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Paul Dény - One of the best experts on this subject based on the ideXlab platform.

  • ICTV Virus Taxonomy Profile: Deltavirus.
    The Journal of general virology, 2018
    Co-Authors: Lars O. Magnius, Paul Dény, John M. Taylor, William S. Mason, Camille Sureau, Helene Norder
    Abstract:

    Hepatitis delta virus, the only member of the only species in the genus Deltavirus, is a unique human pathogen. Its ~1.7 kb circular negative-sense RNA genome encodes a protein, hepatitis delta antigen, which occurs in two forms, small and large, both with unique functions. Hepatitis delta virus uses host RNA polymerase II to replicate via double rolling circle RNA synthesis. Newly synthesized linear RNAs are circularized after autocatalytic cleavage and ligation. Hepatitis delta virus requires the envelope of the helper virus, hepatitis B virus (family Hepadnaviridae), to produce infectious particles. This is a summary of the International Committee on Taxonomy of Viruses (ICTV) Report on the taxonomy of Deltavirus which is available at www.ictv.global/report/Deltavirus.

  • Genetic diversity and worldwide distribution of the Deltavirus genus: A study of 2,152 clinical strains.
    Hepatology (Baltimore Md.), 2017
    Co-Authors: Frédéric Le Gal, Paul Dény, Ségolène Brichler, Tudor Drugan, Chakib Alloui, Dominique Roulot, Jean-michel Pawlotsky, Emmanuel Gordien
    Abstract:

    Hepatitis delta virus (HDV) is responsible for the most severe form of acute and chronic viral hepatitis. We previously proposed that the Deltavirus genus is composed of 8 major clades. However, few sequences were available to confirm this classification. Moreover, little is known about the structural and functional consequences of HDV variability. One practical consequence is the failure of most quantification assays to properly detect or quantify plasmatic HDV RNA. Between 2001 and 2014, 2,152 HDV strains were prospectively collected and genotyped in our reference laboratory by means of nucleotide sequencing and extensive phylogenetic analyses of a 400-nucleotide region of the genome (R0) from nucleotide 889 to 1289 encompassing the 3' end of the delta protein-coding gene. In addition, the full-length genome sequence was generated for 116 strains selected from the different clusters, allowing for in-depth characterization of the HDV genotypes and subgenotypes. This study clearly confirms that HDV genus is composed of eight genotypes (HDV-1 to -8) defined by an inter-genotype similarity >85% or >80%, according to the partial or full-length genome sequence, respectively. Furthermore, genotypes can be segregated into 2 to 4 subgenotypes, characterized by an inter-subgenotype similarity >90% (>84% for HDV-1) over the whole genome sequence. Systematic analysis of genome and protein sequences revealed highly conserved functional nucleotide and amino acid motifs and positions across all (sub)genotypes, indicating strong conservatory constraints on the structure and function of the genome and the protein. Conclusion: this study provides new insights into genetic diversity of HDV, provides a clear view of their geographical localization and allows speculating the hypothesis as to the worldwide spread of the virus, very likely from an initial African origin. This article is protected by copyright. All rights reserved.

  • Current hepatitis delta virus type 1 (HDV1) infections in central and eastern Turkey indicate a wide genetic diversity that is probably linked to different HDV1 origins
    Archives of Virology, 2012
    Co-Authors: Frédéric Le Gal, Elyanne Gault, Emmanuel Gordien, Ségolène Brichler, Selim Badur, Nasser Al Hawajri, Filiz Akyüz, Sabahattin Kaymakoglu, Fabien Zoulim, Paul Dény
    Abstract:

