|
1
|
Molecular characterization of the full-length genome sequences of HDV strains circulating in Tunisia. Arch Virol 2018. [PMID: 29516244 DOI: 10.1007/s00705-018-3790-1] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
While Tunisia is endemic for hepatitis B virus (HBV), a recent large-scale retrospective study, revealed a very low prevalence (2%) of hepatitis Delta virus (HDV) (Yacoubi et al. in J Clin Virol 72:126-132, 2015). All strains were classified within the genotype 1 (HDV-1) as assessed by nucleotide sequencing of the so-called 'R0' region of the genome described previously. In this study, we aimed to determine the full-length genome sequence of HDV isolates in order to fully characterize the HDV strains spreading in Tunisia. Eleven HDV antibody and RNA positive samples were obtained from the 1615 clinical samples previously studied. The whole genome sequence was obtained for 5 strains by sequencing and realignment of four overlapping regions covering the entire genome, followed by extensive phylogenetic analyses. Tunisian sequences segregated together with Turkish and African sequences and showed 60% GC content. Alignment with an HDV-1 consensus sequence revealed that they exhibited several point mutations in different functional domains of the delta proteins that, according to previous studies, might possibly affect their properties. In conclusion, the first full-length genome sequences of Tunisian HDV isolates are provided, isolates which are closely related to Turkish and Sub-Saharan Africa strains, supporting the hypothesis for the spread of HDV-1-strains from Africa via Tunisia to Turkey, before spread to the rest of the world.
Collapse
|
|
2
|
Shirazi R, Ram D, Rakovsky A, Bucris E, Gozlan Y, Lustig Y, Shaked-Mishan P, Picard O, Shemer-Avni Y, Ben-Zvi H, Halutz O, Lurie Y, Veizman E, Carlebach M, Braun M, Naftaly MC, Shlomai A, Safadi R, Mendelson E, Sklan EH, Ben-Ari Z, Mor O. Characterization of hepatitis B and delta coinfection in Israel. BMC Infect Dis 2018; 18:97. [PMID: 29486716 PMCID: PMC6389180 DOI: 10.1186/s12879-018-3008-x] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2017] [Accepted: 02/21/2018] [Indexed: 12/20/2022] Open
Abstract
BACKGROUND Characteristics of hepatitis B (HBV) and delta (HDV) coinfection in various geographical regions, including Israel, remain unclear. Here we studied HDV seroprevalence in Israel, assessed HDV/HBV viral loads, circulating genotypes and hepatitis delta antigen (HDAg) conservation. METHODS Serological anti HDV IgG results from 8969 HBsAg positive individuals tested in 2010-2015 were retrospectively analyzed to determine HDV seroprevalence. In a cohort of HBV/HDV coinfected (n=58) and HBV monoinfected (n=27) patients, quantitative real-time PCR (qRT-PCR) and sequencing were performed to determine viral loads, genotypes and hepatitis delta antigen (HDAg) protein sequence. RESULTS 6.5% (587/8969) of the HBsAg positive patients were positive for anti HDV antibodies. HDV viral load was >2 log copies/ml higher than HBV viral load in most of the coinfected patients with detectable HDV RNA (86%, 50/58). HDV genotype 1 was identified in all patients, most of whom did not express HBV. While 66.6% (4/6) of the HBV/HDV co-expressing patients carried HBV-D2 only 18.5% (5/27) of the HBV monoinfections had HBV-D2 (p=0.03). Higher genetic variability in the HDAg protein sequence was associated with higher HDV viral load. CONCLUSIONS The overall significant prevalence of HDV (6.5%) mandates HDV RNA testing for all coinfected patients. Patients positive for HDV RNA (characterized by low HBV DNA blood levels) carried HDV genotype 1. Taken together, the significant HDV seroprevalence and the lack of effective anti-HDV therapy, necessitates strict clinical surveillance especially in patients with higher HDV viral loads and increased viral evolution.
