterotypic anti-HBs was found to occur together mainly multi-transfused patients. There was no significant correlation between HBsAg and blood group antigens and a relatively higher incidence of HBsAg among the Jain community was observed.

  6. Detection of Rubisco and mycotoxins as potential contaminants of a plantibody against the hepatitis B surface antigen purified from tobacco.

    Science.gov (United States)

    Geada, Déborah; Valdés, Rodolfo; Escobar, Arturo; Ares, Dulce M; Torres, Edel; Blanco, Reinaldo; Ferro, Williams; Dorta, Dayamí; González, Marcos; Alemán, María R; Padilla, Sigifredo; Gómez, Leonardo; Del Castillo, Norma; Mendoza, Otto; Urquiza, Dioslaida; Soria, Yordanka; Brito, José; Leyva, Alberto; Borroto, Carlos; Gavilondo, Jorge V

    2007-10-01

    Antibodies have been one of the proteins widely expressed in tobacco plants for pharmaceutical purposes, which demand contaminant free preparations. Rubisco constitutes 40-60% of tobacco leaf soluble proteins; therefore it is the major potential protein contaminant of plantibodies, while mycotoxins are toxic compounds that could be introduced during the biomass production and post-harvest stages with important consequences to human health. The objective of this paper was to investigate whether Rubisco and mycotoxins are present in Plantibody HB-01 preparations used in the immunopurification of the hepatitis B surface antigen. Rubisco was purified from Nicotiana tabacum yielding 154 microg of protein per gram of leaves and purity over 95%. Among mouse monoclonal antibodies generated against this enzyme, the CBSS.Rub-2 was selected for its immunodetection. It recognizes a conserved sequential epitope of Rubisco large subunit with an affinity constant of 0.13 x 10(8)M(-1). Rubisco quantification limit was 1 microg spreading to the measurement of this contaminant less than 4% of plantibodies samples. Additionally, according to a Reverse Phase-HPLC used to measure the level of adventitiously introduced contaminants, it can be concluded that aflatoxins B1, B2, G1 and G2 were undetected in the purified Plantibody HB-01 samples.

  7. Enhanced cell disruption strategy in the release of recombinant hepatitis B surface antigen from Pichia pastoris using response surface methodology

    Directory of Open Access Journals (Sweden)

    Tam Yew

    2012-10-01

    Full Text Available Abstract Background Cell disruption strategies by high pressure homogenizer for the release of recombinant Hepatitis B surface antigen (HBsAg from Pichia pastoris expression cells were optimized using response surface methodology (RSM based on the central composite design (CCD. The factors studied include number of passes, biomass concentration and pulse pressure. Polynomial models were used to correlate the above mentioned factors to project the cell disruption capability and specific protein release of HBsAg from P. pastoris cells. Results The proposed cell disruption strategy consisted of a number of passes set at 20 times, biomass concentration of 7.70 g/L of dry cell weight (DCW and pulse pressure at 1,029 bar. The optimized cell disruption strategy was shown to increase cell disruption efficiency by 2-fold and 4-fold for specific protein release of HBsAg when compared to glass bead method yielding 75.68% cell disruption rate (CDR and HBsAg concentration of 29.20 mg/L respectively. Conclusions The model equation generated from RSM on cell disruption of P. pastoris was found adequate to determine the significant factors and its interactions among the process variables and the optimum conditions in releasing HBsAg when validated against a glass bead cell disruption method. The findings from the study can open up a promising strategy for better recovery of HBsAg recombinant protein during downstream processing.

  8. [Development of a new hydrophobic interaction chromatography absorbent and its application to the purification of recombinant hepatitis B surface antigen].

    Science.gov (United States)

    Wang, Yang-Mu; Bi, Jing-Xiu; Zhao, Lan; Zhou, Wei-Bin; Li, Yan; Huang, Yong-Dong; Zhang, Yan; Lin, Hai; Su, Zhi-Guo

    2006-03-01

    A new hydrophobic absorbent based on homemade highly cross-linked agarose beads was synthesized by immobilizing butyl derivative onto the matrix linkage. The density of ligand was controlled by adjusting the concentration of butanethiol and the synthesis route was optimized by evaluating the purification efficiency of recombinant Hepatitis B surface antigen (HBsAg) expressed by Chinese hamster ovary (CHO) cell line. A high performance absorbent was finally screened out with up to 80% of HBsAg recovery and purification-fold (PF) about 20. Furthermore, the column pressure was about 0.06 MPa under the flow rate of 500cm/h, and no leaked butyl were detected after exposing the gel in common buffers, chaotropic agents, high concentrations of denaturing agents such as guanidine hydrochloride, urea and polar organic solvents. These results demonstrated that the absorbent have high physico-chemical stability, so it was available for the downstream process. Finally, after scaled up to 2L wet gel/batch, the absorbent was applied to the integration of three-step chromatography and obtained the purified CHO-HBsAg with 95% purity by SDS-PAGE and HPLC, which meet the requirements of SFDA. The purification efficiency and the reproducible ability of the absorbents were also evaluated from batch-to-batch. The results demonstrated that the absorbent met the requirement of scalable, reproducible, economic effect as well. This absorbent is a promising alternative exported HIC gel for wildly being used in Chinese pharmaceutical industries.

  9. Immunogenicity and safety of liposome-vaccine encapsulating hepatitis B surface antigen and phosphodiester CpG oligodeoxynucleotides

    Institute of Scientific and Technical Information of China (English)

    CHUN YAN HE; QING LIANG LIU

    2006-01-01

    CpG oligodeoxynucleotides (CpG ODN) as adjuvant have been extensively studied in recent years. Phosphodiester CpG ODN (PO CpG ODN) can perfectly mimic bacterial DNA in enhancing immune response but are vulnerable to nucleases in vivo. This study aimed to evaluate the immunostimu latory potential and safety of phosphodiester CpG ODN encapsulated in nonphospholipid liposomes.BALB/c mice were immunized intramuscularly with different formulations of liposomes, CpG ODN and hepatitis B surface antigen (HBsAg). The results demonstrated that the encapsulated PO CpG ODN were protected against rapid degradation in vivo and retained their adjuvant activity. PO CpG ODN encapsulated with HBsAg in liposomes induced strong Th1-biased or Th1/Th2 mixed humoral immune response in mice with the magnitude similar to their phosphothioate equivalent in the same formulation.High IFN-gamma production induced by this formulation confirmed the generation of strong cellular immune response. Additionally, co-delivery of HBsAg and PO CpG ODN improved the immune response over that obtained with separate delivery. Safety experiment showed that liposome-encapsulaed PO CpG ODN and HBsAg caused mild systemic and moderate local adverse reaction. In conclusion, our data shows that PO CpG ODN encapsulated in liposomes fully exhibit their Th1-type adjuvant activity and act as a potential adjuvant for vaccines.

  10. E2 GLYCOPROTEIN OF GENOTYPE Ⅲ CHINESE ISOLATES OF HEPATITIS C VIRUS EXPRESSED IN MAMMALIAN CELL AS ANTIGEN FOR ANTI-E2 ANTIBODY DETECTION

    Institute of Scientific and Technical Information of China (English)

    吴朝栋; 陶其敏

    1998-01-01

    Expression vector inserted with E2/NS1 gane derived from ganotype Ⅲ Chinese isolates of HCV was transfected into mammalian cells to express E2 glycoprotein. Expressed protein was used as antigen for anti-E2 antibody detection in 19 cases of hepatitis C patients by Western blot. It was first to express E2 glycoprotein of genotype Ⅲ Chinese hepatitis C virus isolates. For anti-E2 detection, 14 cases of patients were positive of antibodies against E2(73.7%). These results indicated that E2 glycoprotein expressed in mammalian cells had good immunoganicity and cross reactivity to serum infected with genotype Ⅱ Chinese hepatitis C virus isolates.

  11. HD-03/ES: A Herbal Medicine Inhibits Hepatitis B Surface Antigen Secretion in Transfected Human Hepatocarcinoma PLC/PRF/5 Cells.

    Science.gov (United States)

    Varma, Sandeep R; Sundaram, R; Gopumadhavan, S; Vidyashankar, Satyakumar; Patki, Pralhad S

    2013-01-01

    HD-03/ES is a herbal formulation used for the treatment of hepatitis B. However, the molecular mechanism involved in the antihepatitis B (HBV) activity of this drug has not been studied using in vitro models. The effect of HD-03/ES on hepatitis B surface antigen (HBsAg) secretion and its gene expression was studied in transfected human hepatocarcinoma PLC/PRF/5 cells. The anti-HBV activity was tested based on the inhibition of HBsAg secretion into the culture media, as detected by HBsAg-specific antibody-mediated enzyme assay (ELISA) at concentrations ranging from 125 to 1000  μ g/mL. The effect of HD-03/ES on HBsAg gene expression was analyzed using semiquantitative multiplex RT-PCR by employing specific primers. The results showed that HD-03/ES suppressed HBsAg production with an IC50 of 380  μ g/mL in PLC/PRF/5 cells for a period of 24 h. HD-03/ES downregulated HBsAg gene expression in PLC/PRF/5 cells. In conclusion, HD-03/ES exhibits strong anti-HBV properties by inhibiting the secretion of hepatitis B surface antigen in PLC/PRF/5 cells, and this action is targeted at the transcription level. Thus, HD-03/ES could be beneficial in the treatment of acute and chronic hepatitis B infections.

  12. Human hepatitis B viral e antigen and its precursor P20 inhibit T lymphocyte proliferation

    Energy Technology Data Exchange (ETDEWEB)

    Purvina, Maija; Hoste, Astrid; Rossignol, Jean-Michel [Universite de Versailles-Saint-Quentin-en-Yvelines, Laboratoire de Genetique et Biologie Cellulaire, EA 4589, 45 avenue des Etats-Unis, 78035 Versailles (France); Lagaudriere-Gesbert, Cecile, E-mail: cecile.lagaudriere-gesbert@u-psud.fr [Universite de Versailles-Saint-Quentin-en-Yvelines, Laboratoire de Genetique et Biologie Cellulaire, EA 4589, 45 avenue des Etats-Unis, 78035 Versailles (France)

    2012-01-27

    Highlights: Black-Right-Pointing-Pointer P20, precursor of the HBeAg, interacts with the cellular protein gC1qR. Black-Right-Pointing-Pointer HBeAg and P20 bind to T cell surface and inhibit mitogen-induced T cell division. Black-Right-Pointing-Pointer HBeAg and P20 inhibition of T cell proliferation is gC1qR and IL-1RAcP-independent. -- Abstract: The hepatitis B virus (HBV) Precore protein is processed through the secretory pathway directly as HBeAg or with the generation of an intermediate (P20). Precore gene has been shown to be implicated in viral persistence, but the functions of HBeAg and its precursors have not been fully elucidated. We show that the secreted proteins HBeAg and P20 interact with T cell surface and alter Kit-225 and primary T cells proliferation, a process which may facilitate the establishment of HBV persistence. Our data indicate that the N-terminal end of Precore is important for these inhibitory effects and exclude that they are dependent on the association of HBeAg and P20 with two characterized cell surface ligands, the Interleukin-1 Receptor Accessory Protein and gC1qR (present study).

  13. Cationic Lipid-Formulated DNA Vaccine against Hepatitis B Virus : Immunogenicity of MIDGE-Th1 Vectors Encoding Small and Large Surface Antigen in Comparison to a Licensed Protein Vaccine

    NARCIS (Netherlands)

    Endmann, Anne; Klunder, Katharina; Kapp, Kerstin; Riede, Oliver; Oswald, Detlef; Talman, Eduard G.; Schroff, Matthias; Kleuss, Christiane; Ruiters, Marcel H. J.; Juhls, Christiane

    2014-01-01

    Currently marketed vaccines against hepatitis B virus (HBV) based on the small (S) hepatitis B surface antigen (HBsAg) fail to induce a protective immune response in about 10% of vaccinees. DNA vaccination and the inclusion of PreS1 and PreS2 domains of HBsAg have been reported to represent feasible

  14. Correlation between serum hepatitis B virus core-related antigen and intrahepatic covalently closed circular DNA in chronic hepatitis B patients.

    Science.gov (United States)

    Suzuki, Fumitaka; Miyakoshi, Hideo; Kobayashi, Mariko; Kumada, Hiromitsu

    2009-01-01

    Nucleos(t)ide analogues are utilized for the treatment of chronic HBV infection, and HBe seroconversion and HBV DNA levels are commonly used as markers of viral status and as primary treatment endpoints. Recently, a new assay was prepared for the detection of serum HBV core-related antigen (HBcrAg), consisting of HBcAg, HBeAg, and p22cr, which is a precore protein from amino acid -28 to at least amino acid 150, by coding the precore/core region. In this study, we examined the correlation between serum HBcrAg concentration and viral status by the analysis of serum HBeAg, HBsAg, peripheral HBV DNA, and intrahepatic covalently closed circular DNA (cccDNA) in 57 chronic hepatitis B patients. Intrahepatic cccDNA was detected in all 57 patients, 42 patients were HBcrAg-positive, and serum HBcrAg concentration level was closely correlated with cccDNA. Additionally, positive HBcrAg concentration level results were observed in 6 out of 13 HBsAg seroclearance patients and 20 out of 31 HBV DNA-negative patients. Moreover, the correlation between HBcrAg and cccDNA in these 31 HBV DNA-negative patients was statistically significant (r = 0.482, P = 0.006). These data suggest that serum HBcrAg concentration is well correlated with intrahepatic cccDNA level, and that the measurement of serum HBcrAg may be clinically useful for monitoring intrahepatic HBV viral status, especially in patients under treatment with nucleos(t)ide analogues.

  15. Hepatitis

    Science.gov (United States)

    ... inflammation of the liver.” This inflammation can be caused by a wide variety of toxins, drugs, and metabolic diseases, as well as infection. There are at least 5 hepatitis viruses. Hepatitis A is contracted when a child eats food or drinks water that is contaminated with the virus or has ...

  16. Hepatitis

    Institute of Scientific and Technical Information of China (English)

    1997-01-01

    970349 Primary structure and variability of partialsequences in nonstructural gene 5 region of hepatitis Gvirus, CHANG Jinhong(常锦红), et al. Hepatol Instis,People’s Hosp, Beijing Med Univ, Beijing, 100044. NatlMed J China 1997; 77(3): 178-182. Objective: To sequence partial genome of hepatitis G

  17. Hepatitis

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    2009209 Effects of chronic hepatitis B virus infection on human hepatic cytochrome P450 2C9.ZHO Fuping(周福平),et al.Dept Infect Dis,Shanghai Changzheng Hosp,Shanghai 200003.Chin J Infect Dis,2009;27(2):94-98.

  18. Hepatitis

    Institute of Scientific and Technical Information of China (English)

    1992-01-01

    920691 The determination of serum hepa-titis B virus DNA by polymerase chain rea-ction in hepatitis B patients treated withalpha-interferon. XU. Jianye(徐建业), et al.Centr Lab, Chongqing Cancer Instit, 630030.Chin J Intern Med, 1992; 31(5): 278-280. To clarify the status of HBV in serum of

  19. Long-Term Outcome of Sequential Therapy with Lamivudine Followed by Interferon-β in Nucleoside-Naive, Hepatitis B e-Antigen-Positive Patients with Chronic Hepatitis B Virus Genotype C Infection.

    Science.gov (United States)

    Enomoto, Masaru; Nishiguchi, Shuhei; Tamori, Akihiro; Kozuka, Ritsuzo; Hayashi, Takehiro; Kohmoto, Madoka Toyama; Jomura, Hisato; Morikawa, Hiroyasu; Murakami, Yoshiki; Shiomi, Susumu; Kawada, Norifumi

    2015-08-01

    It is unclear whether the combination of a nucleos(t)ide analog and interferon (IFN) is superior to monotherapy for treating chronic hepatitis B. In this study, we report the long-term outcomes of sequential therapy using lamivudine followed by IFN-β. This study included 24 hepatitis B e-antigen (HBeAg)-positive patients with chronic hepatitis B virus (HBV) genotype C infection who were treated with lamivudine alone for 16-32 weeks, then with both IFN-β and lamivudine for 4 weeks, and finally with IFN-β alone for 20 weeks. All patients were followed up for 7.1±2.8 years post-treatment. The rate of response, defined as transaminase normalization, HBeAg loss, and HBV DNA genotype C infection at 24 weeks post-treatment. In the majority of the short-term responders, however, the response was sustainable in the long term.

  20. EVALUATION OF HEPATITIS B SURFACE ANTIGEN POSITIVITY IN ANTENATAL WOMEN AND ROLE OF ANTIVIRAL THERAPY

    Directory of Open Access Journals (Sweden)

    Jhansi Rani

    2015-03-01

    Full Text Available BACKGROUND : Hepatitis B infection is a major global health problem . AIM : of the study is to identify the antenatal women who are HBsAg positive and to evaluate their viremic status to prevent vertical transmission from mother to foetus and role of antiviral therapy in pregnancy. STUDY DESIGN : I s two centres prospective cohort study. All the pregnant women who attended the antenatal OPD in Government Victoria hospital/ Andhra Medical C ollege , Visakhapatnam between February 2013 and September 2014 were evaluated. METHODS AND MATERIAL : HBs Ag screening was done using Rapid Stick test to all the pregnant women attending the OPD. 6400 members were screened. 100 subjects were HBsAg positive and confirmed by using ELISA technique. Evaluation for HBeAg and HBV viral load is done in all subjects. If HBV DNA is > 10 5 log copies/ml and Alanine transaminase (ALT is > 2 ULN or HBV DNA is >10 8 log copies/ml will be offered telbivudine therapy. RESULTS: Of the 6400 members screened , 100(1.5% were HBsAg positive. Of them , 10% were HBe Ag positive and 2% had HBV DNA > 10 5 log copies/ml. These patients were treated with drug , telbivudine in their third trimester. The HBV DNA level at the time of delivery is below 10 5 log copies/ml. The babies of these patients were checked for HBsAg and HBV DNA at birth and at 7th month which were negative and also for anti HBS at 7th month. CONCLUSIONS : The present study shows that HBsAg positive antenatal women are not prone for maternal and foetal complications. HBeAg positive individuals with high viremia need to be treated with antiviral drugs during the last trimester of pregnancy in order to prevent vertical transmission.

  1. Comparison of real-time PCR and antigen assays for detection of hepatitis E virus in blood donors.

    Science.gov (United States)

    Vollmer, T; Knabbe, C; Dreier, J

    2014-06-01

    Hepatitis E virus (HEV) infection is recognized as an emerging and often undiagnosed disease in industrialized countries, with asymptomatic infections actually occurring in blood donors. Sensitive detection of HEV-RNA is crucial for diagnosis and monitoring of disease progression. We evaluated the analytical sensitivity and performance of three HEV RT-PCR assays (RealStar HEV reverse transcription-PCR [RT-PCR], hepatitis@ceeramTools, and ampliCube HEV RT-PCR) for screening of individuals for HEV infections (ID-nucleic acid amplification technology [ID-NAT]) and for blood donor pool screening (minipool-NAT [MP-NAT]). RNA was extracted using NucliSens easyMAG (ID-NAT) and a high-volume extraction protocol (4.8 ml, chemagic Viral 5K, MP-NAT). Three NAT assays were evaluated for ID-NAT but only two assays for MP-NAT due to inhibition of the ampliCube HEV RT-PCR kit using the corresponding RNA extract. Assays provided good analytical sensitivity, ranging from 37.8 to 180.1 IU/ml (ID-NAT) and from 4.7 to 91.2 IU/ml (MP-NAT). The applicability of HEV antigen (HEV-Ag) screening was compared to that of RT-PCR screening and detection of HEV-IgM antibodies using seroconversion panels of 10 HEV genotype 3-infected individuals. Four individuals revealed a positive HEV-Ag detection result, with corresponding viremias ranging from 1.92 E + 03 to 2.19 E + 05 IU/ml, while the progression of HEV-Ag followed that of HEV viremia. The other six individuals showed no presence of HEV-Ag although the corresponding viremias were also in the range of >1.0 E + 03. Anti-HEV-IgM antibodies were detectable in seven donors; one donor presented parallel positivities of HEV-Ag and anti-HEV IgM. The evaluated NAT methods present powerful tools providing sensitive HEV detection. Application of HEV-Ag or anti-HEV IgM screening is currently inferior for the early detection of HEV infection due to the decreased sensitivity compared to NAT methods.

  2. Combination hepatitis C virus antigen and antibody immunoassay as a new tool for early diagnosis of infection.

    Science.gov (United States)

    Ansaldi, F; Bruzzone, B; Testino, G; Bassetti, M; Gasparini, R; Crovari, P; Icardi, G

    2006-01-01

    Reduction of the window period of hepatitis C virus (HCV) infection represents an important goal in the transfusional and diagnostic setting. A prototype assay designed to simultaneously detect circulating HCV antigen and anti-HCV, has been developed. Aim of this study was to evaluate the performance of this new assay in terms of specificity and sensitivity and to compare its efficacy with commercial assays. To evaluate the specificity of the assay, 400 samples from the general population and 100 'difficult' sera, negative for anti-HCV, were tested. To assess sensitivity, the new test was used on 76 PCR-positive and anti-HCV negative sera, seven natural or commercial seroconversion panels that included 17 RNA-positive and anti-HCV negative sera and 31 anti-HCV positive sera, 20 weak anti-HCV positive sera, 80 viraemic and anti-HCV-positive sera from patients infected with different subtypes and 10 sera from patients with HBV-HCV or HIV-HCV co-infections. Of 500 anti-HCV negative samples, 499 (99.8%) were negative with a cut-off index <0.5, while one sample was within the grey zone. Of the 93 HCV-RNA positive and anti-HCV negative sera from patients and panels, 85 (91.4%) resulted positive, and one had the cut-off index in the grey zone. The reduction in the diagnostic window period observed with the new test and HCV-RNA assays were equal, on average, to 24 and 34.4 days respectively. All anti-HCV positive sera were positive. The new assay shows high sensitivity and specificity and could be a useful tool not only in the diagnostic setting, where procedures to reduce the window period, such as antigen or HCV-RNA detection, are not currently recommended, but also in the screening of blood donations, when nucleic acid technologies is not feasible because of costs, organization, emergency and/or logistic difficulties.

  3. Hepatitis

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    2005226 Characteristics of peripheral blood T lymphocyte subsets in hepatitis B patients. FAN Zhen-ping(范振平),et al. Center Bio Ther, Instit Infect Dis, 302 Hosp Chin PLA, Beijing 100039. World Chin J Digestol, 2005;13(2): 194-197. Objective: To characterize the T-lymphocyte subsets in peripheral blood of patients with acute and chronic hepatitis B, and to explore their relations with the disease state. Methods: Peripheral blood

  4. Hepatocellular carcinoma. A study of 50 autopsy cases with detection of hepatitis B surface antigen in fixed tissues.

    Science.gov (United States)

    Perez-Barrios, A; Colina-Ruizdelgado, F; Gallego, I; Martinez-Tello, F J

    1983-03-01

    Fifty patients who died of hepatocellular carcinoma (HCC) were autopsied at the Ciudad Sanitaria "1 degree de Octubre" and the Hospital de la Cruz Roja (Madrid) from 1974 to 1980. Formalin fixed paraffin-embedded autopsy tissue of liver and tumor from the 50 HCC and liver tissue from 50 liver cirrhosis (LC) and from 50 autopsy of non cirrhotic control cases were examined for the presence of cytoplasmic hepatitis B surface antigen (HBsAg). The study was carried out using orcein staining, immunoperoxidase technique (IP) and indirect immunofluorescence (IF). In livers with HCC the HBsAg was detected in the cytoplasm of the hepatocytes in 10 cases (20%) with the orcein staining and in 11 (22%) with the IP and IF techniques. In one case (2%) HBsAg was found in the cytoplasm of tumor cells with the three methods--In four cases (8%) of LC and 2 (4%) control cases cytoplasmic positive cells were found. In 41 patients with HCC HBsAg was studied in the serum by radio-immunoassay (RIA) (13 cases) and immunodiffussion (28 cases). 5 patients (12,1%) were positive and 36 (72%) were negative. In the 5 serum positive HBsAg HCC the staining methods for cytoplasmic HBsAg were positive (100%). In 36 serum negative HBsAg HCC the staining method were positive in 2 cases. The results let us to conclude that HBV is a probable important etiologic factor of HCC in our milieu. 54% of the patients with HCC had a previous history of alcohol abuse; however, histologic features compatible with an alcoholic etiology were found in only 5 cases. Nevertheless we consider that the described histopathologic findings do not exclude excess alcohol consumption as a possible etiologic factor for HCC in our series.

  5. Rapid and transient activation of gamma/delta T cells to interferon gamma production, NK cell-like killing and antigen processing during acute virus infection

    Science.gov (United States)

    Gamma/delta T cells are the majority peripheral blood T cells in young cattle. The role of gamma/delta T cells in innate responses against infection with foot-and-mouth disease virus (FMDV) was analyzed on 5 consecutive days following infection. Before infection, bovine gamma/delta T cells expressed...

  6. Coimmunization with IL-15 plasmid enhances the longevity of CD8 T cells induced by DNA encoding hepatitis B virus core antigen

    Institute of Scientific and Technical Information of China (English)

    Wei Zhang; Sheng-Fu Dong; Shu-Hui Sun; Yuan Wang; Guang-Di Li; Di Qu

    2006-01-01

    AIM: To test the feasibility of delivering a plasmid encoding IL-15 as a DNA vaccine adjuvant for improving the immune responses induced by hepatitis B virus core gene DNA vaccine.METHODS: We used RT-PCR based strategies to develop IL-15 expression constructs. We first confirmed that the gene could be expressed in Escherichia coli due to the poor expression of IL-15. Then the bioactivity of IL-15 plasmid expression product was identified by CTLL-2 proliferation assay. One hundred micrograms of DNA from each of the IL-15 eukaryotic expressed plasmid and the recombinant plasmid harboring DNA encoding the 144 amino acids of the N-terminus of HBV core gene (abbreviated pHBc144) was used to co-immunize C57 BL/6 mice. The titer of anti-HBcIgG was detected by ELISA and the antigen-specific CD8+T cells (CD8+IFN-γ+ T cells) were detected by intracellular cytokine staining at different time points.RESULTS: After co-immunization by pIL-15 and pHBc144 DNA vaccine the antigen-specific CD8+ cells of mice increased gradually, the first peak of immune response appeared 14 d later, then the number of antigen-specific CD8+ Ts cells decreased gradually and maintained at a steady level in 3 mo. After boosting, the number of antigen-specific CD8+ T cells reached the second peak 10 d later with a double of the 1st peak, then the number of antigen-specific CD8+T cells decreased slowly. IL-15 as a gene adjuvant had no significant effect on humoral immune responses induced by hepatitis B virus core gene DNA vaccine, but increased the memory antigen-specific CD8+ T cells induced by hepatitis B virus core gene DNA vaccine.CONCLUSION: DNA vaccine constructed by HBc Ag 1-144 amino acid induces effective cell immunity, and cytokine plasmid-delivered IL-15 enhances the longevity of CD8+ T cells.

  7. Anti-hepatits B core antigen testing, viral markers, and occult hepatitis B virus infection in Pakistani blood donors: implications for transfusion practice.

    Science.gov (United States)

    Bhatti, Farhat Abbas; Ullah, Zia; Salamat, Nuzhat; Ayub, Muhammad; Ghani, Ejaz

    2007-01-01

    The purpose of this study was to determine the seroprevalence of anti-hepatitis B core antigen (HBc) and the impact of its testing along with other markers of hepatitis B, hepatitis B virus (HBV) DNA, hepatitis C virus antibody (anti-HCV), and syphilis in Pakistani blood donors. The study design was cross-sectional. A total of 966 donors were selected randomly for testing of anti-HBc and HBV markers, including HBV DNA, of 94,177 blood donors who were routinely screened for hepatitis B surface antigen (HBsAg), anti-HCV, human immunodeficiency virus antibody (anti-HIV), Treponema pallidum hemagglutination assay (TPHA), and malarial parasites from 2003 to October 2005. The seroprevalence of various infectious markers was as follows: HBsAg, 2.16 percent; anti-HCV, 4.16 percent; anti-HIV, 0.004 percent; TPHA, 0.75 percent; and malaria, 0.002 percent. Anti-HBc prevalence in HBsAg-negative, HBV DNA-negative blood donors was 167 of 966 (17.28%), with 76 percent demonstrating anti-HBs positivity. Younger donors with mean age of 25 years were exposed to HBV to a lesser extent compared to those with a mean age of 29 years. Anti-HBc positivity was significantly higher in anti-HCV-reactive individuals. HBV DNA was detectable in 5 blood donors who were HBsAg-, anti-HBc-positive and were categorized as having occult HBV infection. The study shows that more than 17 percent of healthy, young blood donors in Pakistan are already exposed to HBV, with two-thirds showing anti-HBs levels of greater than 100 mIU per mL. One in 200 blood donors who are HBsAg-, anti-HBc-positive, however, have occult HBV infection, with likelihood of transmission of hepatitis B in recipients of blood components derived from them. HBsAg-negative individuals who are anti-HBc-negative and those who are anti-HBc-positive, anti-HBs-positive, and HBV DNA-negative should be selected as regular blood donors to minimize transmission due to occult hepatitis B infection.

  8. Evaluation of local immune response to Fasciola hepatica experimental infection in the liver and hepatic lymph nodes of goats immunized with Sm14 vaccine antigen

    Directory of Open Access Journals (Sweden)

    Ricardo E Mendes

    2010-08-01

    Full Text Available Protection against Fasciola hepatica in goats immunized with a synthetic recombinant antigen from Schistosoma mansoni fatty acid-binding protein 14 (rSm14 was investigated by assessing worm burdens, serum levels of hepatic enzymes, faecal egg count and hepatic damage, which was evaluated using gross and microscopic morphometric observation. The nature of the local immune response was assessed by examining the distribution of CD2+, CD4+, CD8+ and γ´+ T lymphocytes along with IgG+, IL-4+ and IFN-γ+ cells in the liver and hepatic lymph nodes (HLN. The goats used consisted of group 1 (unimmunized and uninfected, group 2 [infected control - immunized with Quillaia A (Quil A] and group 3 (immunized with rSm14 in Quil A and infected, each containing seven animals. Immunization with rSm14 in Quil A adjuvant induced a reduction in gross hepatic lesions of 56.6% (p < 0.001 and reduced hepatic and HLN infiltration of CD2+, CD4+, CD8+ and γ´+ T lymphocytes as well as IL-4+ and IFN-γ+ cells (p < 0.05. This is the first report of caprine immunization against F. hepatica using a complete rSm14 molecule derived from S. mansoni. Immunization reduced hepatic damage and local inflammatory infiltration into the liver and HLN. However, considering that Quil A is not the preferential/first choice adjuvant for Sm14 immunization, further studies will be undertaken using the monophosphoryl lipid A-based family of adjuvants during clinical trials to facilitate anti-Fasciolavaccine development.

