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Hepatitis B Core Antigen (hepatitis + b_core_antigen)
Selected AbstractsViral safety of a pasteurized, monoclonal antibody-purified factor VIII concentrate in previously untreated haemophilia A patientsHAEMOPHILIA, Issue 2 2001C. S. Philipp The efficacy and viral safety of a pasteurized, immunoaffinity-purified procoagulant factor VIII protein (FVIII:C; Monoclate-P) was studied in two multicentre, prospective, open-label trials in 30 previously untreated patients, 18 with severe (< 1% FVIII:C activity), and 12 with moderate (1% to 5% FVIII:C activity) haemophilia A. Clinical assessments, performed at screening and regularly thereafter for 6 to > 24 months (maximum 34 months), showed that none of 24 assessable patients acquired illnesses consistent with monitored transfusion-transmissible diseases. No patients acquired hepatitis B surface antigen, or antibodies against hepatitis B core antigen, hepatitis C, or human immunodeficiency virus. Likewise, no patients acquired treatment-related hepatitis A antibodies or sustained elevations of alanine aminotransferase levels. The safety profile for Monoclate-P is brought about by a multi-step safety system that incorporates viral inactivation (through a combination of immunoaffinity chromatography and pasteurization) plus donor screening, plasma testing, and quality assurance. The inhibitor development rate (13% low titre, 10% high titre) was similar to that reported in the literature for other FVIII concentrates (24% to 52%). The most frequently reported adverse events were related to typical infant and childhood diseases. Monoclate-P was effective in all patients treated according to protocol, except in two, who developed inhibitors. [source] Targeting TGF-,1 by employing a vaccine ameliorates fibrosis in a mouse model of chronic colitisINFLAMMATORY BOWEL DISEASES, Issue 6 2010Yanbing Ma MSc Abstract Background: Intestinal fibrosis and stricture formation are major complications of inflammatory bowel disease (IBD), for which there are currently few effective treatments. We sought to investigate whether targeting transforming growth factor-beta1 (TGF-,1), a key profibrotic mediator, with a peptide-based virus-like particle vaccine would be effective in suppressing intestinal fibrosis by using a mouse model of 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced chronic colitis. Methods: The vaccine was prepared by inserting a peptide derived from mouse TGF-,1 into a carrier hepatitis B core antigen using gene recombination methods. Chronic colitis was induced in BALB/c mice by 8 weekly TNBS administrations. Mice were subcutaneously injected with vaccine, carrier, or phosphate-buffered saline (PBS) in 2 separate studies: either before or after acute inflammatory responses commenced. Results: Sera from vaccinated mice exhibited significantly elevated levels of TGF-,1-specific immunoglobulin G (IgG), which inhibited TGF-,1-induced luciferase production in mink lung epithelial cells. In the chronic colitis model, mice receiving vaccine showed improved body weight gain and significantly reduced colonic collagen deposition. Hematoxylin and eosin staining and semiquantitative scoring indicated that vaccination even ameliorated colonic inflammation. Cytokine profile analysis revealed that levels of TGF-,1, interleukin (IL)-17, and IL-23 in vaccinated mouse colon tissues were decreased, and that percentages of IL-17-expressing CD4+ lymphocytes in mesenteric lymph node cells were reduced. Furthermore, Smad3 phosphorylation, a key event in TGF-, signaling, was decreased in colonic tissue in vaccinated mice. Conclusions: This TGF-,1 peptide-based vaccine, which suppressed excessive TGF-,1 bioactivity, may prevent the development of intestinal fibrosis and associated complications, presenting a novel approach in the treatment of IBD. (Inflamm Bowel Dis 2010) [source] Occult hepatitis B virus infection and lamivudine-resistant mutations in isolates from renal patients undergoing hemodialysisJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 1 2010Jorge S. Motta Abstract Background and Aims:, Patients undergoing hemodialysis are at risk of infection with both hepatitis B virus (HBV) and hepatitis C virus (HCV). Occult HBV infection is usually associated with