Collapse
Affiliation(s)
- Rachel Shirazi
- Central Virology Laboratory, Ministry of Health, Chaim Sheba Medical Center, Tel - Hashomer, 52621, Ramat Gan, Israel
| | - Daniela Ram
- Central Virology Laboratory, Ministry of Health, Chaim Sheba Medical Center, Tel - Hashomer, 52621, Ramat Gan, Israel
| | - Aviya Rakovsky
- Central Virology Laboratory, Ministry of Health, Chaim Sheba Medical Center, Tel - Hashomer, 52621, Ramat Gan, Israel
| | - Efrat Bucris
- Central Virology Laboratory, Ministry of Health, Chaim Sheba Medical Center, Tel - Hashomer, 52621, Ramat Gan, Israel
| | - Yael Gozlan
- Central Virology Laboratory, Ministry of Health, Chaim Sheba Medical Center, Tel - Hashomer, 52621, Ramat Gan, Israel
| | - Yaniv Lustig
- Central Virology Laboratory, Ministry of Health, Chaim Sheba Medical Center, Tel - Hashomer, 52621, Ramat Gan, Israel
| | | | - Orit Picard
- Gastroenterology Laboratory, Sheba Medical Center, Ramat Gan, Israel
| | - Yonat Shemer-Avni
- Laboratory of Clinical Virology, Soroka University Medical Center, Beer Sheva, Israel
| | - Haim Ben-Zvi
- Microbiology Laboratory, Rabin Medical Center, Petach Tikva, Israel
| | - Ora Halutz
- Microbiology Laboratory, Sorasky Medical Center, Tel Aviv, Israel
| | - Yoav Lurie
- Liver Unit, Shaare Zedek Medical Center, Jerusalem, Israel
| | - Ella Veizman
- Liver Unit, Rambam Medical Center, Haifa, Israel
| | | | - Marius Braun
- Liver Institute, Rabin Medical Center, Petah-Tikva, Israel
| | | | - Amir Shlomai
- Liver Institute, Rabin Medical Center, Petah-Tikva, Israel.,The Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Rifaat Safadi
- Liver Unit, Hadassah Hebrew University Hospital, Jerusalem, Israel
| | - Ella Mendelson
- Central Virology Laboratory, Ministry of Health, Chaim Sheba Medical Center, Tel - Hashomer, 52621, Ramat Gan, Israel.,School of Public Health, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Ella H Sklan
- The Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Ziv Ben-Ari
- The Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.,Liver Disease Center, Sheba Medical Center, Ramat Gan, Israel
| | - Orna Mor
- Central Virology Laboratory, Ministry of Health, Chaim Sheba Medical Center, Tel - Hashomer, 52621, Ramat Gan, Israel. .,School of Public Health, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.
| |
Collapse
|
|
3
|
Le Gal F, Brichler S, Drugan T, Alloui C, Roulot D, Pawlotsky JM, Dény P, Gordien E. Genetic diversity and worldwide distribution of the deltavirus genus: A study of 2,152 clinical strains. Hepatology 2017; 66:1826-1841. [PMID: 28992360 DOI: 10.1002/hep.29574] [Citation(s) in RCA: 84] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/06/2017] [Accepted: 09/29/2017] [Indexed: 12/12/2022]
Abstract
UNLABELLED 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 eight 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 nucleotides 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 confirms that the HDV genus is composed of eight genotypes (HDV-1 to HDV-8) defined by an intergenotype similarity >85% or >80%, according to the partial or full-length genome sequence, respectively. Furthermore, genotypes can be segregated into two to four subgenotypes, characterized by an intersubgenotype 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 insight into the genetic diversity of HDV and a clear view of its geographical localization and allows speculation as to the worldwide spread of the virus, very likely from an initial African origin. (Hepatology 2017;66:1826-1841).
