scholarly journals The global hepatitis delta virus (HDV) epidemic: what gaps to address in order to mount a public health response?

2021 ◽  
Vol 79 (1) ◽  
Author(s):  
Tomoyuki Hayashi ◽  
Yumie Takeshita ◽  
Yvan J.-F. Hutin ◽  
Hande Harmanci ◽  
Philippa Easterbrook ◽  
...  
Keyword(s):  
Public Health ◽  
Hepatitis Delta Virus ◽  
Antibody Detection ◽  
Public Health Response ◽  
Northern Asia ◽  
Hepatitis Delta ◽  
Testing Strategies ◽  
Health Response ◽  
Hdv Infection ◽  
Delta Virus

Abstract Background Co-infection between hepatitis B virus (HBV) and hepatitis delta virus (HDV) causes the severest chronic hepatitis and is associated with a high risk of cirrhosis and hepatocellular carcinoma (HCC). The Global Health Sector Strategy on Viral Hepatitis called for the elimination of hepatitis (− 65% mortality and − 90% incidence) by 2030. Our aims were to summarize key points of knowledge and to identify the gaps that need to be addressed to mount a public health response to HDV. Methods We performed a current literature review in terms of epidemiology by WHO regions, genotypes distribution and their pathogenicity, factors associated with HDV infection, mortality due to HDV infection, testing strategies and treatment. Results Prevalence of infection and genotypes are heterogeneous distributed, with highest prevalence in foci around the Mediterranean, in the Middle East, and in Central, Northern Asia and Eastern Asia. Persons who inject drugs (PWID) and migrants from highly endemic areas are highly affected. While antibody detection tests are available, HDV RNA tests of current infection are not standardized nor widely available. The few therapeutic options, including lofartinib, are not widely available; however several new and promising agents have entered clinical trials. Conclusion HDV infection is an poorly known cause of chronic liver disease. To mount a public health response, we need a better description of the HDV epidemic, standardized testing strategies and better treatment options.

scholarly journals Genetic Changes in Hepatitis Delta Virus from Acutely and Chronically Infected Woodchucks

2006 ◽  
Vol 80 (13) ◽  
pp. 6469-6477 ◽  
Author(s):  
John L. Casey ◽  
Bud C. Tennant ◽  
John L. Gerin
Keyword(s):  
Hepatitis Delta Virus ◽  
Hepatitis Virus ◽  
Consensus Sequence ◽  
Genotype I ◽  
Hepatitis Delta ◽  
Genetic Changes ◽  
Host Immune Responses ◽  
Hepatitis Delta Antigen ◽  
Hdv Infection ◽  
Delta Virus

ABSTRACT A woodchuck-derived hepatitis delta virus (HDV) inoculum was created by transfection of a genotype I HDV cDNA clone directly into the liver of a woodchuck that was chronically infected with woodchuck hepatitis virus. All woodchucks receiving this inoculum became positive for HDV RNA in serum, and 67% became chronically infected, similar to the rate of chronic HDV infection in humans. Analysis of HDV sequences obtained at 73 weeks postinfection indicated that changes had occurred at a rate of 0.5% per year; many of these modifications were consistent with editing by host RNA adenosine deaminase. The appearance of sequence changes, which were not evenly distributed on the genome, was correlated with the course of HDV infection. A limited number of modifications occurred in the consensus sequence of the viral genome that altered the sequence of the hepatitis delta antigen (HDAg). All chronically infected animals examined exhibited these changes 73 weeks following infection, but at earlier times, only one of the HDV carriers exhibited consensus sequence substitutions. On the other hand, sequence modifications in animals that eventually recovered from HDV infection were apparent after 27 weeks. The data are consistent with a model in which HDV sequence changes are selected by host immune responses. Chronic HDV infection in woodchucks may result from a delayed and weak immune response that is limited to a small number of epitopes on HDAg.

