Chapter 56 : Hepatitis D Virus

MyBook is a cheap paperback edition of the original book and will be sold at uniform, low price.

Ebook: Choose a downloadable PDF or ePub file. Chapter is a downloadable PDF file. File must be downloaded within 48 hours of purchase

Buy this Chapter
Digital (?) $30.00

Preview this chapter:
Zoom in

Hepatitis D Virus, Page 1 of 2

| /docserver/preview/fulltext/10.1128/9781555815981/9781555814250_Chap56-1.gif /docserver/preview/fulltext/10.1128/9781555815981/9781555814250_Chap56-2.gif


Hepatitis delta virus (HDV) is the only member of the family , genus . To establish infection in vivo, HDV depends on helper functions provided by hepatitis B virus (HBV). HDV encodes a single protein, the HDAg, which is translated from a 0.8-kb mRNA transcribed from the genomic RNA. The host range of HDV infection includes humans, chimpanzees, woodchucks, and ducks carrying HBV-related hepadnaviruses. A common feature of experimental HDV infection is the inhibition of HBV, shown by a decrease in the levels of HBsAg and HBV DNA in the serum and liver. The liver histologic pattern of hepatitis D is nonspecific and is similar to other types of viral hepatitis. The intralobular inflammatory cells were mainly macrophages containing periodic acid-Schiff-positive nonglycogenic granules. The main strategies for the prevention of HDV infection are (i) behavioral modifications to prevent disease transmission and (ii) active immunization against HBV. Changes in sexual practices in response to human immunodeficiency virus (HIV) infection have probably contributed to the declining incidence of HBV and HDV infection in the developed world and abroad, and improved methods for screening of blood products in blood banks have reduced the risk of transmission-associated hepatitis. HBV antisense oligonucleotides were constructed to alter HBV functions that are considered essential for HDV replication in vitro.

Citation: Smedile A, Ciancio A, Rizzetto M. 2009. Hepatitis D Virus, p 1291-1306. In Richman D, Whitley R, Hayden F (ed), Clinical Virology, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815981.ch56

Key Concept Ranking

Infection and Immunity
Restriction Fragment Length Polymorphism
Highlighted Text: Show | Hide
Loading full text...

Full text loading...


Image of FIGURE 1

Schematic representation of HDV.

Citation: Smedile A, Ciancio A, Rizzetto M. 2009. Hepatitis D Virus, p 1291-1306. In Richman D, Whitley R, Hayden F (ed), Clinical Virology, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815981.ch56
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of FIGURE 2

HDV RNA genome structure.

Citation: Smedile A, Ciancio A, Rizzetto M. 2009. Hepatitis D Virus, p 1291-1306. In Richman D, Whitley R, Hayden F (ed), Clinical Virology, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815981.ch56
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of FIGURE 3

Sequence and secondary structure of the HDV genomic ribozyme. In the left box the specific on/off adaptor (SOFA) delta ribozyme module is shown. BL, blocker; BS, biosensor; ST, stabilizer. A search for ribozymes in the human genome map showed that a ribozyme segment structurally and biochemically related to the HDV ribozyme is contained in a conserved mammalian sequence residing in an intron of the CPEB3 gene, which belongs to a family of genes regulating mRNA polyadenylation ( ). On the basis of these observations, it is thought that HDV ribozymes and the CPEB3 ribozyme are evolutionarily related and that HDV may have arisen from the human transcriptome.

Citation: Smedile A, Ciancio A, Rizzetto M. 2009. Hepatitis D Virus, p 1291-1306. In Richman D, Whitley R, Hayden F (ed), Clinical Virology, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815981.ch56
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of FIGURE 4

HDAg gene and protein domains. ORF, open reading frame.

Citation: Smedile A, Ciancio A, Rizzetto M. 2009. Hepatitis D Virus, p 1291-1306. In Richman D, Whitley R, Hayden F (ed), Clinical Virology, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815981.ch56
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of FIGURE 5

Serologic profile of HBV-HDV coinfection.

Citation: Smedile A, Ciancio A, Rizzetto M. 2009. Hepatitis D Virus, p 1291-1306. In Richman D, Whitley R, Hayden F (ed), Clinical Virology, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815981.ch56
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of FIGURE 6

Serologic course of HDV superinfection evolving to chronicity.

Citation: Smedile A, Ciancio A, Rizzetto M. 2009. Hepatitis D Virus, p 1291-1306. In Richman D, Whitley R, Hayden F (ed), Clinical Virology, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815981.ch56
Permissions and Reprints Request Permissions
Download as Powerpoint