Collapse
Affiliation(s)
- Frédéric Le Gal
- Laboratoire de Microbiologie Clinique, Hôpitaux Universitaires de Paris Seine Saint-Denis, Site Avicenne, Université Sorbonne Paris Cité, Bobigny, France.,Centre national de référence des virus des hépatites B, C et Delta, Laboratoire de Virologie, Bobigny, France
| | - Ségolène Brichler
- Laboratoire de Microbiologie Clinique, Hôpitaux Universitaires de Paris Seine Saint-Denis, Site Avicenne, Université Sorbonne Paris Cité, Bobigny, France.,Centre national de référence des virus des hépatites B, C et Delta, Laboratoire de Virologie, Bobigny, France.,Unité INSERM U955, Equipe 18, Créteil, France
| | - Tudor Drugan
- Department of Medical Informatics and Biostatistics, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania
| | - Chakib Alloui
- Laboratoire de Microbiologie Clinique, Hôpitaux Universitaires de Paris Seine Saint-Denis, Site Avicenne, Université Sorbonne Paris Cité, Bobigny, France.,Centre national de référence des virus des hépatites B, C et Delta, Laboratoire de Virologie, Bobigny, France
| | - Dominique Roulot
- Centre national de référence des virus des hépatites B, C et Delta, Laboratoire de Virologie, Bobigny, France.,Unité d'Hépatologie, Hôpitaux Universitaires de Paris Seine Saint-Denis, Site Avicenne, Université Sorbonne Paris Cité, Bobigny, France
| | - Jean-Michel Pawlotsky
- Unité INSERM U955, Equipe 18, Créteil, France.,Centre national de référence des virus des hépatites B, C et Delta, Département de Virologie, Hôpital Henri Mondor, Université Paris-Est, Créteil, France
| | - Paul Dény
- Laboratoire de Microbiologie Clinique, Hôpitaux Universitaires de Paris Seine Saint-Denis, Site Avicenne, Université Sorbonne Paris Cité, Bobigny, France.,Centre de Recherches en Cancérologie de Lyon, INSERM U1052, UMR CNRS 5286, Team Hepatocarcinogenesis and Viral Infection, Lyon, France
| | - Emmanuel Gordien
- Laboratoire de Microbiologie Clinique, Hôpitaux Universitaires de Paris Seine Saint-Denis, Site Avicenne, Université Sorbonne Paris Cité, Bobigny, France.,Centre national de référence des virus des hépatites B, C et Delta, Laboratoire de Virologie, Bobigny, France.,Unité INSERM U955, Equipe 18, Créteil, France
| |
Collapse
|
|
4
|
Jamjoom GA, El-Daly MM, Azhar EI, Fallatah HI, Akbar HO, Babatin M, Alghamdi AS, Dgdgi MI, Hamid MA, Qari YA, El-Kafrawy SA. Prevalence and molecular characterization of hepatitis D virus in Saudi Arabia: A single-center study. Saudi J Gastroenterol 2017; 23:176-182. [PMID: 28611341 PMCID: PMC5470377 DOI: 10.4103/sjg.sjg_515_16] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/18/2022] Open
Abstract
BACKGROUND/AIMS Hepatitis D virus (HDV) is a defective RNA virus that is dependent on hepatitis B surface antigen (HBsAg) for transmission and replication. HDV significance arises from the possibility of poor prognosis of hepatitis B virus (HBV) infection. In Saudi Arabia, HDV prevalence varied from 8 to 32% before the HBV vaccination program and ranged from 0 to 14.7% after the vaccination program was started. The last study, performed in 2004, showed a prevalence of 8.6% in hospital-based HBV cases and 3.3% in healthy donors. The aim of this study was to investigate the prevalence and molecular characterization of HDV in chronic hepatitis B (CHB) patients at the King Abdulaziz University Hospital in Jeddah, Saudi Arabia by molecular and serological techniques. To the best of our knowledge, this is the first study to detect HDV at the molecular level in Saudi Arabia. PATIENTS AND METHODS The study included samples from 182 CHB patients from Jeddah; 13 samples with HBsAg negative were excluded. Samples were tested for HDV-Ab, viral RNA by reverse transcriptase-polymerase chain reaction (RT-PCR) in the HDV L-Ag region and sequence analysis. RESULTS The mean age of the participants was 44.36 years; 75.1% of the participants were Saudi nationals, 58% were males. Nine samples were positive for HDV-Ab and four were borderline; all were subjected to RT-PCR amplification. Three of the positive HDV-Ab cases and 1 borderline case were positive by RT-PCR. All the positive cases had HBV genotype D, and the positive RT-PCR cases were positive for HBV DNA. One of the HDV viremic samples was of genotype 1 by sequencing. The prevalence of HDV in the study was 7.7%, which was lower in Saudis (6.3%) than in non-Saudis (11.9%). CONCLUSION HDV coinfection does not seem to have an effect on the clinical status of the recruited CHB cases in this study. More studies are needed to investigate the genetic diversity in other areas such as the southern parts of the Kingdom.