The increasing prevalence of hepatitis delta virus (HDV) infection in South London

2007 ◽  
Vol 80 (2) ◽  
pp. 277-282 ◽  
Author(s):  
Timothy J.S. Cross ◽  
Paolo Rizzi ◽  
Mary Horner ◽  
Anita Jolly ◽  
Munther J. Hussain ◽  
...  
Keyword(s):  
Hepatitis Delta Virus ◽  
Hepatitis Delta ◽  
Hdv Infection ◽  
Delta Virus

scholarly journals Characterization of the Genotypic Profile of Hepatitis Delta Virus: Isolation of HDV Genotype-1 in the Western Amazon Region of Brazil

Intervirology ◽  
2015 ◽  
Vol 58 (3) ◽  
pp. 166-171 ◽  
Author(s):  
Luan Felipo Botelho-Souza ◽  
Deusilene Souza Vieira ◽  
Alcione de Oliveira dos Santos ◽  
André Vinycius Cunha Pereira ◽  
Juan Miguel Villalobos-Salcedo
Keyword(s):  
Hepatitis B ◽  
Hepatitis Delta Virus ◽  
Clinical Characteristics ◽  
Amazon Region ◽  
Viral Envelope ◽  
Serum Samples ◽  
Hepatitis Delta ◽  
Pcr Rflp ◽  
Hdv Infection ◽  
Delta Virus

The hepatitis delta virus (HDV) is a hepatotropic subvirus that is dependent on the hepatitis B virus (HBV) and supplies the viral envelope containing the surface antigen of hepatitis B. Viral genetic diversity is related to the geographical origin of the isolates, and there are at least eight genotypes that are referred to as HDV-1 through HDV-8. HDV-3 is responsible for epidemics of severe and fulminant hepatitis, which are common in northeastern South America. HDV-3 is prevalent in the Brazilian Amazon and is associated with the increased aggressiveness of HDV infections. Although isolated, the characteristics of the clinical presentation of HDV-1 in the Amazon region have not yet been clearly reported. Objective: This study aims to assess the genotypic and clinical characteristics of individuals with the HDV-1 genotype in the western Amazon region. Methods: The HDV was genotyped by nested PCR-RFLP and sequencing from serum samples of 56 patients with HBV/HDV infection. The genotypes were correlated with the clinical characteristics presented by patients with HBV/HDV infection. Results: A prevalence of 92.3% for the HDV-3 genotype (n = 48) and 7.6% (n = 4) for the HDV-1 genotype was observed. Conclusion: To date, this is the most extensive clinical study of HDV-1 genotype infections in the nonindigenous population of Western Amazonia.

scholarly journals Nucleic acid polymers are active against Hepatitis Delta Virus infection in vitro.

2017 ◽  
pp. JVI.01416-17 ◽  
Author(s):  
Frauke Beilstein ◽  
Matthieu Blanchet ◽  
Andrew Vaillant ◽  
Camille Sureau
Keyword(s):  
Nucleic Acid ◽  
Viral Entry ◽  
Hepatitis Delta Virus ◽  
Immune Escape ◽  
Envelope Proteins ◽  
Infection Model ◽  
Hepatitis Delta ◽  
Hdv Infection ◽  
Delta Virus

In this study, an in vitro infection model for the hepatitis delta virus (HDV) was used to evaluate the antiviral effects of phosphorothioate nucleic acid polymers (NAPs) and investigate their mechanism of action. The results show that NAPs inhibit HDV infection at less than 4 micromolar concentrations in cultures of differentiated human hepatoma cells. NAPs were shown to be active at viral entry, but inactive post entry on HDV RNA replication. Inhibition was independent of the NAPs nucleotide sequence, but dependent on both size and amphipathicity of the polymer. NAPs antiviral activity was effective against HDV virions bearing the main hepatitis B virus (HBV) immune escape substitutions (D144A and G145R) and was pangenomic with regard to HBV envelope proteins. Furthermore, similar to immobilized heparin, immobilized NAPs could bind HDV particles suggesting that entry inhibition was due, at least in part, to preventing attachment of the virus to cell surface glycosaminoglycans. The results document NAPs as a novel class of antiviral compounds that can prevent HDV propagation.IMPORTANCEHDV infection causes the most severe form of viral hepatitis in humans and one of the most difficult to cure. Currently, treatments are limited to long-term administration of interferon at high doses, which provide only partial efficacy. There is thus an urgent need for innovative approaches to identify new antiviral against HDV. The significance of our study is in demonstrating that nucleic acid polymers (NAPs) are active against HDV by targeting the envelope of HDV virions. In an in vitro infection assay, NAPs activity was recorded at less than 4 micromolar concentrations in the absence of cell toxicity. Furthermore, the fact that NAPs could block HDV at viral entry, suggest their potential to control the spread of HDV in a chronically HBV-infected liver. In addition, NAPs anti-HDV activity was pangenomic with regard to HBV envelope proteins and not circumvented by HBsAg substitutions associated with HBV immune escape.

