scholarly journals Antiviral l-Nucleosides Specific for Hepatitis B Virus Infection

2001 ◽  
Vol 45 (1) ◽  
pp. 229-235 ◽  
Author(s):  
Martin L. Bryant ◽  
Edward G. Bridges ◽  
Laurent Placidi ◽  
Abdesslem Faraj ◽  
Anna-Giulia Loi ◽  
...  
Keyword(s):  
Viral Load ◽  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Hepatitis Virus ◽  
Hbv Infection ◽  
Virus Surface ◽  
Chronic Hbv Infection ◽  
Hbv Replication ◽  
B Virus ◽  
Chronic Hbv

ABSTRACT A unique series of simple “unnatural” nucleosides has been discovered to inhibit hepatitis B virus (HBV) replication. Through structure-activity analysis it was found that the 3′-OH group of the β-l-2′-deoxyribose of the β-l-2′-deoxynucleoside confers specific antihepadnavirus activity. The unsubstituted nucleosides β-l-2′-deoxycytidine, β-l-thymidine, and β-l-2′-deoxyadenosine had the most potent, selective, and specific antiviral activity against HBV replication. Human DNA polymerases (α, β, and γ) and mitochondrial function were not affected. In the woodchuck model of chronic HBV infection, viral load was reduced by as much as 108 genome equivalents/ml of serum and there was no drug-related toxicity. In addition, the decline in woodchuck hepatitis virus surface antigen paralleled the decrease in viral load. These investigational drugs, used alone or in combination, are expected to offer new therapeutic options for patients with chronic HBV infection.

scholarly journals The Enhancer I Core Region Contributes to the Replication Level of Hepatitis B Virus In Vivo and In Vitro

2000 ◽  
Vol 74 (5) ◽  
pp. 2193-2202 ◽  
Author(s):  
C.-Thomas Bock ◽  
Nisar P. Malek ◽  
Hans L. Tillmann ◽  
Michael P. Manns ◽  
Christian Trautwein
Keyword(s):  
Liver Transplantation ◽  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Transcriptional Activity ◽  
Hbv Infection ◽  
Chronic Hbv Infection ◽  
Hbv Replication ◽  
B Virus ◽  
Mutant Strains ◽  
Chronic Hbv

ABSTRACT Chronic hepatitis B virus (HBV) infection can lead to liver cirrhosis and hepatocellular carcinoma. Long-term interaction of the immune system with the virus results in the selection of escape mutants and viral persistence. In this work we characterize mutations in the enhancer I region isolated prior to liver transplantation from the HBV genomes of 10 patients with chronic HBV infection. The HBV-genomes were sequenced, and the enhancer I region was cloned into luciferase reporter constructs to determine the transcriptional activity. Functional studies were performed by transfecting HBV replication-competent plasmids into hepatoma cells. Analyses of the replication fitness of the mutant strains were conducted by biochemical analysis. In all HBV genomes the enhancer I region was mutated. Most of these mutations resulted in decreased transcriptional activity. The strongest effects were detectable in strains with mutations in the hepatocyte nuclear factor 3 and 4 (HNF3 and HNF4) binding sites of the enhancer I core domain. Replication-competent HBV constructs containing these mutations demonstrated up to 10-fold-reduced levels of virus replication. Before liver transplantation, when the mutant strains were detected in the patients' sera, low HBV DNA levels were found. After transplantation and reinfection with a wild-type virus, the levels of replication were up to 240-fold higher. Our results show that mutations in the enhancer I region of HBV have a major impact on HBV replication. These mutations may also determine the switch from high to low levels of viral replication which is frequently observed during chronic HBV infection.

scholarly journals Partially Randomized, Non-Blinded Trial of DNA and MVA Therapeutic Vaccines Based on Hepatitis B Virus Surface Protein for Chronic HBV Infection

PLoS ONE ◽  
2011 ◽  
Vol 6 (2) ◽  
pp. e14626 ◽  
Author(s):  
James S. Cavenaugh ◽  
Dorka Awi ◽  
Maimuna Mendy ◽  
Adrian V. S. Hill ◽  
Hilton Whittle ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Surface Protein ◽  
Hbv Infection ◽  
Therapeutic Vaccines ◽  
Virus Surface ◽  
Chronic Hbv Infection ◽  
B Virus ◽  
Chronic Hbv ◽  
Blinded Trial

scholarly journals Hepatitis B Virus Infection in Pregnancy: Immunological Response, Natural Course and Pregnancy Outcomes

2021 ◽  
Vol 10 (13) ◽  
pp. 2926
Author(s):  
Sirinart Sirilert ◽  
Theera Tongsong
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Pregnancy Outcomes ◽  
Natural Course ◽  
Hbv Infection ◽  
Chronic Hbv Infection ◽  
B Virus ◽  
Chronic Hbv ◽  
Adverse Pregnancy ◽  
The Impact