1. Abe, K.,, E. Hayakawa,, A. V. Sminov,, A. L. Rossina,, X. Ding,, T. T. T. Huy,, T. Sata, and, V. F. Uchaikin. 2004. Molecular epidemiology of hepatitis B, C, D and E viruses among children in Moscow, Russia. J. Clin. Virol. 30:5761.
2. Altuglu, I.,, T. Ozacar,, R. Sertoz, and, S. Erensoy. 2007. Hepatitis Delta virus (HDV) genotypes in patients with chronic hepatitis: molecular epidemiology of HDV in Turkey. Int. J. Infect. Dis. 11:5862.
3. Amengual, M. J.,, M. Catalfamo,, A. Pujol,, C. Juarez,, C. Gelpi, and, J. L. Rodriguez. 1989. Autoantibodies in chronic delta virus infection recognize a common protein of 46 KD in rat forestomach basal cell layer and stellate thymic epithelial cells. Clin. Exp. Immunol. 78:8084.
4. Aragona, M.,, S. Macagno,, F. Caredda,, C. Lavarini,, L. Bertolusso,, P. Farci, and, M. Rizzetto. 1987. Serological response to the hepatitis delta virus in hepatitis D. Lancet i:478480.
5. Asif-Ullah, M.,, M. Lévesque,, G. Robichaud, and, J. P. Perreault. 2007. Development of ribozyme-based gene inactivations: the example of the hepatitis delta virus ribozyme. Curr. Gene Ther. 7:205216.
6. Bart, P. A.,, P. Jacquier,, P. L. Zuber,, D. Lavanchy, and, P. C. Frei. 1996. Seroprevalence of HBV (anti-HBc, HBsAg and anti-HBs) and HDV infections among 9006 women at delivery. Liver 16:110116.
7. Bergeon, L.,, Jr., C. Reymond, and, J. P. Perreault. 2005. Functional characterization of the SOFA delta ribozyme. RNA 11:18581868.
8. Bialek, S. R.,, W. A. Bower,, K. Mottram,, D. Purchase,, T. Nakano,, O. Nainan,, I. T. Williams, and, B. P. Bell. 2005. Risk factors for hepatitis B in an outbreak of hepatitis B and D among injection drug users. J. Urban Health 83:468478.
9. Bonino, F.,, N. Caporaso,, P. Dentico,, G. Marinucci,, L. Valeri,, A. Craxi,, A. Ascione,, G. Raimondo,, F. Piccinino, and, G. Rocca. 1985. Familiar clustering and spreading of delta infection. J. Hepatol. 1:221226.
10. Bordier, B. B.,, H. B. Greenberg,, K. Ohashi,, M. A. Kay, and, J. S. Glenn. 2000. Prospects for prenylation inhibition-based anti-HDV therapy. Antiviral Ther. 5:25.
11. Bordier, B. B.,, J. Ohkanda,, P. Liu,, S. Y. Lee,, F. H. Salazar,, P. L. Marion,, K. Ohashi,, L. Meuse,, M. A. Kay,, J. L. Casey,, A. M. Sebti,, A. D. Hamilton, and, J. S. Glenn. 2003. In vivo antiviral efficacy of prenylation inhibitors against hepatitis delta virus. J. Clin. Investig. 112:407414.
12. Borghesio, E.,, F. Rosina,, A. Smedile,, M. Lagget,, M. G. Niro,, G. Marinucci, and, M. Rizzetto. 1998. Serum IgM anti-HDV as a surrogate marker of hepatitis D in interferon-treated patients and in liver transplants. Hepatology 27:873876
13. Bortolotti, F.,, V. Di Marco,, P. Vajro,, C. Crivellaro,, L. Zancan,, G. Nebbia,, C. Barbera,, M. Tedesco,, A. Craxi, and, M. Rizzetto. 1993. Long-term evolution of chronic delta hepatitis in children. J. Pediatr. 122:736.
14. Burra, P.,, A. Smedile,, A. Angelico,, A. Ascione, and, M. Rizzetto on behalf of the Study Group on Liver Transplantation of the Italian Association for the Study of the Liver (AISF). 2000. Liver transplantation in Italy: current status. Dig. Liver Dis. 32:249256.
15. Buti, M.,, R. Esteban, and, R. Jardi. 1989. Chronic delta hepatitis: detection of hepatitis delta virus antigen in serum by immunoblot and correlation with other markers of delta viral replication. Hepatology 10:907910.
16. Caredda, F.,, S. Antinori,, C. Pastecchia,, P. Coppin,, A. Ponzetto,, M. Rizzetto, and, M. Moroni. 1989. Presence and incidence of hepatitis delta virus infection in acute HBsAg-negative hepatitis. J. Infect. Dis. 159:977979.
17. Caredda, F.,, L. Vag,, F. Mainini,, A. Di Marco,, M. Nebuloni, and, M. Moroni. 1997. Strong association between hepatitis D virus (HDV) infection and liver cirrhosis in chronic carriers of HBsAg with AIDS, p. 906–910. In M. Rizzetto,, R. H. Purcell,, J. L. Gerin, and, G. Verme (ed.), Viral Hepatitis and Liver Disease. Edizioni Minerva Medica, Turin, Italy.
18. Cariani, E.,, A. Ravaggi,, M. Puoti,, G. Mantero,, A. Alberti, and, D. Primi. 1992. Evaluation of hepatitis delta virus RNA levels during interferon therapy by analysis of polymerase chain reaction products with a non radioisotopic hybridization assay. Hepatology 15:685689.
19. Casey, J. L. 2002. RNA editing in hepatitis delta virus genotype III requires a branched double-hairpin RNA structure. J. Virol. 76:73857397.
20. Casey, J. L.,, K. F. Bergman,, T. L. Brown, and, J. L. Gerin. 1992. Structural requirements for RNA editing in hepatitis delta virus: evidence for a uridine-to-cytidine editing mechanism. Proc. Natl. Acad. Sci. USA 89:17491753.