  9. The full-length clone of cucumber green mottle mosaic virus and its application as an expression system for Hepatitis B surface antigen.

    Science.gov (United States)

    Ooi, Aikseng; Tan, Sianghee; Mohamed, Rosmawati; Rahman, Noorsaadah Abdul; Othman, Rofina Yasmin

    2006-02-24

    A cucumber green mosaic mottle virus (CGMMV) full-length clone was developed for the expression of Hepatitis B surface antigen (HBsAg). The expression of the surface displayed HBsAg by the chimeric virus was confirmed through a double antibody sandwich ELISA. Assessment of the coat protein composition of the chimeric virus particles by SDS-PAGE analysis showed that 50% of the coat proteins were fused to the HBsAg. Biological activity of the expressed HBsAg was assessed through the stimulation of in vitro antibody production by cultured peripheral blood mononuclear cells (PBMC). PBMC that were cultured in the presence of the chimeric virus showed up to an approximately three-fold increase in the level of anti HBsAg immunoglobulin thus suggesting the possible use of this new chimeric virus as an effective Hepatitis B vaccine.

  10. [The prevalence of hepatitis C antibodies among volunteer blood donors with elevated blood transaminase and antibodies to the B virus core antigen].

    Science.gov (United States)

    Gavilán Carrasco, J C; González Santos, P; Rosario Díaz, E

    1996-05-01

    The use of non-specific markers before 1989 (increased serum transaminase values and antibodies to hepatitis B core antigen) as a screening method for blood donors in an attempt to decrease the incidence of post-transfusional non-A non-B hepatitis (currently hepatitis C virus) was a matter of controversy. To determine the impact of the use of these markers on the detection of blood donors infected with hepatitis C virus, a prospective study was undertaken in Málaga (1988-1989) with 5,003 volunteer donors with two objectives: a) to know the prevalence of these non-specific markers (anti-HBc and increased serum transaminase) and antibodies to HCV (anti-C100) in our blood donor population; b) to determine whether the presence of some of these non specific markers in blood donors was associated with a higher rate of virus C infection. The prevalence of antibodies to HCV in blood donors with increased serum transaminase and/or anti-HBc was significantly higher than the prevalence found among the general blood donor population.

  11. Hepatitis

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    2008312 Impact of hepatitis B virus infection on the activity of hematopoietic stem cell.SHI Yanmei(石雁梅),et al.Dept Infect Dis,1st Clin Coll,Harbin Med Univ,Harbin 150001.Chin J Infect Dis 2008;26(4):197-201.Objective To study the impact of hepatitis B virus (HBV)infection on the activity of cord hematopoieticstem cells.Methods CD34+cells were isolated from healthy human cord blood by mini MACS.Cells were

  12. Microbiological diagnostics of viral hepatitis

    OpenAIRE

    HASDEMİR, Ufuk

    2016-01-01

    Viral hepatitis is an infection that primarily affects the liverbut may also have systemic clinical manifestations. The vastmajority of viral hepatitis are caused by one of five hepatotropicviruses: hepatitis A virus (HAV), hepatitis B virus (HBV),hepatitis C virus (HCV), hepatitis D (delta) virus (HDV), andhepatitis E virus (HEV) (Table I) [1]. HBV, HCV, and HDValso cause chronic hepatitis, whereas HAV does not. HEVcauses acute hepatitis in normal hosts but can cause protractedand chronic he...

  13. Microbiological diagnostics of viral hepatitis

    OpenAIRE

    HASDEMİR, Ufuk

    2016-01-01

    Viral hepatitis is an infection that primarily affects the liverbut may also have systemic clinical manifestations. The vastmajority of viral hepatitis are caused by one of five hepatotropicviruses: hepatitis A virus (HAV), hepatitis B virus (HBV),hepatitis C virus (HCV), hepatitis D (delta) virus (HDV), andhepatitis E virus (HEV) (Table I) [1]. HBV, HCV, and HDValso cause chronic hepatitis, whereas HAV does not. HEVcauses acute hepatitis in normal hosts but can cause protractedand chronic he...

  14. Dynamic imaging of experimental Leishmania donovani-induced hepatic granulomas detects Kupffer cell-restricted antigen presentation to antigen-specific CD8 T cells.

    Directory of Open Access Journals (Sweden)

    Lynette Beattie

    2010-03-01

    Full Text Available Kupffer cells (KCs represent the major phagocytic population within the liver and provide an intracellular niche for the survival of a number of important human pathogens. Although KCs have been extensively studied in vitro, little is known of their in vivo response to infection and their capacity to directly interact with antigen-specific CD8(+ T cells. Here, using a combination of approaches including whole mount and thin section confocal microscopy, adoptive cell transfer and intra-vital 2-photon microscopy, we demonstrate that KCs represent the only detectable population of mononuclear phagocytes within granulomas induced by Leishmania donovani infection that are capable of presenting parasite-derived peptide to effector CD8(+ T cells. This restriction of antigen presentation to KCs within the Leishmania granuloma has important implications for the identification of new candidate vaccine antigens and for the design of novel immuno-therapeutic interventions.

  15. Hepatitis B virus induces IL-23 production in antigen presenting cells and causes liver damage via the IL-23/IL-17 axis.

    Directory of Open Access Journals (Sweden)

    Qinghong Wang

    Full Text Available IL-23 regulates myriad processes in the innate and adaptive immune systems, and is a critical mediator of the proinflammatory effects exerted by Th17 cells in many diseases. In this study, we investigated whether and how hepatitis B virus (HBV causes liver damage directly through the IL-23 signaling pathway. In biopsied liver tissues from HBV-infected patients, expression of both IL-23 and IL-23R was remarkably elevated. In vivo observations also indicated that the main sources of IL-23 were myeloid dendritic cells (mDCs and macrophages. Analysis of in vitro differentiated immature DCs and macrophages isolated from healthy donors revealed that the HBV surface antigen (HBsAg efficiently induces IL-23 secretion in a mannose receptor (MR-dependent manner. Culture with an endosomal acidification inhibitor and the dynamin inhibitor showed that, upon binding to the MR, the HBsAg is taken up by mDCs and macrophages through an endocytosis mechanism. In contrast, although the HBV core antigen (HBcAg can also stimulate IL-23 secretion from mDCs, the process was MR- and endocytosis-independent. In addition, IL-23 was shown to be indispensible for HBsAg-stimulated differentiation of naïve CD4(+ T cells into Th17 cells, which were determined to be the primary source of IL-17 in HBV-infected livers. The cognate receptor, IL-17R, was found to exist on the hepatic stellate cells and mDCs, both of which might represent the potential target cells of IL-17 in hepatitis B disease. These data provide novel insights into a yet unrecognized mechanism of HBV-induced hepatitis, by which increases in IL-23 expression, through an MR/endocytosis-dependent or -independent manner, produce liver damage through the IL-23/IL-17 axis.

  16. Hepatitis

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    2008449 A cross-sectional survey of occult hepatitis B virus infection in HIV-infected patients. MA Jianxin(马建新), et al.Dept Infect Dis, Shanghai Public Health Clin Center, Shanghai 201508. Chin J Intern Med 2008;47(7):574-577. Objective To assess the prevalence of occult HBV infection in HIV-infected patients.

  17. Human Leukocyte Antigen-E Alleles are Associated with Hepatitis C Virus, Torque Teno Virus, and Toxoplasma Co-infections but are not Associated with Hepatitis B Virus, Hepatitis D Virus, and GB Virus C Co-infections in Human Immunodeficiency Virus Patients

    Science.gov (United States)

    Prasetyo, Afiono Agung; Dharmawan, Ruben; Raharjo, Irvan; Hudiyono

    2016-01-01

    Context: Data regarding the distribution of Human Leukocyte Antigen (HLA)-E alleles and their association with blood-borne pathogen infections/co-infections are limited for many populations, including Indonesia. Aims: The aim of this study was to analyze the association between HLA-E allelic variants and infection with blood-borne pathogens such as hepatitis B virus (HBV), hepatitis C virus (HCV), hepatitis D virus (HDV), torque teno virus (TTV), GB virus C (GBV-C), and Toxoplasma gondii (T. gondii) in Indonesian Javanese human immunodeficiency virus (HIV) patients. Settings and Design: A total of 320 anti-HIV-positive blood samples were analyzed for HBV, HCV, HDV, TTV, GBV-C, and T. gondii infection status and its association with HLA-E allelic variants. Materials and Methods: Nucleic acid was extracted from plasma samples and used for the molecular detection of HBV DNA, HCV RNA, HDV RNA, TTV DNA, and GBV-C RNA, whereas hepatitis B surface antigen, anti-HCV, immunoglobulin M and G (IgM and IgG) anti-T. gondii were detected through serological testing. The blood samples were genotyped for HLA-E loci using a sequence-specific primer-polymerase chain reaction. Statistical Analysis Used: Either the Chi-square or Fisher's exact test was performed to analyze the frequency of HLA-E alleles and blood-borne pathogen infections in the population. Odds ratios (ORs) were calculated to measure the association between the antibodies found and the participants’ possible risk behaviors. A logistic regression analysis was used to assess the associations. Results: HLA-E*101/0101 was associated with HCV/TTV co-infection (adjusted OR [aOR]: 3.5; 95% confidence interval [CI]: 1.156-10.734; P = 0.027) and IgM/IgG anti-Toxo positivity (aOR: 27.0; 95% CI: 3.626-200.472; P = 0.001). HLA-E*103/0103 was associated with TTV co-infection (aOR: 2.7; 95% CI: 1.509-4.796; P = 0.001). Conclusions: HLA-E alleles in Indonesian Javanese HIV patients were found to be associated with HCV, TTV, and

  18. Human leukocyte antigen-e alleles are associated with hepatitis c virus, torque teno virus, and toxoplasma co-infections but are not associated with hepatitis b virus, hepatitis d virus, and GB virus c co-infections in human immunodeficiency virus patients

    Directory of Open Access Journals (Sweden)

    Afiono Agung Prasetyo

    2016-01-01

    Full Text Available Context: Data regarding the distribution of Human Leukocyte Antigen (HLA-E alleles and their association with blood-borne pathogen infections/co-infections are limited for many populations, including Indonesia. Aims: The aim of this study was to analyze the association between HLA-E allelic variants and infection with blood-borne pathogens such as hepatitis B virus (HBV, hepatitis C virus (HCV, hepatitis D virus (HDV, torque teno virus (TTV, GB virus C (GBV-C, and Toxoplasma gondii (T. gondii in Indonesian Javanese human immunodeficiency virus (HIV patients. Settings and Design: A total of 320 anti-HIV-positive blood samples were analyzed for HBV, HCV, HDV, TTV, GBV-C, and T. gondii infection status and its association with HLA-E allelic variants. Materials and Methods: Nucleic acid was extracted from plasma samples and used for the molecular detection of HBV DNA, HCV RNA, HDV RNA, TTV DNA, and GBV-C RNA, whereas hepatitis B surface antigen, anti-HCV, immunoglobulin M and G (IgM and IgG anti-T. gondii were detected through serological testing. The blood samples were genotyped for HLA-E loci using a sequence-specific primer-polymerase chain reaction. Statistical Analysis Used: Either the Chi-square or Fisher′s exact test was performed to analyze the frequency of HLA-E alleles and blood-borne pathogen infections in the population. Odds ratios (ORs were calculated to measure the association between the antibodies found and the participants′ possible risk behaviors. A logistic regression analysis was used to assess the associations. Results: HLA-EFNx010101/0101 was associated with HCV/TTV co-infection (adjusted OR [aOR]: 3.5; 95% confidence interval [CI]: 1.156-10.734; P = 0.027 and IgM/IgG anti-Toxo positivity (aOR: 27.0; 95% CI: 3.626-200.472; P = 0.001. HLA-EFNx010103/0103 was associated with TTV co-infection (aOR: 2.7; 95% CI: 1.509-4.796; P = 0.001. Conclusions: HLA-E alleles in Indonesian Javanese HIV patients were found to be associated

  19. Wide dynamic range of surface-plasmon-resonance-based assay for Hepatitis-B-surface-antigen-antibody optimal detection in comparison with ELISA.

    Science.gov (United States)

    Tam, Yew Joon; Zeenathul, Nazariah Allaudin; Rezaei, Morvarid Akhavan; Mustafa, Nor Hidayah; Azmi, Mohd Lila Mohd; Bahaman, Abdul Rani; Lo, Sewn Cen; Tan, Joo Shun; Hani, Homayoun; Rasedee, Abdullah

    2016-08-10

    Limit of detection (LOD), limit of quantification (LOQ) and the dynamic range of detection of hepatitis B surface antigen antibody (anti-HBs) using surface plasmon resonance (SPR) chip-based approach with Pichia pastoris derived recombinant hepatitis B surface antigen (HBsAg) as recognition element were established through the scouting for optimal conditions for the improvement of immobilization efficiency and in the use of optimal regeneration buffer. Recombinant HBsAg was immobilized onto the sensor surface of CM5 chip at a concentration of 150 mg/L, in sodium acetate buffer at pH 4 with added 0.6% Triton X-100. Regeneration solution of 20 mM HCl was optimally found to effectively unbind analytes from the ligand, thus allowing for multiple screening cycles. A dynamic range of detection of ∼0.00098 to 0.25 mg/L was obtained and a 7-fold higher LOD, as well as a 2-fold increase in coefficient of variance (CV) of the replicated results, were shown as compared to enzyme-linked immunosorbent assay (ELISA). Evaluation of the assay for specificity showed no cross-reactivity with other antibodies tested. The ability of SPR chip-based assay and ELISA to detect anti-HBs in human serum was comparable, indicating that the SPR chip-based assay with its multiple screening capacity has greater advantage over ELISA. This article is protected by copyright. All rights reserved.

  20. Hepatitis

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    2008079 Relationship of HBV genotype and bcp and pc mutations with HBV DNA rebound after lamivudine therapy. SU Minghua(苏明华), et al. Dept Infect Dis Clin Hosp, Guangxi Med Univ, Nanning 530027. World Chin J Digestol 2007;15(33):3507-3513. Objective To investigate the relationship of HBV gene mutations with HBV DNA rebound after lamivudine therapy. Methods Twenty-seven hepatitis B patients with HBV DNA rebound after

  1. Identification of a natural intergenotypic recombinant hepatitis delta virus genotype 1 and 2 in Vietnamese HBsAg-positive patients.

    Science.gov (United States)

    Sy, B T; Nguyen, H M; Toan, N L; Song, L H; Tong, H V; Wolboldt, C; Binh, V Q; Kremsner, P G; Velavan, T P; Bock, C-T

    2015-01-01

    Hepatitis D virus (HDV) infection is acquired as a co- /superinfection of Hepatitis B virus (HBV) and can modulate the pathophysiology of chronic hepatitis B and related liver diseases including hepatocellular carcinoma. Among the eight distinct HDV genotypes reported, relatively few studies have attempted to investigate the prevalence of HDV mixed genotypes and RNA recombination of HDV. With a recorded prevalence of 10-20% HBV infection in Vietnam, this study investigated the HDV variability, HDV genotypes and HDV recombination among twenty-one HDV isolates in Vietnamese HBsAg-positive patients. HDV subgenomic and full-length genome sequences were obtained using newly established HDV-specific RT-PCR techniques. The nucleotide homology was observed from 74.6% to 99.4% among the investigated full-length genome of the HDV isolates. We observed HDV genotype 1 and HDV genotype 2 in the investigated Vietnamese patients. Although no HDV genotype mixtures were observed, we report here a newly identified recombinant of HDV genotypes (HDV 1 and HDV 2). The identified recombinant HDV isolate C03 revealed sequence homology to both HDV genotype 1 (nt1 to nt907) and HDV genotype 2 (nt908 to nt1675; HDAg coding region) with a breakpoint at nt908. Our findings demonstrate the prevalence of intergenotypic recombination between HDV genotypes 1 and 2 in a Vietnamese HBsAg-positive patient. Extended investigation on the distribution and prevalence of HDV, HDV mixed genotypes and recombinant HDV genotypes in a larger Vietnamese population offers vital insights into understanding of the micro-epidemiology of HDV and subsequent pathophysiology in chronic HBV- /HDV-related liver diseases.

  2. 探讨丙肝病毒核心抗原检测诊断丙肝的临床价值%Study on the Clinical Value of Hepatitis C Virus Core Antigen Detection in the Diagnosis of Hepatitis C

    Institute of Scientific and Technical Information of China (English)

    李照丹

    2016-01-01

    Objective To study the hepatitis C patients received hepatitis C virus core antigen (HCV-cAg) diagnostic value.MethodsAccording to our hospital from January 2012 to January 2015 in 38 cases of suspected patients with hepatitis C virus (HCV) or hepatitis C virus (HCV) analysis, selected for the same period in 100 cases of screening group as control group, compared two groups of diagnosis coincidence rate.Results The control group of patients with HCV-Ab results were negative, there were 2 cases of HCV-cAg positive, 1 cases of RT-RNA positive; the study group had 20 cases of HCV-cAg positive, 24 cases of RT-RNA positive, the rate was 83.33%.Conclusion The accuracy of diagnosis of hepatitis C using HCV-cAg has higher detection.%目的:研究分析丙肝患者接受丙肝病毒核心抗原(HCV-cAg)诊断的价值。方法选取2012年1月~2015年1月我院38例疑似丙肝或丙肝患者进行分析研究,选取同期100例健康体检者作为对照组,对比两组诊断符合率。结果对照组患者的HCV-Ab结果为阴性,有2例HCV-cAg结果为阳性,1例RT-RNA证实为阳性;研究组有20例HCV-cAg为阳性,24例RT-RNA证实阳性,符合率是83.33%。结论丙肝诊断使用HCV-cAg检测具有较高的准确率。

  3. Ultra-deep sequencing reveals high prevalence and broad structural diversity of hepatitis B surface antigen mutations in a global population.

    Science.gov (United States)

    Gencay, Mikael; Hübner, Kirsten; Gohl, Peter; Seffner, Anja; Weizenegger, Michael; Neofytos, Dionysios; Batrla, Richard; Woeste, Andreas; Kim, Hyon-Suk; Westergaard, Gaston; Reinsch, Christine; Brill, Eva; Thu Thuy, Pham Thi; Hoang, Bui Huu; Sonderup, Mark; Spearman, C Wendy; Pabinger, Stephan; Gautier, Jérémie; Brancaccio, Giuseppina; Fasano, Massimo; Santantonio, Teresa; Gaeta, Giovanni B; Nauck, Markus; Kaminski, Wolfgang E

    2017-01-01

    The diversity of the hepatitis B surface antigen (HBsAg) has a significant impact on the performance of diagnostic screening tests and the clinical outcome of hepatitis B infection. Neutralizing or diagnostic antibodies against the HBsAg are directed towards its highly conserved major hydrophilic region (MHR), in particular towards its "a" determinant subdomain. Here, we explored, on a global scale, the genetic diversity of the HBsAg MHR in a large, multi-ethnic cohort of randomly selected subjects with HBV infection from four continents. A total of 1553 HBsAg positive blood samples of subjects originating from 20 different countries across Africa, America, Asia and central Europe were characterized for amino acid variation in the MHR. Using highly sensitive ultra-deep sequencing, we found 72.8% of the successfully sequenced subjects (n = 1391) demonstrated amino acid sequence variation in the HBsAg MHR. This indicates that the global variation frequency in the HBsAg MHR is threefold higher than previously reported. The majority of the amino acid mutations were found in the HBV genotypes B (28.9%) and C (25.4%). Collectively, we identified 345 distinct amino acid mutations in the MHR. Among these, we report 62 previously unknown mutations, which extends the worldwide pool of currently known HBsAg MHR mutations by 22%. Importantly, topological analysis identified the "a" determinant upstream flanking region as the structurally most diverse subdomain of the HBsAg MHR. The highest prevalence of "a" determinant region mutations was observed in subjects from Asia, followed by the African, American and European cohorts, respectively. Finally, we found that more than half (59.3%) of all HBV subjects investigated carried multiple MHR mutations. Together, this worldwide ultra-deep sequencing based genotyping study reveals that the global prevalence and structural complexity of variation in the hepatitis B surface antigen have, to date, been significantly underappreciated.

  4. Influence of mutations in hepatitis B virus surface protein on viral antigenicity and phenotype in occult HBV strains from blood donors.

    Science.gov (United States)

    Huang, Cheng-Hao; Yuan, Quan; Chen, Pei-Jer; Zhang, Ya-Li; Chen, Chang-Rong; Zheng, Qing-Bing; Yeh, Shiou-Hwei; Yu, Hai; Xue, Yu; Chen, Yi-Xin; Liu, Ping-Guo; Ge, Sheng-Xiang; Zhang, Jun; Xia, Ning-Shao

    2012-10-01

    This study aimed at investigating mutations in the hepatitis B surface protein (HBsAg) in occult hepatitis B virus (HBV) infection (OBI) and their influence on viral antigenicity and phenotype. The characteristics of 61 carriers with OBI (OBI group), 153 HBsAg(+) carriers with serum HBsAg ≤ 100 IU/ml (HBsAg-L group) and 54 carriers with serum HBsAg >100 IU/ml (HBsAg-H group) from 38,499 blood donors were investigated. Mutations in the major hydrophilic region (MHR) of the viral sequences were determined. Thirteen representative MHR mutations observed in OBI sequences were antigenically characterized with a panel of monoclonal antibodies (MAbs) and commercial HBsAg immunoassays and functionally characterized in HuH7 cells and hydrodynamically injected mice. Of 61 OBI sequences, 34 (55.7%) harbored MHR mutations, which was significantly higher than the frequency in either the HBsAg-L (34.0%, p=0.003) or the HBsAg-H group (17.1%, pMHR mutations identified in the OBI group were assessed by reacting recombinant HBV mutants with 30 different MAbs targeting various epitopes. Four out of the 13 mutations (C124R, C124Y, K141E, and D144A) strongly decreased the analytical sensitivity of seven commercial HBsAg immunoassays, and 10 (G119R, C124Y, I126S, Q129R, S136P, C139R, T140I, K141E, D144A, and G145R) significantly impaired virion and/or S protein secretion in both HuH7 cells and mice. MHR mutations alter antigenicity and impair virion secretion, both of which may contribute to HBsAg detection failure in individuals with OBI. Copyright © 2012 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

  5. Suppression of humoral immune response to hepatitis B surface antigen vaccine in BALB/c mice by 1-methyl-tryptophan co-administration

    Directory of Open Access Journals (Sweden)

    T Sparopoulou

    2011-07-01

    Full Text Available   Background and the purpose of the study:Indoleamine 2,3-dioxygenase (IDO suppresses adaptive immune response. The purpose of this study was to determine the effect of the IDO inhibitor namely 1-methyl-DL-tryptophan (DL-1-MT on antibody production after vaccination with hepatitis B surface (HBs antigen. Methods:Four groups of BALB/c mice were immunized with a HBs antigen vaccine. In the first group the vaccine had no DL-1-MT, whereas in the other three groups the vaccine contained 1 mg , 10 mg and 20 mg DL-1-MT. Blood samples were collected 5 weeks post-vaccination and anti-HBs antibodies in the serum were measured by ELISA. Results:Compared to the three groups of mice that were immunized with the vaccines containing DL-1-MT, serum anti-HBs level was much higher in the mice that were immunized with the vaccine with out DL-1-MT. Conclusions:Inhibition of IDO at the time of vaccination decreased humoral immune response to HBs antigen vaccine. The idea that IDO activity is simply immunosuppressive may need to be re-evaluated.

  6. Freeze-thaw stress of Alhydrogel ® alone is sufficient to reduce the immunogenicity of a recombinant hepatitis B vaccine containing native antigen.

    Science.gov (United States)

    Clapp, Tanya; Munks, Michael W; Trivedi, Ruchit; Kompella, Uday B; Braun, LaToya Jones

    2014-06-24

    Preventing losses in vaccine potency due to accidental freezing has recently become a topic of interest for improving vaccines. All vaccines with aluminum-containing adjuvants are susceptible to such potency losses. Recent studies have described excipients that protect the antigen from freeze-induced inactivation, prevent adjuvant agglomeration and retain potency. Although these strategies have demonstrated success, they do not provide a mechanistic understanding of freeze-thaw (FT) induced potency losses. In the current study, we investigated how adjuvant frozen in the absence of antigen affects vaccine immunogenicity and whether preventing damage to the freeze-sensitive recombinant hepatitis B surface antigen (rHBsAg) was sufficient for maintaining vaccine potency. The final vaccine formulation or Alhydrogel(®) alone was subjected to three FT-cycles. The vaccines were characterized for antigen adsorption, rHBsAg tertiary structure, particle size and charge, adjuvant elemental content and in-vivo potency. Particle agglomeration of either vaccine particles or adjuvant was observed following FT-stress. In vivo studies demonstrated no statistical differences in IgG responses between vaccines with FT-stressed adjuvant and no adjuvant. Adsorption of rHBsAg was achieved; regardless of adjuvant treatment, suggesting that the similar responses were not due to soluble antigen in the frozen adjuvant-containing formulations. All vaccines with adjuvant, including the non-frozen controls, yielded similar, blue-shifted fluorescence emission spectra. Immune response differences could not be traced to differences in the tertiary structure of the antigen in the formulations. Zeta potential measurements and elemental content analyses suggest that FT-stress resulted in a significant chemical alteration of the adjuvant surface. This data provides evidence that protecting a freeze-labile antigen from subzero exposure is insufficient to maintain vaccine potency. Future studies should

  7. Prediction of conformational changes by single mutation in the hepatitis B virus surface antigen (HBsAg identified in HBsAg-negative blood donors

    Directory of Open Access Journals (Sweden)

    Roni Martono

    2010-11-01

    Full Text Available Abstract Background Selection of hepatitis B virus (HBV by host immunity has been suggested to give rise to variants with amino acid substitutions at or around the 'a' determinant of the surface antigen (HBsAg, the main target of antibody neutralization and diagnostic assays. However, there have never been successful attempts to provide evidence for this hypothesis, partly because the 3 D structure of HBsAg molecules has not been determined. Tertiary structure prediction of HBsAg solely from its primary amino acid sequence may reveal the molecular energetic of the mutated proteins. We carried out this preliminary study to analyze the predicted HBsAg conformation changes of HBV variants isolated from Indonesian blood donors undetectable by HBsAg assays and its significance, compared to other previously-reported variants that were associated with diagnostic failure. Results Three HBV variants (T123A, M133L and T143M and a wild type sequence were analyzed together with frequently emerged variants T123N, M133I, M133T, M133V, and T143L. Based on the Jameson-Wolf algorithm for calculating antigenic index, the first two amino acid substitutions resulted in slight changes in the antigenicity of the 'a' determinant, while all four of the comparative variants showed relatively more significant changes. In the pattern T143M, changes in antigenic index were more significant, both in its coverage and magnitude, even when compared to variant T143L. These data were also partially supported by the tertiary structure prediction, in which the pattern T143M showed larger shift in the HBsAg second loop structure compared to the others. Conclusions Single amino acid substitutions within or near the 'a' determinant of HBsAg may alter antigenicity properties of variant HBsAg, which can be shown by both its antigenic index and predicted 3 D conformation. Findings in this study emphasize the significance of variant T143M, the prevalent isolate with highest degree of

  8. Prevalence and predictors for compensated Advanced Chronic Liver Disease (c-ACLD) in patients with chronic Hepatitis Delta Virus (HDV) infection

    Science.gov (United States)

    Couto, Ingrid; Victoria, Marilu; Veloso, Valdiléa G.; Rodrigues, Lorena; Grinsztejn, Beatriz; Lacerda, Marcus; Victoria, Flamir; Perazzo, Hugo

    2017-01-01

    Objective The study aimed to evaluate the prevalence and predictor factors for compensated advanced chronic liver disease (c-ACLD) in patients with hepatitis Delta virus (HDV) infection. Methods This cross-sectional study included consecutive HDV-infected patients defined by positive anti-HDV. Patients with hepatitis C coinfection, liver transplantation or presence of conditions that limit liver (LSM) or spleen stiffness measurement (SSM) were excluded. Blood tests, abdominal ultrasound, SSM and LSM by transient elastography (FibroScan®) were performed at the same day. Alcohol consumption was quantified using the AUDIT score and c-ACLD was defined by LSM ≥ 15 kPa performed by an experimented operator blinded for clinical and laboratory data. Results 101 patients were eligible and few patients were excluded due to negative anti-HDV (n = 7), hepatitis C coinfection (n = 2), liver transplantation (n = 10) and limitation for LSM or SSM (n = 5). Therefore, 77 patients [61% male, age = 43 (IQR,36–52) years] were included. The prevalence of c-ACLD was 57% (n = 44/77). Patients with c-ACLD had a higher rate of detectable HBV viral load (p = 0.039), higher levels of transaminases, GGT, alkaline phosphatases, total bilirubin and INR (p0.001 for both) compared to those without c-ACLD. Patients with c-ACLD had higher SSM [65.2 (IQR,33.8–75.0) vs 21.8 (16.5–32.0) kPa; p10 UI/ml), alkaline phosphatase (per IU/L) and GGT levels (per IU/L) were independently associated with c-ACLD in all multivariate models. Splenic volume [per cm3,OR = 1.01 (95%CI,1.01–1.02);p = 0.002], SSM [per kPa, OR = 1.04 (1.01–1.07);p = 0.012] and splenomegaly [yes vs no,OR = 28.45 (4.42–182.95);p<0.001] were independently associated with c-ACLD. Conclusions The prevalence of c-ACLD was high in patients with chronic HDV infection in western Amazon basin. HBV viral load, liver enzymes and splenic features can be used to predict severe liver disease in HDV-infected patients. PMID:28329027

  9. Hepatitis B and Delta virus are prevalent but often subclinical co-infections among HIV infected patients in Guinea-Bissau, West Africa: a cross-sectional study.