    Hepatitis delta virus (HDV) is a subviral pathogen of humans, a satellite of hepatitis B virus (HBV) that induces severe acute and chronic liver diseases. The genus Deltavirus consists of eight clades or genotypes, with HDV1 being ubiquitous and frequently characterized. In Turkey, HDV1 infection is highly endemic among HBsAg carriers, especially in the southeastern region. In this study, we analyzed 34 samples from patients who were chronically infected with HBV/HDV, originating from 22 cities of rural regions in the central and eastern parts of Turkey, in order to determine the levels of viral replication and genetic diversity. HDV RNA levels ranged between 3.02 and 8.75 Log copies/mL, and HBV DNA was detected in 25 samples (73.5%), with values ranging from 2.53 to 5.30 Log copies/mL. Analysis of nucleotides 900-1280 of HDV genomes (n = 34) and full-length (n = 17) sequences indicated that all of the strains belonged to genotype HDV1. However, a high genetic diversity was observed among the isolates, with a mean full-length dissimilarity score of 13.05%. HDV sequences clustered with sequences from Western Europe (n = 11), Eastern Europe and Asia (n = 19) or Africa (n = 4). HDV1 isolates related to strains of African origin had a serine residue instead of an alanine at position 202 of the large delta protein. HBV preS1 sequences obtained for 34 isolates indicated an HBV/D genotype in all cases. Taken together, our results indicate that in Turkey, where HBV-HDV dual infection is highly endemic, both viruses have high levels of replication, and HDV strains exhibit wide genetic diversity, which might reflect ancient evolution and/or successive outbreaks.

  • Eighth Major Clade for Hepatitis Delta Virus
    Emerging infectious diseases, 2006
    Co-Authors: Frédéric Le Gal, Elyanne Gault, Marie-pierre Ripault, Jeanne Serpaggi, Jean-claude Trinchet, Emmanuel Gordien, Paul Dény
    Abstract:

    Hepatitis delta virus is the only representative of the Deltavirus genus, which consists of 7 differentiated major clades. In this study, an eighth clade was identified from 3 distinct strains. Deltavirus genetic variability should be considered for diagnostic purposes. Clinical consequences of the diversity have yet to be evaluated.

Elyanne Gault - One of the best experts on this subject based on the ideXlab platform.

  • Current hepatitis delta virus type 1 (HDV1) infections in central and eastern Turkey indicate a wide genetic diversity that is probably linked to different HDV1 origins
    Archives of Virology, 2012
    Co-Authors: Frédéric Le Gal, Elyanne Gault, Emmanuel Gordien, Ségolène Brichler, Selim Badur, Nasser Al Hawajri, Filiz Akyüz, Sabahattin Kaymakoglu, Fabien Zoulim, Paul Dény
    Abstract:

    Hepatitis delta virus (HDV) is a subviral pathogen of humans, a satellite of hepatitis B virus (HBV) that induces severe acute and chronic liver diseases. The genus Deltavirus consists of eight clades or genotypes, with HDV1 being ubiquitous and frequently characterized. In Turkey, HDV1 infection is highly endemic among HBsAg carriers, especially in the southeastern region. In this study, we analyzed 34 samples from patients who were chronically infected with HBV/HDV, originating from 22 cities of rural regions in the central and eastern parts of Turkey, in order to determine the levels of viral replication and genetic diversity. HDV RNA levels ranged between 3.02 and 8.75 Log copies/mL, and HBV DNA was detected in 25 samples (73.5%), with values ranging from 2.53 to 5.30 Log copies/mL. Analysis of nucleotides 900-1280 of HDV genomes (n = 34) and full-length (n = 17) sequences indicated that all of the strains belonged to genotype HDV1. However, a high genetic diversity was observed among the isolates, with a mean full-length dissimilarity score of 13.05%. HDV sequences clustered with sequences from Western Europe (n = 11), Eastern Europe and Asia (n = 19) or Africa (n = 4). HDV1 isolates related to strains of African origin had a serine residue instead of an alanine at position 202 of the large delta protein. HBV preS1 sequences obtained for 34 isolates indicated an HBV/D genotype in all cases. Taken together, our results indicate that in Turkey, where HBV-HDV dual infection is highly endemic, both viruses have high levels of replication, and HDV strains exhibit wide genetic diversity, which might reflect ancient evolution and/or successive outbreaks.

  • Eighth Major Clade for Hepatitis Delta Virus
    Emerging infectious diseases, 2006
    Co-Authors: Frédéric Le Gal, Elyanne Gault, Marie-pierre Ripault, Jeanne Serpaggi, Jean-claude Trinchet, Emmanuel Gordien, Paul Dény
    Abstract:

    Hepatitis delta virus is the only representative of the Deltavirus genus, which consists of 7 differentiated major clades. In this study, an eighth clade was identified from 3 distinct strains. Deltavirus genetic variability should be considered for diagnostic purposes. Clinical consequences of the diversity have yet to be evaluated.