21. Casey, J. L.,, T. L. Brown,, E. J. Colan,, F. S. Wignall, and, J. L. Gerin. 1993. A genotype of hepatitis D virus that occurs in northern South America. Proc. Natl. Acad. Sci. USA 90:90169020.
22. Casey, J. L.,, P. J. Cote,, C. K. Chung,, B. C. Tennant,, J. L. Gerin, and, B. E. Korba. 2000. Treatment of chronic hepatitis delta virus infection with L-FMAU strongly inhibits HDV viremia. Antiviral Ther. 5:32.
23. Casey, J. L.,, P. J. Cote,, I. A. Toshkov,, C. K. Chung,, J. L. Gerin,, W. E. Hornbuckle,, B. C. Tennant, and, B. E. Korba. 2005. Clevudine inhibits hepatitis delta virus viremia: a pilot study of chronically infected woodchucks. Antimicrob. Agents Chemother. 49:43964399.
24. Casey, J. L.,, and J. L. Gerin. 1995. Hepatitis delta virus RNA editing and genotype variations, p. 111–124. In G. Dinber-Gottlieb (ed.), The Unique Hepatitis Delta Virus. Springer-Verlag, New York, NY.
25. Casey, J. L.,, and J. L. Gerin. 1998. Genotype-specific complementation of hepatitis delta virus RNA replication by hepatitis delta antigen. J. Virol. 72:28062814.
26. Casey, J. L.,, G. A. Niro,, R. Engle,, A. Vega,, H. Gomez,, M. McCarthy,, D. M. Watts,, K. C. Hyams, and, J. L. Gerin. 1996. Hepatitis B virus/hepatitis D virus coinfection in outbreaks of acute hepatitis in the Peruvian Amazon basin: the role of HDV genotype and HBV genotype F. J. Infect. Dis. 174:920926.
27. Casey, J. L.,, A. G. Polson,, B. L. Bass, and, J. L. Gerin. 1997. Molecular biology of HDV: analysis of RNA editing and genotype variation, p. 290–294. In M. Rizzetto,, R. H. Purcell,, J. L. Gerin, and, G. Verme (ed.), Viral Hepatitis and Liver Disease. Edizioni: Minerva Medica, Turin, Italy.
28. Casey, J. L.,, B. C. Tennant, and, J. L. Gerin. 2006. Genetic changes in hepatitis delta virus from acutely and chronically infected woodchucks. J. Virol. 80:64696477.
29. Castelnau, C.,, F. Le Gal,, M. P. Ripault,, E. Gordien,, M. Martinot-Peignoux,, N. Boyer,, B. N. Pham,, S. Maylin,, P. Bedossa,, P. Dény,, P. Marcellin, and, E. Gault. 2006. Efficacy of peginterferon alpha 2b in chronic hepatitis delta: relevance of quantitative RT-PCR for follow up. Hepatology 44:728735.
30. Castillo, I.,, J. Bartolome,, A. Madejon,, M. Melero,, J. C. Porres, and, V. Carreno. 1991. Hepatitis delta virus RNA detection in chronic HBsAg carriers with and without HIV infection. Digestion 48:149156.
31. Cech, T. R. 1988. Ribozymes and their medical implications. JAMA 260:30303034.
32. Chang, J.,, S. O. Gudima,, C. Tarn,, X. Nie, and, J. M. Taylor. 2005. Development of a novel system to study hepatitis delta virus genome replication. J. Virol. 79:81828188.
33. Chang, J.,, S. O. Gudima, and, J. M. Taylor. 2005. Evolution of hepatitis delta virus RNA genome following long-term replication in cell culture. J. Virol. 79:1331013316.
34. Chou, H.-C.,, T.-Y. Hsieh,, G.-T. Sheu, and, M. C. Lai. 1998. Hepatitis delta antigen mediates the nuclear import of hepatitis delta virus RNA. J. Virol. 72:36843690.
35. Coppola, R. C.,, G. Masia,, P. Pradat,, C. Trepò,, G. Carboni,, F. Argiolas, and, M. Rizzetto. 2000. Impact of hepatitis C virus infection on healthy subjects on an Italian island. J. Viral Hepatitis 7:130137.
36. Crivelli, O.,, C. Lavarini,, E. Chiaberge,, A. Amoroso,, P. Farci,, F. Negro, and, M. Rizzetto. 1983. Microsomal autoantibodies in chronic infection with the HBsAg associated delta (d) agent. Clin. Exp. Immunol. 54:232238.
37. Dalekos, G. N.,, E. Zervou,, F. Karabini, and, E. V. Tsianos. 1995. Prevalence of viral markers among refugees from southern Albania: increased incidence of infection with hepatitis A, B and D viruses. Eur. J. Gastroenterol. 7:553558.
38. de Fonseca, J. C. F.,, L. C. C. Gayotto,, L. C. L. Ferreira,, J. R. Araujo,, W. D. Alecrim,, R. T. Santos,, J. P. Simonetti, and, V. A. Alves. 1985. Labrea hepatitis—hepatitis B and delta antigen expression in liver tissue: report of three autopsy cases. Rev. Inst. Med. Trop. Sao Paulo 27:224.
39. De Man, R. A.,, P. R. Sprey,, H. G. M. Niesters,, R. A. Heijtink,, P. E. Zondervan,, W. Hop, and, S. W. Schalm. 1995. Survival and complications in a cohort of patients with anti-delta positive liver disease presenting in a tertiary referral clinic. J. Hepatol. 23:662667.
40. Denniston, K. J.,, B. H. Hoyer,, A. Smedile,, F. V. Wells,, J. Nelson, and, J. L. Gerin. 1986. Cloned fragment of the hepatitis delta RNA genome sequence and diagnostic application. Science 232:873875.
41. Dingle, K.,, V. Bichko,, H. Zuccola,, J. Hogle, and, J. Taylor. 1998. Initiation of hepatitis delta virus genome replication. J. Virol. 72:47834788.