    Directory of Open Access Journals (Sweden)

    Bo Langhoff Hønge

    Full Text Available BACKGROUND: Co-infection with human immunodeficiency virus (HIV and hepatitis B virus (HBV may lead to accelerated hepatic disease progression with higher rates of liver cirrhosis and liver-related mortality compared with HBV mono-infection. Co or super-infection with hepatitis Delta virus (HDV may worsen the liver disease and complicate treatment possibilities. METHODS: In this cross-sectional study we included HIV-infected individuals who had a routine blood analysis performed at an HIV clinic in Bissau, Guinea-Bissau between the 28th of April and 30th of September 2011. All patients were interviewed, had a clinical exam performed and had a blood sample stored. The patients' samples were tested for HBV and HDV serology, and HBV/HDV viral loads were analyzed using in-house real-time PCR methods. RESULTS: In total, 576 patients (417 HIV-1, 104 HIV-2 and 55 HIV-1/2 were included in this study. Ninety-four (16.3% patients were HBsAg positive of whom 16 (17.0% were HBeAg positive. In multivariable logistic regression analysis, CD4 cell count <200 cells/µl and animist religion were significantly associated with HBsAg positivity. Due to scarcity of available plasma, virological analyses were not performed for eight patients. HBV DNA was detected in 42 of 86 samples (48.8% positive for HBsAg and genotyping was performed in 26 patients; 25 of whom had genotype E and one genotype D. Among 9 patients on antiretroviral treatment (ART, one patient had the [L180M, M204V] mutation associated with lamivudine resistance. Among the HBsAg positive patients 25.0% were also positive for anti-HDV and 4/9 (44.4% had detectable HDV RNA. CONCLUSION: HBV and HDV were frequent co-infections among HIV positive patients in Guinea-Bissau and chronic infection was associated with severe immunosuppression. Lamivudine was widely used among HBsAg positive patients with the risk of developing resistant HBV.

  10. Hepatitis viral B y Delta en el Perú: epidemiología y bases para su control

    OpenAIRE

    César Cabezas

    2007-01-01

    El Perú está catalogado como un país de mediana endemicidad para la infección por la hepatitis B (HBV), sin embargo, esta enfermedad se está dispersando en el país por la intensa migración de áreas de alta endemicidad a zonas de baja que endemicidad. Además de los mecanismos clásicos de transmisión de la infección como la vía parenteral y la vía sexual, debe destacarse la transmisión horizontal sobre todo en población infantil de áreas hiperendémicas y la limitada ocurrencia de transmisión ve...

  11. The putative capsid protein of the newly identified avian hepatitis E virus shares antigenic epitopes with that of swine and human hepatitis E viruses and chicken big liver and spleen disease virus.

    Science.gov (United States)

    Haqshenas, G; Huang, F F; Fenaux, M; Guenette, D K; Pierson, F W; Larsen, C T; Shivaprasad, H L; Toth, T E; Meng, X J

    2002-09-01

    We recently identified a novel virus, designated avian hepatitis E virus (avian HEV), from chickens with hepatitis-splenomegaly (HS) syndrome in the USA. We showed that avian HEV is genetically related to swine and human HEVs. Here we report the antigenic cross-reactivity of the putative open reading frame 2 (ORF2) capsid protein of avian HEV with those of swine and human HEVs and the Australian chicken big liver and spleen disease virus (BLSV). The region encoding the C-terminal 268 amino acid residues of avian HEV ORF2 was cloned into expression vector pRSET-C. The truncated ORF2 protein was expressed in E. coli as a fusion protein and purified by affinity chromatography. Western blot analysis revealed that the avian HEV ORF2 protein reacted with antisera against the Sar-55 strain of human HEV and with convalescent antisera against swine HEV and the US2 strain of human HEV, as well as with antiserum against BLSV. Convalescent sera from specific-pathogen-free chickens experimentally infected with avian HEV also reacted with the recombinant capsid proteins of swine HEV and Sar-55 human HEV. Antisera against the US2 human HEV also reacted with recombinant ORF2 proteins of both swine HEV and Sar-55 human HEV. The antigenic cross-reactivity of the avian HEV putative capsid protein with those of swine and human HEVs was further confirmed, for the most part, by ELISA assays. The data indicate that avian HEV shares certain antigenic epitopes in its putative capsid protein with swine and human HEVs, as well as with BLSV. The results have implications for HEV diagnosis and taxonomy.

  12. Effect on HBs antigen clearance of addition of pegylated interferon alfa-2a to nucleos(t)ide analogue therapy versus nucleos(t)ide analogue therapy alone in patients with HBe antigen-negative chronic hepatitis B and sustained undetectable plasma hepatitis B virus DNA: a randomised, controlled, open-label trial.

    Science.gov (United States)

    Bourlière, Marc; Rabiega, Pascaline; Ganne-Carrie, Nathalie; Serfaty, Lawrence; Marcellin, Patrick; Barthe, Yoann; Thabut, Dominique; Guyader, Dominique; Hezode, Christophe; Picon, Magali; Causse, Xavier; Leroy, Vincent; Bronowicki, Jean Pierre; Carrieri, Patrizia; Riachi, Ghassan; Rosa, Isabelle; Attali, Pierre; Molina, Jean Michel; Bacq, Yannick; Tran, Albert; Grangé, Jean Didier; Zoulim, Fabien; Fontaine, Hélène; Alric, Laurent; Bertucci, Inga; Bouvier-Alias, Magali; Carrat, Fabrice

    2017-03-01

    Findings from uncontrolled studies suggest that addition of pegylated interferon in patients with HBe antigen (HBeAg)-negative chronic hepatitis B receiving nucleos(t)ide analogues with undetectable plasma hepatitis B virus (HBV) DNA might increase HBs antigen (HBsAg) clearance. We aimed to assess this strategy. In this randomised, controlled, open-label trial, we enrolled patients aged 18-75 years with HBeAg-negative chronic hepatitis B and documented negative HBV DNA while on stable nucleos(t)ide analogue regimens for at least 1 year from 30 hepatology tertiary care wards in France. Patients had to have an alanine aminotransferase concentration of less than or equal to five times the upper normal range, no hepatocellular carcinoma, and a serum α fetoprotein concentration of less than 50 ng/mL, normal dilated fundus oculi examination, and a negative pregnancy test in women. Patients with contraindications to pegylated interferon were not eligible. A centralised randomisation used computer-generated lists of random permuted blocks of four with stratification by HBsAg titres (sida et les hépatites virales (France Recherche Nord&sud Sida-vih Hepatites). Copyright © 2017 Elsevier Ltd. All rights reserved.

  13. 124I-HuCC49deltaCH2 for TAG-72 antigen-directed positron emission tomography (PET imaging of LS174T colon adenocarcinoma tumor implants in xenograft mice: preliminary results

    Directory of Open Access Journals (Sweden)

    Mojzisik Cathy M

    2010-08-01

    Full Text Available Abstract Background 18F-fluorodeoxyglucose positron emission tomography (18F-FDG-PET is widely used in diagnostic cancer imaging. However, the use of 18F-FDG in PET-based imaging is limited by its specificity and sensitivity. In contrast, anti-TAG (tumor associated glycoprotein-72 monoclonal antibodies are highly specific for binding to a variety of adenocarcinomas, including colorectal cancer. The aim of this preliminary study was to evaluate a complimentary determining region (CDR-grafted humanized CH2-domain-deleted anti-TAG-72 monoclonal antibody (HuCC49deltaCH2, radiolabeled with iodine-124 (124I, as an antigen-directed and cancer-specific targeting agent for PET-based imaging. Methods HuCC49deltaCH2 was radiolabeled with 124I. Subcutaneous tumor implants of LS174T colon adenocarcinoma cells, which express TAG-72 antigen, were grown on athymic Nu/Nu nude mice as the xenograft model. Intravascular (i.v. and intraperitoneal (i.p. administration of 124I-HuCC49deltaCH2 was then evaluated in this xenograft mouse model at various time points from approximately 1 hour to 24 hours after injection using microPET imaging. This was compared to i.v. injection of 18F-FDG in the same xenograft mouse model using microPET imaging at 50 minutes after injection. Results At approximately 1 hour after i.v. injection, 124I-HuCC49deltaCH2 was distributed within the systemic circulation, while at approximately 1 hour after i.p. injection, 124I-HuCC49deltaCH2 was distributed within the peritoneal cavity. At time points from 18 hours to 24 hours after i.v. and i.p. injection, 124I-HuCC49deltaCH2 demonstrated a significantly increased level of specific localization to LS174T tumor implants (p = 0.001 when compared to the 1 hour images. In contrast, approximately 50 minutes after i.v. injection, 18F-FDG failed to demonstrate any increased level of specific localization to a LS174T tumor implant, but showed the propensity toward more nonspecific uptake within the

  14. Molecular Evolution and Genetic Analysis of the Major Capsid Protein VP1 of Duck Hepatitis A Viruses: Implications for Antigenic Stability.

    Science.gov (United States)

    Ma, Xiuli; Sheng, Zizhang; Huang, Bing; Qi, Lihong; Li, Yufeng; Yu, Kexiang; Liu, Cunxia; Qin, Zhuoming; Wang, Dan; Song, Minxun; Li, Feng

    2015-01-01

    The duck hepatitis A virus (DHAV), a member of the family Picornaviridae, is the major cause of outbreaks with high mortality rates in young ducklings. It has three distinctive serotypes and among them, serotypes 1 (DHAV-1) and 3 (DHAV-3) were recognized in China. To investigate evolutionary and antigenic properties of the major capsid protein VP1 of these two serotypes, a primary target of neutralizing antibodies, we determined the VP1 coding sequences of 19 DHAV-1 (spanning 2000-2012) and 11 DHAV-3 isolates (spanning 2008-2014) associated with disease outbreaks. By bioinformatics analysis of VP1 sequences of these isolates and other DHAV strains reported previously, we demonstrated that DHAV-1 viruses evolved into two genetic lineages, while DHAV-3 viruses exhibited three distinct lineages. The rate of nucleotide substitution for DHAV-1 VP1 genes was estimated to be 5.57 x 10(-4) per site per year, which was about one-third times slower than that for DHAV-3 VP1 genes. The population dynamics analysis showed an upward trend for infection of DHAV-1 viruses over time with little change observed for DHAV-3 viruses. Antigenic study of representative DHAV-1 and DHAV-3 strains covering all observed major lineages revealed no detectable changes in viral neutralization properties within the serotype, despite the lack of cross-neutralization between serotypes 1 and 3 strains. Structural analysis identified VP1 mutations in DHAV-1 and DHAV-3 viruses that underpin the observed antigenic phenotypes. Results of our experiments described here shall give novel insights into evolution and antigenicity of duck picornaviruses.

  15. Virus-like particle production with yeast: ultrastructural and immunocytochemical insights into Pichia pastoris producing high levels of the Hepatitis B surface antigen

    Directory of Open Access Journals (Sweden)

    Adnan Ahmad

    2011-06-01

    Full Text Available Abstract Background A protective immune response against Hepatitis B infection can be obtained through the administration of a single viral polypeptide, the Hepatitis B surface antigen (HBsAg. Thus, the Hepatitis B vaccine is generated through the utilization of recombinant DNA technology, preferentially by using yeast-based expression systems. However, the polypeptide needs to assemble into spherical particles, so-called virus-like particles (VLPs, to elicit the required protective immune response. So far, no clear evidence has been presented showing whether HBsAg assembles in vivo inside the yeast cell into VLPs or later in vitro during down-stream processing and purification. Results High level production of HBsAg was carried out with recombinant Pichia pastoris using the methanol inducible AOX1 expression system. The recombinant vaccine was isolated in form of VLPs after several down-stream steps from detergent-treated cell lysates. Search for the intracellular localization of the antigen using electron microscopic studies in combination with immunogold labeling revealed the presence of HBsAg in an extended endoplasmic reticulum where it was found to assemble into defined multi-layered, lamellar structures. The distance between two layers was determined as ~6 nm indicating that these lamellas represent monolayers of well-ordered HBsAg subunits. We did not find any evidence for the presence of VLPs within the endoplasmic reticulum or other parts of the yeast cell. Conclusions It is concluded that high level production and intrinsic slow HBsAg VLP assembly kinetics are leading to retention and accumulation of the antigen in the endoplasmic reticulum where it assembles at least partly into defined lamellar structures. Further transport of HBsAg to the Golgi apparatus is impaired thus leading to secretory pathway disfunction and the formation of an extended endoplasmic reticulum which bulges into irregular cloud-shaped formations. As VLPs were

  16. 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

    Institute of Scientific and Technical Information of China (English)

    Jing Jin; Jian-Ying Yang; Jing Liu; Yu-Ying Kong; Yuan Wang; Guang-Di Li

    2002-01-01

    AIM: Both Hepatitis B virus (HBV) and Hepatitis C virus(HCV) are major causative agents of transfusion-associatedand community-acquired hepatitis worldwide. Developmentof a HCV vaccine as well as more effective HBV vaccines isan urgent task. DNA immunization provides a promisingapproach to elicit protective humoral and cellular immuneresponses against viral infection. The aim of this study is toachieve immune responses against both HCV and HBV by DNAimmunization with fusion constructs comprising various HCVE2 gene fragments fused to HBsAg gane of HBV.METHODS: C57BL/6 mice were immunized with plasmid DNAexpressing five fragments of HCV E2 fused to the gene forHBsAg respectively. After one primary and one boostingimmunizations, antibodies against HCV E2 and HBsAg weretested and subtyped in ELISA. Splenic cytokine expressionof IFN-γ and IL-10 was analyzed using an RT-PCR assay.Post-immune mouse antisera also were tested for theirability to capture HCV viruses in the serum of a hepatitis Cpatient in vitro.RESUTLTS: After immunization, antibodies against bothHBsAg and HCV E2 were detected in mouse sera, withIgG2a being the dominant immunoglobulin sub-class. High-level expression of INF-γ was deuetected in cultured splenic cells.Mouse antisera against three of the five fusion constructs wereable to capture HCV viruses in an in vitro assay.CONCLUSION: The results indicate that these fusionconstructs could efficiently elicit humoral and Th1 dominantcellular immune responses against both HBV S and HCV E2antigens in DNA-immunized mice. They thus could serve ascandidates for a bivalent vaccine against HBV and HCVinfection. In addition, the capacity of mouse antisera againstthree of the five fusion constnucts to capture HCV virusses invitro suggested that neutralizing epitopes may be present inother regions of E2 besides the hypervariable region 1.

  17. Serum HBV core-related antigen is a good predictor for spontaneous HBeAg seroconversion in chronic hepatitis B patients.

    Science.gov (United States)

    Song, Guangjun; Yang, Ruifeng; Rao, Huiying; Feng, Bo; Ma, Hui; Jin, Qian; Wei, Lai

    2017-03-01

    Early prediction of spontaneous hepatitis B virus e antigen (HBeAg) seroconversion is pivotal in the prevention of unnecessary drug prescription, corresponding financial burden, and adverse reactions. One hundred and thirteen chronic hepatitis B patients with HBeAg-positive in the immune active phase were followed up for about 1.5 years. Patients were classified into two groups: spontaneous HBeAg seroconversion group (group A, n = 18) and non-spontaneous HBeAg seroconversion group. Among the non-spontaneous HBeAg seroconversion group, 35 patients were selected as controls (group B, n = 35). At week 12, there was a significant difference in hepatitis B core-related antigen (HBcrAg) levels between the two groups (group A 4.32 ± 1.05 log10  kU/ml, and group B 5.16 ± 0.53 log10  kU/ml, P = 0.004), and this significance magnified at week 28. Only two variables, HBcrAg level and the reduction in the HBcrAg levels (ΔHBcrAg) at week 28 were enrolled, with the odds ratio of 4.19 and 0.21, respectively. The optimal cutoffs of HBcrAg levels and the ΔHBcrAg at week 28 were 4.90 and 2.00 log10  kU/ml, respectively. The positive predictive value and negative predictive value of HBcrAg levels at week 28 were 73.9% and 96.7%, respectively. The positive predictive value and negative predictive value of the ΔHBcrAg at week 28 were 76.2% and 93.8%, respectively. The measurement of HBcrAg is useful for monitoring the natural course of chronic hepatitis B virus infection. The dynamics of HBcrAg levels could accurately predict the spontaneous HBeAg seroconversion. J. Med. Virol. 89:463-468, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  18. Deficient Knowledge on Hepatitis B Infection in Pregnant Women and Prevalence of Hepatitis B Surface Antigen Carriage in an Endemic Area: A Review

    Directory of Open Access Journals (Sweden)

    Oi Ka Chan

    2012-01-01

    Full Text Available Hepatitis B infection is a major global health problem. Vertical transmission is the commonest route of spreading hepatitis B virus (HBV in many endemic areas. In order to control such transmission in Hong Kong, neonatal immunization programme was implemented for more than two decades. A declining prevalence of HBV infection was expected. However, the prevalence remained unabated at around 10% in recent studies. We suspect that one of the explanations of this persistent high prevalence is deficient knowledge on infection with the HBV and its prevention. Our paper gives an overview of the knowledge on HBV infection among Chinese population in both high and low endemic areas and discusses the potential factors that influenced the knowledge on as well as the implication of the sources of information for HBV infection, which was not addressed in previous studies.

  19. Analysis on the Clinical Value of Hepatitis C Virus Core Antigen Detection in the Diagnosis of Hepatitis C%丙肝病毒核心抗原检测诊断丙肝的临床价值评析

    Institute of Scientific and Technical Information of China (English)

    黄启强; 张子茵; 谢炳龙; 张津; 林思强

    2015-01-01

    Objective:To investigate the diagnosis of hepatitis C hepatitis C virus core antigen(HCV-cAg)diagnostic value. Method:The suspected 38 hepatitis C virus(HCV)or hepatitis C patients as study group,over the same period the screening population 100 cases as the control group. The two groups were serum samples taken from implementation of detection of HCV CAG detection and hepatitis C virus core antibody(AB),and reverse transcription polymerase chain reaction RT-RNA confirmed positive. Result:In the control group AB test was negative,and detection of HCV CAG display positive in 2 cases,the RT-RNA confirmed 1 case was positive;study group with HCV detection was positive in 20 cases,RT-RNA confirmed positive in 24 cases. The diagnostic accordance rate was 83.33%. Conclusion:With higher rate of HCV-cAg detection in the diagnosis of hepatitis C diagnosis,there is a positive significance on early diagnosis,worthy of reference.%目的:探讨丙肝诊断中丙肝病毒核心抗原(HCV-cAg)的诊断价值。方法:将疑似丙肝或丙肝患者38例作为研究组,同期筛查人群100例作为对照组,两组均抽取血清样本实施HCV-cAg检测与丙肝病毒核心抗体(HCV-Ab)检测,并用反转录多聚酶链反应(RT-RNA)证实阳性者。结果:对照组HCV-Ab检测均为阴性,而HCV-cAg检测显示阳性2例,经RT-RNA证实1例为阳性;研究组HCV-cAg检出阳性20例,RT-RNA证实阳性24例,诊断符合率为83.33%。结论:HCV-cAg检测诊断丙肝诊断符合率较高,对早期诊断有着积极的意义,值得借鉴。

  20. 合成肽抗原在戊型肝炎病毒感染诊断中的应用%Serodiagnosis of Hepatitis E Virus Infection by ELISA Based on Synthetic Peptide Antigens

    Institute of Scientific and Technical Information of China (English)

    周小林; 刘云霞; 崔梅萍; 谷娟娟; 张伟; 孙兰英

    2001-01-01

    An ELISA for the detection of anti-HEV using synthetic peptideantigens was developed. The synthetic antigens were encoded by OFR2 and OFR3 genes of HEV. The purpose of this study was to determine the applicability of the synthetic antigens in the serodiagnosis of hepatitis E. The anti-HEV detection using synthetic antigens was carried out in 47 healthy subjects and 89 patients with acute or chronic viral hepatitis. The results showed that the positive rate of anti-HEV-IgG in healthy subjects was 4.2%(2/47), and no IgM antibody to HEV was found. The positive rates of IgG and IgM antibodies to HEV in the hepatitis patients were 8.9% and 10% respectively. In addition, we compared the detecting efficacy of the synthetic antigens with that of the market reagent in 57 serum samples, the total coincident rate was 87.7% (50/57). All of the results accorded with the literatures reported. This study suggests that the ELISA based on the synthetic peptide antigens was specific, sensitive and convenient in diagnosis of HEV infection, it can be widely used in both clinical and epidemiological reseaches.

  1. Translational Enhancer of Tobacco mosaic virus Enhancing Expression of Hepatitis B Surface Antigen in Transgenic Panax ginseng C. A. Meyer Callus

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    The 5'-nontranslated leader(omega sequence) of Tobacco mosaic virus(TMV) was used as a translational enhancer sequence in the expression of the hepatitis B surface antigen(HBsAg) gene in transgenic ginseng callus cultures.The adr subtype HBsAg gene was placed under the control of the Cauliflower mosaic virus(CaMV) 35S promoter linking to the TMV leader sequence. The antisense omega sequence was used in a control construct. The resulting constructs cloned in the binary vector pBI121 were used to transform the ginseng callus tissue via the Agrobacterium-mediated procedure. The integration and expression of the HBsAg gene were evaluated by PCR and western blot, respectively. Enzyme-linked immunoassays(ELISA) using a monoclonal antibody directed against human serum-derived HBsAg revealed a three to four-fold enhanced expression of HBsAg in ginseng cells conferred by the TMV omega element.

  2. Non-muscle myosin as target antigen for human autoantibodies in patients with hepatitis C virus-associated chronic liver diseases.

    Science.gov (United States)

    von Mühlen, C A; Chan, E K; Peebles, C L; Imai, H; Kiyosawa, K; Tan, E M

    1995-04-01

    Three patients with hepatitis C virus (HCV)-related chronic liver disease were shown to have autoantibodies strongly reacting with cytoskeletal fibres of non-muscle cells. The heavy chain of non-muscle myosin microfilament was the main target for those autoantibodies, as determined by (i) cell and tissue immunofluorescence studies showing colocalization with an anti-myosin antibody prototype; (ii) primary reactivity in immunoblotting with a 200-kD protein, using either MOLT-4 cells, human platelets, or affinity-purified non-muscle myosin as antigen extract; and (iii) immunoblotting of similar immunoreactive fragments in papain-digested MOLT-4 cell extracts, by using those human sera and antibody prototype. Autoantibodies to non-muscle myosin heavy chain were not previously reported in patients with chronic liver diseases, especially in those associated with HCV infection.

  3. Fine-mapping of the B-cell epitope domain at the N-terminus of the preS2 region of the hepatitis B surface antigen.

    Science.gov (United States)

    Sominskaya, Irina; Paulij, Wilma; Jansons, Juris; Sobotta, Dirk; Dreilina, Dzidra; Sunnen, Cecile; Meisel, Helga; Gerlich, Wolfram H; Pumpens, Paul

    2002-02-01

    In this study, we report the exact localization and substitutional characterization of a B-cell epitope domain at the N-terminus of the preS2 region of the hepatitis B surface antigen. A set of deletion variants containing preS2 sequences of different length was generated on the basis of frCP as a carrier. It was found after Western blot analysis that three monoclonal antibodies (MAbs) (2-11B1, 3-11C2, HB.OT10) recognized the linear preS2 sequence within the amino acid (aa) stretch 3-WNSTTFHQTLQDP-13. The importance of each aa residue of the epitope was proved by comparison of antibody binding to alanine-substituted peptides in both free-peptide and Pepscan variants.

  4. Hepatitis viral B y Delta en el Perú: epidemiología y bases para su control

    Directory of Open Access Journals (Sweden)

    César Cabezas

    2007-10-01

    Full Text Available El Perú está catalogado como un país de mediana endemicidad para la infección por la hepatitis B (HBV, sin embargo, esta enfermedad se está dispersando en el país por la intensa migración de áreas de alta endemicidad a zonas de baja que endemicidad. Además de los mecanismos clásicos de transmisión de la infección como la vía parenteral y la vía sexual, debe destacarse la transmisión horizontal sobre todo en población infantil de áreas hiperendémicas y la limitada ocurrencia de transmisión vertical a diferencia de Asia. Desde que se cuenta con una vacuna segura y eficaz contra la HBV, se ha desarrollado programas de vacunación piloto en el país, luego de lo cual se ha generalizado la inmunización de la población infantil primero de áreas endémicas y luego a todo el país, según la prioridad y disponibilidad de vacunas. Dada la dispersión de la infección, y para lograr un efectivo control del problema en personas susceptibles, en un menor tiempo, es necesaria la inmunización contra HBV de adolescentes, jóvenes y grupos de riesgo, intervención que es una de las más costo-efectivas en salud pública, mereciendo en el mediano y largo plazo la evaluación de su real impacto. Estos temas son los que se desarrollan en la presente revisión.

  5. SLA/LP/tRNP((Ser)Sec) antigen in autoimmune hepatitis: identification of the native protein in human hepatic cell extract.

    Science.gov (United States)

    Volkmann, Martin; Luithle, Daniel; Zentgraf, Hanswalter; Schnölzer, Martina; Fiedler, Sabine; Heid, Hans; Schulze-Bergkamen, Andrea; Strassburg, Christian P; Gehrke, Sven G; Manns, Michael P

    2010-02-01

    A diagnostic subgroup of AIH type 1 is characterized by specific serum antibodies against soluble liver protein. The respective autoantigen was named SLA/LP/tRNP((Ser)Sec), after three homologous recombinant polypeptides were isolated from expression gene libraries. We analyzed human cultured liver cells for the human homologue of recombinant SLA/LP/tRNP((Ser)Sec) by antigen purification. In addition, a monoclonal antibody was generated against recombinant SLA-p35, a truncated recombinant SLA-reactive polypeptide. With a positive patient serum, immune affinity chromatography was performed on the 52 kD-SLA main antigenic determinant pre-enriched by ion exchange chromatography. By mass spectrometry, the 52 kD-SLA/LP/tRNP ((Ser)Sec) autoantigen was unambiguously identified in the purification product. The identity of the recombinant SLA-p35 and its human homologue was further confirmed by a specific signal of the anti SLA-p35 monoclonal antibody with purified human SLA/LP/tRNP((Ser)Sec). The 48 kD-SLA species frequently comigrating in SLA-immunoblotting however was not identified by either approach. We conclude that the native counterpart of recombinant tRNP((Ser)(Sec)) indeed is detectable with a molecular weight of 52 kD in soluble liver extract of human cells as the major antigenic component of SLA/LP/tRNP((Ser)Sec). Copyright 2009 Elsevier Ltd. All rights reserved.

  6. Immunogenicity of standard and low dose vaccination using yeast-derived recombinant hepatitis B surface antigen in elderly volunteers

    NARCIS (Netherlands)

    S. de Rave (Sjoerd); R.A. Heijtink; M. Bakker-Bendik (M.); J. Boot (Jenneke); S.W. Schalm (Solko)

    1994-01-01

    textabstractThere is no conclusive evidence that age influences the response to vaccination against hepatitis B virus. We therefore studied the immunogenicity of yeast-derived rHBsAg vaccine in elderly volunteers. The study was conducted in the outpatient clinics of an academic and a regional hospit

  7. Measurement of hepatitis B virus core-related antigen is valuable for identifying patients who are at low risk of lamivudine resistance.

    Science.gov (United States)

    Tanaka, Eiji; Matsumoto, Akihiro; Suzuki, Fumitaka; Kobayashi, Mariko; Mizokami, Masashi; Tanaka, Yasuhito; Okanoue, Takeshi; Minami, Masahito; Chayama, Kazuaki; Imamura, Michio; Yatsuhashi, Hiroshi; Nagaoka, Shinya; Yotsuyanagi, Hiroshi; Kawata, Sumio; Kimura, Tatsuji; Maki, Noboru; Iino, Shiro; Kiyosawa, Kendo

    2006-02-01

    The clinical usefulness of hepatitis B virus core-related antigen (HBVcrAg) assay was compared with that of HBV DNA assay in predicting the occurrence of lamivudine resistance in patients with chronic hepatitis B. Of a total of 81 patients who were treated with lamivudine, 25 (31%) developed lamivudine resistance during a median follow-up period of 19.3 months. The pretreatment positive rate of HBe antigen, or pretreatment levels of HBVcrAg or HBV DNA did not differ between patients with and without lamivudine resistance. Levels of both HBVcrAg and HBV DNA decreased after the initiation of lamivudine administration; however, the level of HBVcrAg decreased significantly more slowly than that of HBV DNA. The occurrence of lamivudine resistance was significantly less frequent in the 56 patients whose HBV DNA level was less than 2.6 log copy/ml at 6 months of treatment than in the remaining 25 patients. The cumulative rate of lamivudine resistance was as high as 70% within 2 years in the latter group, while it was only 28% in the former group. Lamivudine resistance did not occur during the follow-up period in the 19 patients whose HBVcrAg level was less than 4.6 log U/ml at 6 months of treatment, while it did occur in 50% of the remaining patients within 2 years. These results suggest that measurement of HBV DNA is valuable for identifying patients who are at high risk of developing lamivudine resistance, and that, conversely, measurement of HBVcrAg is valuable for identifying those who are at low risk of lamivudine resistance.

  8. Dysfunctional CD8+ T cells in hepatitis B and C are characterized by a lack of antigen-specific T-bet induction

    Science.gov (United States)

    Raziorrouh, Bijan; Schraut, Winfried; Backmund, Markus; Wächtler, Martin; Wendtner, Clemens-Martin; Bengsch, Bertram; Thimme, Robert; Denk, Gerald; Zachoval, Reinhart; Dick, Andrea; Spannagl, Michael; Haas, Jürgen; Diepolder, Helmut M.; Jung, Maria-Christina; Gruener, Norbert H.