Collapse
Affiliation(s)
- Ghazi A. Jamjoom
- Special Infectious Agent Unit, King Fahd Medical Research Centre, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Mai M. El-Daly
- Special Infectious Agent Unit, King Fahd Medical Research Centre, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Esam I. Azhar
- Special Infectious Agent Unit, King Fahd Medical Research Centre, King Abdulaziz University, Jeddah, Saudi Arabia
- Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Hind I. Fallatah
- Unit of Gastroenterology and Hepatology, Department of Internal Medicine, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Hisham O. Akbar
- Unit of Gastroenterology and Hepatology, Department of Internal Medicine, King Abdulaziz University, Jeddah, Saudi Arabia
| | | | | | - Mohammed I. Dgdgi
- Gastroenterology Department, King Fahd Central Hospital, Jizan, Saudi Arabia
| | - Mohamed A. Hamid
- Viral Hepatitis Research Laboratory, National Hepatology and Tropical Medicine Research Institute, Cairo, Egypt
- Department of Microbiology and Immunology, Faculty of Medicine, Minia University, Minia, Egypt
| | - Yousef A. Qari
- Department of Medicine, Section of Gastroenterology, King Abdulaziz University Hospital, Jeddah, Saudi Arabia
| | - Sherif A. El-Kafrawy
- Special Infectious Agent Unit, King Fahd Medical Research Centre, King Abdulaziz University, Jeddah, Saudi Arabia
| |
Collapse
|
|
5
|
Sadeghian H, Varasteh N, Esmaeelzadeh A, Nomani H, Alimardani M, Davoodnejad M, Meshkat M, Ahadi M, Sepahi S, Rostami S, Meshkat Z. Distribution of hepatitis delta virus genotypes in mashhad, northeast iran. Jundishapur J Microbiol 2015; 8:e14908. [PMID: 25793092 PMCID: PMC4353030 DOI: 10.5812/jjm.14908] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2013] [Revised: 11/17/2013] [Accepted: 12/25/2013] [Indexed: 12/29/2022] Open
Abstract
Background: Hepatitis delta virus (HDV) is dependent on the hepatitis B virus for transmission and propagation. Based on isolated HDV sequences from different parts of the world, at least three major different genotypes with different geographic distributions are suggested. Studies have shown that genotype 1 is the predominant genotype of HDV in different parts of Iran; however, the genotype distribution of this virus has not been identified in Mashhad, northeast Iran. Objectives: This current study determines the frequency of HDV major genotypes in Mashhad, Iran. Patients and Methods: Twenty-five participants were enrolled in this study. All samples were positive for HBsAg (determined by Enzyme-linked immunosorbent assay (ELISA)) and anti-HDV. RNA extraction and cDNA synthesis was performed. Then, PCR was performed and HDV genotypes were determined by restriction fragment length polymorphism (RFLP). Results: Of 25 patients, 12 (48%) were positive for HDV RNA. Genotype analysis of HDV RNA revealed that the prevalence of HDV genotypes I and II was 83.3% (n = 10) and 16.7% (n = 2), respectively. Conclusions: This study showed that the most prevalent genotype of HDV in Mashhad was genotype I. It was of interest that in contrast to other provinces of Iran, HDV genotype 2 was observed in Mashhad. Similar studies with larger sample sizes could provide valuable information regarding the molecular epidemiology and geographical distribution. It may also help control and prevent the spread of hepatitis D virus infections. In addition, the genotyping of HDV may predict the severity of the disease.