42. D’Ugo, E.,, M. Paroli,, G. Palmieri,, R. Giuseppetti,, C. Argentini,, E. Tritarelli,, R. Bruni,, V. Barnaba,, M. Houghton, and, M. Rapicetta. 2004. Immunization of woodchucks with adjuvanted sHDAg (p24): immune response and outcome following challenge. Vaccine 22:457466.
43. Fagiouli, S.,, G. Leandro,, A. Bellati,, A. Gasbarrini,, G. L. Rapaccini,, M. Pompili,, M. Rendina,, S. De Notariis,, A. Francavilla,, G. Gasbarrini,, G. Ideo, and, R. Naccarato. 1996. Liver transplantation in Italy: preliminary 10-year report. Ital. J. Gastroenterol. 28:343350.
44. Farci, P.,, C. Barbera,, C. Navone,, F. Bortolotti,, P. Vajro,, N. Caporaso,, A. Vegnente,, N. Ansaldi,, M. Rizzetto, and, P. Tolentino. 1985. Infection with delta agent in children. Gut 26:47.
45. Farci, P.,, J. L. Gerin,, M. Aragona,, I. Lindsey,, O. Crivelli,, A. Balestrieri,, A. Smedile,, H. C. Thomas, and, M. Rizzetto. 1986. Diagnostic and prognostic significance of the IgM antibody to the hepatitis delta virus. JAMA 255:14431446.
46. Fattovich, G.,, G. Giustina,, E. Christensen,, M. Pantalena,, I. Zagni,, G. Realdi,, S. W. Schalm, and the European Concerted Action on Viral Hepatitis (EUROHEP). 2000. Influence of hepatitis delta virus infection on morbidity and mortality in compensated cirrhosis type B. Gut 46:420426.
47. Ferre-D’Amare, A. R.,, K. Zhou, and, J. A. Doudna. 1998. Crystal structure of a hepatitis delta virus ribozyme. Nature 395:567574.
48. Fielder, M.,, M. Lu,, F. Siegel,, J. Whipple, and, M. Roggendorf. 2001. Immunization of woodchucks (Marmotta monax) with hepatitis delta virus DNA vaccine. Vaccine 19:46184626.
49. Flodgren, E.,, S. Bengtsson,, M. Knutsson,, E. A. Strebkova,, H. A. Kidd,, O. A. Alexeyev, and, K. Kidd-Ljunggren. 2000. Recent high incidence of fulminant hepatitis in Samara, Russia: molecular analysis of prevailing hepatitis B and D virus strains. J. Clin. Microbiol. 38:33113316.
50. Flodgren, E.,, S. Bengtsson,, O. Alexeyev, and, K. Kidd-Ljunggren. 2000. Samara, Russia—a previously isolated city facing a real hepatitis D virus challenge. Antiviral Ther. 5:D3.
51. Gaeta, G. B.,, D. F. Precone,, A. Cozzi-Lepri,, P. Cicconi, and, A. D’Arminio Monforte. 2006. Multiple viral infections. J. Hepatol. 44:S108S113.
52. Gaeta, G. B.,, T. Stroffolini,, M. Chiaramonte,, T. Ascione,, G. Stornaiuolo,, S. Lobello,, E. Sagnelli,, M. R. Brunetto, and, M. Rizzetto. 2000. Chronic hepatitis D: a vanishing disease? A multicenter Italian study. Hepatology 32:824827.
53. Gerin, J. L. 1994 The taxonomy of hepatitis delta virus, p. 63–64. In K. Nishioka,, H. Suzuki,, S. Mishiro, and, T. Oda (ed.), Viral Hepatitis and Liver Disease. Springer-Verlag, Tokyo, Japan.
54. Glenn, J. S.,, J. A. Watson,, C. M. Havel, and, J. M. White. 1992. Identification of a prevalent site in delta virus large antigen. Science 256:13311333.
55. Glenn, J. S.,, J. C. Marsters, and, H. B. Greenberg. 1998. Use of a prenylation inhibitor as a novel antiviral agent. J. Virol. 72:93039306.
56. Grattagliano, I.,, V. O. Palmieri,, P. Portincasa, and, G. Palasciano. 2006. Adefovir dipivoxyl for the treatment of delta-related liver cirrhosis. Ann. Pharmacother. 40:16811684.
57. Hadler, S. C.,, M. de Monzon,, A. Ponzetto,, E. Anzola,, D. Rivero,, A. Mondolfi,, A. Bracho,, D. P. Francis,, M. A. Gerber, and, S. Thung. 1984. Delta virus infection and severe hepatitis. An epidemic in Yupca Indians of Venezuela. Ann. Intern. Med. 100:339344.
58. Hsu, S. C.,, W. J. Syu,, I. J. Sheen,, H. T. Liu,, K. S. Jeng, and, J. C. Wu. 2002. Varied assembly and RNA efficiencies between genotype I and II hepatitis D virus and their implications. Hepatology 35:665672.
59. Huang, Y. H.,, J. C. Wu,, S. C. Hsu, and, W. Syu, Jr. 2003. Varied immunity generated in mice by DNA vaccines with large and small hepatitis Delta antigens. J. Virol. 77:1298012985.
60. Imazeki, F.,, M. Omata, and, M. Otho. 1990. Heterogeneity and evolution rates of delta virus RNA sequences. J. Virol. 64:5594.
61. Inoue, J.,, M. Takahashi,, T. Nishizawa,, L. Narantuya,, M. Sakuma,, Y. Kagawa,, T. Shimosegawa, and, H. Okamoto. 2005. High prevalence of hepatitis delta virus infection detectable by enzyme immunoassay among apparently healthy individuals in Mongolia. J. Med. Virol. 76:333340.
62. Jayan, G. C.,, and J. L. Casey. 2002. Increased RNA editing and inhibition of hepatitis delta virus replication by high-level expression of ADAR1 and ADAR2. J. Virol. 76:38193827.