  • Molecular Phylogenetic Analyses Indicate a Wide and Ancient Radiation of African Hepatitis Delta Virus, Suggesting a Deltavirus Genus of at Least Seven Major Clades
    Journal of virology, 2004
    Co-Authors: Nadjia Radjef, Elyanne Gault, Jean-claude Trinchet, Emmanuel Gordien, Tudor Drugan, Dominique Roulot, Valeria Ivaniushina, Patricia Anaïs, Mathieu C. Tamby, Michel C. Milinkovitch
    Abstract:

    Hepatitis D virus (HDV) is a satellite of hepatitis B virus (HBV) for transmission and propagation and infects nearly 20 million people worldwide. The HDV genome is a compact circular single-stranded RNA genome with extensive intramolecular complementarity. Despite its different epidemiological and pathological patterns, the variability and geographical distribution of HDV are limited to three genotypes and two subtypes that have been characterized to date. Phylogenetic reconstructions based on the delta antigen gene and full-length genome sequence data show an extensive and probably ancient radiation of African lineages, suggesting that the genetic variability of HDV is much more complex than was previously thought, with evidence of additional clades. These results relate the geographic distribution of HDV more closely to the genetic variability of its helper HBV.

Frédéric Le Gal - One of the best experts on this subject based on the ideXlab platform.

  • Genetic diversity and worldwide distribution of the Deltavirus genus: A study of 2,152 clinical strains.
    Hepatology (Baltimore Md.), 2017
    Co-Authors: Frédéric Le Gal, Paul Dény, Ségolène Brichler, Tudor Drugan, Chakib Alloui, Dominique Roulot, Jean-michel Pawlotsky, Emmanuel Gordien
    Abstract:

    Hepatitis delta virus (HDV) is responsible for the most severe form of acute and chronic viral hepatitis. We previously proposed that the Deltavirus genus is composed of 8 major clades. However, few sequences were available to confirm this classification. Moreover, little is known about the structural and functional consequences of HDV variability. One practical consequence is the failure of most quantification assays to properly detect or quantify plasmatic HDV RNA. Between 2001 and 2014, 2,152 HDV strains were prospectively collected and genotyped in our reference laboratory by means of nucleotide sequencing and extensive phylogenetic analyses of a 400-nucleotide region of the genome (R0) from nucleotide 889 to 1289 encompassing the 3' end of the delta protein-coding gene. In addition, the full-length genome sequence was generated for 116 strains selected from the different clusters, allowing for in-depth characterization of the HDV genotypes and subgenotypes. This study clearly confirms that HDV genus is composed of eight genotypes (HDV-1 to -8) defined by an inter-genotype similarity >85% or >80%, according to the partial or full-length genome sequence, respectively. Furthermore, genotypes can be segregated into 2 to 4 subgenotypes, characterized by an inter-subgenotype similarity >90% (>84% for HDV-1) over the whole genome sequence. Systematic analysis of genome and protein sequences revealed highly conserved functional nucleotide and amino acid motifs and positions across all (sub)genotypes, indicating strong conservatory constraints on the structure and function of the genome and the protein. Conclusion: this study provides new insights into genetic diversity of HDV, provides a clear view of their geographical localization and allows speculating the hypothesis as to the worldwide spread of the virus, very likely from an initial African origin. This article is protected by copyright. All rights reserved.

  • Current hepatitis delta virus type 1 (HDV1) infections in central and eastern Turkey indicate a wide genetic diversity that is probably linked to different HDV1 origins
    Archives of Virology, 2012
    Co-Authors: Frédéric Le Gal, Elyanne Gault, Emmanuel Gordien, Ségolène Brichler, Selim Badur, Nasser Al Hawajri, Filiz Akyüz, Sabahattin Kaymakoglu, Fabien Zoulim, Paul Dény
    Abstract:

    Hepatitis delta virus (HDV) is a subviral pathogen of humans, a satellite of hepatitis B virus (HBV) that induces severe acute and chronic liver diseases. The genus Deltavirus consists of eight clades or genotypes, with HDV1 being ubiquitous and frequently characterized. In Turkey, HDV1 infection is highly endemic among HBsAg carriers, especially in the southeastern region. In this study, we analyzed 34 samples from patients who were chronically infected with HBV/HDV, originating from 22 cities of rural regions in the central and eastern parts of Turkey, in order to determine the levels of viral replication and genetic diversity. HDV RNA levels ranged between 3.02 and 8.75 Log copies/mL, and HBV DNA was detected in 25 samples (73.5%), with values ranging from 2.53 to 5.30 Log copies/mL. Analysis of nucleotides 900-1280 of HDV genomes (n = 34) and full-length (n = 17) sequences indicated that all of the strains belonged to genotype HDV1. However, a high genetic diversity was observed among the isolates, with a mean full-length dissimilarity score of 13.05%. HDV sequences clustered with sequences from Western Europe (n = 11), Eastern Europe and Asia (n = 19) or Africa (n = 4). HDV1 isolates related to strains of African origin had a serine residue instead of an alanine at position 202 of the large delta protein. HBV preS1 sequences obtained for 34 isolates indicated an HBV/D genotype in all cases. Taken together, our results indicate that in Turkey, where HBV-HDV dual infection is highly endemic, both viruses have high levels of replication, and HDV strains exhibit wide genetic diversity, which might reflect ancient evolution and/or successive outbreaks.

  • Eighth Major Clade for Hepatitis Delta Virus
    Emerging infectious diseases, 2006
    Co-Authors: Frédéric Le Gal, Elyanne Gault, Marie-pierre Ripault, Jeanne Serpaggi, Jean-claude Trinchet, Emmanuel Gordien, Paul Dény
    Abstract:

    Hepatitis delta virus is the only representative of the Deltavirus genus, which consists of 7 differentiated major clades. In this study, an eighth clade was identified from 3 distinct strains. Deltavirus genetic variability should be considered for diagnostic purposes. Clinical consequences of the diversity have yet to be evaluated.

Emmanuel Gordien - One of the best experts on this subject based on the ideXlab platform.

  • Genetic diversity and worldwide distribution of the Deltavirus genus: A study of 2,152 clinical strains.
    Hepatology (Baltimore Md.), 2017
    Co-Authors: Frédéric Le Gal, Paul Dény, Ségolène Brichler, Tudor Drugan, Chakib Alloui, Dominique Roulot, Jean-michel Pawlotsky, Emmanuel Gordien
    Abstract:

    Hepatitis delta virus (HDV) is responsible for the most severe form of acute and chronic viral hepatitis. We previously proposed that the Deltavirus genus is composed of 8 major clades. However, few sequences were available to confirm this classification. Moreover, little is known about the structural and functional consequences of HDV variability. One practical consequence is the failure of most quantification assays to properly detect or quantify plasmatic HDV RNA. Between 2001 and 2014, 2,152 HDV strains were prospectively collected and genotyped in our reference laboratory by means of nucleotide sequencing and extensive phylogenetic analyses of a 400-nucleotide region of the genome (R0) from nucleotide 889 to 1289 encompassing the 3' end of the delta protein-coding gene. In addition, the full-length genome sequence was generated for 116 strains selected from the different clusters, allowing for in-depth characterization of the HDV genotypes and subgenotypes. This study clearly confirms that HDV genus is composed of eight genotypes (HDV-1 to -8) defined by an inter-genotype similarity >85% or >80%, according to the partial or full-length genome sequence, respectively. Furthermore, genotypes can be segregated into 2 to 4 subgenotypes, characterized by an inter-subgenotype similarity >90% (>84% for HDV-1) over the whole genome sequence. Systematic analysis of genome and protein sequences revealed highly conserved functional nucleotide and amino acid motifs and positions across all (sub)genotypes, indicating strong conservatory constraints on the structure and function of the genome and the protein. Conclusion: this study provides new insights into genetic diversity of HDV, provides a clear view of their geographical localization and allows speculating the hypothesis as to the worldwide spread of the virus, very likely from an initial African origin. This article is protected by copyright. All rights reserved.

