Biological Sciences
Hepatitis D
Hepatitis D, also known as delta hepatitis, is a liver infection caused by the hepatitis D virus (HDV). It is considered the most severe form of viral hepatitis, as it can only occur in individuals who are already infected with hepatitis B. HDV is transmitted through contact with infected blood or bodily fluids, and the infection can lead to a more severe liver disease than hepatitis B alone.
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10 Key excerpts on "Hepatitis D"
eBook - ePub- Howard C. Thomas, Anna S. Lok, Stephen A. Locarnini, Arie J. Zuckerman, Howard C. Thomas, Anna S. F. Lok, Stephen A. Locarnini, Arie J. Zuckerman, Anna S. Lok, Howard C. Thomas, Anna S. F. Lok, Stephen A. Locarnini, Arie J. Zuckerman(Authors)
- 2013(Publication Date)
- Wiley-Blackwell(Publisher)
Section V Hepatitis D Virus
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Chapter 27
Structure and molecular virology
Francesco Negro
Divisions of Clinical Pathology and Gastroenterology and Hepatology, University Hospital, Geneva, Switzerland
SummaryThe Hepatitis D virus (HDV) is a defective RNA infectious agent needing the presence of the hepatitis B virus (HBV) to complete its life cycle. HDV is present worldwide, but the distribution pattern is not uniform. Different viral strains are classified into eight genotypes found in specific geographical areas and often associated with severe disease outcome. The HDV particle is composed of an envelope, provided by the helper HBV, surrounding the 1.7 kB RNA genome and the HDV antigen. Replication occurs in the hepatocyte nucleus via a rolling-circle mechanism that leads to a full-length, complementary RNA as a replication intermediate. Since HDV does not possess the encoding capability for a RNA polymerase, replication is brought about by cellular polymerases.Introduction
The HDV discovery dates back to 1977, when Rizzetto and coworkers reported the detection of a novel nuclear antigen – initially dubbed the delta antigen – in the hepatocytes of patients with a severe form of chronic hepatitis B [1,2]. Later experiments in chimpanzees showed that the Hepatitis Delta (or D) antigen (HDAg) was a structural component of a transmissible virus requiring the simultaneous presence of HBV to complete its life cycle. This premise is necessary to understand fully the unusual structure of HDV particles, which are composed of HBV envelope proteins surrounding a ribonucleoprotein inner structure, comprising the HDAg and the HDV RNA genome [3]. Initially known as “delta agent” or hepatitis “delta” virus, currently the term “Hepatitis D virus” is preferred, even if “delta” is still frequently used.
eBook - ePubZakim and Boyer's Hepatology
A Textbook of Liver Disease E-Book
- Thomas D. Boyer, Keith D Lindor, Arun J. Sanyal, Norah A Terrault, Arun J. Sanyal, Norah A Terrault(Authors)
- 2016(Publication Date)
- Elsevier(Publisher)
34Hepatitis D
Theo Heller, Christopher Koh, Jeffrey S. GlennAbbreviationsALT alanine aminotransferaseHBsAg hepatitis B surface antigenHBV hepatitis B virusHCC hepatocellular carcinomaHCV hepatitis C virusHDV Hepatitis Delta virusIntroduction
Hepatitis Delta virus (HDV) is the sole member of the genus Deltavirus and is estimated to infect 15 million to 20 million people of all age groups worldwide. HDV is a human pathogen, and HDV infection can exist as an acute or chronic infection and occurs only in individuals who have active hepatitis B virus (HBV) infection. It is a defective RNA virus that requires hepatitis B surface antigen for assembly and transmission. It is currently the only chronically infecting human hepatitis virus that is without an FDA-approved therapy. Although rare, hepatitis D is known to be the most rapidly progressive viral hepatitis and the most likely to lead to cirrhosis, and as such may be viewed as the most severe form of human viral hepatitis.Historical Perspective