63. Jayan, G. C.,, and J. L. Casey. 2002. Inhibition of hepatitits delta virus RNA editing by short inhibitory RNA-mediated knockdown of ADAR1 but not ADAR2 expression. J. Virol. 76:1239912404
64. Kuo, M. Y. P.,, M. Chao, and, J. Taylor. 1989. Initiation of replication of the human hepatitis delta virus genome from cloned DNA: role of delta antigen. J. Virol. 63:19451950.
65. Le Gal, F.,, E. Gordien,, D. Affolabi,, T. Hanslik,, C. Alloui,, P. Dény, and, E. Gault. 2005. Quantification of hepatitis delta virus RNA in serum by consensus real-time PCR indicates different patterns of virological response to interferon therapy in chronically infected patients. J. Clin. Microbiol. 43:23632369.
66. Leone, N.,, B. Lavezzo,, A. Smedile,, M. Salizzoni,, V. Ghisetti, and, M. Rizzetto. 2001. Clinical and virological course of multiple viral infections after liver transplantation. Transplant. Proc. 33:25982599.
67. Li, Y. J.,, T. Macnaughton,, L. Gao, and, M. M. C. Lai. 2006. RNA-templated replication of hepatitis delta virus: genomic and antigenomic RNAs associate with different nuclear bodies. J. Virol. 80:64786486.
68. Liaw, Y. F. 1995. Role of hepatitis C virus in dual and triple hepatitis virus infection. Hepatology 22:11011108.
69. Liaw, Y. F.,, K. W. Chin,, C. M. Chen,, I. S. Sheen, and, M. J. Huang. 1990. Heterosexual transmission of hepatitis delta virus in the general population of an area endemic for hepatitis B virus infection: a prospective study. J. Infect. Dis. 162:11701172.
70. Lin, J. H.,, M. F. Chang,, S. C. Baker,, S. Govindarajan, and, M. M. C. Lai. 1990. Characterization of hepatitis delta antigen: specific binding to hepatitis delta virus RNA. J. Virol. 64:40514058.
71. Macnaughton, T.,, M. Beard,, M. Chao,, E. Gowans, and, M. Lai. 1993. Endogenous promoters can direct the transcription of hepatitis delta virus RNA from a recircularized cDNA template. Virology 196:629636.
72. Mariano, A.,, A. Mele,, M. E. Tosti,, A. Piolato,, G. Gallo,, P. Ragno,, C. Zotti,, P. Lopalco,, M. G. Pompa,, G. Graziani, and, T. Stroffolini. 2004. Role of beauty transmission on the spread of parenterally transmitted hepatitis viruses in Italy. J. Med. Virol. 74:216220.
73. Marzano, A.,, S. Gaia,, V. Ghisetti,, S. Carenzi,, A. Premoli,, W. Debernardi-Venon,, C. Alessandria,, A. Franchello,, M. Salizzoni, and, M. Rizzetto. 2005. Viral load at the time of liver transplantation and risk of hepatitis B virus recurrence. Liver Transpl. 11:402409.
74. Mauch, C.,, C. Grimm,, S. Meckel,, J. R. Wands,, H. E. Blum,, M. Roggendorf, and, M. Geissler. 2001. Induction of cytotoxic T lymphocyte responses against hepatitis delta virus antigens which protect against tumor formation in mice. Vaccine 20:170180.
75. Modahl, L. E.,, and M. M. C. Lai. 2000. The large delta antigen of hepatitis delta virus potently inhibits genomic but not antigenomic RNA synthesis: a mechanism enabling initiation of viral replication. J. Virol. 74:73757380.
76. Nakano, S.,, and P. C. Bevilacqua. 2007. Mechanism characterization of the HDV genomic ribozyme: a mutant of the C41 motif provides insight into the positioning and thermodynamic linkage of metal ions and protons. Biochemistry 46:30013012.
77. Nakano, T.,, C. N. Shapiro,, S. Hadler, and, J. L. Casey. 2000. Characterization of hepatitis D virus among the indigenous population in Venezuela. Antiviral Ther. 5(Suppl. 1):D3.
78. Navascues, C. A.,, M. Rodriguez,, N. G. Sotorrio,, P. Sala,, A. Linares,, A. Suarez, and, L. Rodrigo. 1995. Epidemiology of hepatitis D virus infection: changes in the last 14 years. Am. J. Gastroenterol. 90:19811984.
79. Negro, F.,, and M. Rizzetto. 1993. Pathobiology of hepatitis delta virus. J. Hepatol. 17:S149S153.
80. Netter, H. J.,, K. Kajino, and, J. M. Taylor. 1993. Experimental transmission of human hepatitis delta virus to the laboratory mouse. J. Virol. 67:33573362.
81. Niro, G. A.,, J. L. Casey,, E. Gravinese,, M. Garubba,, P. Conoscitore,, E. Sagnelli,, M. Durazzo,, N. Caporaso,, F. Perri,, G. Leandro,, D. Facciorusso,, M. Rizzetto, and, A. Andriulli. 1999. Intrafamilial transmission of hepatitis delta virus: molecular evidence. J. Hepatol. 30:564569.
82. Niro, G. A.,, F. Rosina, and, M. Rizzetto. 2005. Treatment of hepatitis D. J. Viral Hepat. 12:29.
83. Niro, G. A.,, A. Ciancio,, G. B. Gaeta,, A. Smedile,, A. Marrone,, A. Olivero,, M. Stanzione,, E. David,, G. Brancaccio,, R. Fontana,, F. Perri,, A. Andriulli, and, M. Rizzetto. 2006. Pegylated interferon alpha-2b as monotherapy or in combination with ribavirin in chronic hepatitis delta. Hepatology 44:713720.