scholarly journals Prevalence of Hepatitis Delta Virus (HDV) Infection in Chronic Hepatitis B Patients with Unusual Clinical Pictures

2013 ◽  
Vol 13 (8) ◽  
Author(s):  
Shiva Ghamari ◽  
Seyed Moayed Alavian ◽  
Mario Rizzetto ◽  
Antonella Olivero ◽  
Antonina Smedile ◽  
...  
Keyword(s):  
Chronic Hepatitis ◽  
Hepatitis B ◽  
Chronic Hepatitis B ◽  
Hepatitis Delta Virus ◽  
Hepatitis Delta ◽  
Hdv Infection ◽  
Clinical Pictures ◽  
Delta Virus

scholarly journals New Enzyme-Linked Immunosorbent Assay for Detection of Antibodies against Hepatitis Delta Virus Using a Hepatitis Delta Antigen Derived from a Taiwanese Clone and Comparison to the Abbott Radioimmunoassay

2012 ◽  
Vol 19 (5) ◽  
pp. 817-819 ◽  
Author(s):  
Yung-Bin Kuo ◽  
Mei Chao ◽  
Yi-Hsuan Lee ◽  
Chau-Ting Yeh ◽  
Err-Cheng Chan
Keyword(s):  
Immunosorbent Assay ◽  
Hepatitis Delta Virus ◽  
Detection Efficiency ◽  
Enzyme Linked Immunosorbent Assay ◽  
Hepatitis Delta ◽  
Hepatitis D ◽  
Delta Antigen ◽  
Hepatitis Delta Antigen ◽  
Hdv Infection ◽  
Delta Virus

ABSTRACTAn anti-hepatitis delta (HD) enzyme-linked immunosorbent assay (ELISA) using a specific recombinant hepatitis delta antigen derived from a local dominant hepatitis delta virus (hepatitis D virus; HDV) strain in Taiwan has been established. The detection efficiency of this assay was comparable to that of the commercially available Abbott anti-HD radioimmunoassay (RIA) and could be useful in routine laboratory diagnoses of HDV infection.

scholarly journals Hepatitis delta virus genotypes I and II cocirculate in an endemic area of Yakutia, Russia

2001 ◽  
Vol 82 (11) ◽  
pp. 2709-2718 ◽  
Author(s):  
Valeria Ivaniushina ◽  
Nadjia Radjef ◽  
Marfa Alexeeva ◽  
Elyanne Gault ◽  
Sergei Semenov ◽  
...  
Keyword(s):  
Hepatitis Delta Virus ◽  
Restriction Pattern ◽  
Type I ◽  
Type Ii ◽  
Genotype I ◽  
Northern Asia ◽  
Hepatitis Delta ◽  
Genotype Ii ◽  
Hdv Genotype ◽  
Delta Virus