Collapse
Affiliation(s)
- Hamid Sadeghian
- Department of Laboratory Sciences, School of Paramedical Sciences, Mashhad University of Medical Sciences, Mashhad, IR Iran
| | - Naiemeh Varasteh
- School of Medicine, Islamic Azad University, Mashhad Branch, Mashhad, IR Iran
| | - Abbas Esmaeelzadeh
- Department of Internal Medicine, School of Medicine, Mashhad University of Medical Sciences, Mashhad, IR Iran
| | - Hosein Nomani
- Antimicrobial Resistance Research Center, Mashhad University of Medical Sciences, Mashhad, IR Iran
| | - Maliheh Alimardani
- Department of Laboratory Sciences, School of Paramedical Sciences, Mashhad University of Medical Sciences, Mashhad, IR Iran
| | - Mahdieh Davoodnejad
- Department of Human Genetic, School of Medicine, Mashhad University of Medical Sciences, Mashhad, IR Iran
| | - Mojtaba Meshkat
- Department of Biostatistics, School of Allied Medical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, IR Iran
| | - Mitra Ahadi
- Department of Internal Medicine, School of Medicine, Mashhad University of Medical Sciences, Mashhad, IR Iran
| | - Samaneh Sepahi
- Targeted Drug Delivery Research Center, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, IR Iran
| | - Sina Rostami
- Department of Biology, Faculty of Sciences, Ferdowsi University of Mashhad, Mashhad, IR Iran
| | - Zahra Meshkat
- Department of Human Genetic, School of Medicine, Mashhad University of Medical Sciences, Mashhad, IR Iran
- Corresponding author: Zahra Meshkat, Antimicrobial Resistance Research Center, Mashhad University of Medical Sciences, Mashhad, IR Iran. Tel: +98-5118012453, Fax: +98-5118002960, E-mail:
| |
Collapse
|
|
6
|
Huang CR, Lo SJ. Hepatitis D virus infection, replication and cross-talk with the hepatitis B virus. World J Gastroenterol 2014; 20:14589-14597. [PMID: 25356023 PMCID: PMC4209526 DOI: 10.3748/wjg.v20.i40.14589] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/28/2013] [Revised: 05/12/2014] [Accepted: 06/23/2014] [Indexed: 02/06/2023] Open
Abstract
Viral hepatitis remains a worldwide public health problem. The hepatitis D virus (HDV) must either coinfect or superinfect with the hepatitis B virus (HBV). HDV contains a small RNA genome (approximately 1.7 kb) with a single open reading frame (ORF) and requires HBV supplying surface antigens (HBsAgs) to assemble a new HDV virion. During HDV replication, two isoforms of a delta antigen, a small delta antigen (SDAg) and a large delta antigen (LDAg), are produced from the same ORF of the HDV genome. The SDAg is required for HDV replication, whereas the interaction of LDAg with HBsAgs is crucial for packaging of HDV RNA. Various clinical outcomes of HBV/HDV dual infection have been reported, but the molecular interaction between HBV and HDV is poorly understood, especially regarding how HBV and HDV compete with HBsAgs for assembling virions. In this paper, we review the role of endoplasmic reticulum stress induced by HBsAgs and the molecular pathway involved in their promotion of LDAg nuclear export. Because the nuclear sublocalization and export of LDAg is regulated by posttranslational modifications (PTMs), including acetylation, phosphorylation, and isoprenylation, we also summarize the relationship among HBsAg-induced endoplasmic reticulum stress signaling, LDAg PTMs, and nuclear export mechanisms in this review.
Collapse
|
|
7
|
Abstract
Hepatitis D virus (HDV) is a satellite of hepatitis B virus (HBV), and infection with this virus aggravates acute and chronic liver disease. While HBV seroprevalence is very high across sub-Saharan Africa, much less is known about HDV in the region. In this study, almost 2,300 blood serum samples from Burkina Faso (n=1,131), Nigeria (n=974), Chad (n=50), and the Central African Republic (n = 118) were screened for HBV and HDV. Among 743 HBsAg-positive serum samples, 74 were positive for HDV antibodies and/or HDV RNA, with considerable differences in prevalence, ranging from <2% (pregnant women from Burkina Faso) to 50% (liver patients from Central African Republic). HDV seems to be much more common in chronic liver disease patients in the Central African Republic (CAR) than in similar cohorts in Nigeria. In a large nested mother-child cohort in Burkina Faso, the prevalence of HDV antibodies was 10 times higher in the children than in their mothers, despite similar HBsAg prevalences, excluding vertical transmission as an important route of infection. The genotyping of 16 full-length and 8 partial HDV strains revealed clade 1 (17/24) in three of the four countries, while clades 5 (5/24) and 6 (2/24) were, at least in this study, confined to Central Nigeria. On the amino acid level, almost all our clade 1 strains exhibited a serine at position 202 in the hepatitis D antigen, supporting the hypothesis of an ancient African HDV-1 subgroup. Further studies are required to understand the public health significance of the highly varied HDV prevalences in different cohorts and countries in sub-Saharan Africa.