84. Niro, G. A.,, A. Ciancio,, H. L. Tillman,, M. Lagget,, A. Olivero,, F. Perri,, R. Fontana,, N. Little,, F. Campbell,, A. Smedile,, M. P. Manns,, A. Andriulli, and, M. Rizzetto. 2005. Lamivudine therapy in chronic delta hepatitis: a multicentre randomized-controlled pilot study. Aliment. Pharmacol. Ther. 22:227232.
85. Novick, D. M.,, P. Farci,, T. S. Croxson,, M. B. Taylor,, C. W. Schneebaum,, M. E. Lai,, N. Bach,, R. T. Senie,, A. M. Gelb, and, M. J. Kreek. 1988. Hepatitis D virus and human immunodeficiency virus antibodies in parenteral drug abusers who are hepatitis B surface antigen positive. J. Infect. Dis. 158:795.
86. Obaid Shakil, A.,, S. Hadziyannis,, J. H. Hoofnagle,, A. M. Di Bisceglie,, J. L. Gerin, and, J. L. Casey. 1997. Geographic distribution and genetic variability of hepatitis delta virus genotype 1. Virology 234:160167.
87. Perrotta, A. T.,, and M. D. Been. 1991. A pseudoknot-like structure required for efficient self-cleavage of hepatitis delta virus RNA. Nature 350:434436.
88. Perrotta, A. T.,, I.-H. Shih, and, M. D. Been. 1999. Imidazole rescue of a cytosine mutation in a self-cleaving ribozyme. Science 286:36.
89. Perotta, A. T.,, and M. D. Been. 2007. A single nucleotide linked to a switch in metal ion reactivity preference in the HDV ribozymes. Biochemistry 46:51245130.
90. Perotta, A. T.,, T. S. Wadkins, and, M. D. Been. 2006. Chemical rescue, multiple ionizable groups, and general acid-base catalysis in the HDV genomic ribozyme. RNA 12:12821291.
91. Philipp, T.,, M. Durazzo,, C. Trautwein,, B. Alex,, P. Straub,, J. G. Lamb,, E. F. Johnson,, R. H. Tukey, and, M. P. Manns. 1994. Recognition of uridine diphosphate glucuronosyl transferases by LKM-3 autoantibodies in chronic hepatitis D. Lancet 344:578581.
92. Polson, A.,, B. Bass, and, J. Casey. 1996. RNA editing of hepatitis delta virus antigenome by dsRNA-adenosine deaminase. Nature 380:454456.
93. Polson, A. G.,, H. L. Ley III,, B. L. Brass, and, J. L. Casey. 1998. Hepatitis delta virus RNA editing is highly specific for the Amber/W site and is suppressed by hepatitis delta antigen. Mol. Cell. Biol. 18:19191926.
94. Ponzetto, A.,, P. J. Cote,, H. Popper,, B. H. Hoyer,, W. T. London,, E. C. Ford,, F. Bonino,, R. H. Purcell, and, J. L. Gerin. 1984. Transmission of the hepatitis B-virus associated delta agent to the eastern woodchuck. Proc. Natl. Acad. Sci. USA 81:22082212.
95. Ponzetto, A.,, B. Forzani,, I. Forzani,, N. D’Urso,, L. Avanzini,, A. Smedile, and, G. Verme. 1989. Immunization with hepatitis delta antigen does not prevent superinfection with hepatitis delta virus in the woodchuck. Gastroenterology 96:646.
96. Ponzetto, A.,, B. Forzani,, P. P. Parravicini,, C. Hele,, A. Zanetti, and, M. Rizzetto. 1985. Epidemiology of hepatitis delta virus infection. Eur. J. Epidemiol. 1:257263.
97. Ponzetto, A.,, F. Negro,, H. Popper,, F. Bonino,, R. Engle,, M. Rizzetto,, R. H. Purcell, and, J. L. Gerin. 1988. Serial passage of hepatitis delta virus in chronic hepatitis B virus carrier chimpanzees. Hepatology 8:16551661.
98. Popper, H.,, S. N. Thung,, M. A. Gerber,, S. C. Hadler,, M. de Monzon,, A. Ponzetto,, E. Anzola,, D. Rivera,, A. Mondolfi, and, A. Bracho. 1983. Histologic studies of severe delta agent infection in Venezuelan Indians. Hepatology 3:906912.
99. Radjef, N.,, E. Gordien,, V. Ivaniushina,, E. Gault,, P. Anais,, T. Drugan,, J. C. Trinchet,, D. Roulot,, M. Tamby,, M. C. Milinkovitch, and, P. Dény. 2004. Molecular phylogenetic analyses indicate a wide and ancient radiation of African hepatitis delta virus, suggesting a Deltavirus genus of at least seven major clades. J. Virol. 78:25372544.
100. Raimondo, G.,, M. R. Brunetto,, P. Pontisso,, A. Smedile,, A. M. Maina,, C. Saitta,, G. Squadrito,, N. Tono, and the AISF Cooperative Group. 2006. Longitudinal evaluation reveals a complex spectrum of virological profiles in hepatitis B virus/hepatitis C virus-coinfected patients. Hepatology 43:100107.
101. Rizzetto, M.,, M. G. Canese,, S. Aricò,, O. Crivelli,, C. Trepò,, F. Bonino, and, G. Verme. 1977. Immunofluorescence detection of a new antigen-antibody system (delta/anti delta) associated with hepatitis B virus in liver and in serum of HBsAg carriers. Gut 18:9971003.
102. Rizzetto, M.,, M. G. Canese,, J. L. Gerin,, W. T. London,, L. D. Sly, and, R. H. Purcell. 1980. Transmission of the hepatitis B virus-associated delta antigen to chimpanzees. J. Infect. Dis. 141:590602.
103. Rizzetto, M.,, S. Hadziyannis,, B. G. Hansson,, A. Toukan, and, I. Gust. 1992. Hepatitis delta virus infection in the world, epidemiological patterns and clinical expression. Gastroenterol. Int. 5:1832.