low levels of HBV and is frequently detected in HCV-infected patients. The aims of the present study were to compare the prevalence of occult HBV infection among anti-HCV-positive and anti-HCV-negative patients undergoing hemodialysis, and characterize the molecular patterns of HBV isolates from patients with occult infection. Methods:, Serum samples from 100 patients negative for hepatitis B surface antigen undergoing hemodialysis, half of whom were positive for anti-HCV antibodies, were tested for the presence of HBV-DNA using semi-nested polymerase chain reaction (PCR). PCR products of the S gene were directly sequenced. Results:, HBV-DNA was detected in 15 samples. There were no significant differences in HCV status, sex, age, time of dialysis, alanine aminotransferase levels or HBV serological markers between patients with or without occult HBV infection, with the exception of antibody to hepatitis B core antigen (anti-HBc)-only serological marker (P = 0.003). All six HBV isolates that could be sequenced were of genotype A/subgenotype A1. Four of these six HBV isolates contained mutations associated with lamivudine resistance in the DNA polymerase (two with L180M/M204V and two with rt173V/180M/204V) and a specific substitution (Y100C) in the HBV small surface protein. Conclusions:, HBV isolates with the identified substitutions have the potential to spread silently by nosocomial transmission within the hemodialysis unit. These results have potential implications for the management of patients with occult HBV infection undergoing hemodialysis. [source] Population-based study on the seroprevalence of hepatitis A, B, and C virus infection in Amsterdam, 2004,JOURNAL OF MEDICAL VIROLOGY, Issue 12 2007G.G.G. Baaten Abstract In order to enhance screening and preventive strategies, this study investigated the seroprevalence of hepatitis A, B, and C in the general adult urban population and in subgroups. In 2004, sera from 1,364 adult residents of Amsterdam were tested for viral markers. Sociodemographic characteristics were collected using a standardized questionnaire. For hepatitis A, 57.0% was immune. Of first-generation immigrants from Turkey and Morocco, 100% was immune. Of all Western persons and second-generation non-Western immigrants, approximately half was still susceptible. For hepatitis B, 9.9% had antibodies to hepatitis B core antigen (anti-HBc) and 0.4% had hepatitis B surface antigen. Anti-HBc seroprevalences were highest among first-generation immigrants from Surinam, Morocco, and Turkey, and correlated with age at the time of immigration, and among men with a sexual preference for men. Seroprevalence among second-generation immigrants was comparable to Western persons. The seroprevalence of hepatitis C virus antibodies was 0.6%. In conclusion, a country with overall low endemicity for viral hepatitis can show higher endemicity in urban regions, indicating the need for differentiated regional studies and prevention strategies. More prevention efforts in cities like Amsterdam are warranted, particularly for hepatitis A and B among second-generation immigrants, for hepatitis B among men with a sexual preference for men, and for hepatitis C. Active case finding strategies are needed for both hepatitis B and C. J. Med. Virol. 79:1802,1810, 2007. © Wiley-Liss, Inc. [source] Molecular and serological aspects of HBsAg-negative hepatitis B virus infections in North AmericaJOURNAL OF MEDICAL VIROLOGY, Issue 1 2003C.C. Hsia Abstract A few hepatitis B virus (HBV) infections are characterized by the presence of HBV DNA in serum or liver tissue, or both, in the absence of detectable hepatitis B surface antigen (HBsAg) in serum. However, such infections have rarely been described previously in North American patients. In the present study, 31 hepatocellular carcinoma (HCC) patients from the United States and Canada who had no detectable HBsAg in their serum were studied. In these 31 HBsAg-negative HCC patients, HBV DNA was detected in HCC and/or in adjacent nontumorous liver tissue using nested polymerase chain reaction (PCR) in 5/9 (56%) patients from the United States and in 12/22 (55%) from Canada. The 17 HBV DNA-positive/HBsAg-negative patients from the United States and Canada included 9 without any serological markers for HBV and 8 with