    2014-01-01

    The transcription factor T-bet regulates the production of interferon-γ and cytotoxic molecules in effector CD8 T cells, and its expression correlates with improved control of chronic viral infections. However, the role of T-bet in infections with differential outcome remains poorly defined. Here, we report that high expression of T-bet in virus-specific CD8 T cells during acute hepatitis B virus (HBV) and hepatitis C virus (HCV) infection was associated with spontaneous resolution, whereas T-bet deficiency was more characteristic of chronic evolving infection. T-bet strongly correlated with interferon-γ production and proliferation of virus-specific CD8 T cells, and its induction by antigen and IL-2 stimulation partially restored functionality in previously dysfunctional T-bet–deficient CD8 T cells. However, restoration of a strong interferon-γ response required additional stimulation with IL-12, which selectively induced the phosphorylation of STAT4 in T-bet+ CD8 T cells. The observation that T-bet expression rendered CD8 T cells responsive to IL-12 suggests a stepwise mechanism of T cell activation in which T-bet facilitates the recruitment of additional transcription factors in the presence of key cytokines. These findings support a critical role of T-bet for viral clearance and suggest T-bet deficiency as an important mechanism behind chronic infection. PMID:25225458

  9. Acute Exacerbations of Chronic Hepatitis B Are Accompanied by Decline of Core Antigen-Specific Regulatory T-Cell Frequencies: Implications for Successful Anti-HBV Treatments

    Directory of Open Access Journals (Sweden)

    Sun-Lung Tsai

    2007-11-01

    Full Text Available Background and Aims: Acute exacerbations (AEs of perinatally-acquired chronic hepatitis B (CHB are accompanied by increased T cell responses to hepatitis B core and e antigens (HBcAg & HBeAg. Naturally-arising forkhead transcription factor Foxp3 (forkhead box p3-expressing CD4+CD25+ regulatory T (Treg cells are thought to be important in the control of infectious diseases. This study aimed to investigate whether HBcAg-specific Treg cells play a role in modulating spontaneous AEs and in influencing the outcome of anti-hepatitis B virus (HBV treatments.Methods: The SYFPEITHI scoring system was employed to predict epitope peptides on HBcAg overlapping with HBeAg for the construction of peptide-HLA class II tetramers to measure HBcAg-specific Treg cell frequencies (Treg f . Results: HBcAg-specific Treg f declined significantly in association with increased HBcAg-specific cytotoxic T lymphocyte frequencies during spontaneous AEs without treatment. Vigorous in vitro expansion of CD4+CD25+ Treg cells from CHB patients responding to HBcAg and/or its peptides plus interleukin-2 (IL-2 was consistently detected. Depletion of Treg cells from peripheral blood mononuclear cells enhanced proliferation to HBcAg. In contrast, patients with AEs who received anti-HBV treatments with oral nucleoside analogues or interferon-alpha injection revealed that more post-treatment increase of HBcAg-specific Treg f correlated with a higher sustained remission rate to the therapy.Conclusions: These data indicate that HBcAg-specific Treg cells from perinatally-acquired CHB patients are proliferative to HBcAg and its peptides and exhibit suppressor activity. They play a crucial role in modulating spontaneous AEs and in successful anti-HBV treatments.

  10. Perinatal hepatitis B virus detection by hepatitis B virus-DNA analysis.

    OpenAIRE

    De Virgiliis, S; Frau, F; Sanna, G; Turco, M P; Figus, A L; Cornacchia, G; Cao, A.

    1985-01-01

    Maternal transmission of hepatitis B virus infection in relation to the hepatitis B e antigen/antibody system and serum hepatitis B virus-DNA were evaluated. Results indicate that hepatitis B virus-DNA analysis can identify hepatitis B serum antigen positive mothers who may transmit infection to their offspring.

  11. Perinatal hepatitis B virus detection by hepatitis B virus-DNA analysis.

    Science.gov (United States)

    De Virgiliis, S; Frau, F; Sanna, G; Turco, M P; Figus, A L; Cornacchia, G; Cao, A

    1985-01-01

    Maternal transmission of hepatitis B virus infection in relation to the hepatitis B e antigen/antibody system and serum hepatitis B virus-DNA were evaluated. Results indicate that hepatitis B virus-DNA analysis can identify hepatitis B serum antigen positive mothers who may transmit infection to their offspring. Images Figure PMID:3970570

  12. Perinatal hepatitis B virus detection by hepatitis B virus-DNA analysis.

    OpenAIRE

    De Virgiliis, S; Frau, F; Sanna, G; Turco, M P; Figus, A L; Cornacchia, G; Cao, A

    1985-01-01

    Maternal transmission of hepatitis B virus infection in relation to the hepatitis B e antigen/antibody system and serum hepatitis B virus-DNA were evaluated. Results indicate that hepatitis B virus-DNA analysis can identify hepatitis B serum antigen positive mothers who may transmit infection to their offspring.

  13. Impacts of the G145R Mutation on the Structure and Immunogenic Activity of the Hepatitis B Surface Antigen: A Computational Analysis

    Directory of Open Access Journals (Sweden)

    Rezaee

    2016-06-01

    Full Text Available Background Vaccine-escaped hepatitis B virus (HBV mutations occur within the “a” determinant area, which is located in the major hydrophilic region (MHR of the hepatitis B surface antigen (HBsAg protein. It is now well established that the common G145R mutation is highly capable of escaping from HBsAg immune recognition. However, the impacts of this mutation on the structure and immunogenic activity of HBsAg have been poorly investigated. Objectives The present study analyzed the effects of the G145R mutation on the structure and immunogenic activity of the HBsAg. Materials and Methods Three-dimensional (3D structure of HBsAg for both the wild-type and G145R mutant were predicted and refined using several web tools. After quantitative evaluations, the effects of the G145R mutation on the secondary and 3D structures of the HBsAg were investigated. In parallel, the immunogenic activity of the wild-type and mutant HBsAg was also analyzed using a ClusPro docking server as well as the IEDB web tool. Further analyses were performed via molecular dynamics (MD simulations using the GROMACS v5.0.2 simulation package. Results The G145R mutation causes a considerable reduction in the immunogenic activity of the HBsAg through a conformational change in the HBsAg antigenic loops. This mutation inserts a new β-strand in the “a” determinant region of the HBsAg, leading to a reduced binding affinity to its monoclonal antibody, MAb12. The G145R mutation also increased the compactness and stability of the HBsAg by enhancing the rigidity of the “a” determinant. Conclusions These data will be beneficial for designing more advanced antibodies for the recognition of the HBsAg in diagnostics. In addition, the results of this study may assist in the design or development of more effective hepatitis B vaccines.

  14. Specific recognition of mycobacterial protein and peptide antigens by gamma-delta T cell subsets following infection with virulent Mycobacterium bovis

    Science.gov (United States)

    Promoting effective immunity to Mycobacterium tuberculosis complex pathogens is a challenge that is of interest to the fields of human and veterinary medicine alike. We report that gamma delta T cells from virulent Mycobacterium bovis-infected cattle respond specifically and directly to complex, pro...

  15. Glycolipid antigens for treating hepatic colorectal cancer metastases and their effect on the therapeutic efficacy of live attenuated Listeria monocytogenes.

    Science.gov (United States)

    Olino, Kelly; Edil, Barish H; Meckel, Kristen F; Pan, Xiaoyu; Thuluvath, Avesh; Pardoll, Drew M; Schulick, Richard D; Yoshimura, Kiyoshi; Weber, Walter P

    2012-05-01

    Previous work demonstrated that a subset of natural killer T cells in mice decreased the antitumor efficacy of live attenuated Listeria monocytogenes where the actin A and internalin B genes were genetically deleted (LMD) against murine hepatic colorectal cancer metastases. Therefore, we hypothesized that the use of specific glycolipids known to selectively stimulate natural killer T-cell subsets used alone or co-administered with LMD would increase survival. We found that early or multiple administrations of glycolipids after tumor challenge had a strong impact on survival with or without LMD. Solitary administration or treatment given later was less efficacious but still showed a strong trend toward enhancing the antitumor activity of LMD. These results underscore the potential of glycolipids in the treatment of hepatic metastases and encourage further investigations into the immunomodulation of natural killer T cells to enhance the antitumor activity of LMD.

  16. Viral blips during long-term treatment with standard or double dose lamivudine in HBe antigen negative chronic hepatitis B

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    AIM: To evaluate safety and effect on hepatitis B virus (HBV) suppression of a long-term treatment with lamivudine (LAM) at standard (100 mg/d) or double (200 mg/d) dose in chronic hepatitis B. METHODS: This was a case study with matched controls (1:3) in patients with chronic hepatitis B with anti-Hbe antibodies. RESULTS: Twelve patients received LAM 200 mg/d and 35 LAM 100 mg/d, for a median of 28 mo. A primary response (PR; I.e. Negative HBV-DNA with Amplicor assay) was achieved in 100% of LAM-200 patients and 83% of LAM-100 patients. A virological breakthrough occurred in 16.7 and 24.7%, respectively, of the PR-patients, with the appearance of typical LAM resistance mutations in all but one patient. Viremia blips (I.e. Transient HBV-DNA below 80 IU/Ml in patients who tested negative at Amplicor assay) were detected using a real time polymerase chain reaction (PCR) and occurred in seven out of nine patients with subsequent BT and in four out of 32 patients with end-of-study response (77.7% vs 12.5%; P = 0.001) at chi-square test). At the end of the study, 51.4% of LAM-100 patients and 83.3% of LAM-200 patients had remained stably HBV-DNA negative. Double-dose LAM was well tolerated. CONCLUSION: Long-term treatment of anti-Hbe positive chronic hepatitis B with double dose lamivudine causes a more profound and stable viral suppression as compared to conventional treatment.

  17. KIR3DS1/HLA-B Bw4-80Ile Genotype Is Correlated with the IFN-α Therapy Response in hepatitis B e antigen-Positive Chronic Hepatitis B

    Directory of Open Access Journals (Sweden)

    Wenting Li

    2017-10-01

    Full Text Available To date, several on-treatment-level virological and serological indices that may predict the response to interferon alpha (IFN-α have been reported. However, no effective predictors, such as drug–response genes, that can be detected before administration of anti-hepatitis B virus (HBV therapy with IFN-α, have been found. In the diverse range of chronic viral infection, genes that affect human immunity play important roles in understanding host and viral co-evolution. Killer-cell immunoglobulin-like receptors (KIRs, which are highly polymorphic at the allele and haplotype levels, participate in the antiviral function of natural killer (NK cells via fine-tuning inhibition and activation of NK-cell responses that occur when the NK cells interact with human leukocyte antigen (HLA class I molecules on target cells. For each individual, the pairing of KIR and HLA ligand is genetically determined. To investigate whether a particular KIR and HLA repertoire influences the risk of HBV infection and response to IFN-α treatment for chronic hepatitis B (CHB, we genotyped the KIRs and HLA ligands of 119 hepatitis B e antigen (HBeAg-positive CHB patients. These patients included 43 patients who achieved sustained response (SR induced by IFN-α treatment for 48 weeks, 76 patients who achieved no response (NR, and 96 healthy subjects as controls. SR was defined as HBeAg loss with HBV DNA < 2,000 IU/ml and alanine aminotransferase normalization at 24 weeks posttreatment (week 72. In this study, we showed that activating KIR genes were less prevalent in Han Chinese, especially in Han Chinese with CHB, than in Caucasians. Furthermore, the KIR3DS1 gene, in combination with HLA-B Bw4-80Ile, strongly influenced the therapeutic outcomes for CHB patients who were treated with IFN-α. The frequency of the combination of genes encoding KIR3DS1 and HLA-B Bw4-80Ile was higher in patients who had a sustained treatment response than in patients who had NR [35

  18. The risk of perinatal hepatitis B virus transmission: hepatitis B e antigen (HBeAg prevalence estimates for all world regions

    Directory of Open Access Journals (Sweden)

    Ott Jördis J

    2012-06-01

    Full Text Available Abstract Background HBeAg presence in childbearing-age women is a major determinant of perinatal hepatitis B virus (HBV transmission. The risk of developing chronic HBV infection and liver disease is highest at young age. Our aim was to assess perinatal HBV transmission risk by means of estimating age- and region-specific HBeAg prevalence. Methods Based on observed HBeAg seroprevalence data obtained from a systematic literature review, we modeled HBeAg prevalence using an empirical Bayesian hierarchical model. Age- and region-specific estimates were generated for 1990 and 2005. Results Globally, highest HBeAg prevalence of over 50 % was found in 0–9 years old girls. At reproductive age, HBeAg prevalence was 20-50 %. Prevalence was highest in young females in East Asia in 1990 (78 %, the infection was less common in Sub-Saharan and North Africa. Regional differences in prevalence were smaller in 2005. There was an overall decrease in HBeAg between 1990 and 2005, which was strongest among girls in Oceania (23.3 % decline, South and South-East Asia (14 % decline. However, in these regions, prevalence remained high at 67 % among young females in 2005. Smaller decreases were observed in women at reproductive age, at which 24-32 % of all HBsAg-positive women were HBeAg-positive in 2005, with lowest prevalence in Southern Sub-Saharan Africa and highest prevalence in Oceania and South-East Asia. Conclusions HBeAg estimates are crucial for understanding the epidemiology of HBV and for prioritizing implementation of WHO`s prevention recommendations for all infants to receive the first dose of hepatitis B vaccine within 24 hours of birth. Results will have importance as access to treatment for chronic HBV infection is expanded.

  19. Structural mimicry between SLA/LP and Rickettsia surface antigens as a driver of autoimmune hepatitis: insights from an in silico study.

    Science.gov (United States)

    Paiardini, Alessandro; Pascarella, Stefano

    2013-04-10

    Autoimmune hepatitis (AIH) is a chronic, progressive liver disease, characterized by continuing hepatocellular inflammation and necrosis. A subgroup of AIH patients presents specific autoantibodies to soluble liver antigen/liver-pancreas (SLA/LP) protein, which is regarded as a highly specific diagnostic marker. Autoantigenic SLA/LP peptides are targeted by CD4+ T cells, and restricted by the allele HLA-DRB1*03:01, which confers disease susceptibility in Europeans and Americans. A positively charged residue at position 71 has been indicated as critical for AIH susceptibility in all of the HLA alleles identified to date. Though the exact molecular mechanisms underlying pathogenesis of AIH are not clear, molecular mimicry between SLA/LP and viral/bacterial antigens has been invoked. The immunodominant region of SLA/LP was used as query in databank searches to identify statistically significant similarities with viral/bacterial peptides. Homology modeling and docking was used to investigate the potential interaction of HLA-DRB1*03:01 with the identified peptides. By molecular mechanics means, the interactions and energy of binding at the HLA binding site was also scrutinized. A statistically significant structural similarity between the immunodominant regions of SLA/LP and a region of the surface antigen PS 120 from Rickettsia spp. has been detected. The interaction of the SLA/LP autoepitope and the corresponding Rickettsia sequence with the allele HLA-DRB1*03:01 has been simulated. The obtained results predict for both peptides a similar binding mode and affinity to HLA-DRB1*03:01. A "hot spot" of interaction between HLA-DRB1*03:01 and PS 120 is located at the P4 binding pocket, and is represented by a salt bridge involving Lys at position 71 of the HLA protein, and Glu 795 of PS120 peptide. These findings strongly support the notion that a molecular mimicry mechanism can trigger AIH onset. CD4+ T cells recognizing peptides of SLA/LP could indeed cross-react with

  20. Viral Load Pattern Among Hepatitis B Surface Antigen-positive Patients: Laboratory Perspective and Implications for Therapy

    Science.gov (United States)

    Iregbu, KC; Nwajiobi-Princewill, PI

    2016-01-01

    Background: Hepatitis B viral infection is an old medical problem with worldwide distribution. It is usually diagnosed using serologic methods. However, the decision as to which patient to treat or not remains challenging due to the poor sensitivity of serologic markers as prognostic or severity markers. Viral load (VL) determination using polymerase chain reaction techniques is a useful tool in decision-making. Aim: To determine the proportion of hepatitis B-positive patients who fall into different care groups based on the Society for Gastroenterology and Hepatology in Nigeria (SOGHIN) and National Institute for Health and Care Excellence guidelines, respectively, using result of hepatitis B virus (HBV) DNA determination. Materials and Methods: This is a retrospective and descriptive study. Data from all patients sent to the medical microbiology laboratory, National Hospital Abuja over a period of 28 months (November 2012 to February 2015) for hepatitis B DNA VL determinations were analyzed using Microsoft Excel 2010 (Microsoft Corporation, Redmond, WA, USA) and IBM SPSS version 20.0 (IBM SPSS, Inc., Chicago, IL, USA). Results: A total 666 patients, with mean age of 33.2 years, were tested. For those whose ages were known 36.2% (100/276) were below 30 years and 63.8% (176/276) 30 years and above. Exactly 66.7% (444/666) were males and the remaining 33.3% (222/666) were females. The VL of the patients varied from 20 to 1.7 × 108 IU/ml, with an average of 3.5 × 106 IU/ml. Around 76.1% (507/666) had measurable assay levels (20 − 1.7 × 108 IU/ml); 10.8% (76/666) had below 20 IU/ml and 3.8% (25/666) above 1.7 × 108 IU/ml. About 9.3% (62/666) had no detectable HBV DNA in their samples. About 46.8% (312/666) of the patients had levels between 20 and 2 × 103 IU/ml; 16.4% (109/666) had between 2001 and 2 × 104 IU/ml while 16.7% (111/666) had VL of between 20,001 and 1.7 × 108 IU/ml. Males tended to have detectable and higher VLs than females (P = 0

  1. Genetic Association of Human Leukocyte Antigens with Chronicity or Resolution of Hepatitis B Infection in Thai Population

    OpenAIRE

    2014-01-01

    BACKGROUND: Previous studies showed that single nucleotide polymorphisms (SNPs) in the HLA-DP, TCF19 and EHMT2 genes may affect the chronic hepatitis B (CHB). To predict the degree of risk for chronicity of HBV, this study determined associations with these SNPs. METHODS: The participants for this study were defined into 4 groups; HCC (n = 230), CHB (n = 219), resolved HBV infection (n = 113) and HBV uninfected subjects (n = 123). The HLA-DP SNPs (rs3077, rs9277378 and rs3128917), TCF19 SNP (...

  2. [Autoimmune hepatitis].

    Science.gov (United States)

    Ostojić, Rajko

    2003-01-01

    Autoimmune hepatitis is an unresolving, hepatocellular inflammation of unknown cause that is characterized by the presence of periportal hepatitis on histologic examination, tissue autoantibodies in serum, and hypergammaglobulinemia. By international consensus, the designation autoimmune hepatitis has replaced alternative terms for the condition. Three types of autoimmune hepatitis have been proposed based on immunoserologic findings. Type 1 autoimmune hepatitis is characterized by the presence of antinuclear antibodies (ANA) or smooth muscle antibodies (SMA) (or both) in serum. Seventy percent of patients with type 1 of autoimmune hepatitis are women. This type is the most common form and accounts for at least 80% of cases. Type 2 is characterized by the presence of antibodies to liver-kidney microsome type 1 (anti-LKM1) in serum. Patients with this type of autoimmune hepatitis are predominantly children. Type 3 autoimmune hepatitis is characterized by the presence of antibodies to soluble liver antigen (anti-SLA) in serum. There are no individual features that are pathognomonic of autoimmune hepatitis, and its diagnosis requires the confident exclusion of other conditions. The large majority of patients show satisfactory response to corticosteroid (usually prednisone or prednisolone) therapy. For the past 30 years it has been customary to add azathioprine as a "steroid sparing" agent to allow lower doses of steroids to be used and remission, once achieved, can be sustained in many patients with azathioprine alone after steroid withdrawal. Patients with autoimmune hepatitis who have decompensated during or after corticosteroid therapy are candidates for liver transplantation.

  3. The IgG antibody reactivity of sera from patients with active chronic hepatitis to a crude liver antigen and liver specific protein (LSP): analysis by ELISA and immunoblotting.

    Science.gov (United States)

    Sundin, U; Heigl, Z; Sundqvist, K G

    1988-11-01

    The antibody reactivity to liver specific protein (LSP) and a crude liver antigen of sera from patients with chronic active hepatitis (CAH) were studied along with other related diseases and healthy individuals. CAH sera containing liver reacting antibodies were selected using an ELISA with a crude liver preparation as antigen and subsequently the specificity was analysed by immunoblotting of SDS-PAGE-separated LSP. The incidence of IgG antibodies to the crude liver antigen and LSP in sera from 15 patients with CAH was 94% and 55% respectively. In the healthy control group (n = 30) the corresponding figures were 3% and 17%. Sera from patients with other autoimmune conditions with considerable reactivity in the crude liver ELISA test were those with antibodies against extractable nuclear antigens (ENA) and thyroid gland antigens, while the anti-nuclear antibody (ANA) group as a whole did not differ from the control group. In immunoblotting of SDS-PAGE-separated crude liver and LSP antigens, the IgG binding pattern of ELISA IgG positive CAH sera and sera from patients with thyroid disease was distinct, with bands corresponding to antigens of molecular weights of 38, 45 and 50 kD which were not observed in ELISA negative CAH sera or in sera from patients with other diseases and among healthy controls.

  4. Assessment of metal-assisted nucleophile activation in the hepatitis delta virus ribozyme from molecular simulation and 3D-RISM.

    Science.gov (United States)

    Radak, Brian K; Lee, Tai-Sung; Harris, Michael E; York, Darrin M

    2015-09-01

    The hepatitis delta virus ribozyme is an efficient catalyst of RNA 2'-O-transphosphorylation and has emerged as a key experimental system for identifying and characterizing fundamental features of RNA catalysis. Recent structural and biochemical data have led to a proposed mechanistic model whereby an active site Mg(2+) ion facilitates deprotonation of the O2' nucleophile, and a protonated cytosine residue (C75) acts as an acid to donate a proton to the O5' leaving group as noted in a previous study. This model assumes that the active site Mg(2+) ion forms an inner-sphere coordination with the O2' nucleophile and a nonbridging oxygen of the scissile phosphate. These contacts, however, are not fully resolved in the crystal structure, and biochemical data are not able to unambiguously exclude other mechanistic models. In order to explore the feasibility of this model, we exhaustively mapped the free energy surfaces with different active site ion occupancies via quantum mechanical/molecular mechanical (QM/MM) simulations. We further incorporate a three-dimensional reference interaction site model for the solvated ion atmosphere that allows these calculations to consider not only the rate associated with the chemical steps, but also the probability of observing the system in the presumed active state with the Mg(2+) ion bound. The QM/MM results predict that a pathway involving metal-assisted nucleophile activation is feasible based on the rate-controlling transition state barrier departing from the presumed metal-bound active state. However, QM/MM results for a similar pathway in the absence of Mg(2+) are not consistent with experimental data, suggesting that a structural model in which the crystallographically determined Mg(2+) is simply replaced with Na(+) is likely incorrect. It should be emphasized, however, that these results hinge upon the assumption of the validity of the presumed Mg(2+)-bound starting state, which has not yet been definitively verified

  5. Evaluation of the performance of four methods for detection of hepatitis B surface antigen and their application for testing 116,455 specimens.

    Science.gov (United States)

    Liu, Can; Chen, Tianbin; Lin, Jinpiao; Chen, Huijuan; Chen, Jing; Lin, Sheng; Yang, Bin; Shang, Hongyan; Ou, Qishui

    2014-02-01

    Hepatitis B surface antigen (HBsAg) is a crucial serum marker for the diagnosis of hepatitis B virus (HBV) infection. It is imperative to compare test results from different detection methods based on different principles. Four methods, chemiluminescent microparticle immunoassay (CMIA), electrochemiluminescent immunoassay (ECLIA), enzyme-linked immunosorbent assay (ELISA) and golden immunochromato-graphic assay (GICA) were applied to test the HBsAg level in 250 specimens. According to the EP12-A2 and EP15-A2 documents from Clinical and Laboratory Standards Institute (CLSI), the concentration at which repeated results are 50% positive (C50) of HBsAg detected by CMIA, ECLIA, ELISA and GICA was 0.05, 0.08, 0.15 and 15.0IU/ml, respectively. When the detection concentration of HBsAg was 0.5IU/ml, the imprecision degree of CMIA, ECLIA and ELISA was 8.1%, 5.9% and 14.9% respectively. When detecting high HBsAg level (≥20.0IU/ml) and HBsAg negative specimens, the consistency of the four methods was high, while for the low level (0.05-20.0IU/ml), the consistency was poor (except for the CMIA and ECLIA, Pevaluation of the four methods in qualitative diagnosis of HBsAg level in the 116,455 specimens, there was no significant discrepancy among CMIA, CMIA and ECLIA, however, GICA was significantly different from the other 3 methods. Compared with CMIA, the false negative rate of ECLIA, ELISA and GICA was 0.2%, 1.3% and 12.3% respectively. In conclusion, GICA was only suitable for the preliminary screening of HBsAg positive individuals and ELISA can be applied to the qualitative diagnosis of HBsAg. Both CMIA and ECLIA were suitable for the quantitative determination of HBsAg.

  6. DNA-based vaccination induces humoral and cellular immune responses against hepatitis B virus surface antigen in mice without activation of C-myc.

    Science.gov (United States)

    Zhao, Lian-San; Qin, Shan; Zhou, Tao-You; Tang, Hong; Liu, Li; Lei, Bing-Jun

    2000-04-01

    AIM:To develop a safe and effective DNA vaccine for inducing humoral and cellular immunological responses against hepatitis B virus surface antigen (HBsAg).METHODS:BALB/c mice were inoculated with NV-HB/s, a recombinant plasmid that had been inserted S gene of hepatitis B virus genome and could express HBsAg in eukaryotes. HBsAg expression was measured by ABC immunohis tochemical assay, generation of anti-HBs by ELISA and cytotoxic T lymphocyte (CTL), by MTT method, existence of vaccine DNA by Southern blot hybridization and activation of oncogene C-myc by in situ hybridization.RESULTS:With NV-HB/s vaccination by intramuscular injection, anti-HBs was initially positive 2 weeks after inoculation while all mice tested were HBsAg positive in the muscles.The titers and seroconversion rate of anti-HBs were steadily increasing as time went on and were dose dependent. All the mice inoculated with 100&mgr;g NV-HB/s were anti-HBs positive one month after inoculation, the titer was 1 1024 or more. The humoral immune response was similar induced by either intramuscular or intradermal injection. CTL activities were much stronger (45.26%) in NV-HB/s DNA immunized mice as compared with those (only 6%) in plasma-derived HBsAg vaccine immunized mice. Two months after inoculation, all muscle samples were positive by Southernblot hybridization for NV-HB/s DNA detection, but decreased to 25% and all were undetectable by in situ hybridiza-tion after 6 months.No oncogene C-myc activation was found in the muscle of inoculation site.CONCLUSION:NV-HB/s could generate humoral and cellular immunolo-gical responses against HBsAg that had been safely expressed in situ by NV-HB/s vaccination.

  7. Glycosylation analysis and protein structure determination of murine fetal antigen 1 (mFA1)--the circulating gene product of the delta-like protein (dlk), preadipocyte factor 1 (Pref-1) and stromal-cell-derived protein 1 (SCP-1) cDNAs

    DEFF Research Database (Denmark)

    Krogh, T N; Bachmann, E; Teisner, B

    1997-01-01

    By means of sequence analysis, murine fetal antigen 1 (mFA1) isolated from Mus musculus amniotic fluid was shown to be the circulating protein of the delta-like protein, stromal-cell-derived protein 1 (SCP-1) and preadipocyte factor 1 (Pref-1) gene products. The protein contains 36 cysteine resid...

  8. Targeting hepatitis B virus antigens to dendritic cells by heat shock protein to improve DNA vaccine potency

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    AIM: To investigate a novel DNA vaccination based upon expression of the HBV e antigen fused to a heat shock protein (HSP) as a strategy to enhance DNA vaccine potency.METHODS: A pCMV-HBeAg-HSP DNA vaccine and a control DNA vaccine were generated. Mice were immunized with these different construct. Immune responses were measured 2 wk after a second immunization by a T cell response assay, CTL cytotoxicity assay, and an antibody assay in C57BL/6 and BALB/c mice. CT26-HBeAg tumor cell challenge test in vivo was performed in BALB/c mice to monitor anti-tumor immune responses.RESULTS: In the mice immunized with pCMV-HBe-HSP DNA, superior CTL activity to target HBV-positive target cells was observed in comparison with mice immunized with pCMV-HBeAg (44% ± 5% vs 30% ± 6% in E: T > 50:1, P < 0.05). ELISPOT assays showed a stronger T-cell response from mice immunized with pCMV-HBe-HSP than that from pCMV-HBeAg immunized animals when stimulated either with MHC class Ⅰ or class Ⅱ epitopes derived from HBeAg (74% ± 9% vs 31% ± 6%, P < 0.01). ELISA assays revealed an enhanced HBeAg antibody response from mice immunized with pCMV-HBe-HSP than from those immunized with pCMV-HBeAg. The lowest tumor incidence and the slowest tumor growth were observed in mice immunized with pCMV-HBe-HSP when challenged with CT26-HBeAg.CONCLUSION: The results of this study demonstrate a broad enhancement of antigen-specific CD4+ helper,CD8+ cytotoxic T-cell, and B-cell responses by a novel DNA vaccination strategy. They also proved a stronger antigen-specific immune memory, which may be superior to currently described HBV DNA vaccination strategies for the treatment of chronic HBV infection.

  9. Humoral and cellular immunity to hepatitis B virus-derived antigens: comparative activity of Freund complete adjuvant alum, and liposomes.