The initial identification of HDV dates back to the mid-1970s during an investigation of a group of patients with HBV infection who developed severe hepatitis.1 During this investigation a novel nuclear antigen, coined the delta antigen , was discovered and initially thought to be a hepatitis B antigen. In subsequent chimpanzee experiments the delta antigen was identified as a structural component of a distinct pathogen that required HBV for its life cycle.2 , 3 The precise molecular origin of HDV remains a subject of speculation.4Since the discovery of HDV, HDV infection has been found in all age groups worldwide. Worldwide prevalence data, although improving through increased awareness, testing, and reporting, are still limited, and most reports are based on studies of seroprevalence of anti-HDV in hepatitis B surface antigen (HBsAg)-positive patients (Fig. 34-1
- James S. Dooley, Anna S. Lok, Guadalupe Garcia-Tsao, Massimo Pinzani, James S. Dooley, Anna S. F. Lok, Guadalupe Garcia-Tsao, Massimo Pinzani, James S. Dooley, Anna S. F. Lok, Guadalupe Garcia-Tsao, Massimo Pinzani(Authors)
- 2018(Publication Date)
- Wiley-Blackwell(Publisher)
[2] . In 1983, the delta agent was renamed Hepatitis Delta virus (HDV) and the disease it causes Hepatitis D. The association of HDV with hepatitis B virus (HBV) stems from the fact that HDV is a hybrid virus that incorporates the hepatitis B virus surface antigen (HBsAg) as its envelope protein. As a consequence, HDV can establish infection only in individuals who simultaneously harbour HBV. Infection with HDV is found worldwide and is associated with the most severe forms of acute, including fulminant, hepatitis and chronic liver disease in HBsAg‐positive subjects.Hepatitis D virus (Table 22.1 )Characteristics of Hepatitis D virus (HDV)Table 22.1Classification Genus Deltavirus Defective Requires the helper function of HBV Virion 35–37 nm particle, coated by HBsAg Genome 1.7 kb single‐stranded, circular RNA, negative polarity Open reading frame One, encoding HDAg Genotypes Eight Pathogenicity High, acute and chronic hepatitis Distribution Worldwide, 15 million HBsAg carriers coinfected with HDV HDV is a defective RNA virus that requires the helper function of HBV for virion assembly, release, and transmission [3] . HDV does not resemble any known transmissible agent of animals, but shares similarities with plant viroids. Owing to its uniqueness, it has been classified as the type species of a separate genus, Deltavirus [4] . HDV is the smallest animal virus, 35–37 nm in diameter, and the only one to possess a circular RNA genome, which contains a single‐stranded negative RNA of about 1700 nucleotides (Fig. 22.1 ) [5] . The HDV genome encodes a single structural protein, the Hepatitis Delta antigen (HDAg). Within the virus particle is a nucleocapsid, a ribonucleoprotein complex formed by the RNA genome with the HDAg [3] . There are two related forms of HDAg, the short (HDAg‐S; 195 amino acids) and the long (HDAg‐L; 214 amino acids). HDAg‐S is essential for viral replication, whereas HDAg‐L is required for virus assembly and inhibits viral replication [3] . HDAg‐L contains an isoprenylation motif at the C‐terminus that plays an essential role in HDV assembly [6] . The virion is coated by HBsAg, which is the only helper function provided by HBV. The HBsAg levels and the sequence of natural HBsAg variants influence the assembly and secretion of HDV [7]
eBook - PDF- Shiela Sherlock, James Dooley, James S. Dooley(Authors)
- 2008(Publication Date)
- Wiley-Blackwell(Publisher)