detectable antibodies to hepatitis B core antigen. In these patients, HBV genotype C was the most prevalent genotype (11/17; 64%). HBV genotypes have not been previously reported in HCC patients from North America. Replicative intermediate forms of HBV (covalently closed circular HBV DNA) were detected in 2/17 (12%) HBV DNA-positive/HBsAg-negative patients, indicating that at least two of these patients had actively replicating HBV infections. The use of tests to detect HBV DNA permitted the identification of HBV infections in HBsAg-negative HCC patients from North America. Among these patients, those with antibody to hepatitis C virus (HCV) would otherwise have been designated "HCV-associated HCCs" based on serological tests alone. These findings provide a new perspective on determining the possible viral etiologies of HCCs in North America. J. Med. Virol. 70: 20,26, 2003. © 2003 Wiley-Liss, Inc. [source] Clinical significance of a highly sensitive enzyme immunoassay of hepatitis B surface antigen using a novel electron spin resonance techniqueJOURNAL OF MEDICAL VIROLOGY, Issue 2 2002Masanori Aoki Abstract We developed a highly sensitive enzyme immunoassay (EIA), the p-AP/HHTIO method, that detects serum hepatitis B surface antigen (HBsAg) by measuring stabilized nitroxide radicals using a novel electron spin resonance technique [Matsuo et al. (1998) Free Radic Biol Med 25:929,935]. To demonstrate the clinical significance of this method and to reveal occult hepatitis B virus (HBV) infection in patients, we used the method to analyze serum samples of 30 patients with acute or fulminant hepatitis who were negative for HBsAg by standard EIA, and those of seven chronic HBV carriers who became negative for HBsAg during a follow-up period by standard EIA. We also examined serum HBV DNA by amplification of the HBV S gene, using the polymerase chain reaction (PCR) technique. The p-AP/HHTIO method showed that 9 of 20 (45%) patients with acute hepatitis and 2 of 10 (20%) with fulminant hepatitis were positive for HBsAg; PCR detected HBV DNA in these HBsAg-positive patients. Antibody against hepatitis B core antigen was detected in one patient with fulminant hepatitis. The p-AP/HHTIO method demonstrated prolonged seropositivity of HBsAg even after standard EIA showed a loss of HBsAg in all seven HBV carriers. Our p-AP/HHTIO method is useful for screening and diagnosing HBV infection in patients with liver diseases who are negative for conventional HBV-related serological markers. J. Med. Virol. 66:166,170, 2002. © 2002 Wiley-Liss, Inc. [source] Occult hepatitis B virus infection: a covert operationJOURNAL OF VIRAL HEPATITIS, Issue 1 2010F. B. Hollinger Summary., Detection of occult hepatitis B requires assays of the highest sensitivity and specificity with a lower limit of detection of less than 10 IU/mL for hepatitis B virus (HBV) DNA and <0.1 ng/mL for hepatitis B surface antigen (HBsAg). This covert condition is relatively common in patients with chronic hepatitis C virus (HCV) that seems to exert some influence on the replicative capacity and latency of HBV. Detection of virus-specific nucleic acid does not always translate into infectivity, and the occurrence of primer-generated HBV DNA that is of partial genomic length in immunocompetent individuals who have significant levels of hepatitis B surface antibody (anti-HBs) may not be biologically relevant. Acute flares of alanine aminotransferase (ALT) that occur during the early phase of therapy for HCV or ALT levels that remain elevated at the end of therapy in biochemical nonresponders should prompt an assessment for occult hepatitis B. Similarly, the plasma from patients with chronic hepatitis C that is hepatitis B core antibody (anti-HBc) positive (±anti-HBs at levels of <100 mIU/mL) should be examined for HBV DNA with the most sensitive assay available. If a liver biopsy is available, immunostaining for hepatitis B surface antigen (HBsAg) and hepatitis B core antigen (HBcAg) should be contemplated and a portion of the sample tested for HBV DNA. This is another reason for optimal collection of a specimen (e.g. two passes with a 16-guage needle under ultrasound guidance). Transmission of HBV to immunosuppressed orthotopic liver transplant recipients by donors with occult hepatitis B (OHB) will