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Query: UMLS:C0019163 (hepatitis B)
 38,309 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A new hepatitis B vaccine (FENDrix, GlaxoSmithKline Biologicals) containing as active substance 20 microg of recombinant hepatitis B virus surface antigen produced in Saccharomyces cerevisiae has recently been licensed in Europe. It is prepared with a novel adjuvant system: aluminum phosphate and 3-O-desacyl-4 -monophosphoryl lipid A. It is intended for use in adults from the age of 15 years onwards for active immunization against hepatitis B virus infection for patients with renal insufficiency (including prehemodialysis and hemodialysis patients). It is applied in a four-dose scheme: day 0, month 1, 2 and 6 after day 0. Due to the improved adjuvant system it induces higher antibody concentrations that reach protective levels in a faster fashion. Furthermore, due to higher titers reached after the primary immunization course, protective levels are retained for a longer period of time. Vaccination with FENDrix induces more transient local symptoms, with pain at the injection site being the most frequently reported solicited local symptom. Other symptoms such as fatigue, gastrointestinal disorders and headaches were also frequently observed but resolved without sequelae. The higher risk of hepatitis B transmission in patients with end-stage renal disease and the often immunocompromised status of these patients afford a tailored vaccination strategy that, up to now, has consisted of injecting double doses of ordinary hepatitis B vaccines. With the introduction of FENDrix there now exists an efficient alternative with superior immunogenicity that is, despite comparatively higher reactogenicity, well tolerated.
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PMID:New hepatitis B vaccine formulated with an improved adjuvant system. 1740 63

Woodchuck hepatitis virus (WHV)-infected woodchucks have been used for preclinical development of drugs against hepatitis B virus (HBV). However, there is no simple in vivo model to evaluate small amounts of compounds against HBV. To develop such a model, HepAD38 cells, in which HBV replication is regulated by tetracycline (tet), were grown as subcutaneous tumours in nude mice. Mice developing viraemia were then left untreated or given tet in the drinking water. In some of the mice given tet, it was removed and the mice were injected intraperitoneally with phosphate buffer saline (PBS), lamivudine (3TC), clevudine (CLV) or tenofovir dipivoxil fumarate (TDF). Virus DNA titres were measured by real-time PCR during and after drug treatment. In water-fed and PBS-injected mice, virus titres reached approximately 10(9) copies/ml serum within 35 days of HepAD38 injection, whereas in tet-treated mice, virus titres remained at 10(4)-10(5) copies/ml. HBV DNA levels were suppressed by 3TC, TDF and CLV, with the latter two drugs showing more sustained virus suppression compared with 3TC. Combination therapy with CLV plus TDF was much more effective than either drug alone in suppressing virus titre for at least 3 weeks after the end of treatment. There was no demonstrable toxicity to HepAD38 cells in drug-treated mice. Hence, a robust tet-controlled system for HBV replication in vivo was demonstrated, validated with monotherapies against HBV and shown to be useful in assessing combination therapy. This system will be useful for preclinical assessment of small amounts of single or multiple compounds against HBV in vivo.
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PMID:Development of a novel mouse model to evaluate drug candidates against hepatitis B virus. 1790 79

In addition to conventional vaccination, DNA-mediated immunization has been developed as an alternative approach in the prevention and treatment of different infectious diseases, including hepatitis B. To define sets of serum protein and metabolite biomarkers that could be employed to determine the efficacy and safety of DNA vaccines, an integrated multiple systems biology approach was undertaken on mice immunized with DNA vaccine, recombinant protein, plasmid vector, and phosphate-buffered solution. Their sera were analyzed by two-dimensional electrophoresis and HPLC coupled with time-of-flight mass spectrometry. We detected an increase in phytosphingosine, dihydrosphingosine, palmitoylcarnitine, and ceramide in the sera of DNA-vaccinated mice. Several protein molecules were found to be altered in DNA-vaccinated mice, including apolipoprotein A-I precursor. Taken together, these results indicated that DNA vaccine stimulated hepatic sphingolipid synthesis, which may have altered the structure of circulating lipoproteins and promoted atherogenesis. This study also underscores the power of metabolomics and proteomics in the definition of DNA-vaccine-mediated metabolic phenotypes.
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PMID:DNA immunization perturbs lipid metabolites and increases risk of atherogenesis. 1816 9