  • Current hepatitis delta virus type 1 (HDV1) infections in central and eastern Turkey indicate a wide genetic diversity that is probably linked to different HDV1 origins
    Archives of Virology, 2012
    Co-Authors: Frédéric Le Gal, Elyanne Gault, Emmanuel Gordien, Ségolène Brichler, Selim Badur, Nasser Al Hawajri, Filiz Akyüz, Sabahattin Kaymakoglu, Fabien Zoulim, Paul Dény
    Abstract:

    Hepatitis delta virus (HDV) is a subviral pathogen of humans, a satellite of hepatitis B virus (HBV) that induces severe acute and chronic liver diseases. The genus Deltavirus consists of eight clades or genotypes, with HDV1 being ubiquitous and frequently characterized. In Turkey, HDV1 infection is highly endemic among HBsAg carriers, especially in the southeastern region. In this study, we analyzed 34 samples from patients who were chronically infected with HBV/HDV, originating from 22 cities of rural regions in the central and eastern parts of Turkey, in order to determine the levels of viral replication and genetic diversity. HDV RNA levels ranged between 3.02 and 8.75 Log copies/mL, and HBV DNA was detected in 25 samples (73.5%), with values ranging from 2.53 to 5.30 Log copies/mL. Analysis of nucleotides 900-1280 of HDV genomes (n = 34) and full-length (n = 17) sequences indicated that all of the strains belonged to genotype HDV1. However, a high genetic diversity was observed among the isolates, with a mean full-length dissimilarity score of 13.05%. HDV sequences clustered with sequences from Western Europe (n = 11), Eastern Europe and Asia (n = 19) or Africa (n = 4). HDV1 isolates related to strains of African origin had a serine residue instead of an alanine at position 202 of the large delta protein. HBV preS1 sequences obtained for 34 isolates indicated an HBV/D genotype in all cases. Taken together, our results indicate that in Turkey, where HBV-HDV dual infection is highly endemic, both viruses have high levels of replication, and HDV strains exhibit wide genetic diversity, which might reflect ancient evolution and/or successive outbreaks.

  • Eighth Major Clade for Hepatitis Delta Virus
    Emerging infectious diseases, 2006
    Co-Authors: Frédéric Le Gal, Elyanne Gault, Marie-pierre Ripault, Jeanne Serpaggi, Jean-claude Trinchet, Emmanuel Gordien, Paul Dény
    Abstract:

    Hepatitis delta virus is the only representative of the Deltavirus genus, which consists of 7 differentiated major clades. In this study, an eighth clade was identified from 3 distinct strains. Deltavirus genetic variability should be considered for diagnostic purposes. Clinical consequences of the diversity have yet to be evaluated.

  • Molecular Phylogenetic Analyses Indicate a Wide and Ancient Radiation of African Hepatitis Delta Virus, Suggesting a Deltavirus Genus of at Least Seven Major Clades
    Journal of virology, 2004
    Co-Authors: Nadjia Radjef, Elyanne Gault, Jean-claude Trinchet, Emmanuel Gordien, Tudor Drugan, Dominique Roulot, Valeria Ivaniushina, Patricia Anaïs, Mathieu C. Tamby, Michel C. Milinkovitch
    Abstract:

    Hepatitis D virus (HDV) is a satellite of hepatitis B virus (HBV) for transmission and propagation and infects nearly 20 million people worldwide. The HDV genome is a compact circular single-stranded RNA genome with extensive intramolecular complementarity. Despite its different epidemiological and pathological patterns, the variability and geographical distribution of HDV are limited to three genotypes and two subtypes that have been characterized to date. Phylogenetic reconstructions based on the delta antigen gene and full-length genome sequence data show an extensive and probably ancient radiation of African lineages, suggesting that the genetic variability of HDV is much more complex than was previously thought, with evidence of additional clades. These results relate the geographic distribution of HDV more closely to the genetic variability of its helper HBV.

Mario Rizzetto - One of the best experts on this subject based on the ideXlab platform.

  • An update on HDV: virology, pathogenesis and treatment.
    Antiviral therapy, 2013
    Co-Authors: Mónica V Alvarado-mora, Mario Rizzetto, Stephen Locarnini, João Renato Rebello Pinho
    Abstract:

    Hepatitis delta is an inflammatory liver disease caused by infection with HDV. HDV is a single-stranded circular RNA pathogen with a diameter of 36 nm. HDV is classified in the genus Deltavirus and is still awaiting a final taxonomic classification up to the family level. HDV shares similarities with satellite RNA and viroids including a small circular single-stranded RNA with secondary structure that replicates through the 'double rolling circle' mechanism. The HDV RNA genome is capable of self-cleavage through a ribozyme and encodes only one structural protein, the hepatitis delta antigen (HDAg), from the antigenomic RNA. There are two forms of HDAg, a shorter (S; 22 kDa) and a longer (L; 24 kDa) form, the latter generated from an RNA editing mechanism. The S form is essential for viral genomic replication. The L form participates in the assembly and formation of HDV. For complete replication and transmission, HDV requires the hepatitis B surface antigen (HBsAg). Thus, HDV infection only occurs in HBsAg-positive individuals, either as acute coinfection in treatment-naive HBV-infected persons, or as superinfection in patients with pre-existing chronic hepatitis B (CHB). HDV is found throughout the world, but its prevalence, incidence, clinical features and epidemiological characteristics vary by geographic region. There are eight genotypes (1 to 8) distributed over different geographic areas: HDV-1 is distributed worldwide, whereas HDV-2 to 8 are seen more regionally. Levels of HDV viraemia change over the course of HDV infection, being significantly higher in patients with early chronic hepatitis than in cirrhosis. Chronic HDV infection leads to more severe liver disease than chronic HBV monoinfection with an accelerated course of fibrosis progression, an increased risk of hepatocellular carcinoma and early decompensation in the setting of established cirrhosis. Current treatments include pegylated interferon-α and liver transplantation; the latter of which can be curative. Further studies are needed to develop better treatment strategies for this challenging disease.

  • hepatitis d thirty years after
    Journal of Hepatology, 2009
    Co-Authors: Mario Rizzetto
    Abstract:

    The key to the discovery of the Hepatitis D Virus (HDV) was the description in Turin, Italy in the mid-1970s of the delta antigen and antibody in carriers of the hepatitis B surface antigen. The new antigen was first thought to be a marker of the Hepatitis B Virus (HBV) and in view of its intricate true nature, it would have possibly died away as another odd antigenic subtype of HBV, like many that were described in the 1970s. Fortunately, instead, a collaboration started in 1978 between the Turin group, and the National Institute of Health and Georgetown University in the US. With American facilities and expertise this collaboration led just a year later, in 1979, to the unfolding of an unexpected and amazing chapter in virology. Experiments in chimpanzees demonstrated that the delta antigen was not a component of the HBV but of a separate defective virus requiring HBV for its infection; it was named the hepatitis D virus to conform to the nomenclature of hepatitis viruses and classified within the genus Deltavirus. The animal experiments were also seminal in proposing to future clinical interpretation, the paradigm of a pathogenic infection (hepatitis D), that could develop only in HBV-infected patients, was mainly transmitted by superinfection of HDV on chronic HBV carriers and had the ability to strongly inhibit the helper HBV. The discovery of the HDV has driven three directions of further research: (1) The understanding of the replicative and infectious mechanisms of the HDV. (2) The assessment of its epidemiological and medical impact. (3) The search for a therapy for chronic hepatitis D (CHD). This review summarizes the progress achieved in each field of research in the thirty years that have passed since the discovery of HDV.

  • Review Hepatitis D: Thirty years after q
    2009
    Co-Authors: Mario Rizzetto
    Abstract:

    The key to the discovery of the Hepatitis D Virus (HDV) was the description in Turin, Italy in the mid-1970s of the delta antigen and antibody in carriers of the hepatitis B surface antigen. The new antigen was first thought to be a marker of the Hepatitis B Virus (HBV) and in view of its intricate true nature, it would have possibly died away as another odd antigenic subtype of HBV, like many that were described in the 1970s. Fortunately, instead, a collaboration started in 1978 between the Turin group, and the National Institute of Health and Georgetown University in the US. With American facilities and expertise this collaboration led just a year later, in 1979, to the unfolding of an unexpected and amazing chapter in virology. Experiments in chimpanzees demonstrated that the delta antigen was not a component of the HBV but of a separate defective virus requiring HBV for its infection; it was named the hepatitis D virus to conform to the nomenclature of hepatitis viruses and classified within the genus Deltavirus. The animal experiments were also seminal in proposing to future clinical interpretation, the paradigm of a pathogenic infection (hepatitis D), that could develop only in HBV-infected patients, was mainly transmitted by superinfection of HDV on chronic HBV carriers and had the ability to strongly inhibit the helper HBV. The discovery of the HDV has driven three directions of further research: (1) The understanding of the replicative and infectious mechanisms of the HDV. (2) The assessment of its epidemiological and medical impact. (3) The search for a therapy for chronic hepatitis D (CHD). This review summarizes the progress achieved in each field of research in the thirty years that have passed since the discovery of HDV. 2009 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.