    Science.gov (United States)

    Sanchez, Y; Ionescu-Matiu, I; Dreesman, G R; Kramp, W; Six, H R; Hollinger, F B; Melnick, J L

    1980-01-01

    Complete Freud adjuvant, aluminum gel, and liposomes were compared for their ability to enhance the immunogenicity of an intact 22-nm HBsAg particle vaccine and an HBsAg-derived polypeptide vaccine in guinea pigs. Both humoral and cell-mediated immune responses were evaluated. The greatest immune response was obtained with complete Freund adjuvant, regardless of the antigen preparation. Aluminum gel appeared to be a better adjuvant for 22-nm HBsAg particles, but the liposomes rendered polypeptide preparations more immunogenic. The possibility that various proportions were entrapped in aqueous compartments instead of being inserted into the lipid bilayers of liposomes might account for this difference. The development of both humoral and cellular immunity was dependent upon the use of an adjuvant, because aqueous preparations had poor immunogenicity. PMID:7014445

  10. Anti-hepatitis B core antigen testing with detection and characterization of occult hepatitis B virus by an in-house nucleic acid testing among blood donors in Behrampur, Ganjam, Orissa in southeastern India: implications for transfusion

    Directory of Open Access Journals (Sweden)

    Panigrahi Rajesh

    2010-08-01

    Full Text Available Abstract Background Occult hepatitis B virus (HBV infection might transmit viremic units into the public blood supply if only hepatitis B surface antigen (HBsAg testing is used for donor screening. Our aim was to evaluate the prevalence of occult HBV infection among the HBsAg negative/antiHBc positive donations from a highly HIV prevalent region of India. Methods A total of 729 HBsAg negative donor units were included in this study. Surface gene and precore region were amplified by in house nucleic acid test (NAT for detection of occult HBV infection and surface gene was analyzed after direct sequencing. Results A total of 220 (30.1% HBsAg negative donors were antiHBc positive, of them 66 (30% were HBV DNA positive by NAT. HBV DNA positivity among 164 antiHBc only group, was 27.1% and among 40 antiHBs positive group was 30.0%. HBV/D (93.3% was predominant and prevalence of both HBV/C and HBV/A was 3.3%. Single or multiple amino acids substitutions were found in 95% samples. Conclusion Thus, a considerable number of HBV infected donors remain undiagnosed, if only HBsAg is used for screening. Addition of antiHBc testing for donor screening, although will lead to rejection of a large number of donor units, will definitely eliminate HBV infected donations and help in reducing HBV transmission with its potential consequences, especially among the immunocompromised population. The HBV genetic diversity found in this donor population are in accordance with other parts of India.

  11. [Comparison of antibody responses to hepatitis B surface antigen among four recipient groups of hepatitis B vaccines that have been approved in Japan: evaluation using passive hemagglutination assay and chemiluminescent immunoassay].

    Science.gov (United States)

    Ogata, Norio

    2009-10-01

    In hepatitis B virus (HBV) infection-preventing programs, serum or plasma levels of antibody to hepatitis B surface antigen (anti-HBs) are important to determine whether individuals are protective or not. We compared anti-HBs responses using passive hemagglutination assay (Mycell) and chemiluminescent immunoassay (Architect) among four recipient groups of HB vaccines, Meinyu, HBY, Bimmugen and Heptavax II, that have been approved in Japan. Overall, in a total of 1875 vaccinees Mycell results showed recipient groups of Meinyu and HBY acquired higher anti-HBs levels than those of Bimmugen and Heptavax II. Comparison of anti-HBs responses by both Mycell and Architect in recipient groups of Meinyu (n=150), HBY (n=218), Bimmugen (n=260), and Heptavax II (n=47) demonstrated the order of vaccinees' responses, such as geometric mean titers, ratios of acquiring high antibody levels (Mycell titers over 1024, Architect measurements over 1000 mIU/mL), and ratios of having unsuccessful antibody responses (Mycell titers under 8, Architect measurements under 10 mIU/mL), were somewhat different between the two assays. Comparison of Architect measurements at given Mycell titers revealed Bimmugen-recipients showed significantly lower values than HBY- or Heptavax II-recipients. Around critical protective levels, 5 of 22 Bimmugen-recipients with Mycell titers 16 or 32 showed Architect measurements under 10 mIU/mL, while 8 of 11 Heptavax II-recipients with Mycell titers below 8 demonstrated Architect measurements over 10 mIU/mL. Thus, discrepancies in anti-HBs evaluation between Mycell and Architect seemed to partly depend on administered vaccines. These results indicate anti-HBs concentration should be evaluated carefully so that we could completely prevent HBV infection.

  12. Evaluation on Core Antigen in Diagnosis of Hepatitis C Virus%丙型肝炎病毒核心抗原诊断价值的研究

    Institute of Scientific and Technical Information of China (English)

    赵蕊; 和文博; 陈茂伟

    2014-01-01

    Objective To investigate the correlation of chronic hepatitis C virus core antigen ( HCV-cAg ) quantitative detection with viral load ,hepatitis C virus antibody ( HCV-Ab) and ALT.Methods The serum samples of 88 patients with chronic hepatitis C were collected to detect the HCV-cAg,HCV-Ab,ALT and HCV RNA levels ,and a comparative analysis was conducted .Results Among 88 patients with chronic hepatitis C ,the positive rate of HCV RNA was 64.8%(57/88),and the positive rate of HCV-cAg was 51.1%(45/88).The positive rate and concentration of HCV-cAg decreased gradually with the decreasing HCV RNA concentration ( P0.05).Conclusion HCV-cAg can be used as one of the indicators for the auxiliary diagnosis of chronic hepatitis C .%目的:探讨慢性丙型肝炎病毒核心抗原( HCV-cAg )定量与患者病毒载量、丙型肝炎病毒抗体(HCV-Ab)、丙氨酸氨基转移酶(ALT)的相关性。方法检测88例慢性丙型肝炎患者血清HCV-cAg、HCV-Ab、ALT及HCV RNA,并进行对比分析。结果88例慢性丙型肝炎患者中,HCV RNA阳性率为64.8%(57/88), HCV-cAg阳性率51.1%(45/88)。随HCV RNA浓度降低,HCV-cAg阳性率逐渐下降(P<0.05),HCV-cAg浓度逐渐降低(P<0.05)。 HCV-Ab阳性率为92.0%(81/88),HCV-Ab阳性组HCV-cAg浓度显著高于HCV-Ab阴性组(P<0.05)。丙型肝炎患者HCV-cAg浓度与HCV-Ab浓度呈正相关关系(P<0.05)。 ALT浓度151~250 U/L者25例(28.4%),61~150 U/L者29例(33.0%),≤60 U/L者34例(38.6%)。3组HCV-cAg浓度比较,差异无统计学意义(P>0.05)。结论 HCV-cAg可作为慢性丙型肝炎患者辅助诊断的指标之一。

  13. Human leucocyte antigen Class I and II alleles associated with anti-hepatitis C virus-positive patients of North India

    Directory of Open Access Journals (Sweden)

    M Chowdhry

    2016-01-01

    Full Text Available Purpose: Humans are the only known natural hosts of hepatitis C virus (HCV. This study was undertaken to examine the frequencies of human leucocyte antigens (HLAs Class I and Class II genotype profiles in anti-HCV-infected patients of Northern India. Materials and Methods: From a period of January 2013 to August 2014, 148 anti-HCV-positive patients of North India referred to the Department of Molecular Biology and Transplant Immunology, Indraprastha Apollo Hospitals, New Delhi, for performing HLA typing were included in the study. Results: AFNx0102, AFNx0131 allele frequency decreased significantly in anti-HCV-positive patients. Frequencies for HLA-B loci did not reach any statistical significance. Among the Class II alleles, HLA-DRB1FNx0103 and HLA-DRB1FNx0110 were significantly higher in the patient population, and HLA-DRB1FNx0115 was significantly decreased in the patient population as compared to the controls. Conclusion: HLA-AFNx0133 was significantly increased as compared to control population and showed geographic variation in HCV-infected individuals of India.

  14. Enhancement of cytotoxic T lymphocyte activity by dendritic cells loaded with Tat-protein transduction domain-fused hepatitis B virus core antigen

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    The protein transduction domain (PTD) of human immuno-deficiency virus-1-Tat protein has a unique potency to pen-etrate the cellular membranes. To synthesize the sequence of Tat-PTD and hepatitis B virus core antigen (HBcAg), we spliced these sequences and linked a fusion gene into the pMAL-c2x vector. The fusion proteins were purified by affin-ity chromatography and pulsed with bone marrow -derived den-dritic cells (DCs), and the transduction of recombinant pro-tein was detected by immunofluorescence antibody assay.Results showed that recombinant PTD-HBcAg could pen-etrate into DC cytoplasm while recombinant HBcAg was de-tected on the surface of cells. The percentage of DC surface molecules, such as CD80, CD86 and major histocompatibii-ity complex Ⅱ, and production of cytokine (IL-12pT0) induced by recombinant PTD-HBcAg were significantly higher than those induced by recombinant HBcAg or tumor necrosis fac-tor-α. DCs treated with PTD-HBcAg induced T cells to dif-ferentiate into specific cytotoxic T lymphocytes (CTLs) and enhanced the CTL killing response. In conclusion, the ex-pressed and purified PTD-HBcAg fusion protein could pen-etrate into cells through the plasma membrane, promote DC maturation, and enhance T cells response to generate HBcAg-specific CTLs efficiently.

  15. Development of a Recombinant Cell-Based Indirect Immunofluorescence Assay for the Determination of Autoantibodies against Soluble Liver Antigen in Autoimmune Hepatitis

    Directory of Open Access Journals (Sweden)

    Christiane Radzimski

    2013-01-01

    Full Text Available Autoantibodies against soluble liver antigen (SLA are specific markers for autoimmune hepatitis (AIH type 1. In contrast to the determination of other AIH-associated autoantibodies by indirect immunofluorescence assay (IFA, detection of anti-SLA relied up to now on ELISA or immunoblot based on bacterially expressed recombinant protein. In order to develop a complementary IFA substrate, SLA isoform 1 was recombinantly produced in the human cell line HEK293 and controlled by a rabbit hyperimmune serum against SLA. The recombinant cells were used in IFA (RC-IFA to analyze sera from 20 AIH patients with anti-SLA positivity predetermined by ELISA together with 80 controls (20 anti-SLA negative AIH, 15 primary biliary cirrhosis, 15 HCV, and 30 healthy blood donors. Using RC-IFA, anti-SLA was detected in all ELISA positive AIH sera but in none of the controls. Furthermore, a cytosolic fraction of HEK293 containing SLA was able to neutralize the autoantibodies in all positive sera in a dose-dependent manner. HEK293 cells expressing SLA are a valid substrate for the serodiagnosis of AIH relevant autoantibodies by IFA. In concert with cryosections of primate liver, rat kidney, rat liver, rat stomach, and HEp-2 cells, they enable the parallel determination of all autoantibodies associated with autoimmune liver diseases.

  16. Association of cytotoxic T-lymphocyte antigen 4 genetic polymorphism, hepatitis C viral infection and B-cell non-Hodgkin lymphoma: an Egyptian study.

    Science.gov (United States)

    Khorshied, Mervat Mamdooh; Gouda, Heba Mahmoud; Khorshid, Ola M Reda

    2014-05-01

    Abstract Genetic and environmental factors are involved in the pathogenesis of non-Hodgkin lymphoma (NHL). The present study aimed to investigate the association between cytotoxic T-lymphocyte antigen 4 (CTLA-4) genetic polymorphism, hepatitis C virus (HCV) infection and B-cell NHL risk in Egypt. Genotyping of CTLA-4 single nucleotide polymorphisms (SNPs) was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay for 181 adult patients with B-NHL and 200 controls. Our study revealed that CTLA-4 + 49 A/G polymorphism conferred increased risk of B-NHL (odds ratio [OR] = 1.7, 95% confidence interval [CI] = 1.36-2.565). The prevalence of HCV infection in individuals harboring the mutant genotype + 49 A/G and - 318 C/T SNPs was higher in patients with B-NHL and was associated with increased risk of B-NHL (OR = 2.79, 95% CI = 1.24-6.93 for + 49 A/G and OR = 3.9, 95% CI = 1.01-15.98 for - 318 C/T). In conclusion, some SNPs of CTLA-4 are genetic risk factors for B-NHL. Moreover, this study identified an association of CTLA-4 + 49 A/G and - 318 C/T promoter polymorphisms with HCV infection.

  17. Long-term efficacy of hepatitis B vaccination as post-transplant prophylaxis in hepatitis B surface antigen (HBsAg) positive recipients and HBsAg negative recipients of anti-hepatitis B core positive grafts.

    Science.gov (United States)

    Yoshizawa, Atsushi; Yamashiki, Noriyo; Ueda, Yoshihide; Kaido, Toshimi; Okajima, Hideaki; Marusawa, Hiroyuki; Chiba, Tsutomu; Uemoto, Shinji

    2016-05-01

    Hepatitis B virus (HBV) reactivation after liver transplantation in HBV patients, or in HBV negative recipients of anti-hepatitis B core (HBc) positive grafts, has been prevented by prophylactic use of hepatitis B immunoglobulin (HBIG) and/or nucleoside/nucleotide analogs (NA). Vaccination against HBV is an alternative that may provide a chance to discontinue prophylaxis by producing anti-hepatitis B surface (HBs) antibodies. We retrospectively reviewed 40 HBV positive recipients (HBV+ group) and 27 HBV negative recipients of anti-HBc positive grafts (HBV-/anti-HBc+ graft group), who were administrated double-dose hepatitis B vaccination. Recipients were regarded as responders when anti-HBs greater than 100 IU/L was maintained for 6 months or more without HBIG. Response rates of vaccine and long-term outcomes were analyzed. Eighteen of the 40 patients in the HBV+ group (45%) and 18 of the 27 patients in the HBV-/anti-HBc+ graft group (67%) responded to vaccination after a median of four and three times, respectively. Younger age was the only independent factor associated with vaccine response in the HBV-/anti-HBc+ graft group (P = 0.03), whereas no factor was found to be an independent predictor for vaccine response in the HBV+ group. Among the 18 responders in the HBV+ group, 17 remained without NA or HBIG 8.2 years after the start of vaccination. Ten of those required periodic booster vaccination. All 18 responders in the HBV-/anti-HBc+ graft group remained free from HBV prophylaxis 6.2 years after the start of vaccination. Younger recipients have a greater chance to develop sufficient anti-HBs after double-dose HBV vaccination, leading to discontinue HBV prophylaxis. © 2015 The Japan Society of Hepatology.

  18. Identification of Hepatitis B Virus Surface Antigen (HBsAg Genotypes and Variations in Chronic Carriers from Isfahan Province, Iran

    Directory of Open Access Journals (Sweden)

    A Khedive

    2012-04-01

    Full Text Available Background: Hepatitis B virus (HBV gene and protein variations are frequently been seen in chronic patients. The aims of study were to determine the genotypes as well as the patterns of variations distribution in chronically-infected patients from the central part of Iran.Methods: The surface gene was amplified, sequenced and subsequently aligned using international and national Iranian database. Results: All strains belonged to genotype D, subgenotype D1 and subtype ayw2. Of all 62 mutations occurred at 39 nucleotide positions, 31 (50% were missense (amino acid altering and 31 (50% were silent (no amino acid changing. At the amino acid level, 30 substitutions occurred, however, 3 were in positions 122 and 127, corresponded to subtypic determination. 22 (73% out of 30 amino acid mutations occurred in different immune epitopes within surface protein, of which 12 (54.54% in B cell epitopes in 10 residues; 5 (45.45% in T helper epitopes in positions; 5 (22.73% in inside CTL epitopes in 4 residues. Conclusion: The distribution of amino acid mutations as well as the ratio between silent and missense nucleotide mutations showed a narrowly focused immune pressure had already been on the surface protein in these patients, led to the emergence of escape mutants in these patients.

  19. Genetic association of human leukocyte antigens with chronicity or resolution of hepatitis B infection in thai population.

    Directory of Open Access Journals (Sweden)

    Nawarat Posuwan

    Full Text Available BACKGROUND: Previous studies showed that single nucleotide polymorphisms (SNPs in the HLA-DP, TCF19 and EHMT2 genes may affect the chronic hepatitis B (CHB. To predict the degree of risk for chronicity of HBV, this study determined associations with these SNPs. METHODS: The participants for this study were defined into 4 groups; HCC (n = 230, CHB (n = 219, resolved HBV infection (n = 113 and HBV uninfected subjects (n = 123. The HLA-DP SNPs (rs3077, rs9277378 and rs3128917, TCF19 SNP (rs1419881 and EHMT2 SNP (rs652888 were genotyped. RESULTS: Due to similar distribution of genotype frequencies in HCC and CHB, we combined these two groups (HBV carriers. The genotype distribution in HBV carriers relative to those who resolved HBV showed that rs3077 and rs9277378 were significantly associated with protective effects against CHB in minor dominant model (OR = 0.45, p<0.001 and OR = 0.47, p<0.001. The other SNPs rs3128917, rs1419881 and rs652888 were not associated with HBV carriers. CONCLUSIONS: Genetic variations of rs3077 and rs9277378, but not rs3128917, rs1419881 and rs652888, were significantly associated with HBV carriers relative to resolved HBV in Thai population.

  20. Intranasal Administration of Novel Chitosan Nanoparticle/DNA Complexes Induces Antibody Response to Hepatitis B Surface Antigen in Mice.

    Science.gov (United States)

    Lebre, F; Borchard, G; Faneca, H; Pedroso de Lima, M C; Borges, O

    2016-02-01

    The generation of strong pathogen-specific immune responses at mucosal surfaces where hepatitis B virus (HBV) transmission can occur is still a major challenge. Therefore, new vaccines are urgently needed in order to overcome the limitations of existing parenteral ones. Recent studies show that this may be achieved by intranasal immunization. Chitosan has gained attention as a nonviral gene delivery system; however, its use in vivo is limited due to low transfection efficiency mostly related to strong interaction between the negatively charged DNA and the positively charged chitosan. We hypothesize that the adsorption of negatively charged human serum albumin (HSA) onto the surface of the chitosan particles would facilitate the intracellular release of DNA, enhancing transfection activity. Here, we demonstrate that a robust systemic immune response was induced after vaccination using HSA-loaded chitosan nanoparticle/DNA (HSA-CH NP/DNA) complexes. Furthermore, intranasal immunization with HSA-CH NP/DNA complexes induced HBV specific IgA in nasal and vaginal secretions; no systemic or mucosal responses were detected after immunization with DNA alone. Overall, our results show that chitosan-based DNA complexes elicited both humoral and mucosal immune response, making them an interesting and valuable gene delivery system for nasal vaccination against HBV.

  1. The Lumipulse G HBsAg-Quant assay for screening and quantification of the hepatitis B surface antigen.

    Science.gov (United States)

    Yang, Ruifeng; Song, Guangjun; Guan, Wenli; Wang, Qian; Liu, Yan; Wei, Lai

    2016-02-01

    Qualitative HBsAg assay is used to screen HBV infection for decades. The utility of quantitative assay is also rejuvenated recently. We aimed to evaluate and compare the performance of a novel ultra-sensitive and quantitative assay, the Lumipulse assay, with the Architect and Elecsys assays. As screening methods, specificity was compared using 2043 consecutive clinical routine samples. As quantitative assays, precision and accuracy were assessed. Sera from 112 treatment-naïve chronic hepatitis B patients, four patients undergoing antiviral therapy and one patient with acute infection were tested to compare the correlations. Samples with concurrent HBsAg/anti-HBs were also quantified. The Lumipulse assay precisely quantified ultra-low level of HBsAg (0.004 IU/mL). It identified additional 0.98% (20/2043) clinical samples with trance amount of HBsAg. Three assays displayed excellent linear correlations irrespective of genotypes and S-gene mutations (R(2)>0.95, PLumipulse assay did not yield higher HBsAg concentrations in samples with concomitant anti-HBs. Compared with other assays, the Lumipulse assay is sensitive and specific for detecting HBsAg. The interpretation of the extremely low-level results, however, is challenging. Quantitative HBsAg results by different assays are highly correlated, but they should be interpreted interchangeably only after conversion to eliminate the biases.

  2. PreC and C Regions of Woodchuck Hepatitis Virus Facilitate Persistent Expression of Surface Antigen of Chimeric WHV-HBV Virus in the Hydrodynamic Injection BALB/c Mouse Model

    Science.gov (United States)

    Wu, Weimin; Liu, Yan; Lin, Yong; Pan, Danzhen; Yang, Dongliang; Lu, Mengji; Xu, Yang

    2017-01-01

    In the hydrodynamic injection (HI) BALB/c mouse model with the overlength viral genome, we have found that woodchuck hepatitis virus (WHV) could persist for a prolonged period of time (up to 45 weeks), while hepatitis B virus (HBV) was mostly cleared at week four. In this study, we constructed a series of chimeric genomes based on HBV and WHV, in which the individual sequences of a 1.3-fold overlength HBV genome in pBS-HBV1.3 were replaced by their counterparts from WHV. After HI with the WHV-HBV chimeric constructs in BALB/c mice, serum viral antigen, viral DNA (vDNA), and intrahepatic viral antigen expression were analyzed to evaluate the persistence of the chimeric genomes. Interestingly, we found that HI with three chimeric WHV-HBV genomes resulted in persistent antigenemia in mice. All of the persistent chimeric genomes contained the preC region and the part of the C region encoding the N-terminal 1–145 amino acids of the WHV genome. These results indicated that the preC region and the N-terminal part of the C region of the WHV genome may play a role in the persistent antigenemia. The chimeric WHV-HBV genomes were able to stably express viral antigens in the liver and could be further used to express hepadnaviral antigens to study their pathogenic potential. PMID:28230775

  3. [Prevalence of hepatitis B surface antigen in general population of coast, mountain and forest regions of Peru. A preliminary report].

    Science.gov (United States)

    Vildósola, H; Farfán, G; Colan, E; Delgado, G; Mendoza, L; Pineda, R; Linares, O; Miyasato, D; Lescano, R

    1990-01-01

    A prospective study was performed in order to establish HBsAg prevalence on population living in urban areas of three geographical regions of Peru. There were included 100 apparently healthy people of each city, with a residence major to 5 years, no migrate neither transitory. Each subdivided group in 50 adults and 50 children. Of these last ones 15 between 1 to 7 years old and 20 cases between 7 to 14 years old. Samples were obtained by venipuncture, then they were centrifuged and the serum obtained was stored at -20 degrees C before being sent to Lima for processing. Determination of HBsAg was made by the Elisa's technic (Abbott Lab-III.-USA). In this preliminary report we informed about results in 7 cities (Lima, Iquitos, Chiclayo, Arequipa,Ica, Chachapoyas y Tarapoto) that include 680 persons of which 373 were adults and 307 children. The HBsAg, was positive in 26 cases (3.8%). In the adult group were 13 positives (3.4%), and in the children also 13 cases (4.2%). Result of all sample shows figures of prevalence (3.8%) major to that reported before at national level. The same phenomenon was observed in the cost while in the jungle our results were similar to those found before. In the andean area not studied previously there were obtained similar results to the rest of the country. It is also interesting to mention the high percentages of prevalence in children. These results indicate that hepatitis B is a serious problem of public health in our country that merit to take immediate prophylactic measures.

  4. Interactive Effects of Immunoglobulin Gamma and Human Leucocyte Antigen Genotypes on Response to Interferon Based Therapy of Hepatitis C Virus

    Directory of Open Access Journals (Sweden)

    Howayda E. Gomaa

    2015-04-01

    Full Text Available AIM: We examined the role that immunoglobulin GM 23 and KM allotypes—genetic markers of γ and κ chains, respectively—play in response to treatment of hepatitis C virus (HCV infection in Egyptian patients. MATERIAL AND METHODS: A total of 120 persons who had responded to HCV treatment and 125 with persistent HCV infection were genotyped for the presence of GM23 and KM determinants. HLA –C genotyping was also done. RESULTS: Association of GM 23+ and KM3 was significantly associated with non response to treatment (P < 0.0001. Individuals who lacked this GM genotype (but were positive for KM1,2 and 3 were likely to respond to treatment (P=0.045. Association of heterozygous GM23 (+/- with KM 1,2 and 3 or KM3 alone was significantly associated with SVR (P = 0.001 and (P = 0.0001 respectively. Particular combinations of HLA and GM genotypes were associated significantly with the response to HCV treatment. The combination of HLAC2C2 and GM23+ was associated with persistence of infection (P = 0.027 while the association of HLAC2C2 and heterozygous GM23+/- was associated with SVR (P = 0.001.The association of HLAC1C1 and heterozygous GM23+/- was significantly associated with SVR (P = 0.001 and also subjects with HLA C1/C2 and heterozygous GM23+/- were likely to respond to treatment (P = 0.003 while subjects with HLA C1/C2 and GM23+ show tendency to resist to treatment (P = 0.0001. CONCLUSION: Our results didn’t support a role for KM allotypes, GM23 allotype plays a role in the persistence of HCV infection in the presence or absence of KM1,3. Interaction between certain GM and HLA-C genotypes may favor adequate response to interferon based therapies.

  5. Significance of the hepatitis C virus (HCV core antigen as an alternative plasma marker of active HCV infection

    Directory of Open Access Journals (Sweden)

    Daniel HDJ

    2007-01-01

    Full Text Available Purpose: To evaluate the role of core antigen (Ortho trak-C assay as a marker of active HCV infection in comparison to HCV RNA as detected by reverse transcription polymerase chain reaction (RT-PCR. Methods: This evaluation was carried out during January 2000 to December 2003 in HCV infected individuals who were treatment naοve or were on anti-viral therapy. Additionally, sequential plasma samples from patients on clinical follow-up were included in this study. A total of 167 samples from 61 patients were tested by trak-C and RT-PCR. HCV RNA detection was achieved by a RT-PCR. Trak-C assay results were also compared in a limited proportion of these samples with known HCV viral load and genotype. Results: Of 167 samples tested, 56.9% were RNA positive and 43.1% were RNA negative while 50.3% were trak-C positive and 49.7% were trak-C negative, yielding a sensitivity of 85.3% and a specificity of 95.8% for the trak-C assay (Kappa co-efficient = 0.8. The concentration of HCVcAg and HCV RNA showed significant correlation (n=38, r=0.334, P =0.04. The trak-C assay detected the most prevalent HCV genotypes in India without significant difference ( P =0.335. The difference between mean absorbance values of HCV RNA positive samples compared to HCV RNA negative samples in the trak-C assay was highly significant ( P < 0.000. Qualitative results of trak-C assay and RT-PCR were comparable in 93% of follow-up samples. Conclusions: Trak-C assay can be recommended for confirmation of HCV infection and follow-up in laboratories with resource-poor facilities.

  6. Immunogenicity of three recombinant hepatitis B vaccines administered to students in three doses containing half the antigen amount routinely used for adult vaccination

    Directory of Open Access Journals (Sweden)

    Baldy José Luís da Silveira

    2004-01-01

    Full Text Available We evaluated the immunogenicity of three recombinant hepatitis B vaccines, one Brazilian (Butang, Instituto Butantan and two Korean vaccines (Euvax-B, LG Chemical Ltd. and Hepavax-Gene, Greencross Vaccine Corp., administered intramuscularly to students aged 17 to 19 years in three 10-µg doses (corresponding to half the amount of antigen routinely used for adult vaccination at intervals of one month between the first and second dose, and of four months between the second and third dose. A total of 316 students non-reactive for any serological marker of hepatitis B virus infection were vaccinated: 77 (24.4% with the Butang vaccine, 71 (22.5% with Euvax-B, 85 (26.9% with Hepavax-Gene and, for comparison, 83 (26.2% with Engerix-B (GlaxoSmithKline, whose efficacy in young adults at the dose used here has been confirmed in previous studies. Similar seroconversion rates (anti-HBs > 10 mIU/mL about one month after application of the third dose were obtained for the Butang, Euvax-B, Hepavax-Gene and Engerix-B vaccines (96.2%, 98.6%, 96.5% and 97.6%, respectively. The frequency of good responders (anti-HBs > 100 mIU/mL was also similar among students receiving the four vaccines (85.8%, 91.6%, 89.4% and 89.2%, respectively. The geometric mean titers (GMT of anti-HBs about one month after the third dose obtained with these vaccines were 727.78 ± 6.46 mIU/mL, 2009.09 ± 7.16 mIU/mL, 1729.82 ± 8.85 mIU/mL and 2070.14 ± 11.69 mIU/mL, respectively. The GMT of anti-HBs induced by the Euvax-B and Engerix-B vaccines were higher than those obtained with the Butang vaccine (p < 0.05; this difference was not significant when comparing the other vaccines two-by-two. No spontaneous adverse effects attributable to the application of any dose of the four vaccines were reported.

  7. Hepatitis C Virus-Specific T Cell Receptor mRNA-Engineered Human T Cells: Impact of Antigen Specificity on Functional Properties.

    Science.gov (United States)

    Balasiddaiah, Anangi; Davanian, Haleh; Aleman, Soo; Pasetto, Anna; Frelin, Lars; Sällberg, Matti; Lohmann, Volker; Koh, Sarene; Bertoletti, Antonio; Chen, Margaret

    2017-05-01

    Therapy with genetically modified autologous T cells has shown great promise in cancer therapy. For an efficient control of hepatitis C virus (HCV) infection, cytotoxic T cells (CTL) are pivotal, but persistence of activated T cells may lead to liver toxicity. Here, anti-HCV T cell receptors (TCRs) recognizing the HCV nonstructural (NS) NS3 or NS5 viral peptide target were examined by mRNA transfection of human peripheral blood lymphocytes (PBLs) derived from healthy donors as well as chronically infected HCV patients. Immunological analysis shows that while the CTLs expressing the NS5-specific TCR reduced HCV RNA replication by a noncytotoxic mechanism, the NS3-specific TCR-redirected CTLs were polyfunctional and inhibited HCV RNA replication through antigen-specific cytotoxicity. Transcriptome signatures from these two types of CTL responses revealed uniquely expressed gene clusters upon encountering hepatoma target cells presenting endogenously expressed HCV proteins. The NS3 TCR induced a rapid expression of apoptotic signaling pathways and formation of embryonic gene clusters, whereas the NS5A TCR activation induced extended proliferative and metabolic pathways as the HCV target cells survived. Our results provide detailed insights into basic HCV T cell immunology and have clinical relevance for redirecting T cells to target virally infected hepatoma cells.IMPORTANCE Due to the protective ability of HCV-specific T cells and the hepatotoxic potential that they possess, there is a great need for the understanding of the functional aspects of HCV-specific T cells. To circumvent the low level of precursor frequency in patients, we engineered primary CD8(+) T cells by mRNA TCR vectors to confer HCV specificity to new T cells. HCV TCRs that differ in antigen specificity and polyfunctionality were examined. mRNA TCR engineering of peripheral blood lymphocytes from healthy donors or chronically infected HCV patients resulted in strikingly high levels of HCV TCR

  8. Phase I Hepatic Immunotherapy for Metastases Study of Intra-Arterial Chimeric Antigen Receptor-Modified T-cell Therapy for CEA+ Liver Metastases.