Hepatocellular carcinoma (HCC) occurring in a 66-year-old male patient with early stage primary biliary cirrhosis (PBC) was successfully treated by radiofrequency ablation (RFA) therapy. He was diagnosed with PBC based on the findings of pruritus, elevated serum alkaline phosphate level and positive serum antimitochondrial antibody in 2005. The serologic tests for hepatitis B surface antigen, hepatitis B surface antibody and hepatitis C virus antibody were all negative. But antibody against hepatitis B core antigen was positive. Abdominal ultrasonography and dynamic computed tomography revealed 1 hypervascular tumor, 2.6 cm in diameter, in segment V of the liver in 2007. Liver biopsy showed a moderately differentiated HCC. Non-tumorous liver was compatible with Scheuer's classification of stage II PBC. The tumor was successfully treated by RFA. This case report demonstrates that HCC can arise from precirrhotic PBC and can be successfully treated by RFA. Regular surveillance for HCC is warranted for all patients with PBC, irrespective of stage.
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PMID:Successful radiofrequency ablation therapy for hepatocellular carcinoma in a male patient with early stage primary biliary cirrhosis and positive serum hepatitis B core antibody. 1821 59

Vaccination with diphtheria-tetanus-acellular pertussis (DTPa)-Haemophilus influenzae type b (Hib) combinations generally elicits anti-polyribosyl-ribitol-phosphate (PRP) antibody concentrations of more than 0.15 microg/ml, a criterion that is linked to the protection of infants against Hib disease. In the UK, vaccination with DTPa3-Hib elicited atypically low anti-PRP antibody levels and was associated with breakthrough Hib cases. While the absence of a toddler booster is considered to be a key factor explaining the lowered control of Hib disease, we propose that the coadministration of serogroup C Neisseria meningitidis conjugate vaccine (MenC)-CRM197, which coincided with the introduction of DTPa3-Hib in the UK, may have played a role. However, other data suggest that the response to Hib after DTPa(HBV) inactivated polio vaccine (IPV)-Hib combinations is not affected by the coadministration of CRM197, which we postulate to be attributed to the presence of IPV. These observations underline the need to carefully evaluate upcoming pediatric conjugate vaccines for possible interference effects on the coadministered antigens, with particular attention to hepatitis B and Hib-tetanus toxoid.
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PMID:Combination vaccines containing DTPa-Hib: impact of IPV and coadministration of CRM197 conjugates. 1825 97

The response to booster vaccination at 15-18 months of age and the presence of immune memory in 10-month old children, primed with a new combined diphtheria-tetanus-hepatitis B-whole cell pertussis vaccine extemporaneously mixed with Haemophilus influenzae type b-tetanus toxoid conjugate (DTPw-HBV/Hib) from new antigen sources and containing 2.5 microg polyribosyl-ribitol-phosphate (PRP) was assessed. Primary vaccination with the new DTPw-HBV/Hib vaccine was immunogenic and of comparable tolerability to commercially available Tritanrix HepB/Hiberix. Children were boosted with DTPw-HBV, DTPw-HBV/Hib or separate DTPw-HBV+Hiberix. Immune memory was assessed through administration of 10 microg PRP polysaccharide. Anti-PRP antibody GMCs increased substantially after the challenge in DTPw-HBV/Hib-primed subjects indicating the presence of immune memory. One month after the booster dose, 100% of subjects had seroprotective antibody concentrations against PRP, diphtheria and tetanus, >95% were seroprotected against hepatitis B, > or =94.0% had a pertussis booster response. Substantial increases in antibody GMCs against all antigens were observed. Swelling >20 mm was the most common Grade 3 solicited symptom reported (up to 26.0% of subjects). Fever >39.5 degrees C was uncommon (>2.5%). Eleven large swelling reactions were reported; none involved an adjacent joint. One serious adverse event occurred that was considered unrelated to vaccination. This new DTPw-HBV/Hib vaccine with new vaccine components and 2.5 microg PRP induced effective priming against Hib evidenced by a vigorous anamnestic response on exposure to PRP polysaccharide. The booster dose was immunogenic and the safety profile was acceptable. Combined DTPw-HBV and DTPw-HBV/Hib vaccines using new vaccine antigen sources will promote continued supply of combined DTPw-based vaccines to global mass vaccination campaigns.
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PMID:A new DTPw-HBV/Hib vaccine: immune memory after primary vaccination and booster dosing in the second year of life. 1837 48

In recent years, several six-membered ring phosph(on)ates and phosphonamides have been reported as potent prodrugs against liver diseases such as hepatitis B and C and also as antitumor agents. Apparently, the success for their biological activity depends on the selective cleavage of the C4-O3 bond within the respective P-heterocyclic ring. Empirical observations have suggested that the group attached to the C4 position (aryl or pyridyl group) is responsible for the selective cleavage. In this regard, we show in the present work that the configuration at the P-atom, the conformation of the P-heterocyclic ring, and particularly, the anomeric effect are involved in the spontaneous and selective cleavage of the C4-O3 bond in cyclic phosph(on)ates. We arrived at this assumption based on the conformational and configurational study of simple model phosphates and phosphonates, where it was observed that the spontaneous conversion of unstable six-membered ring phosphates to their most stable six-membered ring phosphate (4d, 6d and 7d to 5d), by a selective C4-O3 bond cleavage, depends on both: the stereochemistry of the aryl group at C4 and the electronic nature of the substituent attached to the P-atom. Thus, we postulated that the anomeric effect weakens the C4-O3 bond within the 1,3,2-dioxaphosphorinane ring, favoring thus their selective cleavage and spontaneous conversion, similarly to the proposed mechanistic mode of action of six-membered ring P-heterocyclic prodrugs.
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PMID:Six-membered ring phosphates and phosphonates as model compounds for cyclic phosphate prodrugs: is the anomeric effect involved in the selective and spontaneous cleavage of cyclic phosphate prodrugs? 1905 87