Heptatitis D viremia fol-lowing orthotopic liver transplantation involves a typical HDV virion with a hepatitis B surface antigen envelope . Hepatology 1998; 27 : 1723. 24 Smedile A, Rosina F, Saracco G et al . Hepatitis B virus repli-cation modulates pathogenesis of Hepatitis D virus in chronic Hepatitis D. Hepatology 1991; 13 : 413. 25 Stroffolini T, Ferrigno L, Cialdea L et al . Incidence and risk factors of acute delta hepatitis in Italy: results from a national surveillance system. J. Hepatol . 1994; 21 : 1123. 26 Weisfuse IB, Hadler SC, Fields HA et al . Delta hepatitis in homosexual men in the United States. Hepatology 1989; 9 : 872. 27 Wu J-C, Chen T-A, Huang Y-S et al . Natural history of Hepatitis D viral superinfection: significance of viremia detected by polymerase chain reaction. Gastroenterology 1995; 108 : 796. 28 Wu J-C, Choo K-B, Chen C-M et al . Genotyping of Hepatitis D virus by restriction-fragment length polymerase and rela-tion to outcome of Hepatitis D. Lancet 1995; 346 : 939. Hepatitis B Virus and Hepatitis Delta Virus 303 The ability to diagnose hepatitis virus A and B infection did not resolve the problem of acute and chronic hepati-tis. A third major category had always been suspected but, in the absence of a diagnostic test, had been desig-nated non-A, non-B virus hepatitis. A third type has now been identified and called hepatitis C virus (HCV) [119]. This followed identification of a viral clone of the HCV virus from chimpanzee liver which had been infected with non-A, non-B virus [119]. An antibody test followed. Hepatitis C is a major health problem [20]. Global prevalence of chronic hepatitis C is estimated to average 3% (ranging from 0.1 to 5% in different countries). There are some 175 million chronic HCV carriers throughout the world, of which an estimated 2 million are in the USA and 5 million in Western Europe.
eBook - PDF- E.A. Fagan, T.J. Harrison(Authors)
- 2003(Publication Date)
- Garland Science(Publisher)
Chapter 3 Hepatitis B (HBV) and Hepatitis D (HDV, delta) Viruses 3.0 Introduction HBV and HDV share with hepatitis C virus a major route of transmission (parenteral), risk factors for infection and the propensity for persistent infection leading to chronic hepatitis and cirrhosis. Individuals in high-risk groups (Table 3.1) may be infected with all three viruses. Epidemiological differences, including high rates of sexual and vertical transmission for HBV, but low for HDV and HCV, may reflect differing efficiencies of transmission and levels of viremia. HCV is reviewed in Chapter 4. Aspects of hepatitis B and D relating to acute liver failure, organ transplantation, pregnancy and pediatric issues are dealt with in Chapters 5, 6 and 7. 3.1 Epidemiology HBV and HDV share the same epidemiology and dual infection accounts for significant morbidity and mortality. HBV is endemic worldwide. An estimated 350 million people carry hepatitis B surface antigen (HBsAg) and around 5% (at least 5 million) of these are superinfected with HDV (Table 3.2). HBV is a major cause of liver disease worldwide, including chronic hepatitis, cirrhosis and hepatocellular carcinoma (HCC or primary liver cancer, PLC). Worldwide, HCC is one of the most common cancers, at least in males, and HBV has been implicated in over Table 3.1. Risks for transmission of HBV High prevalence areas • Infants of carrier mothers • Household contacts of carriers • Inadequately sterilized instruments for percutaneous use Low prevalence areas • Sexual contact with carriers • Intravenous drug use • Multiply transfused and recipients of blood products 80% of cases. The 750 000 deaths per annum from HCC are expected to rise with population growth and falling infant mortality. The long-term risk for a HBsAg seropositive carrier male dying from cirrhosis and other complications may exceed 40%.