This review aimed to provide an update on the impact of pregnancy on the natural course of hepatitis B virus (HBV) infection and also on the impact of HBV infection on adverse pregnancy outcomes, including mother-to-child transmission (MTCT). For the literature review, original research articles, review articles, and guidelines were narratively reviewed and comprehensively validated. The databases of PubMed, EMBASE, and CINAHL were carefully searched for articles in English on topics related to HBV infection, pregnancy, and vertical transmission from 1960 to May 2021. Immunological changes during pregnancy such as suppression of Th1 response and induction of Th2 immunity lead to an impaired immune reaction to HBV and stimulate viral activity along with the reduction of CD8 T cells to escape immune detection. The impact of pregnancy on the natural course of chronic HBV infection seems to be minimal, while pregnancy can increase morbidity and mortality in the case of advanced HBV hepatitis or cirrhosis. Importantly, hepatitis flare or alanine aminotransferase (ALT) flare can occur during pregnancy and is more common during the postpartum period due to the interaction between HBV and the immune response. Interestingly, the impact of HBV infection on adverse pregnancy outcomes is more serious than ever thought. Updated evidence indicates that pregnancies with chronic HBV infection increase the risk of preterm birth and gestational diabetes, especially in cases of positive hepatitis e antigen (HBeAg).

scholarly journals G‐to‐A Hypermutation in Hepatitis B Virus (HBV) and Clinical Course of Patients with Chronic HBV Infection

2009 ◽  
Vol 199 (11) ◽  
pp. 1599-1607 ◽  
Author(s):  
Chiemi Noguchi ◽  
Michio Imamura ◽  
Masataka Tsuge ◽  
Nobuhiko Hiraga ◽  
Nami Mori ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Clinical Course ◽  
Hbv Infection ◽  
Chronic Hbv Infection ◽  
B Virus ◽  
Chronic Hbv

A Method to Detect Hepatitis B Virus-specific Cytotoxic T Lymphocytes in Patients with Acute and Chronic HBV Infection

1994 ◽  
pp. 168-172
Author(s):  
Geert Leroux-Roels ◽  
Els Van Hecke ◽  
Jozef Paradijs ◽  
Chantal Molitor ◽  
Carine Bastin ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
T Lymphocytes ◽  
Hepatitis B ◽  
Cytotoxic T Lymphocytes ◽  
Hbv Infection ◽  
Chronic Hbv Infection ◽  
B Virus ◽  
Chronic Hbv

scholarly journals Association of STAT3 and STAT4 polymorphisms with susceptibility to chronic hepatitis B virus infection and risk of hepatocellular carcinoma: a meta-analysis

2019 ◽  
Vol 39 (6) ◽  
Author(s):  
Han Shi ◽  
Hongyan He ◽  
Suvash Chandra Ojha ◽  
Changfeng Sun ◽  
Juan Fu ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Chronic Hepatitis ◽  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Chronic Hepatitis B ◽  
Meta Analysis ◽  
Hbv Infection ◽  
Chronic Hbv Infection ◽  
B Virus ◽  
Chronic Hbv

Abstract Background: It has been reported that polymorphisms of signal transducer and activator of transcription (STAT) 3 and STAT4 might be associated with susceptibility to hepatitis B virus (HBV) infection and risk of chronic hepatocellular carcinoma (HCC). Owing to limitation of sample size and inconclusive results, we conducted a meta-analysis to clarify the association. Methods: We identified relevant studies by a systematic search of Medline/PubMed, Embase, Web of Science and the Cochrane Library up to 20 February 2019. The strength of the association measured by odds ratios (OR) with 95% confidence intervals (CIs) was studied. All the statistical analyses were conducted based on Review Manager 5.3 software. Results: A total of 5242 cases and 2717 controls from five studies were included for the STAT3 polymorphism, 5902 cases and 7867 controls from nine studies for the STAT4 polymorphism. Our results suggested that STAT3 rs1053004 polymorphism was a significant risk factor of chronic HBV infection (C vs. T: OR = 1.17, 95% CI: 1.07–1.29, PA=0.0007; CC + CT vs. TT: OR = 1.38, 95% CI: 1.09–1.76, PA=0.008). Validation with all the genetic models revealed that rs7574865 polymorphism of STAT4 gene was closely associated with chronic HBV infection (PA<0.01) and chronic hepatitis B (CHB)-related HCC (PA<0.05). Meanwhile, the authenticity of the above meta-analysis results was confirmed by trial sequential analysis (TSA). Conclusions: The meta-analysis showed that STAT3 rs1053004 polymorphism may be the risk for developing chronic HBV infection but not associated with HCC. The present study also indicates that STAT4 rs7574865 polymorphism increased the risk of chronic HBV infection and HCC.