    Science.gov (United States)

    Katz, Steven C; Burga, Rachel A; McCormack, Elise; Wang, Li Juan; Mooring, Wesley; Point, Gary R; Khare, Pranay D; Thorn, Mitchell; Ma, Qiangzhong; Stainken, Brian F; Assanah, Earle O; Davies, Robin; Espat, N Joseph; Junghans, Richard P

    2015-07-15

    Chimeric antigen receptor-modified T cells (CAR-T) have demonstrated encouraging results in early-phase clinical trials. Successful adaptation of CAR-T technology for CEA-expressing adenocarcinoma liver metastases, a major cause of death in patients with gastrointestinal cancers, has yet to be achieved. We sought to test intrahepatic delivery of anti-CEA CAR-T through percutaneous hepatic artery infusions (HAIs). We conducted a phase I trial to test HAI of CAR-T in patients with CEA(+) liver metastases. Six patients completed the protocol, and 3 received anti-CEA CAR-T HAIs alone in dose-escalation fashion (10(8), 10(9), and 10(10) cells). We treated an additional 3 patients with the maximum planned CAR-T HAI dose (10(10) cells × 3) along with systemic IL2 support. Four patients had more than 10 liver metastases, and patients received a mean of 2.5 lines of conventional systemic therapy before enrollment. No patient suffered a grade 3 or 4 adverse event related to the CAR-T HAIs. One patient remains alive with stable disease at 23 months following CAR-T HAI, and 5 patients died of progressive disease. Among the patients in the cohort that received systemic IL2 support, CEA levels decreased 37% (range, 19%-48%) from baseline. Biopsies demonstrated an increase in liver metastasis necrosis or fibrosis in 4 of 6 patients. Elevated serum IFNγ levels correlated with IL2 administration and CEA decreases. We have demonstrated the safety of anti-CEA CAR-T HAIs with encouraging signals of clinical activity in a heavily pretreated population with large tumor burdens. Further clinical testing of CAR-T HAIs for liver metastases is warranted. ©2015 American Association for Cancer Research.

  9. Human leukocyte antigen class Ⅱ DQB1*0301, DRB1*1101 alleles and spontaneous clearance of hepatitis C virus infection: A meta-analysis

    Institute of Scientific and Technical Information of China (English)

    Xin Hong; Rong-Bin Yu; Nan-Xiong Sun; Bin Wang; Yao-Chu Xu; Guan-Ling Wu

    2005-01-01

    AIM: To assess the associations of human leukocyte antigen (HLA) class Ⅱ DQB1*0301 and/or DRB1*1101 allele with spontaneous hepatitis C virus (HCV) clearance by meta-analysis of individual dataset from all studies published till date.METHODS: To clarify the impact of HLA class Ⅱ polymorphisms on viral clearance, we performed a metaanalysis of the published data from 11 studies comparing the frequencies of DQB1*0301 and DRB1*1101 alleles in individuals with spontaneous resolution to those with persistent infection. As we identified the heterogeneity between studies, summary statistical data were calculated based on a random-effect model.RESULTS: Meta-analyses yielded summary estimatesodds ratio (OR) of 2.36 [95%CI (1.62, 3.43), P<0.00001]and 2.02 [95%CI (1.56, 2.62), P<0.00001] for the effects of DQB1*0301 and DRB1*1101 alleles on spontaneous clearance of HCV, respectively.CONCLUSION: These results support the hypothesis that specific HLA class Ⅱ alleles might influence the susceptibility or resistance to persistent HCV infection.Both DQB1*0301 and DRB1*1101 are protective alleles and present HCV epitopes more effectively to CD4+T lymphocytes than others, and subjects with these two alleles are at a lower risk of developing chronic HCV infection. Large, multi-ethnic confirmatory and welldesigned studies are needed to determine the host genetic determinants of HCV infection.

  10. Mapping of immunodominant B-cell epitopes and the human serum albumin-binding site in natural hepatitis B virus surface antigen of defined genosubtype.

    Science.gov (United States)

    Sobotta, D; Sominskaya, I; Jansons, J; Meisel, H; Schmitt, S; Heermann, K H; Kaluza, G; Pumpens, P; Gerlich, W H

    2000-02-01

    Twelve MAbs were generated by immunization of BALB/c mice with plasma-derived hepatitis B virus surface spherical antigen particles subtype ayw2 (HBsAg/ayw2 genotype D). Their epitopes were mapped by analysis of reactivity with plasma-derived HBsAg/ayw2 and HBsAg/adw2 (genotype A) in enzyme immunoassays and blots. Mapping was supported by nested sets of truncated preS2 proteins and preS2 peptides. Five antibodies were S domain-specific, seven were preS2-specific and 11 had a preference for genotype D. According to our data, group I of the three known epitope groups of preS2 has to be divided into IA and IB. Three preS2-specific MAbs forming the new group IA reacted with genotype D residues 3-15 which have not yet been described as an epitope region. IA antibodies strongly inhibited the binding of polymerized human serum albumin. Two antibodies (group II) reacted with the glycosylated N-terminal region of preS2 in plasma-derived HBsAg, but not with a preparation from transfected murine cells. One group III antibody was subtype-specific and reacted with the highly variable preS2 sequence 38-48. Only one antibody (group IB) mapped to the region (old group I) which was believed to be immunodominant and genotype-independent. Geno(sub)type-specific epitopes of preS2 are obviously the immunodominant components of natural HBsAg in BALB/c mice, but these epitopes may be masked by serum albumins in humans. The data may explain why it is difficult to detect anti-preS2 antibodies in human recipients of preS2-containing vaccines, in spite of the preS2 immunodominance in mice.

  11. Use of radioimmune assay in investigating reagents to be used in the immunocytochemical localization of hepatitis B surface antigen in immune complexes in the kidney of patients with membranous nephropathy and Australia antigenaemia

    Energy Technology Data Exchange (ETDEWEB)

    Wolfe-Coote, S. (South African Medical Research Council, Tygerberg (South Africa). Inst. for Electron Microscopy)

    1983-09-01

    Radioimmune assay (RIA) was used to investigate the effect of fixatives on antigenicity of the hepatitis B surface antigen (HBsAg) and the effect of pronase on the elution of antibody (Ab) from the HBsAg-Ab complex. The effect of pronase on Ab elution was also tested on sections of kidney from a patient with the immune complex disease systemic lupus erythematosus (SLE). Immunoglobulin G (IgG) was located in pronase treated and untreated sections using the indirect immunoperoxidase technique. Glutareldehyde was shown to be the fixative of choice for studies involving HBsAg. All fixatives were shown to have less effect on antigenicity at 4/sup 0/C than at room temperature. Osmium tetroxide reduced antigenicity to one-third, even at 4/sup 0/C. RIA and SLE kidney section studies showed that Ab was eluted from immune complexes by pronase. Pre-fixation of the antigen (Ag) by glutaraldehyde appears to have no effect on the final elution, although fixation after pronase treatment seemed to enhance the elution effects. The availability of an RIA kit with HBsAg- and Ab-coated beads was of great assistance in evaluating reagents to be used in immunoperoxidase studies of HBsAg in immune complexes of patients with membranous nephropathy and Australia antigenaemia.

  12. Occult hepatitis B among Iranian hepatitis C patients

    OpenAIRE

    Ahmad shavakhi; Babak Norinaier; Fatomeh Esteghamat; Mohamad Seghatoleslami; Mahsa Khodadustan; Mohamad hossein Somi; Mohsen Masoodi; Mohamad reza Zali

    2009-01-01

    • BACKGROUND: Occult hepatitis B is defined as presence of HBV DNA in tissue or serum without hepatitis B surface antigen. The aim of this study is to determine frequency of occult hepatitis B among hepatitis C patients in Tehran and compare the route of transmission and liver enzymes between positive and negative HBV DNA patients.
    • METHODS: In a cross sectional study, serum of 103 hepatitis C cas...

    • Limited junctional diversity of V delta 5-J delta 1 rearrangement in multiple sclerosis patients.

      Science.gov (United States)

      Nowak, J S; Michałowska-Wender, G; Januszkiewicz, D; Wender, M

      1997-01-01

      T-cell receptor (TCR) delta gene repertoire, as assessed by V delta-J delta rearrangements, has been analyzed in nine multiple sclerosis (MS) cases and in 30 healthy individuals by seminested PCR technique. Among the V delta-J delta junctional diversities studied, the most striking result has been observed in V delta 5-J delta 1 rearrangement. The detection of repeated V delta 5-J delta 1 nucleotide sequences in all analyzed clones from seven out of nine patients studied proved the monoclonal nature of gamma delta T-cells with V delta 5-J delta 1 rearrangement. The clonal nature of this rearrangement proved by PAGE and sequencing analysis may suggest an antigen-driven expansion of gamma delta T cells and argues for a significant role of gamma delta T-cells with V delta 5-J delta 1 rearrangement in MS pathogenesis. However, it cannot be excluded that clonal expansion of these lymphocytes may represent secondary change to central nervous system damage.

    • Chronic Hepatitis B: Individualized Antiviral Therapy

      NARCIS (Netherlands)

      E.H.C.J. Buster (Erik)

      2009-01-01

      textabstractThe hepatitis B virus (HBV) was discovered in 1966 with the identification of the Australia antigen in Aboriginals by Dr. Baruch Blumberg, who received the 1976 Nobel Prize in Medicine for his work. We now know the Australia antigen as hepatitis B surface antigen (HBsAg). HBV belongs to

    • 丙型肝炎病毒核心抗原检测技术的应用评价%Evaluation of hepatitis C virus core antigen detection

      Institute of Scientific and Technical Information of China (English)

      杨静; 黄锦江; 刘小琦

      2011-01-01

      目的 探讨丙型肝炎病毒核心抗原(HCV-cAg)检测技术筛查丙型肝炎的应用价值.方法 对门诊体检人群、无偿献血人群进行HCV抗体初检、复检,筛选HCV阳性血清标本、HCV可疑血清标本检测HCV-cAg;同时对单项丙氨酸氨基转移酶(ALT)增高的标本和血液筛查合格的标本进行HCV-cAg的检测.对HCV-cAg阳性标本进行HCV逆转录PCR(RT-PCR)检测.结果 共检测了264例血清标本,其中56例HCV阳性血清标本中检测出HCV-cAg阳性15例,49例HCV可疑血清标本中检测出HCV-cAg阳性11例,47例单项ALT增高的标本中检测出HCV-cAg阳性1例,112例合格标本中未检出HCV-cAg阳性.HCV-cAg阳性标本经PCR测定HCV RNA阳性23例.结论 HCV-cAg的检出时间早于抗体.HCV-cAg和HCV抗体联合检测,缩短了检测窗口期(PWP),有助于丙型肝炎的早期诊断.%Objective To investigate the value of HCV core antigen(HCV cAg) detection in screening of hepatitis C. Methods The first and repeat assays of HCV antibody were performed among outpatient medical groups and unpaid blood donors. HCV posi rive serum samples and HCV suspicious serum samples were screened and detected for HCV-cAg. ALT increased individual sam ples and qualified samples of blood screening were detected for HCV-cAg. HCV-cAg positive samples were tested by HCV RT-PCR detection. Results In 264 serum specimen,15 cases were positive with HCV-cAg among 56 cases of HCV positive serum samples,11 cases were positive with HCV-cAg among 49 cases of HCV suspicious serum samples,1 case was positive with HCV-cAg among 47 cases of ALT increased individual samples. HCV-cAg was negative among 112 cases of qualified samples. 23 cases were positive with HCV-RNA by RT-PCR detection among HCV-cAg positive samples. Conclusion HCV-cAg could be detected earlier than an tibody. Combined tests of HCV cAg and HCV antibody could be useful for early diagnosis of hepatitis C by shorting the PWP.

    • Comparison of Serum Hepatitis C Virus (HCV) RNA and Core Antigen Levels in Patients Coinfected with Human Immunodeficiency Virus and HCV and Treated with Interferon plus Ribavirin

      Science.gov (United States)

      Pivert, A.; Payan, C.; Morand, P.; Fafi-Kremer, S.; Deshayes, J.; Carrat, F.; Pol, S.; Cacoub, P.; Perronne, C.; Lunel, F.

      2006-01-01

      Trak-C (Ortho-Clinical Diagnostics) is an enzyme-linked immunosorbent assay-based method capable of quantifying hepatitis C virus (HCV) core antigen (CA) in serum and could be an alternative to molecular detection and quantification of HCV RNA. We have evaluated the Trak-C assay in comparison with an HCV RNA quantitative assay (Versant HCV v3.0; Bayer Diagnostics) in the follow-up of 348 treated, human immunodeficiency virus (HIV)/HCV-coinfected patients included in the ANRS HC02 RIBAVIC trial. ANRS HC02 RIBAVIC is a therapeutic, multicenter, randomized protocol comparing the efficacy of alpha interferon 2b (IFN-α2b) (3 million units three times a week)-ribavirin (800 mg/day) to that of pegylated IFN-α2b (1.5 μg/kg of body weight/week)-ribavirin (800 mg/day) during 48 weeks of treatment of HIV/HCV-coinfected patients naïve to HCV treatment. Patients were assessed for virological analysis at day 0 and weeks 4, 12, 24, 48, and 72. Correlation of HCV RNA and HCV CA at the initiation of treatment was excellent (r = 0.92). HCV RNA and CA kinetics were similar during follow-up of HCV treatment from day 0 to week 72 whatever the group of response and genotype. The positive and negative predictive values of response to the treatment at week 4 were 59 and 94%, respectively, for HCV RNA load reduction of >2 log and 54 and 94%, respectively, for HCV CA below the threshold value (4.18 log10 pg/ml · 104). Trak-C, a new assay able to quantify CA in HIV/HCV-coinfected patients, correlates well with quantitative HCV RNA assays and is cheaper and easier to perform than molecular technology. HCV CA could be a valuable alternative test for therapeutic follow-up of coinfected patients treated with IFN plus ribavirin in developing countries. PMID:16455894

    • The characteristics of hepatitis B surface antigen (HBsAg)-negative hepatitis B virus (HBV) infection in Chinese blood donors: a follow-up study of donors tested negative for HBsAg and reactive for simultaneous nucleic acid testing of HBV, hepatitis C virus, and human immunodeficiency virus.

      Science.gov (United States)

      Guo, Zhaofu; Fu, Ping; Yin, Yijin; Wang, Funeng; Yin, Yiqing; Wang, Jingxing; Liu, Yu

      2017-03-01

      The real infection status of hepatitis B virus (HBV) of hepatitis B surface antigen (HBsAg)-negative yet nucleic acid test (NAT)-positive blood donors is difficult to clarify. Detailed follow-up study is needed for analyzing the infectivity of these blood donors. Blood donors who screened negative for HBsAg and reactive for simultaneous NAT of HBV, hepatitis C virus (HCV), and human immunodeficiency virus (HIV) were included in a follow-up epidemiologic questionnaire survey and contributed follow-up samples for further testing. The follow-up samples were tested repeatedly for the serologic markers and HBV DNA. The genotypes and sequence mutations of HBV infected by 11 HBV DNA-positive donors were analyzed through the amplification and sequencing of HBV S region. Of the 46 donors included in this study, 89.1% were infected with HBV (41/46), including one (2.2%) window period infection, three (6.5%) recovered infections, and 37 (80.4%) occult HBV infections (OBIs). The S region of HBV was successfully amplified and sequenced for seven donors, five infected with Genotype B (71.4%), one with Genotype C (14.3%), and one with Genotype D (14.3%). Mutations in the S region were detected in four donors (57.1%) CONCLUSIONS: This is the first detailed study with multiple follow-up testing of the HBV infection status among blood donors who were tested negative for HBsAg and reactive for simultaneous NAT of HBV, HCV, and HIV. Most of these donors were infected with HBV with very low viral load. Our findings indicate that it is important to improve the sensitivity of NAT so as to decrease the residual risk of transfusion-transmitted HBV infection. © 2017 AABB.

    • Observational $\\Delta\

      CERN Document Server

      Hernández, Antonio García; Monteiro, Mário J P F G; Suárez, Juan Carlos; Reese, Daniel R; Pascual-Granado, Javier; Garrido, Rafael

      2015-01-01

      Delta Scuti ($\\delta$ Sct) stars are intermediate-mass pulsators, whose intrinsic oscillations have been studied for decades. However, modelling their pulsations remains a real theoretical challenge, thereby even hampering the precise determination of global stellar parameters. In this work, we used space photometry observations of eclipsing binaries with a $\\delta$ Sct component to obtain reliable physical parameters and oscillation frequencies. Using that information, we derived an observational scaling relation between the stellar mean density and a frequency pattern in the oscillation spectrum. This pattern is analogous to the solar-like large separation but in the low order regime. We also show that this relation is independent of the rotation rate. These findings open the possibility of accurately characterizing this type of pulsator and validate the frequency pattern as a new observable for $\\delta$ Sct stars.

    • A novel chimeric Hepatitis B virus S/preS1 antigen produced in mammalian and plant cells elicits stronger humoral and cellular immune response than the standard vaccine-constituent, S protein.

      Science.gov (United States)

      Dobrica, Mihaela-Olivia; Lazar, Catalin; Paruch, Lisa; Skomedal, Hanne; Steen, Hege; Haugslien, Sissel; Tucureanu, Catalin; Caras, Iuliana; Onu, Adrian; Ciulean, Sonya; Branzan, Alexandru; Clarke, Jihong Liu; Stavaru, Crina; Branza-Nichita, Norica

      2017-08-01

      Chronic Hepatitis B Virus (HBV) infection leads to severe liver pathogenesis associated with significant morbidity and mortality. As no curable medication is yet available, vaccination remains the most cost-effective approach to limit HBV spreading and control the infection. Although safe and efficient, the standard vaccine based on production of the small (S) envelope protein in yeast fails to elicit an effective immune response in about 10% of vaccinated individuals, which are at risk of infection. One strategy to address this issue is the development of more immunogenic antigens. Here we describe a novel HBV antigen obtained by combining relevant immunogenic determinants of S and large (L) envelope proteins. Our approach was based on the insertion of residues 21-47 of the preS1 domain of the L protein (nomenclature according to genotype D), involved in virus attachment to hepatocytes, within the external antigenic loop of S. The resulting S/preS1(21-47) chimera was successfully produced in HEK293T and Nicotiana benthamiana plants, as a more economical recombinant protein production platform. Comparative biochemical, functional and electron microscopy analysis indicated assembly of the novel antigen into subviral particles in mammalian and plant cells. Importantly, these particles preserve both S- and preS1-specific epitopes and elicit significantly stronger humoral and cellular immune responses than the S protein, in both expression systems used. Our data promote this antigen as a promising vaccine candidate to overcome poor responsiveness to the conventional, S protein-based, HBV vaccine. Copyright © 2017 Elsevier B.V. All rights reserved.

    • Radioimmunoassays of hidden viral antigens

      Energy Technology Data Exchange (ETDEWEB)

      Neurath, A.R. (Lindsley F. Kimbell Research Inst., New York, NY); Strick, N.; Baker, L.; Krugman, S.

      1982-07-01

      Antigens corresponding to infectious agents may be present in biological specimens only in a cryptic form bound to antibodies and, thus, may elude detection. We describe a solid-phase technique for separation of antigens from antibodies. Immune complexes are precipitated from serum by polyethylene glycol, dissociated with NaSCN, and adsorbed onto nitrocellulose or polystyrene supports. Antigens remain topographically separated from antibodies after removal of NaSCN and can be detected with radiolabeled antibodies. Genomes from viruses immobilized on nitrocellulose can be identified by nucleic acid hybridization. Nanogram quantities of sequestered hepatitis B surface and core antigens and picogram amounts of hepatitis B virus DNA were detected. Antibody-bound adenovirus, herpesvirus, and measles virus antigens were discerned by the procedure.

  1. Radioimmunoassays of hidden viral antigens.

    Science.gov (United States)

    Neurath, A R; Strick, N; Baker, L; Krugman, S

    1982-01-01

    Antigens corresponding to infectious agents may be present in biological specimens only in a cryptic form bound to antibodies and, thus, may elude detection. We describe a solid phase technique for separation of antigens from antibodies. Immune complexes are precipitated from serum by polyethylene glycol, dissociated with NaSCN, and adsorbed onto nitrocellulose or polystyrene supports. Antigens remain topographically separated from antibodies after removal of NaSCN and can be detected with radiolabeled antibodies. Genomes from viruses immobilized on nitrocellulose can be identified by nucleic acid hybridization. Nanogram quantities of sequestered hepatitis B surface and core antigens and picogram amounts of hepatitis B virus DNA were detected. Antibody-bond adenovirus, herpesvirus, and measles virus antigens were discerned by the procedure. Images PMID:6956871

  2. HIV, Hepatitis B, and Hepatitis C in Zambia

    OpenAIRE

    Kenneth C Kapembwa; GOLDMAN, Jason D.; Shabir Lakhi; Yolan Banda; Kasonde Bowa; Vermund, Sten H.; Joseph Mulenga; David Chama; Chi, Benjamin H.

    2011-01-01

    Objectives : Epidemiologic data of HIV and viral hepatitis coinfection are needed in sub-Saharan Africa to guide health policy for hepatitis screening and optimized antiretroviral therapy (ART). Materials and Methods: We screened 323 HIV-infected, ART-eligible adults for hepatitis B surface antigen (HBsAg) and hepatitis C antibody (HCV Ab) at a tertiary hospital in Lusaka, Zambia. We collected basic demographic, medical, and laboratory data to determine predictors for coinfection. Results: Of...

  3. Physiological response of Pichia pastoris GS115 to methanol-induced high level production of the Hepatitis B surface antigen: catabolic adaptation, stress responses, and autophagic processes

    Directory of Open Access Journals (Sweden)

    Vanz Ana Leticia

    2012-08-01

    Full Text Available Abstract Background Pichia pastoris is an established eukaryotic host for the production of recombinant proteins. Most often, protein production is under the control of the strong methanol-inducible aox1 promoter. However, detailed information about the physiological alterations in P. pastoris accompanying the shift from growth on glycerol to methanol-induced protein production under industrial relevant conditions is missing. Here, we provide an analysis of the physiological response of P. pastoris GS115 to methanol-induced high-level production of the Hepatitis B virus surface antigen (HBsAg. High product titers and the retention of the protein in the endoplasmic reticulum (ER are supposedly of major impact on the host physiology. For a more detailed understanding of the cellular response to methanol-induced HBsAg production, the time-dependent changes in the yeast proteome and ultrastructural cell morphology were analyzed during the production process. Results The shift from growth on glycerol to growth and HBsAg production on methanol was accompanied by a drastic change in the yeast proteome. In particular, enzymes from the methanol dissimilation pathway started to dominate the proteome while enzymes from the methanol assimilation pathway, e.g. the transketolase DAS1, increased only moderately. The majority of methanol was metabolized via the energy generating dissimilatory pathway leading to a corresponding increase in mitochondrial size and numbers. The methanol-metabolism related generation of reactive oxygen species induced a pronounced oxidative stress response (e.g. strong increase of the peroxiredoxin PMP20. Moreover, the accumulation of HBsAg in the ER resulted in the induction of the unfolded protein response (e.g. strong increase of the ER-resident disulfide isomerase, PDI and the ER associated degradation (ERAD pathway (e.g. increase of two cytosolic chaperones and members of the AAA ATPase superfamily indicating that potential

  4. Delta robot

    NARCIS (Netherlands)

    Herder, J.L.; Van der Wijk, V.

    2010-01-01

    The invention relates to a delta robot comprising a stationary base (2) and a movable platform (3) that is connected to the base with three chains of links (4,5,6), and comprising a balancing system incorporating at least one pantograph (7) for balancing the robot's center of mass, wherein the at le

  5. Delta robot

    NARCIS (Netherlands)

    Herder, J.L.; Van der Wijk, V.

    2010-01-01

    The invention relates to a delta robot comprising a stationary base (2) and a movable platform (3) that is connected to the base with three chains of links (4,5,6), and comprising a balancing system incorporating at least one pantograph (7) for balancing the robot's center of mass, wherein the at le

  6. Hepatitis C

    Science.gov (United States)

    ... Events Follow Us Home Health Information Liver Disease Hepatitis (Viral) Hepatitis C Related Topics English English Español Section Navigation Hepatitis (Viral) What Is Viral Hepatitis? Hepatitis A Hepatitis B ...

  7. Glycosylation analysis and protein structure determination of murine fetal antigen 1 (mFA1)--the circulating gene product of the delta-like protein (dlk), preadipocyte factor 1 (Pref-1) and stromal-cell-derived protein 1 (SCP-1) cDNAs

    DEFF Research Database (Denmark)

    Krogh, T N; Bachmann, E; Teisner, B

    1997-01-01

    By means of sequence analysis, murine fetal antigen 1 (mFA1) isolated from Mus musculus amniotic fluid was shown to be the circulating protein of the delta-like protein, stromal-cell-derived protein 1 (SCP-1) and preadipocyte factor 1 (Pref-1) gene products. The protein contains 36 cysteine resid......, Ser193 and fucose at Thr201) was tentatively ascertained by combining Edman degradation and MALDI-MS. The results presented shows mFA1 to be the circulating heterogeneous cleavage products of the membrane-bound protein encoded by the murine cDNAs dlk, pref-1 and SCP-1....

  8. Tuberculosis, hepatitis C and hepatitis B co-infections in patients with HIV in the Great Tehran Prison, Iran

    Directory of Open Access Journals (Sweden)

    Behnam Farhoudi

    2016-01-01

    Full Text Available We conducted a study to evaluate tuberculosis (TB, hepatitis C and hepatitis B co-infections in male patients with HIV in the Great Tehran Prison from October 2013 to May 2014. Among 85 HIV positive patients, five persons (5.9% had TB. Also, 56 new HIV-infected patients were checked for hepatitis B surface antigen and hepatitis C virus antibody. There were three hepatitis B surface antigen (5.4% and 50 hepatitis C virus antibody (89.3% results. This study suggests that it is necessary to investigate TB, hepatitis C and hepatitis B in HIV positive prisoners in Iran.

  9. Severe Acute Hepatitis B Treated With Entecavir.

    OpenAIRE

    De Socio, Giuseppe Vittorio Luigi; Sgrelli, Alessio; Tosti, Andrea; Baldelli, Franco

    2011-01-01

    Hepatitis B virus (HBV) infection constitutes a serious global health problem. Nowadays there are divergent data regarding the use of antiviral drugs to treat acute hepatitis B. We present here a case of a 62-year-old man affected by severe acute hepatitis B with progressive worsening of clinical and hepatic function. The patient was treated with entecavir without critical side effects. We observed rapid clinical and laboratory improvements and the disappearance of hepatitis B surface antigen...

  10. Cationic lipid-formulated DNA vaccine against hepatitis B virus: immunogenicity of MIDGE-Th1 vectors encoding small and large surface antigen in comparison to a licensed protein vaccine.

    Directory of Open Access Journals (Sweden)

    Anne Endmann

    Full Text Available Currently marketed vaccines against hepatitis B virus (HBV based on the small (S hepatitis B surface antigen (HBsAg fail to induce a protective immune response in about 10% of vaccinees. DNA vaccination and the inclusion of PreS1 and PreS2 domains of HBsAg have been reported to represent feasible strategies to improve the efficacy of HBV vaccines. Here, we evaluated the immunogenicity of SAINT-18-formulated MIDGE-Th1 vectors encoding the S or the large (L protein of HBsAg in mice and pigs. In both animal models, vectors encoding the secretion-competent S protein induced stronger humoral responses than vectors encoding the L protein, which was shown to be retained mainly intracellularly despite the presence of a heterologous secretion signal. In pigs, SAINT-18-formulated MIDGE-Th1 vectors encoding the S protein elicited an immune response of the same magnitude as the licensed protein vaccine Engerix-B, with S protein-specific antibody levels significantly higher than those considered protective in humans, and lasting for at least six months after the third immunization. Thus, our results provide not only the proof of concept for the SAINT-18-formulated MIDGE-Th1 vector approach but also confirm that with a cationic-lipid formulation, a DNA vaccine at a relatively low dose can elicit an immune response similar to a human dose of an aluminum hydroxide-adjuvanted protein vaccine in large animals.

  11. Clinical significance of monitoring hepatitis B virus core-related antigens%乙型肝炎病毒核心相关抗原的监测及临床意义

    Institute of Scientific and Technical Information of China (English)

    刘成; 慕永平; 杨宗国; 陈晓蓉

    2012-01-01

    Antiviral nucleot( s) ide analogs are the common therapy for patients with chronic hepatitis B ( CHB) infection. HBV DNA in peripheral blood is a sufficient and convenient indicator of treatment response and resistance; however, intrahepatic HBV DNA and covalently closed circular (ccc) DNA are superior indicators of treatment failure at earlier stages. Unfortunately, monitoring of intrahepatic nucleic acids, including HBV DNA, cccDNA and RNA, is complicated and expensive. Since serum levels of hepatitis B virus core -related antigen ( HBcrAg) correlate well with intrahepatic levels of HBV cccDNA it may represent an accurate and convenient indicator of treatment response and resistance in CHB patients. In this review, we discuss the recent research efforts to develop strategies for HBcrAg monitoring and to define the underlying mechanisms of this clinical indicator system. Besides its promising clinical value, large - scale dynamic measures of HBcrAg in CHB patients may provide useful insights into the risk and causative factors of resistance to antiviral nucleot(s) analoge therapy.%监测乙型肝炎病毒核心相关抗原(HBcrAg),能有效预测核苷(酸)类药物抗病毒治疗后产生的病毒学反弹及耐药风险,具有重要的临床实用价值.