continue to occupy the interests of the transplant hepatologist. As patients with OHB may have detectable HBV DNA in serum, peripheral blood mononuclear cells (PBMC) and/or liver that can be reactivated following immunosuppression or intensive cytotoxic chemotherapy, the patient needs to be either monitored or treated depending on the pretreatment serological results such as an isolated anti-HBc reaction or a detectable HBV DNA. [source] The correlation of hepatocyte nuclear factor 4 alpha and 3 beta with hepatitis B virus replication in the liver of chronic hepatitis B patientsJOURNAL OF VIRAL HEPATITIS, Issue 8 2009Y. Long Summary., Hepatocyte nuclear factors 4 alpha (HNF4,) and 3 beta (HNF3,) are members of a group of liver-enriched transcription factors (LETFs) that play important roles in regulating the replication of hepatitis B virus (HBV). Using cell culture and animal models, we showed that HNF4, supports HBV replication in nonhepatic cells and HNF3, inhibits HBV replication. However, the expression of HNF4, and HNF3, in the liver tissue of chronic HBV-infected patients and the relationship between the levels of HNF4, and HNF3, and HBV replication are unclear. In this study, liver biopsy specimens from 86 chronic HBV-infected patients were collected. The expression levels of HNF4,, HNF3,, hepatitis B surface antigen (HBsAg) and hepatitis B core antigen (HBcAg) were detected by an immunohistochemical technique and the level of HBV DNA was checked by in situ hybridization with serial sections from liver biopsy tissue samples. We show here that samples with higher levels of HNF4, expression also have higher levels of HBsAg, HBcAg and HBV DNA. In contrast, in samples with higher levels of HNF3, expression, levels of HBsAg, HBcAg and HBV DNA were lower. There was a positive correlation between HNF4, expression and HBV replication, and a negative correlation between HNF3, expression and HBV replication, in the liver of chronic HBV-infected patients. This suggests that HNF4, and HNF3, likely participate in HBV replication in patients with HBV infection, or that HBV replication may somehow influence the expression of HNF4, and HNF3, in the liver. [source] Survival after orthotopic liver transplantation: The impact of antibody against hepatitis B core antigen in the donor,,§LIVER TRANSPLANTATION, Issue 10 2009Lei Yu Liver transplantation using grafts from donors with antibody against hepatitis B core antigen (anti-HBc) increases the recipients' risk of developing hepatitis B virus (HBV) infection post-transplantation. Our aim was to assess whether using such grafts was associated with reduced posttransplantation survival and whether this association depended on recipients' prior exposure to HBV on the basis of their pretransplantation serological patterns. Data were derived from the United Network for Organ Sharing on adult, cadaveric, first-time liver transplants performed between 1994 and 2006. Among recipients who did not have HBV infection before transplantation, those with anti-HBc,positive donors had significantly worse unadjusted posttransplantation patient survival than recipients with anti-HBc,negative donors [hazard ratio, 1.35; 95% confidence interval (CI), 1.21-1.50]. However, after adjustments for other predictors of posttransplantation survival, including donor age, donor race, and recipient underlying liver diseases, patient survival was not significantly different between the 2 groups (hazard ratio, 1.09; 95% CI, 0.97-1.24). Among recipients without antibody against hepatitis B surface antigen (anti-HBs), use of anti-HBc,positive donor grafts was associated with a trend toward worse survival (adjusted hazard ratio, 1.18; 95% CI, 0.95-1.46), whereas no such trend was observed among recipients positive for anti-HBs. In conclusion, in patients without HBV infection before transplantation, using anti-HBc,positive donors was not independently associated with worse posttransplantation survival. Matching these donors to recipients with anti-HBs pre-transplantation may be especially safe. Liver Transpl 15:1343,1350, 2009. © 2009 AASLD. [source] Histologic findings in recurrent HBVLIVER TRANSPLANTATION, Issue S2 2006Swan N. Thung Key Concepts: 1The histopathologic presentation of hepatitis B (HB) infection in liver allografts is generally similar to that seen in the nonallografts. 