Comparison of Envelope and Precore/Core Variants of Hepatitis B Virus (HBV) during Chronic HBV Infection

Virology ◽  
1993 ◽  
Vol 196 (1) ◽  
pp. 138-145 ◽  
Author(s):  
Masahiro Takayanagi ◽  
Shinichi Kakumu ◽  
Tetsuya Ishikawa ◽  
Yasuyuki Higashi ◽  
Kentaro Yoshioka ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Hbv Infection ◽  
Chronic Hbv Infection ◽  
B Virus ◽  
Chronic Hbv

scholarly journals Soluble immune markers in the different phases of chronic hepatitis B virus infection

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Steffen B. Wiegand ◽  
Bastian Beggel ◽  
Anika Wranke ◽  
Elmira Aliabadi ◽  
Jerzy Jaroszewicz ◽  
...  
Keyword(s):  
Chronic Hepatitis ◽  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Hbeag Seroconversion ◽  
Hbv Infection ◽  
Immune Markers ◽  
Chronic Hbv Infection ◽  
Chronic Hepatitis B Virus ◽  
B Virus ◽  
Chronic Hbv

Abstract Chronic hepatitis B virus (HBV) infection may follow four different consecutive phases, which are defined by virology as well as biochemical markers and differ in terms of prognosis and need for antiviral treatment. Currently, host responses reflected by immune markers are not considered in this definition. We aimed to study soluble immune markers and their distribution in different phases of chronic HBV infection. In this cross-sectional retrospective study, we investigated a panel of 14 soluble immune markers (SIM) including CXCL10 in 333 patients with chronic HBV infection. In a small cohort of HBeAg positive patients we analyzed SIM before and after HBeAg seroconversion and compared seroconverters to patients with unknown outcome. Significant differences were documented in the levels of several SIM between the four phases of chronic HBV infection. The most pronounced difference among all investigated SIM was observed for CXCL10 concentrations with highest levels in patients with hepatitis. TGF-β and IL-17 revealed different levels between HBeAg negative patients. HBeAg positive patients with HBeAg seroconversion presented higher amounts of IL-12 before seroconversion compared to HBeAg positive patients with unknown follow up. SIM such as CXCL10 but also IL-12, TGF-β and IL-17 may be useful markers to further characterize the phase of chronic HBV infection.

scholarly journals Chronic hepatitis B virus infection and total and cause-specific mortality: a prospective cohort study of 0.5 million people

BMJ Open ◽  
2019 ◽  
Vol 9 (4) ◽  
pp. e027696 ◽  
Author(s):  
Jiahui Si ◽  
Canqing Yu ◽  
Yu Guo ◽  
Zheng Bian ◽  
Ruogu Meng ◽  
...  
Keyword(s):  
Chronic Hepatitis ◽  
Cohort Study ◽  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Hbv Infection ◽  
Chronic Hbv Infection ◽  
Chronic Hepatitis B Virus ◽  
B Virus ◽  
Specific Mortality ◽  
Chronic Hbv

ObjectivesChronic hepatitis B virus (HBV) infection is associated with a higher risk of liver diseases. Substantial uncertainty remains, however, about the associations of HBV infection with mortality from extrahepatic causes, especially from subtypes of cardiovascular diseases. We prospectively examined the association of chronic HBV infection with total and cause-specific mortality.DesignPopulation-based prospective cohort study.SettingChina Kadoorie Biobank in which participants from 10 geographically diverse areas across China were enrolled between 2004 and 2008.Participants475 801 participants 30–79 years of age without reporting major chronic diseases at baseline were enrolled. Hepatitis B surface antigen (HBsAg) was tested using an on-site rapid test strip at baseline.Primary and secondary outcome measuresTotal and cause-specific mortality.ResultsA total of 35 822 deaths were recorded during ~10 years of follow-up. In multivariable-adjusted analyses, compared with HBsAg-negative participants, HBsAg-positive participants had an increased risk of total mortality (HR=2.01, 95% CI: 1.91 to 2.12), which was higher in men (HR=2.16, 95% CI: 2.01 to 2.31) than in women (HR=1.74, 95% CI: 1.60 to 1.90). Presence of HBsAg was associated with increased mortality from liver cancer (1339 deaths, HR=13.95, 95% CI: 12.46 to 15.62), infections (410 deaths, HR=10.30, 95% CI: 8.21 to 12.94), digestive diseases (688 deaths, HR=6.83, 95% CI: 5.49 to 8.50), intracerebral haemorrhage (4077 deaths, HR=1.38, 95% CI: 1.14 to 1.68) and ischaemic heart diseases (4624 deaths, HR=1.31, 95% CI: 1.09 to 1.58). The positive association between HBsAg status and risk of death was stronger in participants younger than 50 years, smokers, physically active or non-hypertensive participants.ConclusionsAmong Chinese adults, chronic HBV infection was associated with increased mortality from a range of hepatic and extrahepatic diseases.

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