Collapse
|
|
8
|
Abstract
Hepatitis delta virus (HDV) is a unique human virus, showing similarities with plant viroids. Although impressive knowledge on virus structure and replication has been achieved, several questions like HBV/HDV interaction and post translational modifications of HD antigens remain to be answered. Potential targets for therapeutic strategies are now emerging. To date, eight major genotypes of the HDV have been identified. The HDV-1 is the prevailing genotype in Europe, but migration phenomena may change this profile. Immune response is likely to play an important role in the pathogenesis of HDV-induced liver disease; few data are available on T cells response either during infection and therapy. HDV usually suppresses HBV replication; recent studies show as viral dominances may change over time. Delta infection leads to severe liver disease, with different patterns of progression to liver fibrosis and decompensation. Beside the association between HDV/HBV and HCC is demonstrated a risk specifically related to HDV remains controversial.
Collapse
|
|
9
|
Abstract
Hepatitis delta virus (HDV) is a small, defective RNA virus that can infect only individuals who have hepatitis B virus (HBV); worldwide more than 15 million people are co-infected. There are eight reported genotypes of HDV with unexplained variations in their geographical distribution and pathogenicity. The hepatitis D virion is composed of a coat of HBV envelope proteins surrounding the nucleocapsid, which consists of a single-stranded, circular RNA genome complexed with delta antigen, the viral protein. HDV is clinically important because although it suppresses HBV replication, it causes severe liver disease with rapid progression to cirrhosis and hepatic decompensation. The range of clinical presentation is wide, varying from mild disease to fulminant liver failure. The prevalence of HDV is declining in some endemic areas but increasing in northern and central Europe because of immigration. Treatment of HDV is with pegylated interferon alfa; however, response rates are poor. Increased understanding of the molecular virology of HDV will identify novel therapeutic targets for this most severe form of chronic viral hepatitis.
Collapse
Affiliation(s)
- Sarah A Hughes
- Institute of Liver Studies, King's College Hospital, London, UK
| | | | | |
Collapse
|
|
10
|
Kim HS, Kim SJ, Park HW, Shin WG, Kim KH, Lee JH, Kim HY, Jang MK. Prevalence and clinical significance of hepatitis D virus co-infection in patients with chronic hepatitis B in Korea. J Med Virol 2011; 83:1172-7. [DOI: 10.1002/jmv.22095] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/16/2011] [Indexed: 12/18/2022]
|
|
11
|
Abstract
Hepatitis D virus (HDV) infection involves a distinct subgroup of individuals simultaneously infected with the hepatitis B virus (HBV) and characterized by an often severe chronic liver disease. HDV is a defective RNA agent needing the presence of HBV for its life cycle. HDV is present worldwide, but the distribution pattern is not uniform. Different strains are classified into eight genotypes represented in specific regions and associated with peculiar disease outcome. Two major specific patterns of infection can occur, i.e. co-infection with HDV and HBV or HDV superinfection of a chronic HBV carrier. Co-infection often leads to eradication of both agents, whereas superinfection mostly evolves to HDV chronicity. HDV-associated chronic liver disease (chronic hepatitis D) is characterized by necro-inflammation and relentless deposition of fibrosis, which may, over decades, result in the development of cirrhosis. HDV has a single-stranded, circular RNA genome. The virion is composed of an envelope, provided by the helper HBV and surrounding the RNA genome and the HDV antigen (HDAg). Replication occurs in the hepatocyte nucleus using cellular polymerases and via a rolling circle process, during which the RNA genome is copied into a full-length, complementary RNA. HDV infection can be diagnosed by the presence of antibodies directed against HDAg (anti-HD) and HDV RNA in serum. Treatment involves the administration of pegylated interferon-α and is effective in only about 20% of patients. Liver transplantation is indicated in case of liver failure.
Collapse
Affiliation(s)
- Stéphanie Pascarella
- Department of Pathology and Immunology, University of Geneva, Geneva, Switzerland
| | | |
Collapse
|