2An atypical pattern of recurrent HB, i.e., fibrosing cholestatic hepatitis (FCH) occurs in a small number of patients. These patients present with a severe cholestatic syndrome, which may clinically resemble acute or chronic rejection. 3There are several other possible causes of acute and chronic hepatitis in liver allografts that may need to be considered. 4Hepatitis B virus (HBV) infection in the liver allograft can easily be confirmed by performing immunohistochemical stains for hepatitis B surface antigen (HBsAg) and hepatitis B core antigen (HBcAg). The expression pattern of these HBV antigens varies and is sometimes helpful in determining whether the liver injury is mainly from the HBV or from other causes in coexistence with the HBV infection. 5Histological grading of the necroinflammatory activity and staging of the fibrosis should only be applied when the changes are related to the recurrent HB. 6The pathology of liver transplantation is complex; therefore, clinical correlations remain extremely important in arriving at the final and correct diagnosis. Liver Transpl 12:S50,S53, 2006. © 2006 AASLD. [source] Vaccination against hepatitis B virus in cirrhotic patients on liver transplant waiting listLIVER TRANSPLANTATION, Issue 4 2000Mercedes Domínguez Patients with cirrhosis may fail to respond to anti,hepatitis B vaccine. An adequate response would be especially interesting when patients are on a liver transplant waiting list. Posttransplantation de novo hepatitis B has been well documented. One possible source is the grafting of organs from hepatitis B surface antigen (HBsAg),negative, antibody to HBsAg (anti-HBs),positive, antibody to hepatitis B core antigen,positive donors. The achievement of high titers of anti-HBs could be protective in this setting. We studied prospectively the response rate to recombinant hepatitis B vaccine (3 40-,g doses administered at 0, 1, and 2 months) in 62 patients with end-stage liver disease awaiting liver transplantation. Twenty-two patients showed antibody response (44%). A further 3 doses were administered in 15 of 28 nonresponders and were effective in 9 patients. Thus, the response rate reached 62% (31 of 50 patients completing 1 or 2 vaccination schedules before liver transplantation). Classic hepatitis B vaccination studies of patients with cirrhosis yield lower response rates. Vaccination with this double-dose schedule should be considered in such patients before liver transplantation. [source] A DNA replicon system for rapid high-level production of virus-like particles in plantsBIOTECHNOLOGY & BIOENGINEERING, Issue 4 2009Zhong Huang Abstract Recombinant virus-like particles (VLPs) represent a safe and effective vaccine strategy. We previously described a stable transgenic plant system for inexpensive production and oral delivery of VLP vaccines. However, the relatively low-level antigen accumulation and long-time frame to produce transgenic plants are the two major roadblocks in the practical development of plant-based VLP production. In this article, we describe the optimization of geminivirus-derived DNA replicon vectors for rapid, high-yield plant-based production of VLPs. Co-delivery of bean yellow dwarf virus (BeYDV)-derived vector and Rep/RepA-supplying vector by agroinfiltration of Nicotiana benthamiana leaves resulted in efficient replicon amplification and robust protein production within 5 days. Co-expression of the P19 protein of tomato bush stunt virus, a gene silencing inhibitor, further enhanced VLP accumulation by stabilizing the mRNA. With this system, hepatitis B core antigen (HBc) and Norwalk virus capsid protein (NVCP) were produced at 0.80 and 0.34 mg/g leaf fresh weight, respectively. Sedimentation analysis and electron microscopy of transiently expressed antigens verified the efficient assembly of VLPs. Furthermore, a single replicon vector containing a built-in Rep/RepA cassette without P19 drove protein expression at similar levels as the three-component system. These results demonstrate the advantages of fast and high-level production of VLP-based vaccines using the BeYDV-derived DNA replicon system for transient expression in plants. Biotechnol. Bioeng. 2009;103: 706,714. © 2009 Wiley Periodicals, Inc. [source] | |||||||||||||