eBook - PDFDrug Discovery and Development
From Molecules to Medicine
- Omboon Vallisuta, Suleiman Olimat, Omboon Vallisuta, Suleiman Olimat(Authors)
- 2015(Publication Date)
- IntechOpen(Publisher)
Section 4 Management and Development of Drugs Against Infectious Diseases Chapter 8 Current Management and Novel Therapeutic Strategies to Combat Chronic Delta Hepatitis Hrvoje Roguljic, Sonja Sarcevic, Robert Smolic, Nikola Raguz Lucic, Aleksandar Vcev and Martina Smolic Additional information is available at the end of the chapter http://dx.doi.org/10.5772/59936 1. Introduction Forty years ago Mario Rizzeto’s group identified a new antigen-antibody system (delta antibody and delta antigen (HDAg)) in HBsAg carriers with severe hepatitis [1, 2]. Further experiments in chimpanzees showed that this HDAg marked transmissible pathogen requires coexistence of HBV infection for its life cycle, proving its defective nature which requires HBsAg for transmission and replication [3]. As the cause of Hepatitis D was identified, a virion particle (Figure 1.) composed of outer coat containing HBV envelope proteins (HBsAg) and inner nuclocapsid was described [4]. Internal nuclear like structure is comprised of single stranded, circular RNA molecule of 1700 nucleotides associated with two distinctive forms of Hepatitis D antigen (HDAg), small and large subunit [5, 6]. Although HDV in its structure possesses HBsAg, HDV is classified as separate pathogen with own genus called Deltavirus [7]. This unusual virus is the smallest infectious pathogen in human virology, with unique replication cycle unknown to animal cells. During replication process a viral RNA is transcri‐ bed by hosts RNA polymerases [8], which usually transcribe DNA molecules, and after transcription HDV RNA is cleaved by its own ribozyme [9]. Dependence on the HBsAg presence results in two patterns of HDV infection. HDV can be transmitted simultaneously with HBV (co-infection pattern) or infection may occur at preced‐ ing HBV infected individual (super-infection pattern). Due to differences of HDV acquisition clinical course and outcome of HDV infection varies.
eBook - PDF- Joao Monjardino(Author)
- 1998(Publication Date)
- ICP(Publisher)
PART 3 DELTA HEPATITIS VIRUS This page intentionally left blank History Hepatitis Delta virus was first detected in 1977 as a new hepatocyte nuclear antigen in patients infected with hepatitis B virus and was shown to be frequently associated with acute fulminant or rapidly progressing chronic disease (Rizzetto etal, 1977). The antigen (HDAg) was first shown to be un-related to HBV and later to be associated with a new agent, an RNA-containing virus enveloped in HBV surface antigen (Rizzetto etal., 1980). Detection of HDAg in liver and assays for detection of serum antibodies and viral antigen made possible the diagnosis of HDV infection and the characterization of its natural history. Analysis of the virus at the molecular level, including the cloning of its genome, have since made important contributions to our understanding of virus replication, assembly, virus detection and pathogenesis. The Virus Classification HDV has a circular single-stranded RNA genome of negative polarity. The virus has yet to be classified. The structure of its genome and the mechanism of its replication show striking similarities with some plant pathogens (viroids, virusoids and satellite RNAs). It is however clearly distinct from viroids in containing a larger genome which encodes one protein, delta antigen (HDAg), and in possessing an envelope (Riesner and Gross, 1985). The agent is also quite different from virusoids and satellite RNAs, the former being similar in size and structure to viroids but encapsidated together with single-stranded 65 66 Molecular Biology of Human Hepatitis Viruses plant RNA viruses and the latter enveloped in helper virus protein coats (as HDV) but incapable of autonomous replication. The agent is the smallest human pathogen known and the only example of a human virus containing a circular RNA genome. The Virion HDV is a small RNA virus consisting of spherical particles about 36 nm in diameter and with a buoyant density of 1.25 gm/cm 3 (Bonino et al., 1984).
eBook - ePub- Lawrence S. Friedman, Paul Martin(Authors)
- 2017(Publication Date)
- Elsevier(Publisher)
Chapter 4Hepatitis B and Hepatitis D
Tram T. Tran, MDAbstract
Hepatitis B virus (HBV) is a major cause of chronic liver disease and hepatocellular carcinoma worldwide. The development of chronic infection after exposure is inversely related to age; therefore global prevention strategies are aimed at infant vaccination and prevention of mother-to-child transmission. HBV infection is often asymptomatic, and screening of high-risk persons and treatment of those at risk for disease progression are indicated. Treatment with nucleoside or nucleotide analog therapy leads to long-term viral suppression with a reduction in the risk disease progression and hepatocellular carcinoma. Resistance and adverse events are uncommon with first-line therapies.Key PointsKeywords
entecavir; hepatitis B; Hepatitis D; hepatocellular carcinoma; tenofovir1 Hepatitis B virus (HBV) infection is a major cause of acute liver failure, cirrhosis, and hepatocellular carcinoma (HCC). 2 HBV infection can be prevented by hepatitis B vaccination.3 Acute HBV infection is most likely to resolve spontaneously in immunocompetent adults, especially if symptomatic. Progression to chronic infection is typical in children, the elderly, and immunocompromised persons, including hemodialysis patients.