104. Rosina, F.,, P. Conoscitore,, R. Cuppone,, G. Rocca,, A. Giuliani,, R. Cozzolongo,, G. Niro,, A. Smedile,, G. Saracco,, A. Andriulli,, O. G. Manghisi, and, M. Rizzetto. 1999. Changing pattern of chronic hepatitis D in Southern Europe. Gastroenterology 117:161166.
105. Rosina, F.,, A. Fabiano,, A. Garripoli,, A. Smedile,, A. Mattalia,, M. R. Eckart,, M. Houghton, and, F. Bonino. 1991. Rabbit-derived anti-HDV antibodies for HDVAg immunoblotting. J. Hepatol. 13(Suppl. 4):S130S133.
106. Sagnelli, E.,, T. Stroffolini,, A. Ascione,, F. Bonino,, M. Chiaramonte,, M. Colombo,, A. Craxi,, G. Giusti,, O. G. Manghisi, and, G. Pastore. 1992. The epidemiology of hepatitis delta infection in Italy. J. Hepatol. 15:211215.
107. Sakugawa, H.,, H. Nakasone,, T. Nakayoshi,, Y. Kawakami,, S. Miyazato,, F. Kinjo,, A. Saito,, S. P. Ma,, H. Hotta, and, M. Kinoshita. 1999. Hepatitis delta virus genotype II b predominates in an endemic area, Okinawa, Japan. J. Med. Virol. 58:366372.
108. Salehi-Ashtiani, K.,, A. Luptak,, A. Litovchick, and, J. W. Szostak. 2006. A genomewide search for ribozymes reveals an HDV-like sequence in the human CPEB3 gene. Science 313:17881792.
109. Salizzoni, M.,, E. Cerutti,, R. Romagnoli,, F. Lupo,, A. Franchello,, F. Zamboni,, F. Gennari,, P. Strignano,, A. Ricchiuti,, A. Brunati,, M. M. Schellino,, A. Ottobrelli,, A. Marzano,, B. Lavezzo,, E. David, and, M. Rizzetto. 2005. The first one thousand liver transplants in Turin: a single-center experience in Italy. Transplant Int. 18:13281335.
110. Samuel, D.,, X. Forns,, M. Berenguer,, C. Trautwein,, A. Burroughs,, M. Rizzetto, and, M. Trepò. 2006. Report of the monothematic EASL conference on liver transplantation for viral hepatitis (Paris, France, January 12–14, 2006). J. Hepatol. 45:127143.
111. Saracco, G.,, S. Maccagno,, F. Caredda,, S. Antinori, and, M. Rizzetto. 1988. Serologic markers with fulminant hepatitis in persons positive for hepatitis B surface antigen. A worldwide epidemiologic and clinical survey. Ann. Intern. Med. 106:380384.
112. Scott, W. G.,, J. T. Finch, and, A. Klung. 1995. The crystal structure of an all-RNA hammerhead ribozyme: a proposed mechanism for RNA catalytic cleavage. Cell 81:9911002.
113. Sefcikova, J.,, M. V. Krasovska,, J. Sponer, and, N. G. Walter. 2007. The genomic HDV ribozyme utilizes a previously unnoticed U-turn motif to accomplish fast site-specific catalysis. Nucleic Acids Res. 35:19331946.
114. Sheng, W. H.,, C. C. Hung,, J. H. Kao,, S. Y. Chang,, M. Y. Chen,, S. M. Hsieh,, P. J. Chen, and, S. C. Chang. 2007. Impact of hepatitis D virus infection on the long-term outcome of patients with hepatitis B virus and HIV coinfection in the era of highly active antiretroviral therapy: a matched cohort study. Clin. Infect. Dis. 44:988995.
115. Shiau, Y. T.,, Y. H. Huang,, J. C. Wu,, M. H. Tao,, W. Syu, Jr.,, F. Y. Chang, and, S. D. Lee. 2006. Analysis of humoral immunity of hepatitis D virus DNA vaccine generated in mice by using different dosage, gene gun immunization and in vivo electroporation. J. Chin. Med. Assoc. 69:713.
116. Singh, V.,, M. K. Goenka,, D. K. Bhasin,, R. Kochahar, and, K. Singh. 1995. A study of delta virus infection in patients with acute and chronic liver disease from northern India. J. Viral Hepat. 2:151154.
117. Sjogren, M. H.,, A. Colichon,, H. Vildosola,, R. Cantella, and, J. Romero. 1997. Initial and 8 years serologic follow-up of HBV and HDV in resident of a hyperendemic area in the Amazon basin, p. 119. A28. In M. Rizzetto,, R. H. Purcell,, J. L. Gerin, and, G. Verme (ed.), Viral Hepatitis and Liver Disease. Edizioni Minerva Medica, Turin, Italy.
118. Smedile, A.,, K. F. Bergmann,, B. M. Baroudi,, F. V. Wells,, R. H. Purcell,, F. Bonino,, M. Rizzetto, and, J. L. Gerin. 1990. Riboprobe assay for HDV-RNA: a sensitive method for the detection of the HDV genome in clinical serum samples. J. Med. Virol. 30:2024.
119. Smedile, A.,, C. Lavarini,, O. Crivelli,, G. Raimondo,, M. Fassone, and, M. Rizzetto. 1982. Radioimmunoassay detection of IgM antibodies to the HBV-associated delta (d) antigen: clinical significance in delta infection. J. Med. Virol. 9:131138.
120. Smedile, A.,, C. Lavarini, and, P. Farci. 1983. Epidemiologic patterns of infection with the hepatitis B virus-associated delta antigen in Italy. Am. J. Epidemiol. 117:223229.
121. Smedile, A.,, M. Rizzetto,, K. Denniston,, F. Bonino,, F. Wells,, G. Verme,, F. Consolo,, B. Hoyer,, R. H. Purcell, and, J. L. Gerin. 1986. Type D hepatitis: the clinical significance of hepatitis D virus RNA in serum as detected by a hybridization based-assay. Hepatology 6:12971302.