  12. Seroepidemiology of Hepatitis B Virus Infection in Khuzestan Province, Southwest of Iran

    Directory of Open Access Journals (Sweden)

    Abuul Rahim Masjedizadeh

    2009-02-01

    Full Text Available Background: Hepatitis B is a disease of public health importance in Iran. We conducted this study to determine the epidemiology, clinical presentations of hepatitis B infection in Khuzestan province, Southwest of Iran.Methods: A cross-sectional study was conducted on hepatitis B virus (HBV positive individuals referred to the Ahwaz Jondishapour University Hospitals (AJSUH and Hepatitis Clinic from February 2002 to May 2007. Based on a specially-designed protocol, standard commercially-available tests and physical examinations were performed. All subjects were evaluated using a face-to-face questionnaire about demographic aspects. The analysis included data on past medical history, physical examination and periodic evaluation clinically and serologically.Results: 1264 patients infected with hepatitis B virus participated in the study. The patients consisted of 874 male and 390 female patients with the age range of 8-72 years. The most frequent age group was 20-40 years (56.4%. Anti-delta antibodies were observed in 4.7% of the carriers (59⁄1264, anti hepatitis C virus (anti-HCV antibodies in 0.9% (12⁄1095 and anti human immunodeficiency virus (anti-HIV antibodies in 0.1% (1⁄1095 of active carriers, respectively. Of 1264 patients infected with hepatitis B virus, 71 (5.6% were also hepatitis B e antigen (HBeAg positive, no difference in female to male ratio was observed between HBeAg-positive and HBeAg-negative patients with chronic hepatitis B.Conclusions: The family history of hepatitis, dental procedures and a history of transfusion are important risk factors for HBV infection in our area. More careful screening and preventive measures, strict attention to asepsis, evaluation of risk factors, and improvements in certain lifestyle patterns and customs in this area may be essential to prevent transmission of the infection.

  13. The Prevalence and Risk Factors of Hepatitis Delta Virus in HIV/HBV Co-Infected Patients in Shiraz, Iran, 2012

    Directory of Open Access Journals (Sweden)

    Mohammad Motamedifar

    2015-09-01

    Full Text Available 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 37.4±7.4 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.

  14. Tissue-specific transplantation antigen P35B (TSTA3) immune response-mediated metabolism coupling cell cycle to postreplication repair network in no-tumor hepatitis/cirrhotic tissues (HBV or HCV infection) by biocomputation.

    Science.gov (United States)

    Wang, Lin; Huang, Juxiang; Jiang, Minghu; Lin, Hong

    2012-06-01

    We constructed the low-expression tissue-specific transplantation antigen P35B (TSTA3) immune response-mediated metabolism coupling cell cycle to postreplication repair network in no-tumor hepatitis/cirrhotic tissues (HBV or HCV infection) compared with high-expression (fold change ≥ 2) human hepatocellular carcinoma in GEO data set, by using integration of gene regulatory network inference method with gene ontology analysis of TSTA3-activated up- and downstream networks. Our results showed TSTA3 upstream-activated CCNB2, CKS1B, ELAVL3, GAS7, NQO1, NTN1, OCRL, PLA2G1B, REG3A, SSTR5, etc. and TSTA3 downstream-activated BAP1, BRCA1, CCL20, MCM2, MS4A2, NTN1, REG1A, TP53I11, VCAN, SLC16A3, etc. in no-tumor hepatitis/cirrhotic tissues. TSTA3-activated network enhanced the regulation of apoptosis, cyclin-dependent protein kinase activity, cell migration, insulin secretion, transcription, cell division, cell proliferation, DNA replication, postreplication repair, cell differentiation, T-cell homeostasis, neutrophil-mediated immunity, neutrophil chemotaxis, interleukin-8 production, inflammatory response, immune response, B-cell activation, humoral immune response, actin filament organization, xenobiotic metabolism, lipid metabolism, phospholipid metabolism, leukotriene biosynthesis, organismal lipid catabolism, phosphatidylcholine metabolism, arachidonic acid secretion, activation of phospholipase A2, deoxyribonucleotide biosynthesis, heterophilic cell adhesion, activation of MAPK activity, signal transduction by p53 class mediator resulting in transcription of p21 class mediator, G-protein-coupled receptor protein signaling pathway, response to toxin, acute-phase response, DNA damage response, intercellular junction assembly, cell communication, and cell recognition, as a result of inducing immune response-mediated metabolism coupling cell cycle to postreplication repair in no-tumor hepatitis/cirrhotic tissues.

  15. The Value of Core Antigen and RNA HCV in the Diagnosis of Chronic Hepatitis C%核心抗原与HCV RNA检查在慢性丙型肝炎诊断中的价值探讨

    Institute of Scientific and Technical Information of China (English)

    汪峻岭; 李照丹; 徐兴伟; 徐萌; 李惠

    2016-01-01

    目的:探讨核心抗原与HCV RNA检查在慢性丙型肝炎的诊断价值。方法回顾性分析2013年3月~2015年10月我院收治的慢性丙型肝炎患者65例抗HCV抗体、核心抗原及HCV RNA病毒载量结果。结果以抗HCV抗体为金标准,HCV RNA的敏感度为57.38%,特异度为100%;HCV核心抗原的敏感度为45.90%,特异度为100%。不同HCV RNA载量的核心抗原的阳性率分布经秩和检验Z=5.2935,P<0.0001。结论核心抗原与HCV RNA不适合丙型肝炎感染的筛查,二者可用于病毒复制的检测。%ObjectiveTo investigate the value of core antigen and RNA HCV in the diagnosis of chronic hepatitis C(CHC).Methods 65 cases of CHC in our hospital from March 2013 to October 2015 were included. The results of HCV antibody,core antigen and RNA HCV viral load were analyzed. ResultsThe sensitivity of RNA HCV was 57.38%,the specificity was 100%,the sensitivity of HCV core antigen was 45.90%,the specificity was 100%.The positive rate distribution of the core antigen of different RNA HCV load was tested by rank sum test Z=5.293 5,P<0.000 1.Conclusion Core antigen and RNA HCV are not suitable for CHC infection screening,the two can be used for the detection of viral replication.

  16. An ELISA method using serum derived HDAg for the sorological detection of HDV antigens and antibodies

    Directory of Open Access Journals (Sweden)

    Celso Granato

    1987-12-01

    Full Text Available One of the main difficulties related to the detection of the Hepatitis Delta Virus (HDV antigen and antibody has been the source of the needed HD antigen since HDV containing human and animal livers are very difficult to obtain and since yield is low. This fact prompted us to try to use the serum of patients in the acute phase of HDV infection as a source of HDAg and turn to enzyme immunoassays (EIA instead of RIA for the sake of easiness and economy in the amount of HDAg needed. The antigen for EIA was obtained from patients during the acute phase of HDV infection and the antibody from patients who have been carriers for many years. For the detection of the antigen, a sandwich type method was employed, whereas for the antibody a competition assay was developed. In order to assess the relative specificity and sensibility of the test, the antibody assay was compared to a commercial RIA (C. RIA, Abbott and to a non-commercial RIA (NC RIA. Forty-two sera were tested by the two methods and only in two cases discrepant results were obtained. Its is concluded that: 1 sera from patients in the acute and chronic phases of HDV infection can be used as source of both antigen and antibody, for immunoassays; 2 EIA and RIA have comparable relative specificity and sensibility and 3 EIA is easier to perform, cheaper, non-hazardous, has a longer shelf-life and saves scarce HDAg.

  17. Increased intrahepatic quasispecies heterogeneity correlates with off-treatment sustained response to nucleos(t)ide analogues in e antigen-positive chronic hepatitis B patients.

    Science.gov (United States)

    Chen, L; Gan, Q R; Zhang, D Q; Yao, L F; Lin, R S; Li, Q; Lin, M H; Yu, D M; Zhang, X X; Pan, C

    2016-02-01

    Finite treatment with nucleos(t)ide analogues (NAs) remains a great challenge for chronic hepatitis B in the clinic. This study aimed to investigate the relationship between intrahepatic quasispecies heterogeneity and the NAs off-treatment outcomes in a prospective cohort. Eighteen HBeAg-positive patients with chronic hepatitis B who achieved the cessation criteria underwent liver biopsy, and stopped treatment thereafter. Patients were followed up prospectively for 1 year. The reverse transcriptase (RT) gene of intrahepatic hepatitis B virus (HBV) was cloned and sequenced. Intrahepatic quasispecies heterogeneity and specific gene mutations were analysed using bioinformatic methods. Ten patients achieved sustained response, and eight patients developed viral relapse. The intrahepatic quasispecies Shannon entropy and nucleotide diversity within either RT or the surface (S) region of patients with sustained response were significantly higher (p quasispecies Shannon entropy at the nucleotide level predicted the sustained off-treatment response (area under receiver operating characteristics curve 0.925; 95% CI 0.807-1.000; p 0.003). More positive selection sites and N-glycosylation mutations within the S region were found in patients with sustained response than in the patients with viral relapse (p quasispecies heterogeneity at the end of treatment was correlated with off-treatment outcomes in HBeAg-positive patients with chronic hepatitis B. More immune escape mutations were found within the S region in patients with sustained response. The higher intrahepatic quasispecies heterogeneity indicated a more robust immune control over HBV, which in turn maintained a sustained response after withdrawal of NAs.

  18. Defective mutations of hepatitis D viruses in chronic hepatitis D patients

    Institute of Scientific and Technical Information of China (English)

    Jaw-Ching Wu; Sheng-Chieh Hsu; Shen-Yung Wang; Yi-Hsiang Huang; I-Jane Sheen; Hsuan-Hui Shih; Wan-Jr Syu

    2005-01-01

    AIM: To verify whether "defective" mutations existed in hepatitis D virus (HDV).METHODS: Hepatitis delta antigen (HDAg)-codingsequences were amplified using Pfu DNA polymerases with proof-reading activities from sera of five patients with chronic hepatitis D. Multiple colonies were sequenced for each patient. Pfu analyzed a total of 270 HDV clones.Three representative defective HDV clones were constructed in expression plasmids and transfected into a human hepatoma cell line. Cellular proteins were extracted and analyzed by Western blot.RESULTS: Four of five cases (80%) showed defective HDV genomes in their sera. The percentage of defective genomes was 3.7% (10/270). The majority (90%) of the defective mutations were insertions or deletions that resulted in frameshift and abnormal stop translation of the HDAg. The predicted mutated HDAg ranged from 45amino acids to >214 amino acids in length. Various domains of HDAg associated with viral replication or packaging were affected in different HDV isolates. Western blot analysis showed defected HDAg in predicted positions.CONCLUSION: "Defective" viruses do exist in chronic HDV infected patients, but represented as minor strains. The clinical significance of the "defected" HDV needs further study to evaluate.

  19. [Presence of Australia antigen in blood donors].

    Science.gov (United States)

    Gota, F

    1980-01-01

    The differential diagnosis of type A and B viral hepatitis is discussed and guidelines for the prevention of post-transfusional hospital hepatitis are proposed. Methods for the immunological demonstration of HBs antigen are illustrated, together with the respective positivity percentages in blood donors.

  20. Prevalencia de marcadores serológicos para hepatitis B y delta e infección intrafamiliar en el valle del río Pampas, Perú¹

    Directory of Open Access Journals (Sweden)

    Gualberto Segovia M

    2002-04-01

    Full Text Available Objetivo: Determinar la prevalencia de marcadores serológicos para hepatitis viral B (HBV y Delta (HDV en la población escolar de las localidades del valle del Río Pampas y evaluar el riesgo de transmisión intrafamiliar de HBV. Materiales y métodos: esta investigación fue realizada en 8 localidades del valle del Río Pampas (Ayacucho-Andahuaylas de marzo a noviembre de 2000 y estuvo compuesta por dos fases: en la primera fase (seroprevalencia, se seleccionó una muestra en forma aleatoria y estratificada de 130 del total de escolares registrados, quienes fueron evaluados para identificar la presencia de HBsAg, anticuerpos anti-HBcAg y anti-HDV (sólo a los HBsAg positivos. En la segunda fase (riesgo de transmisión intrafamiliar, se anidó un estudio caso-control, en el cual los casos fueron los familiares de los niños reactivos al HBsAg y los controles fueron los familiares de los escolares no reactivos (relación 1/1. En todos se evaluó la presencia de anticuerpos anti-HBcAg, HBsAg y HbeAg. Resultados: 18 (13,8% escolares resultaron ser portadores de HBsAg, 93 (71,5% tuvieron anticuerpos anti-HBcAg y 3 (16,7% de 18 portadores de HBsAg tuvieron anticuerpos anti-HDV. No se encontró diferencias significativas en los marcadores serológicos de HBV entre los casos y controles. Conclusión: las localidades del valle del río Pampas (Ayacucho-Andahuaylas, presentan una alta endemicidad para el HBV y una endemicidad intermedia para el HDV. No se halló riesgo de transmisión intrafamiliar.

  1. Participation of CD45, NKR-P1A and ANK61 antigen in rat hepatic NK cell (pit cell)-mediated target cell cytotoxicity

    Institute of Scientific and Technical Information of China (English)

    Dian Zhong Luo; David Vermijlen; B lent Ahishali; Vasilis Triantis; Eddie Wisse; Karin Vanderkerken; Peter J.K. Kuppen

    2000-01-01

    AIM Several triggering receptors have been described to be involved in natural killer (NK) cellmediated target cytotoxicity. In these studies, NK cells derived from blood or spleen were used. Pit cells are liver-specific NK cells that possess a higher level of natural cytotoxicity and a different morphology when compared to blood NK cells. The aim of this study was to characterize the role of the NK-triggering molecules NKR-P1A, ANK61 antigen, and CD45 in pit cell-mediated killing of target cells. METHODS 51 Cr-release and DNA fragmentation were used to quantify target cell lysis and apoptosis, respectively. RESULTS Flow cytometric analysis showed that pit cells expressed CD45, NKR-P1A, and ANK61 antigen. Treatment of pit cells with monoclonal antibody ( mAb ) to CD45 ( ANK74 ) not only inhibited CC531s or YAC-1 target lysis but also apoptosis induced by pit cells. The mAbs to NKRP1A (3.2.3) and ANK61 antigen (ANK61) had no effect on pit cell-mediated CC531s or YAC-1 target cytolysis or apoptosis, while they did increase the Fcγ receptor positive (FcγR+) P815 cytolysis and apoptosis. This enhanced cytotoxicity could he inhibited by 3,4-dichloroisocoumarin, an inhibitor of granzymes. CONCLUSION These results indicate that CD45 participates in pit cell-mediated CC531s and YAC-1 target cytolysis and apoptosis. NKR-P1A and ANK61 antigen on pit cells function as activation structures against FcγR+ P815 cells, which was mediated by the perforin/granzyme pathway.

  2. Hepatitis C Virus Subtype 3a Envelope Protein 1 Binding with Human Leukocyte Antigen Class I Types of Pakistani Population: Candidate Epitopes for Synthetic Peptide Vaccine

    Directory of Open Access Journals (Sweden)

    Hamid Nawaz-Tipu

    2015-10-01

    Full Text Available The object of this cross sectional study was to determine the HCV subtype 3a envelope protein binding affinity with Human Leukocyte Antigen. Envelope 1 (E1 protein is one of the structural proteins responsible for entering the cells through the receptors. The binding affinity of E1 protein epitopes to the selected Human Leukocyte Antigen (HLA class I alleles was investigated using the computer-based tools. These prediction tools were also used to design the synthetic vaccine’s candidate epitopes and to identify the individuals/populations who are likely to be responder to those vaccines.The mean frequency of HLA I antigens in Pakistani population was calculated. Threealleles each from HLA A and B were selected. E1 protein sequence extracted from HCV 3a isolates was retrieved and twenty-four sequences of it were selected. NetMHCcons 1.0 server was used to determine the binding affinities of HLA alleles to the epitope sequences of 10 amino acids in length.A02, A03, A11, A24, A33, B08, B13, B15, B35 and B40 were the first five antigens moreprevalent in Pakistan each from HLA A and HLA B.. We did not find any binding affinity between HLA A*201, B*1501 and B*4001 and epitopes from E1 sequences in a threshold of50 nM. Totally five various epitopes derived from different isolates were characterized.The prediction of HLA-E1 epitope specific bindings and the forthcoming response can be a useful bioinformatics tool to uncover the right synthetic peptides for vaccine design purposes.

  3. Hepatitis C Virus Subtype 3a Envelope Protein 1 Binding with Human Leukocyte Antigen Class I Types of Pakistani Population: Candidate Epitopes for Synthetic Peptide Vaccine.

    Science.gov (United States)

    Nawaz-Tipu, Hamid

    2015-10-01

    The object of this cross sectional study was to determine the HCV subtype 3a envelope protein binding affinity with Human Leukocyte Antigen. Envelope 1 (E1) protein is one of the structural proteins responsible for entering the cells through the receptors. The binding affinity of E1 protein epitopes to the selected Human Leukocyte Antigen (HLA) class I alleles was investigated using the computer-based tools. These prediction tools were also used to design the synthetic vaccine's candidate epitopes and to identify the individuals/populations who are likely to be responder to those vaccines.The mean frequency of HLA I antigens in Pakistani population was calculated. Three alleles each from HLA A and B were selected. E1 protein sequence extracted from HCV 3a isolates was retrieved and twenty-four sequences of it were selected. NetMHCcons 1.0 server was used to determine the binding affinities of HLA alleles to the epitope sequences of 10 amino acids in length.A02, A03, A11, A24, A33, B08, B13, B15, B35 and B40 were the first five antigens more prevalent in Pakistan each from HLA A and HLA B.. We did not find any binding affinity between HLA A*201, B*1501 and B*4001 and epitopes from E1 sequences in a threshold of 50 nM. Totally five various epitopes derived from different isolates were characterized.The prediction of HLA-E1 epitope specific bindings and the forthcoming response can be a useful bioinformatics tool to uncover the right synthetic peptides for vaccine design purposes.

  4. Solitary expression of CD7 among T-cell antigens in acute myeloid leukemia: identification of a group of patients with similar T-cell receptor beta and delta rearrangements and course of disease suggestive of poor prognosis

    DEFF Research Database (Denmark)

    Jensen, A W; Hokland, M; Jørgensen, H

    1991-01-01

    to the French-American-British type M4, and four were under the age of 40. Despite intensive chemotherapy, four never obtained a complete remission and the fifth died of relapse after an allogenic bone marrow transplantation. While 12 randomly selected T-cell antigen negative AML patients showed only few....... These data suggest that the solitary presence of CD7 among T-cell antigens in otherwise clearcut AML cases identifies a group of patients with similarities in antigen receptor gene configuration as well as outcome. Udgivelsesdato: 1991-Sep-1...

  5. Prevalence of Serologic Hepatitis B Markers in Blood Donors From Puebla, Mexico: The Association of Relatively High Levels of Anti-Core Antibodies With the Detection of Surface Antigen and Genomic DNA.

    Science.gov (United States)

    Sosa-Jurado, Francisca; Hilda Rosas-Murrieta, Nora; Guzman-Flores, Belinda; Perez Zempoaltecalt, Cintia; Patricia Sanchez Torres, Ana; Ramirez Rosete, Leticia; Bernal-Soto, Maribel; Marquez-Dominguez, Luis; Melendez-Mena, Daniel; Angel Mendoza Torres, Miguel; Teresa Lopez Delgado, Maria; Reyes-Leyva, Julio; Vallejo-Ruiz, Veronica; Santos-Lopez, Gerardo

    2016-06-01

    The hepatitis B virus (HBV) causes chronic hepatitis, hepatic cirrhosis, and hepatocellular carcinoma. Surface antigen (HBsAg) detection is a definitive test that can confirm HBV infection, while the presence of antibodies against the core protein (anti-HBc) suggests either a previous or ongoing infection or occult hepatitis B infection (OBI). The aim of the present study was to determine the prevalence of anti-HBc and HBsAg in blood donors. Further, the study aimed to estimate the anti-HBc level at which HBV DNA is detected in putative OBI cases, as well as to search for mutations in the "a" determinant associated with the non-detection of HBsAg in serum. We conducted a cross-sectional study from 2003-2009. The study included 120,552 blood donors from the state of Puebla, Mexico. Different commercial systems based on microparticles (enzymatic (MEIA) or chemiluminescent (CMIA)) were used to determine the HBsAg and anti-HBc levels. For the detection of HBV DNA, a nested polymerase chain reaction (nested PCR) was used and the genotypes were determined using Sanger sequencing. Of the 120,552 blood donors, 1437 (1.19%, 95% CI: 1.12 - 1.26) were reactive to anti-HBc, while 82 (0.066%, 95% CI: 0.053 - 0.079) were reactive to HBsAg. Some 156 plasma samples collected in 2009 from anti-HBc-positive/HBsAg-negative blood donors were submitted for HBV DNA detection in a search for probable OBI. Viral DNA was detected in 27/156 (17.3%, 95% CI: 11.5 - 23.1). Our results show an association between HBV DNA or HBsAg and anti-HBc S/CO levels ≥ 4.0. All DNA samples were identified as genotype H and some "a" determinant mutations were identified, although none corresponded to mutations previously reported to hinder the detection of HBsAg by commercial immunoassays. We observed that as the anti-HBc levels increase, there is a higher prevalence of the viral protein HBsAg in blood donors. Samples testing positive for HBV-DNA were seen to exhibit a ten-fold higher presence of anti

  6. Prevalence of Serologic Hepatitis B Markers in Blood Donors From Puebla, Mexico: The Association of Relatively High Levels of Anti-Core Antibodies With the Detection of Surface Antigen and Genomic DNA

    Directory of Open Access Journals (Sweden)

    Sosa-Jurado

    2016-06-01

    Full Text Available Background The hepatitis B virus (HBV causes chronic hepatitis, hepatic cirrhosis, and hepatocellular carcinoma. Surface antigen (HBsAg detection is a definitive test that can confirm HBV infection, while the presence of antibodies against the core protein (anti-HBc suggests either a previous or ongoing infection or occult hepatitis B infection (OBI. Objectives The aim of the present study was to determine the prevalence of anti-HBc and HBsAg in blood donors. Further, the study aimed to estimate the anti-HBc level at which HBV DNA is detected in putative OBI cases, as well as to search for mutations in the “a” determinant associated with the non-detection of HBsAg in serum. Patients and Methods We conducted a cross-sectional study from 2003–2009. The study included 120,552 blood donors from the state of Puebla, Mexico. Different commercial systems based on microparticles (enzymatic (MEIA or chemiluminescent (CMIA were used to determine the HBsAg and anti-HBc levels. For the detection of HBV DNA, a nested polymerase chain reaction (nested PCR was used and the genotypes were determined using Sanger sequencing. Results Of the 120,552 blood donors, 1437 (1.19%, 95% CI: 1.12 - 1.26 were reactive to anti-HBc, while 82 (0.066%, 95% CI: 0.053 - 0.079 were reactive to HBsAg. Some 156 plasma samples collected in 2009 from anti-HBc-positive/HBsAg-negative blood donors were submitted for HBV DNA detection in a search for probable OBI. Viral DNA was detected in 27/156 (17.3%, 95% CI: 11.5 - 23.1. Our results show an association between HBV DNA or HBsAg and anti-HBc S/CO levels ≥ 4.0. All DNA samples were identified as genotype H and some “a” determinant mutations were identified, although none corresponded to mutations previously reported to hinder the detection of HBsAg by commercial immunoassays. Conclusions We observed that as the anti-HBc levels increase, there is a higher prevalence of the viral protein HBsAg in blood donors. Samples testing

  7. Antibodies against non-structural c100/3 and structural core antigen of hepatitis C virus (HCV) in hemodialysis patients

    OpenAIRE

    Yoshida,C.F.T.; Takahashi, Y.; B.O.M. Vanderborght; Rouzere,C. D.; França,M. S. de; Takahashi,C.; Takamizawa, A; Yoshida, I.; Schatzmayr, H. G.

    1993-01-01

    Two groups of patients undergoing hemodialysis (HD) maintenance were evaluated for their antibody response to non-structural c100/3 protein and structural core protein of hepatitis C virus (HCV). Forty-six patients (Group 1) never presented liver abnormalities during HD treatment, while 52 patients (Group 2) had either current or prior liver enzyme elevations. Prevalence rates of 32.6% and 41.3% were found for anti-c100/3 and anti-HCV core antibodies, respectively, in patients with silent inf...

  8. De Novo Hepatitis B Infection From Hepatitis B Core Antibody-Positive Donors During Hepatitis B Immunoglobulin Prophylaxis.

    Science.gov (United States)

    Shin, Milljae; Chang, Seong-Hwan

    2016-02-01

    De novo hepatitis B infection in patients receiving liver transplants from hepatitis B core antibody-positive donors is well known, but the effective prevention strategy has not been well established. In our hospital, recipients receive hepatitis B immunoglobulin monotherapy if they are hepatitis B surface antigen negative at the time of transplant and are receiving a liver from a hepatitis B core antibody-positive donor. Since August 2006, we have had 4 patients who were naïve to hepatitis B virus and received a hepatitis B core antibody-positive graft. Two patients died of other causes, and 2 patients, who had liver transplant in October 2006 and October 2009, developed de novo hepatitis B. Both patients were tested annually for serum hepatitis B surface antigen as part of routine visit. Tests were negative; however, both patients recently became hepatitis B surface antigen positive. Other laboratory results, including liver function test, were unremarkable, except HBsAb titer was undetectable even though hepatitis B immunoglobulin monotherapy had been administrated 2 months previously in both patients. The patients had hepatitis B virus DNA levels of 3.07E+08 copies/mL and 1.51E+08 copies/mL. We suggest that additional prophylactic therapies above hepatitis B immunoglobulin monotherapy are needed for these recipients.

  9. Transplacentally acquired antibodies against hepatitis B surface antigen in full term infants%足月新生儿母源性抗-HBs及其亚型的特性

    Institute of Scientific and Technical Information of China (English)

    武巧珍; 胡娅莉; 周乙华; 王志群; 陈建琴; 叶晓东; 蒋红

    2008-01-01

    Objective To analyze the correlation of the concentration of antibodies against hepatitis B surface antigen (anti-HBs) between normal full term pregnant women and their newborns.Methods Sixty-three paired serum samples from infants and their anti-HBs positive mothers,who delivered in the Affiliated Drum Tower Hospital of Nanjing Medical University School from Dec.2006 to Feb.2007,were quantitatively tested for anti-HBs by AxSYM AUSAB immunoassay.Subclasses of anti-HBs IgG were analyzed.The neutralizing activity of maternal anti-HBs in infants was assessed by surrogate assay. Results All infants born to anti-HBs positive mothers were also seropositive.Anti-HBs 1evels in infants were correlated with the maternal concentration(rs=0.976,P<0.01),and majority of the infants had higher concentrations than their mothers(195.4 mIU/ml vs 141.6 mIU/ml,P<0.01).The mean half-life of maternal anti-HBs in infants was estimated to be 41 days.Anti-HBs IgGl subclass was predominantly in infants,which was in agreement with that in their mothers.Transplacentally transferred anti-HBs in infants efficiently bound the hepatitis B surface antigen derived from hepatitis B patients. Conclusions Anti-HBs IgG carl efficiently transfer through the placenta.Infants born to anti-HBs positive mothers may be immune to hepatitis B virus in the early life of several months.%目的 分析了解足月新生儿母源性乙型肝炎表面抗体(抗-HBs)及其亚型的特性.方法 2006年12月至2007年02月在南京大学附属鼓楼医院住院分娩的单胎足月孕妇及其新生儿为研究对象,AxSYM全自动免疫分析仪定量检测63例抗-HBs阳性的单胎足月孕妇及其新生儿脐血婴儿和1月龄时的血清抗-HBs浓度,用固相酶联免疫法检测孕妇和脐血中抗-HBs 4种IgG亚型的含量,及其中和乙型肝炎患者血清中HBsAg的能力.结果 63例抗-HBs阳性孕妇分娩的新生儿脐血抗-HBs均为阳性,几何平均浓度为195.4 mIU/ml,

  10. [delta-Aminolevulinate dehydratase deficiency].

    Science.gov (United States)

    Fujita, H; Ishida, N; Akagi, R

    1995-06-01

    delta-Aminolevulinate dehydratase (ALAD: E. C. 4.2.1.24), the second enzyme in the heme biosynthetic pathway, condenses two moles of delta-aminolevulinic acid to form porphobilinogen. ALAD deficiency is well known to develop signs and symptoms of typical hepatic porphyria, and classified into three categories as follows: (i) ALAD porphyria, a genetic defect of the enzyme, (ii) tyrosinemia type I, a genetic defect of fumarylacetoacetase in the tyrosine catabolic pathway, producing succinylacetone (a potent inhibitor of ALAD), and (iii) ALAD inhibition by environmental hazards, such as lead, trichloroethylene, and styrene. In the present article, we will describe molecular and biochemical mechanisms to cause the enzyme defect to discuss the significance of ALAD defect on human health.

  11. Soluble expression and purifiation of hepatitis B core antigen (HBcAg subgenotype B3 in Escherichia coli using thioredoxin fusion tag

    Directory of Open Access Journals (Sweden)

    Rahmah Waty

    2017-08-01

    Full Text Available Objective: To express HBcAg protein (hepatitis B virus subgenotype B3 in Escherichia coli in soluble form. Methods: HBcAg sequence of hepatitis B virus subgenotype B3 was cloned into plasmid pET32a and introduced to E. coli BL21 (DE3. The E. coli was grown in Luria-Bertani (LB medium supplemented with ampicillin with agitation. Protein expression was induced by adding isopropyl-β-D-thiogalactopyranoside (IPTG at concentrations of 0.1 mmol/L, 0.3 mmol/L, and 0.5 mmol/L at room temperature (28 °C. The bacteria were dissolved in lysis buffer and lysed by freeze-thawing method then sonication. The fusion protein [thioredoxin A-(His6tag-HBcAg] was purified using immobilized metal affinity chromatography. The protein expression was analyzed by SDS-PAGE, dot blot, and western blot. Results: This research showed that DNA sequence of HBcAg could be propagated in pET32a and soluble protein was successfully expressed in E. coli. Induction with 0.3 mmol/L IPTG and 4-hour incubation was the best condition to express the HBcAg protein. SDS-PAGE and dot blot analysis showed that HBcAg protein could be expressed in E. coli. Western blot analysis showed that molecular weight of HBcAg fusion protein was about 38.5 kDa. Conclusions: This study confirmed that HBcAg protein could be expressed in soluble form in E. coli.