eBook - PDF- Dongyou Liu(Author)
- 2016(Publication Date)
- CRC Press(Publisher)
At the other end of the clinical spectrum are patients with chronic HDV disease and marked elevation of ALT, and HBeAg-positive or -negative patients with active HBV and HDV replication or with histological evidence of severe hepatitis. In such patients, cirrhosis develops at an annual rate of 4% and a cumulative probability of 35% at 10 and 55% at 20 years [55,91,99]. The usual presentation of end-stage liver disease in patients with florid HDV infection is that of liver failure rather than complications of portal hypertension [91,99]. However, HCC may also complicate chronic HDV infection with an incidence rate of 2.8% per year and a cumu-lative probability of 13% at 10 and 18% at 20 years [91]. End-stage HDV liver disease, with or without HCC amounts for 45% of the HBsAg-positive cases requiring liver transplantation in Italy, the high percentage reflecting both the aggressive course of the disease and the lack of specific therapy [103]. Pathogenesis. Besides acute or chronic infection HDV can also run a self-limited latent course, as initially observed in the liver transplantation setting. In patients with HDV infection undergoing liver transplantation, HDAg can be immunohistochemically detected in the grafted liver within a few hours in the absence of serum HDV RNA, or HBsAg, indicating that HDV infection is not productive [104]. Latent HDV infection, in the absence of concomitant HBV infec-tion is transient. It is not associated with histological injury of the transplanted liver, unless active HBV infection is also present. The pathogenesis of liver damage in HDV infection is not completely clear. On the basis of morphological and other observations, a direct cytopathic effect has been postulated in acute HDV infection, but this issue is controversial [92,98,105].
eBook - PDFPerspectives in Medical Virology, vol. 1
Perspectives in Medical Virology, vol. 1
- Brian Evans(Author)
- 2003(Publication Date)
- Elsevier(Publisher)
615 CHAPTER 16 Hepatitis virus infections Jaundice has been known as a symptom of serious disease since ancient times. Sev- eral virus infections can result in jaundice or hepatitis but only a few viruses are characterized as hepatitis viruses. At least three distinct hepatitis viruses have been found and some of their properties are listed in Table 16.1. Although hepatitis A virus is a picornavirus (Chapter 4) it is discussed in this chapter together with hepa- titis B which is a DNA virus, the &agent and the non A-, non B hepatitis viruses. This should not be taken as an indication of similarities in the molecular biology of these viruses but is rather an adherence to the normal clinical grouping of these viruses. The differential clinical diagnosis of the hepatitis viruses has presented con- siderable problems. The hepatitis viruses have been the subject of several excellent reviews and these should be consulted by readers requiring more detailed informa- tion (Zuckerman, 1975, Cossart, 1977, Vyas et al., 1978, Zuckerman and Howard, TABLE 16.1 Hepatitis viruses Properties Virus Hepatitis A Hepatitis B &Agent Non-A, non- B hepatitis Transfusion Epidemic Viral nucleic acid RNA DNA RNA ? RNA? Chronic infections - + + Helper virus - - Hepatitis B - - + - 616 1979, Gerety, 1981, Bianchi et al., 1980, Sherlock, 1980, Szmuness et al., 1982, Deinhardt and Gust, 1982). 16.1. Hepatitis A virus infections I 6. I . I . THE VIRUS Hepatitis A virus is a small RNA virus classified as human enterovirus 72 (Gust et al., 1983). It is 27 nm in diameter (Fig. 16.l), has no envelope or lipids and con- tains a single stranded infectious RNA with a molecular weight of 2.5 x 10s indi- cated in Table 16.2. The virus is fairly stable to heat, ether and acids. One serotype has been described and the nomenclature of viral antigens and antibodies is listed in Table 16.3.
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