Currently, three genotypes of hepatitis delta virus (HDV) are described. The most common, genotype I, has a worldwide distribution; in contrast, genotype II has been found previously only in Japan and Taiwan, while genotype III is found exclusively in South America. Considering the high prevalence of HDV in Northern Siberia (Russia), restriction fragment length polymorphism (RFLP) was used to analyse HDV genotypes from 29 infected patients living in Yakutia. Of these isolates, 11 were characterized by partial nucleotide sequencing and two isolates were completely sequenced. Phylogenetic inference methods included maximum parsimony, maximum likelihood and distance analyses. A restriction pattern consistent with HDV genotype I was found in 14 samples, while the remaining 15 showed a different restriction pattern, inconsistent with any known genotype. Five Yakutian HDV isolates with the type I restriction pattern were sequenced and confirmed to be affiliated with genotype I, although the phylogenetic results indicate that they were heterogeneous and did not cluster together. Sequencing of eight isolates with the new RFLP pattern revealed that these isolates were most closely related to HDV genotype II. In contrast to HDV Yakutian genotype I sequences, all of these type II sequences formed a well-defined clade on phylogenetic trees. Comparison of clinical presentations during hospitalization between patients infected with HDV type I (n=14) and type II (n=15) did not reveal any differences in the severity of infection. These data indicate that the distribution of genotype II is not restricted to Taiwan or Japan, but spreads over Northern Asia, appearing in the native population of Yakutia. Type II Yakutian strains appeared to form a well-defined subclade and could be associated with severe chronic hepatitis in this area.

scholarly journals Amino Acid Substitutions within HLA-B*27-Restricted T Cell Epitopes Prevent Recognition by Hepatitis Delta Virus-Specific CD8+T Cells

2018 ◽  
Vol 92 (13) ◽  
pp. e01891-17 ◽  
Author(s):  
Hadi Karimzadeh ◽  
Muthamia M. Kiraithe ◽  
Anna D. Kosinska ◽  
Manuel Glaser ◽  
Melanie Fiedler ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Response ◽  
Hepatitis Delta Virus ◽  
Cd8 T Cell ◽  
T Cell Response ◽  
Viral Escape ◽  
T Cell Epitopes ◽  
Hepatitis Delta ◽  
Hdv Infection ◽  
Delta Virus

ABSTRACTVirus-specific CD8 T cell response seems to play a significant role in the outcome of hepatitis delta virus (HDV) infection. However, the HDV-specific T cell epitope repertoire and mechanisms of CD8 T cell failure in HDV infection have been poorly characterized. We therefore aimed to characterize HDV-specific CD8 T cell epitopes and the impacts of viral mutations on immune escape. In this study, we predicted peptide epitopes binding the most frequent human leukocyte antigen (HLA) types and assessed their HLA binding capacities. These epitopes were characterized in HDV-infected patients by intracellular gamma interferon (IFN-γ) staining. Sequence analysis of large hepatitis delta antigen (L-HDAg) and HLA typing were performed in 104 patients. The impacts of substitutions within epitopes on the CD8 T cell response were evaluated experimentally and byin silicostudies. We identified two HLA-B*27-restricted CD8 T cell epitopes within L-HDAg. These novel epitopes are located in a relatively conserved region of L-HDAg. However, we detected molecular footprints within the epitopes in HLA-B*27-positive patients with chronic HDV infections. The variant peptides were not cross-recognized in HLA-B*27-positive patients with resolved HDV infections, indicating that the substitutions represent viral escape mutations. Molecular modeling of HLA-B*27 complexes with the L-HDAg epitope and its potential viral escape mutations indicated that the structural and electrostatic properties of the bound peptides differ considerably at the T cell receptor interface, which provides a possible molecular explanation for the escape mechanism. This viral escape from the HLA-B*27-restricted CD8 T cell response correlates with a chronic outcome of hepatitis D infection. T cell failure resulting from immune escape may contribute to the high chronicity rate in HDV infection.IMPORTANCEHepatitis delta virus (HDV) causes severe chronic hepatitis, which affects 20 million people worldwide. Only a small number of patients are able to clear the virus, possibly mediated by a virus-specific T cell response. Here, we performed a systematic screen to define CD8 epitopes and investigated the role of CD8 T cells in the outcome of hepatitis delta and how they fail to eliminate HDV. Overall the number of epitopes identified was very low compared to other hepatotropic viruses. We identified, two HLA-B*27-restricted epitopes in patients with resolved infections. In HLA-B*27-positive patients with chronic HDV infections, however, we detected escape mutations within these identified epitopes that could lead to viral evasion of immune responses. These findings support evidence showing that HLA-B*27 is important for virus-specific CD8 T cell responses, similar to other viral infections. These results have implications for the clinical prognosis of HDV infection and for vaccine development.

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