  12. Inhibition of maternal antibody to hepatitis B surface antigen on antibody response to hepatitis B vaccine in infants%母源性抗乙型肝炎病毒表面抗原抗体对婴儿乙型肝炎疫苗接种的影响

    Institute of Scientific and Technical Information of China (English)

    胡娅莉; 武巧珍; 耿全林; 陈宏; 王志群; 周镇先; 李瑛; 周乙华

    2010-01-01

    Objective To investigate whether maternal antibody to hepatitis B surface antigen (anti-HBs)in infants may interfere with the antibody response to hepatitis B vaccine. Methods Infants from singleton pregnant mothers,who delivered at full term at the Affiliated Drum Tower Hospital of Nanjing University Medical School from October 2006 to January 2007,were divided into two groups based on their mothers'status of anti-HBs(43 positive and 29 negative).All infants were vaccinated with hepatitis B vaccine at birth and one month thereafter.Serum anti-HBs were quantitatively determined for the mothers before delivery and for infants in cord blood at delivery and in serum at the age of 1 and 3.5 months. Results Anti-HBs of all 43 newborns in the positive group were positive in cord blood with the coefficiency of 0.98 to the maternal serum anti-HBs level(t=39.05,P1000 mIU/ml,3 did not produce active antibodies against two doses of hepatitis B vaccination. Conclusions Passively acquired maternal anti-HBs in infants can inhibit the active antibody response to hepatitis B vaccine,and the extent of this effect is associated with maternal anti-HBs level.%目的 了解母源性抗乙型肝炎病毒表面抗原抗体(anti-hepatitis B surface antigen antibody,抗-HBs抗体)对婴儿乙型肝炎疫苗接种后抗体应答的影响.方法 2006年10月至2007年1月在南京大学医学院附属鼓楼医院产前检查并住院分娩的单胎足月妊娠妇女中,选择抗-HBs抗体阳性孕妇43例(阳性组)和阴性孕妇29例(阴性组),其足月儿出生时和出生后1个月分别接种乙型肝炎疫苗.定量检测孕妇分娩前、脐动脉血及婴儿1月龄和3.5月龄的抗-HBs抗体水平.结果 阳性组43例新生儿脐血抗-HBs抗体也为阳性,与母血清抗体水平的相关系数r=0.98(t=39.05,P1000 mIU/ml的5例婴儿中,3例在接种2次疫苗后没有产生主动抗体应答.结论 母源性抗-HBs抗体可抑制乙型肝炎疫苗前2次接种后的抗体应答.

  13. File list: ALL.Bld.50.AllAg.delta-47 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ALL.Bld.50.AllAg.delta-47 hg19 All antigens Blood delta-47 SRX1091819,SRX1091817,SR...X1091818,SRX1091820 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/ALL.Bld.50.AllAg.delta-47.bed ...

  14. File list: ALL.Bld.20.AllAg.delta-47 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ALL.Bld.20.AllAg.delta-47 hg19 All antigens Blood delta-47 SRX1091819,SRX1091817,SR...X1091818,SRX1091820 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/ALL.Bld.20.AllAg.delta-47.bed ...

  15. File list: ALL.Bld.10.AllAg.delta-47 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ALL.Bld.10.AllAg.delta-47 hg19 All antigens Blood delta-47 SRX1091819,SRX1091820,SR...X1091817,SRX1091818 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/ALL.Bld.10.AllAg.delta-47.bed ...

  16. File list: ALL.Bld.05.AllAg.delta-47 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ALL.Bld.05.AllAg.delta-47 hg19 All antigens Blood delta-47 SRX1091819,SRX1091820,SR...X1091818,SRX1091817 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/ALL.Bld.05.AllAg.delta-47.bed ...

  17. Association between Hepatitis B Virus Chronic Infection and Mutations of Surface Antigen Gene%乙型肝炎病毒慢性感染与其表面抗原基因突变的相关性

    Institute of Scientific and Technical Information of China (English)

    王卫华; 宋建新

    2013-01-01

    目的 基于一个完整的乙型肝炎病毒(HBV)感染自然史的4个时期(免疫耐受期、免疫清除期、不活动期和HBeAg阴性肝炎阶段),研究HBV表面抗原各抗原表位的免疫逃逸突变分布.方法 收集280例患者的临床资料及血清标本,按照HBV自然史的不同时期分为4组,提取DNA并荧光定量,通过巢式PCR扩增HBV表面基因序列,以PCR产物作为模板进行DNA测序.分析比较4组乙肝表面抗原中辅助性T细胞(Th)表位、细胞毒性T淋巴细胞(CTL)表位及B细胞抗原表位的突变差异.结果 Th抗原表位突变中,4组间比较具有差异的是17-31、37-51、67-81等区域,CTL抗原表位突变中具有差异的是14-22、41-49等区域,在B细胞抗原表位区域发现了Q101K、P120S、T126S、Q129H、M133L、M133I、和M133T等7个乙肝表面抗原免疫逃逸突变.结论在HBV感染自然史中,表面抗原突变的累积发生在免疫清除期,突变的产生有利于HBV逃避免疫系统的攻击.%Objective To investigate the distribution of the immune escape mutations of hepatitis B virus surface antigen across the natural history of hepatitis B virus infection. Methods A total of 280 patients were divided into four groups according to the natural history of hepatitis B virus infection. DNA was extracted ,and the gene sequences of hepatitis B virus surface autigen were amplified by using nested PCR. The PCR product served as a template for DNA sequencing. The differences of mutations in epitopes of helper T cells (Th) ,cytotoxic T lymphocytes (CTL ) and B cells were analyzed. Results Among the four groups ,there were significant differences in mutations of epitopes of Th at regions of 17-31 ,37-51 ,67-81 ,and in mutations of epitopes of CTL at regions of 14-22 and 41-49 among the four groups. Immune escape mutations of hepatitis B virus surface an -tigen were found in epitopes of B cells in all four groups , namely Q101K, P120S , T126S , Q129H , M133L,M133I and M133T

  18. Severe Acute Hepatitis B Treated with Entecavir

    OpenAIRE

    Giuseppe Vittorio Luigi De Socio; Alessio Sgrelli; Andrea Tosti; Franco Baldelli

    2011-01-01

    Hepatitis B virus (HBV) infection constitutes a serious global health problem. Nowadays there are divergent data regarding the use of antiviral drugs to treat acute hepatitis B. We present here a case of a 62-year-old man affected by severe acute hepatitis B with progressive worsening of clinical and hepatic function. The patient was treated with entecavir without critical side effects. We observed rapid clinical and laboratory improvements and the disappearance of surface antigen (HBsAg). Th...

  19. Occurrence of hepatocellular carcinoma and decompensation in western European patients with cirrhosis type B. The EUROHEP Study Group on Hepatitis B Virus and Cirrhosis

    DEFF Research Database (Denmark)

    Fattovich, G; Giustina, G; Schalm, S W

    1995-01-01

    . At entry into the study all patients were tested for hepatitis B e antigen (HBeAg; 34% of patients were HBeAg-positive) and antibody to hepatitis delta virus (anti-HDV; 20% of patients were anti-HDV-positive); 48% of 252 patients tested were hepatitis B virus (HBV)-DNA-positive. During follow-up HCC......To examine the morbidity of compensated cirrhosis type B, a cohort of 349 Western European, white patients (86% men; mean age, 44 years) with biopsy-proven cirrhosis was followed up for a mean period of 73 months and was studied for occurrence of hepatocellular carcinoma (HCC) and decompensation...... developed in 32 (9%) of the 349 patients and decompensation was observed in 88 (28%) of 317 tumor-free patients. Five years after diagnosis, the probability of HCC appearance was 6% and the probability of decompensation was 23%. After the first episode of decompensation the probability of survival was 35...

  20. Expression of Hepatitis B virus surface antigen (HBsAg from genotypes A, D and F and influence of amino acid variations related or not to genotypes on HBsAg detection

    Directory of Open Access Journals (Sweden)

    Natalia M. Araujo

    Full Text Available The impact of hepatitis B virus (HBV genotypes on the sensitivity of surface antigen (HBsAg detection assays has been poorly investigated. Here, plasmids carrying consensus or variant coding sequences for HBV surface proteins from genotypes A, D and F, were constructed. HBsAg levels were evaluated in medium and extracts of transfected CHO cells by a commercial polyclonal-based assay. We show that HBsAg detection values of consensus forms from genotypes D and F were, respectively, 37% and 30% lower than those obtained by genotype A. However, the presence of two single variations, T143M in genotype A, and T125M in genotype D, produced a decrease of 44% and an increase of 34%, respectively, on HBsAg mean values in comparison with their consensus forms. In conclusion, HBsAg detection levels varied among HBV genotypes. However, unique amino acid substitutions not linked to genotypes, such as T125M and T143M described here, should have more implications in HBV immunological diagnostics than the set of variations characteristic of each HBV genotype.

  1. Polyfunctional type-1, -2, and -17 CD8⁺ T cell responses to apoptotic self-antigens correlate with the chronic evolution of hepatitis C virus infection.

    Directory of Open Access Journals (Sweden)

    Debora Franceschini

    Full Text Available Caspase-dependent cleavage of antigens associated with apoptotic cells plays a prominent role in the generation of CD8⁺ T cell responses in various infectious diseases. We found that the emergence of a large population of autoreactive CD8⁺ T effector cells specific for apoptotic T cell-associated self-epitopes exceeds the antiviral responses in patients with acute hepatitis C virus infection. Importantly, they endow mixed polyfunctional type-1, type-2 and type-17 responses and correlate with the chronic progression of infection. This evolution is related to the selection of autoreactive CD8⁺ T cells with higher T cell receptor avidity, whereas those with lower avidity undergo prompt contraction in patients who clear infection. These findings demonstrate a previously undescribed strict link between the emergence of high frequencies of mixed autoreactive CD8⁺ T cells producing a broad array of cytokines (IFN-γ, IL-17, IL-4, IL-2… and the progression toward chronic disease in a human model of acute infection.

  2. Combination of Human Leukocyte Antigen and Killer Cell Immunoglobulin-Like Receptor Genetic Background Influences the Onset Age of Hepatocellular Carcinoma in Male Patients with Hepatitis B Virus Infection

    Directory of Open Access Journals (Sweden)

    Ning Pan

    2013-01-01

    Full Text Available To investigate whether killer cell immunoglobulin-like receptor (KIR and human leukocyte antigen (HLA genetic background could influence the onset age of hepatocellular carcinoma (HCC in patients with hepatitis B virus (HBV infection, one hundred and seventy-one males with HBV-related HCC were enrolled. The presence of 12 loci of KIR was detected individually. HLA-A, -B, and -C loci were genotyped with high resolution by a routine sequence-based typing method. The effect of each KIR locus, HLA ligand, and HLA-KIR combination was examined individually by Kaplan-Meier (KM analysis. Multivariate Cox hazard regression model was also applied. We identified C1C1-KIR2DS2/2DL2 as an independent risk factor for earlier onset age of HCC (median onset age was 44 for C1C1-KIR2DS2/2DL2 positive patients compared to 50 for negative patients, P=0.04 for KM analysis; HR = 1.70, P=0.004 for multivariate Cox model. We conclude that KIR and HLA genetic background can influence the onset age of HCC in male patients with HBV infection. This study may be useful to improve the current HCC surveillance program in HBV-infected patients. Our findings also suggest an important role of natural killer cells (or other KIR-expressing cells in the progress of HBV-related HCC development.

  3. Immunological response to parenteral vaccination with recombinant hepatitis B virus surface antigen virus-like particles expressing Helicobacter pylori KatA epitopes in a murine H. pylori challenge model.

    Science.gov (United States)

    Kotiw, Michael; Johnson, Megan; Pandey, Manisha; Fry, Scott; Hazell, Stuart L; Netter, Hans J; Good, Michael F; Olive, Colleen

    2012-02-01

    Virus-like particles (VLPs) based on the small envelope protein of hepatitis B virus (HBsAg-S) are immunogenic at the B- and T-cell level. In this study, we inserted overlapping sequences encoding the carboxy terminus of the Helicobacter pylori katA gene product into HBsAg-S. The HBsAg-S-KatA fusion proteins were able to assemble into secretion-competent VLPs (VLP-KatA). The VLP-KatA proteins were able to induce KatA-specific antibodies in immunized mice. The mean total IgG antibody titers 41 days post-primary immunization with VLP-KatA (2.3 × 10(3)) were significantly greater (P < 0.05) than those observed for vaccination with VLP alone (5.2 × 10(2)). Measurement of IgG isotypes revealed responses to both IgG1 and IgG2a (mean titers, 9.0 × 10(4) and 2.6 × 10(4), respectively), with the IgG2a response to vaccination with VLP-KatA being significantly higher than that for mice immunized with KatA alone (P < 0.05). Following challenge of mice with H. pylori, a significantly reduced bacterial load in the gastric mucosa was observed (P < 0.05). This is the first report describing the use of VLPs as a delivery vehicle for H. pylori antigens.

  4. Expression of Hepatitis B virus surface antigen (HBsAg from genotypes A, D and F and influence of amino acid variations related or not to genotypes on HBsAg detection

    Directory of Open Access Journals (Sweden)

    Natalia M. Araujo

    2009-08-01

    Full Text Available The impact of hepatitis B virus (HBV genotypes on the sensitivity of surface antigen (HBsAg detection assays has been poorly investigated. Here, plasmids carrying consensus or variant coding sequences for HBV surface proteins from genotypes A, D and F, were constructed. HBsAg levels were evaluated in medium and extracts of transfected CHO cells by a commercial polyclonal-based assay. We show that HBsAg detection values of consensus forms from genotypes D and F were, respectively, 37% and 30% lower than those obtained by genotype A. However, the presence of two single variations, T143M in genotype A, and T125M in genotype D, produced a decrease of 44% and an increase of 34%, respectively, on HBsAg mean values in comparison with their consensus forms. In conclusion, HBsAg detection levels varied among HBV genotypes. However, unique amino acid substitutions not linked to genotypes, such as T125M and T143M described here, should have more implications in HBV immunological diagnostics than the set of variations characteristic of each HBV genotype.

  5. Improved humoral and cellular immune responses against the gp120 V3 loop of HIV-1 following genetic immunization with a chimeric DNA vaccine encoding the V3 inserted into the hepatitis B surface antigen

    DEFF Research Database (Denmark)

    Fomsgaard, A; Nielsen, H V; Bryder, K

    1998-01-01

    with the HIV MN gp160 envelope plasmid induced a slow and low titred anti-MN V3 antibody response at 12 weeks post-inoculation (p.i.) and a late appearing (7 weeks), weak and variable CTL response. In contrast, DNA vaccination with the HBsAg-encoding plasmid induced a rapid and high titred anti-HBsAg antibody...... response and a uniform strong anti-HBs CTL response already 1 week p.i. in all mice. DNA vaccination with the chimeric MN V3/HBsAg plasmid elicited humoral responses against both viruses within 3-6 weeks which peaked at 6-12 weeks and remained stable for at least 25 weeks. In addition, specific CTL......-2d-restricted cytotoxic T lymphocyte (CTL) epitope. In an attempt to improve the immunogenicity of V3 in DNA vaccines, a plasmid expressing MN V3 as a fusion protein with the highly immunogenic middle (pre-S2 + S) surface antigen of hepatitis B virus (HBsAg) was constructed. Epidermal inoculation...

  6. Liposome entrapment and immunogenic studies of a synthetic lipophilic multiple antigenic peptide bearing VP1 and VP3 domains of the hepatitis A virus: a robust method for vaccine design.

    Science.gov (United States)

    Haro, Isabel; Pérez, Silvia; García, Mónica; Chan, Weng C; Ercilla, Guadalupe

    2003-04-10

    Multiple antigen peptides (MAP) have been demonstrated to be efficient immunological reagents for the induction of immune responses to a variety of infectious agents. Several peptide domains of the hepatitis A virus (HAV) capsid proteins, mainly VP1 and VP3, are the immunodominant targets for a protective antibody response. In the present study we analyse the immunogenic properties of a tetrameric heterogeneous palmitoyl-derivatised MAP containing two defined HAV peptide sequences, VP1(11-25) and VP3(102-121), in rabbits immunised with either Freund's adjuvant or multilamellar liposomes. The immune response was evaluated with a specific enzyme immunoassay using MAP[VP1+VP3], VP1 and VP3 as targets. The avidity of the immune response was measured by a non-competitive enzyme-linked immunosorbent assay and by the surface plasmon resonance technology. Antisera raised against the lipo-MAP peptide entrapped in liposomes demonstrated high avidity of binding with affinity rate constants approximately one order of magnitude greater than those obtained with the Freund's protocol.

  7. Delta III—an evolutionary delta growth

    Science.gov (United States)

    Arvesen, R. J.; Simpson, J. S.

    1996-03-01

    In order to remain competitive in the future and expand the McDonnell Douglas Aerospace market share, MDA has developed an expendable launch system strategy that devices cost-effective launch systems from the Delta II with a growth vehicle configuration called Delta III. The Delta III evolves from the Delta II launch system through development of a larger payload fairing (4-meter diameter), new cryogenically propelled upper stage, new first stage fuel tank, and larger strap-on solid rocket motors. We are developing the Delta III using Integrated Product Development Teams that capitalize on the experience base that has led us to a world record breaking mission success of 49 consecutive Delta II missions. The Delta III first-launch capability is currently planned for the spring of 1998 in support of our first spacecraft customer, Hughes Space and Communications International.

  8. Detection of antibodies to hepatitis B core antigen using the Abbott ARCHITECT anti-HBc assay: analysis of borderline reactive sera.

    Science.gov (United States)

    Ollier, Laurence; Laffont, Catherine; Kechkekian, Aurore; Doglio, Alain; Giordanengo, Valérie

    2008-12-01

    Routine use of the automated chemiluminescent microparticle immunoassay Abbott ARCHITECT anti-HBc for diagnosis of hepatitis B is limited in case of borderline reactive sera with low signal close to the cut-off index. In order to determine the significance of anti-HBc detection when borderline reactivity occurs using the ARCHITECT anti-HBc assay, a comparative study was designed. 3540 serum samples collected over a 2-month period in the hospital of Nice were examined for markers of HBV infection (HBsAg, anti-HBs and anti-HBc). One hundred seven samples with sufficient volume and with borderline reactivity by the ARCHITECT assay were tested by two other anti-HBc assays, a microparticle enzyme immunoassay (MEIA, AxSYM Core, Abbott Laboratories, IL, USA) and an enzyme linked fluorescent assay (ELFA, VIDAS Anti-HBc Total II, bioMérieux, Lyon, France). Only 46 samples were confirmed by the AxSYM and the VIDAS assays. Additional serological information linked to patient history showed that the remaining samples (61) were false positives (11), had low titer of anti-HBc antibodies (13), or were inconclusive (37). This comparative study highlighted the existence of a grey zone around the cut-off index. Confirmative results through a different immunoassay are needed to confirm the diagnosis of HBV on borderline reactive sera using the ARCHITECT anti-HBc assay.

  9. The effects of booster vaccination of hepatitis B vaccine on anti-HBV surface antigen negative children 11-15 years after primary vaccination.

    Science.gov (United States)

    Yao, Jun; Ren, Jingjing; Shen, Lingzhi; Chen, Yongdi; Liang, Xiaofeng; Cui, Fuqiang; Li, Qian; Jiang, Zhenggang; Wang, Fuzhen

    2011-10-01

    The twin aims of this study were to investigate the changes in anti-HBs IgG levels after booster vaccinations and to compare the effects of different vaccine doses in children aged 11-15 years who were both negative for HBsAg and had an Anti-HBs vaccination. Children who were born between 1993 and 1998 and who had completed their Hepatitis B vaccination program in infancy were randomly recruited to the study. The participants were divided into three groups according to their anti-HBs IgG levels: group I had a level vaccination program comprised three (20μg) doses of HepB (CHO) vaccine administered at zero, one and six months after they are join this program: anti-HBs levels were measured one month after the first and third vaccinations. Among 448 HBsAg-negative infants, anti-HBs seroconversion rates (defined as an anti-HBs >= 10 mIU/mL) after the first and third vaccinations were 85.5% and 98.6% respectively - these observed differences were statistically significant (χ2 [1dof] = 50.11, panti-HBsanti-HBs titer levels decay to 10mIU/ml in 11-15 years of age children completed HepB Basic immunization, which need for booster immunization. The effect is better for those children with a relatively higher antibody titer before booster, and the effect of three doses booster is best.

  10. The Delta 2 launcher

    Science.gov (United States)

    Ousley, Gilbert W., Sr.

    1991-12-01

    The utilization of the Delta 2 as the vehicle for launching Aristoteles into its near Sun synchronous orbit is addressed. Delta is NASA's most reliable launch vehicle and is well suited for placing the present Aristoteles spacecraft into a 400 m circular orbit. A summary of some of the Delta 2 flight parameters is presented. Diagrams of a typical Delta 2 two stage separation are included along with statistics on delta reliability and launch plans.

  11. Antibodies against non-structural c100/3 and structural core antigen of hepatitis C virus (HCV) in hemodialysis patients.

    Science.gov (United States)

    Yoshida, C F; Takahashi, Y; Vanderborght, B O; Rouzere, C D; França, M S; Takahashi, C; Takamizawa, A; Yoshida, I; Schatzmayr, H G

    1993-01-01

    Two groups of patients undergoing hemodialysis (HD) maintenance were evaluated for their antibody response to non-structural c100/3 protein and structural core protein of hepatitis C virus (HCV). Forty-six patients (Group 1) never presented liver abnormalities during HD treatment, while 52 patients (Group 2) had either current or prior liver enzyme elevations. Prevalence rates of 32.6% and 41.3% were found for anti-c100/3 and anti-HCV core antibodies, respectively, in patients with silent infections (Group 1). The rate of anti-c100/3 in patients of Group 2 was 71.15% and reached 86.5% for anti-HCV core antibodies. The recognition of anti-c100/3 and anti-core antibodies was significantly higher in Group 2 than in Group 1. A line immunoassay composed of structural and non-structural peptides was used as a confirmation assay. HBV infection, measured by the presence of anti-HBc antibodies, was observed in 39.8% of the patients. Six were HBsAg chronic carriers and 13 had naturally acquired anti-HBs antibodies. The duration of HD treatment was correlated with anti-HCV positivity. A high prevalence of 96.7% (Group 2) was found in patients who underwent more than 5 years of treatment. Our results suggest that anti-HCV core ELISA is more accurate for detecting HCV infection than anti-c100/3. Although the risk associated with the duration of HD treatment and blood transfusion was high, additional factors such as a significant non-transfusional spread of HCV seems to play a role as well. The identification of infective patients by more sensitive methods for HCV genome detection should help to control the transmission of HCV in the unit under study.

  12. Hepatitis B virus screening in contacts of blood donors with antibodies against core protein (anti-HBc, but without surface antigen (HBsAg

    Directory of Open Access Journals (Sweden)

    Hildenete Monteiro Fortes

    2006-03-01

    Full Text Available To increase blood safety Brazil introduced screening for anti-HBc among blood donors in 1993. There was a decrease in the hepatitis B virus (HBV transmission, but this measure identified a great number of HBsAg-negative, anti-HBc-positive donors. Surveillance policy determines that contacts of HBV carriers should be screened to HBV markers, but there is no recommendation about how to guide contacts of HBsAg-negative, anti-HBc-positive donors. Aiming to evaluate whether the contacts of this group are at greater risk for HBV infection, a cross-sectional study was performed to compare prevalence of HBV infection between contacts of HBsAg-positive blood donors (group I and contacts of HBsAg-negative, anti-HBc-positive donors (group II. Contacts were submitted to a questionnaire and blood tests for HBV markers. In group I (n = 143, 53 (37.1% were anti-HBc-positive and 11 (7.7% were HBsAg-positive. In group II (n = 111, there were 9 and 0.9%, respectively. HBV exposure was associated with group I, sexual activity, blood transfusion, being one of the donor's parents, and living for more than ten years with the donor. Regarding the families as sample units, it was more common to find at least one member with HBV markers (p < 0.05 among the families of group I compared to group II. Contacts of HBsAg-negative, anti-HBc-positive individuals presented a much lower risk of having already been exposed to HBV and there is no need to screen them for HBV in low to moderate prevalence populations.

  13. De Novo Superinfection of Hepatitis B Virus in an Anti-HBs Positive Patient with Recurrent Hepatitis C Following Liver Transplantation.

    Science.gov (United States)

    Ha, Sung-Hae; Park, Young-Min; Hong, Sun-Pyo; Back, So-Ya; Shin, Soo-Kyeong; Ji, Seung-Il; Kim, Soo-Ok; Yoo, Wang-Don; Kim, Bo-Hyun; Park, Sang-Jong; Hong, Zheng

    2011-06-01

    A 60-year-old woman with end stage liver cirrhosis caused by genotype 2 hepatitis C virus (HCV) infection received an orthotopic liver transplantation (OLT). The patient was negative for the hepatitis B surface antigen (HBsAg) and positive for the anti-hepatitis B surface antibody (anti-HBs) prior to and one and a half months following the OLT. Due to reactivation of hepatitis C, treatment with interferon-alpha and Ribavirin started two months following the OLT and resulted in a sustained virological response. We performed a liver biopsy because a biochemical response was not achieved. Surprisingly, liver pathology showed HBsAg-positive hepatocytes with a lobular hepatitis feature, which had been negative in the liver biopsy specimen obtained one and a half months post-OLT. High titers of both HBsAg and HBeAg were detected, while anti-HBs antibodies were not found. Tests for IgM anti-hepatitis B core antibody and anti-delta virus antibodies were negative. The serum HBV DNA titer was over 1×10(7) copies/mL. A sequencing analysis showed no mutation in the "a" determinant region, but revealed a mixture of wild and mutant strains at an overlapping region of the S and P genes (S codon 213 (Leu/Ile); P codons 221 (Phe/Tyr) and 222 (Ala/Thr)). These findings suggest that de novo hepatitis B can develop in patients with HCV infection during the post-OLT period despite the presence of protective anti-HBs.

  14. 联合检测丙型肝炎抗体和核心总抗原的临床价值探讨%Clinical value of combined detection of hepatitis C virus antibody and core antigen

    Institute of Scientific and Technical Information of China (English)

    吴建华; 夏先考; 白驹

    2009-01-01

    目的 探讨联合检测丙型肝炎抗体和核心总抗原(HCV-cAg)在临床中的应用价值.方法 用酶联免疫吸附试验(ELISA)法联合检测HCV抗体和HCV-cAg,并与荧光定量PCR法检测丙型肝炎核酸(HCV-RNA)的结果进行对照.结果 157例患者中共检出HCV抗体阳性149例、HCV-cAg阳性99例、HCV-RNA阳性115例;5例HCV抗体阴性而HCV-cAg阳性的患者,经HCV-RNA证实为HCV感染;共检出HCV抗体或HCV-cAg阳性154例,另外3例经HCV-RNA排除HCV感染.结论 联合检测HCV抗体和HCV-cAg提高了HCV感染的检出效率,可有效避免漏检,适合在普通医疗机构推广使用.%Objective To discuss the clinical application value of combined detection of hepatitis C virus antibody and core antigen(HCV-cAg).Methods Serum sample were combined tested for HCV antibody and HCV-cAg by enzyme-linked immnosorbent assy(ELISA)kit,then the results were compared with those detected by fluores-cent quantitation PCR for hepatitis C virus ribonucleic acid(HCV-RNA).Results Among the 157 patients,149 were positive for HCV-Ab,99 positive for HCV-cAg and 115 for HCV-RNA.Respectively:5 patients who were negative for HCV antibody and positive for HCV-cAg were confirmed to be HCV infection by HCV-RNA.154 patients were positive for HCV antibody or HCV-cAg,the other 3 were excluded from HCV infection.Conclusion Combined detection of HCV antibody and HCV-cAS can improve the detection rate of HCV infection,avoid omission effectively,and is suitable for promotion in common medical institutions.

  15. Evaluation of modified ELISA method to detect Hepatitis B surface antigen in saliva specimens%ELISA 检测唾液中乙肝表面抗原方法的优化与评价

    Institute of Scientific and Technical Information of China (English)

    张进

    2012-01-01

      目的优化用于检测唾液中乙肝表面抗原的 ELISA 法,并对其进行评价.方法对 ELISA 的不同条件:样品类型、加样体积和孵育温度及时间进行优化,筛选最佳条件;并采用三种不同的临界值计算方法,判断最佳临界值.结果采用优化后方法,47例血清阳性对应的唾液样品中,44例检测结果为阳性;68例血清阴性对应的唾液样品中,63例检测结果为阴性.血清和唾液样品检测结果的一致性比较高,κ指数为0.87.且该方法的特异度和敏感度分别达到92.6%和93.6%.结论优化后的 ELISA 方法在唾液样品的乙肝表面抗原检测中具有潜在的应用价值.%  Objective To evaluated a modified ELISA method for detecting the Hepatitis B surface antigen (HBsAg) in saliva samples. Meyhods Optimized the different conditions, including sample type, sample volume and incubation condition, to screen the best condition. Three different methods to calculate cut-off value was evaluated to screen the most acceptable. Results HBsAg was detected in 44 saliva samples out of 47 paired positive serum specimens and not detected in 63 saliva samples out of 68 matched negative serum samples by the optimized ELISA assay. There was excelent agreement between the results for the serum and saliva specimens and the kappa value was 0.87 for saliva specimens. Using an optimized protocol, the sensitivities and specificities were 93.6% and 92.6%, respectively. Conclusion Our data showed a significant promise for the use of the modified commercial ELISA in saliva sample for Hepatitis B virus infection surveilance.

  16. 乙型肝炎病毒核心抗原在慢性乙型肝炎病毒感染者肝细胞内的分布及临床意义%The distribution and it's clinical significance of hepatitis B core antigen in hepatocytes of chronic hepatitis B virus in