Hepatitis B surface antigen (HBsAg) is known to adsorb to aluminum hydroxide adjuvant (AH) by ligand exchange between its accessible phosphate groups and surface hydroxyl groups of the adjuvant. To study the effect of the binding strength, five vaccines were prepared with AH or four samples of AH that were modified by pretreatment with different concentrations of potassium dihydrogen phosphate. The adsorptive coefficients ranged from 3660 to 250mL/mg based on the Langmuir adsorption isotherm and degrees of elution ranged from 1 to 31% when the vaccines were exposed to interstitial fluid in vitro. When tested in mice the four vaccines containing phosphate-treated AH (PTAH) induced significantly greater antibody responses than the vaccine containing AH, which had the highest adsorptive coefficient and the smallest degree of elution of HBsAg. The results indicated that antibody production is reduced when the antigen is adsorbed too strongly. Thus, the strength of adsorption of the antigen to an aluminum-containing adjuvant can affect the immunogenicity of the vaccine and should be optimized during vaccine formulation.
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PMID:Effect of the strength of adsorption of hepatitis B surface antigen to aluminum hydroxide adjuvant on the immune response. 1907 Nov 82

Combination vaccines improve parental and provider satisfaction and schedule compliance by decreasing the number of injections. In a Phase 2, randomized, double-blind, multicenter study, we compared four formulations of a liquid, hexavalent diphtheria-tetanus-acellular pertussis-inactivated poliovirus-Haemophilus influenzae b conjugate-hepatitis B virus (DTaP-IPV-Hib-HBV) vaccine in 708 infants immunized at 2, 3, 4, and 12-14 months of age. The formulations contained identical DTaP and IPV components, differing in the contents of Hib polyribosylribitol phosphate (PRP) conjugate component (tetanus-toxoid [PRP-T, 12microg] or Neisseria meningitidis outer-membrane-protein-complex [PRP-OMPC, 3microg or 6microg]), and in hepatitis B surface antigen (HBsAg, 10microg or 15microg). A minimum acceptable postdose 3 antibody response rate was defined by the lower limit of the 95% confidence interval exceeding a prespecified target. Rates of adverse events (AEs) were similar among groups, with a trend for increased solicited injection-site reactions (pain, redness, swelling) with increasing PRP-OMPC and HBsAg concentration. Serious AEs reported by eight subjects were not considered to be vaccine related. All PRP-OMPC formulations met prespecified acceptability criteria for postdose 3 immunogenicity for all antigens: PRP, HBsAg, pertussis, diphtheria, tetanus and polio. Apart from the Hib response, the postdose 3 responses obtained with the PRP-T formulation met the acceptability criterion for each antigen. Postdose 4 responses were acceptable for all antigens in all formulations. All vaccine formulations were well tolerated. The three PRP-OMPC formulations met prespecified immunogenicity criteria, and the one with the lowest PRP-OMPC concentration was selected for further optimization of immunogenicity.
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PMID:Safety and immunogenicity of a hexavalent diphtheria-tetanus-acellular pertussis-inactivated poliovirus-Haemophilus influenzae b conjugate-hepatitis B vaccine at 2, 3, 4, and 12-14 months of age. 1912 57

The association of viral hepatitis and acute pancreatitis is well described in the literature. Most of the cases occur in conjunction with fulminant hepatitis A and hepatitis B virus infections. The recent literature reports increasing number of cases of this complication secondary to hepatitis E virus (HEV) infection, mostly in young adults in regions endemic for the virus. Till date, to the authors' knowledge, there are 14 well-documented cases of HEV-associated acute pancreatitis in the literature. This study reports on a 7-year-old boy from India deficient in glucose 6 phosphate dehydrogenase (G6PD) with moderately severe pancreatitis, manifesting during the course of nonfulminant acute HEV infection. He developed extremely high serum bilirubin levels, probably attributed to the concomitant viral infection and his G6PD status. He recovered completely with conservative therapy. The present child is the youngest ever reported case till date with this complication secondary to HEV infection.
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PMID:Acute pancreatitis--complicating hepatitis E virus infection in a 7-year-old boy with glucose 6 phosphate dehydrogenase deficiency. 1912 25


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