122. Smedile, A.,, M. Rizzetto, and, J. L. Gerin. 1994. Advances in hepatitis D virus biology and disease, p. 157–175. In J. L. Boyer, and, R. K. Okner (ed.), Progress in Liver Disease, vol. XII. The W. B. Saunders Co, Philadelphia, PA.
123. Su, C. W.,, Y. H. Huang,, T. I. Huo,, H. H. Shih,, I. J. Sheen,, S. W. Chen,, P. C. Lee,, D. S. Lee, and, J. C. Wu. 2006. Genotypes and viremia of hepatitis B and D viruses are associated with outcome of chronic hepatitis D patients. Gastroenterology 130:16251635.
124. Tanner, N. K.,, S. Schaff,, G. Thill,, E. Petit-Koskas,, A. M. Crain-Denoyelle, and, E. Westhof. 1994. A three-dimensional model of hepatitis delta virus ribozyme based on biochemical and mutational analyses. Curr. Biol. 4:488498.
125. Taylor, J. M. 2006. Hepatitis delta virus. Virology 344:7176.
126. Taylor, J. M. 1990. Structure and replication of hepatitis delta virus. Semin. Virol. 1:135141.
127. Taylor, J. M. 1990. Hepatitis delta virus: cis and trans functions required for replication. Cell 61:371373.
128. Taylor, J. M.,, J. Mason,, J. Summers,, C. Goldenberg,, L. Aldrich,, J. Coates,, J. L. Gerin, and, E. Gowans. 1987. Replication of human hepatitis delta virus in primary cultures of woodchuck hepatocytes. J. Virol. 61:28912895.
129. Tinsley, R. A.,, and N. G. Walter. 2007. Long-range impact of peripheral joining elements on structure and function of the hepatitis delta virus ribozyme. Biol. Chem. 388:705715.
130. Verme, G.,, P. Amoroso,, G. Lettieri,, P. Pierri,, E. David,, F. Sessa,, R. Rizzi,, F. Bonino,, S. Recchia, and, M. Rizzetto. 1986. A histologic study of hepatitis delta virus liver disease. Hepatology 6:1303.
131. Viana, S.,, R. Parana,, R. C. Moreira,, A. P. Compri, and, V. Macedo. 2005. High prevalence of hepatitis B and hepatitis D virus in the western Brazilian Amazon. Am. J. Trop. Med. Hyg. 73:808814.
132. Vietheer, P. T. K.,, H. J. Netter,, T. Sozzi, and, A. Bartholomeusz. 2005. Failure of the lamivudine-resistant rtM204I hepatitis B virus mutants to efficiently support hepatitis delta virus secretion. J. Virol. 79:65706573.
133. Wedemeyer, H.,, B. Heidrich, and, T. Manns. 2007. Hepatitis D virus infection—not a vanishing disease in Europe! Hepatology 45:13311332.
134. Wesierka-Gadek, J.,, E. Penner,, E. R. Hitchaman, and, G. Sauermann. 1990. Antibodies to nuclear lamin C in chronic hepatitis delta virus infection. Hepatology 12:11291133.
135. Wong, S. K.,, and D. W. Lazinski. 2002. Replicating hepatitis Delta virus RNA is edited in the nucleus by the small form of ADAR1. Proc. Natl. Acad. Sci. USA 99:1511815123.
136. Wright, T. L.,, and B. Pereira. 1995. Liver transplantation for chronic viral hepatitis. Liver Transplant Surg. 1:3042.
137. Wu, J.-C.,, T.-Y. Chaing, and, I. J. Sheen. 1998. Characterization and phylogenetic analysis of a novel hepatitis D virus strain discovered by restriction fragment length polymorphism analysis. J. Gen. Virol. 79:11051113.
138. Wu, J. C.,, K. B. Choo,, C. M. Chen,, T. Z. Chen,, T. I. Huo, and, S. D. Lee. 1995. Genotyping of hepatitis D virus by restriction fragment length polymorphism and relation to outcome of hepatitis D. Lancet 346:939.
139. Wu, J. C.,, S. Y. Wang,, W. J. Syu,, Y. S. Huang,, C. C. Lin, and, I. J. Sheen. 2000. Replacement of dominant strains of hepatitis D virus in chronic hepatitis D: clustering of amino acid changes within immunogenic domains. Antiviral Ther. 5:D4.
140. Yamaguchi, Y.,, T. Mura,, S. Chanarat,, A. Okamoto, and, H. Handa. 2007. Hepatitis delta antigen binds to the clamp of RNA polymerase II and affects transcriptional fidelity. Genes Cells 12:863875.
141. Zakaria, S.,, R. Fouad,, O. Shaker,, S. Zaki,, A. Hashem,, S. S. El-Kamary,, G. Esmat, and, S. Zakaria. 2007. Changing patterns of acute viral hepatitis at a major urban referral center in Egypt. Clin. Infect. Dis. 44:e30e36.
142. Zaki, H.,, G. L. Darmstadt,, A. Baten,, C. R. Ahsan, and, S. K. Saha. 2003. Seroepidemiology of hepatitis B and Delta virus infections in Bangladesh. J. Trop. Pediatr. 49:371374.
143. Zanetti, A. R.,, P. Ferroni,, E. M. Magliani,, P. Pirovano,, C. Lavarini,, A. L. Massaro,, R. Gavinelli,, C. Fabris, and, M. Rizzetto. 1982. Perinatal transmission of hepatitis B virus associated delta agent from mothers to off-spring in Northern Italy. J. Med. Virol. 9:139148.
144. Zauli, D.,, C. Crespi,, F. B. Bianchi,, A. Craxi, and, E. Pisi. 1986. Autoimmunity in chronic liver disease caused by hepatitis delta virus. J. Clin. Pathol. 39:897899.


Generic image for table

Genotypes of HDV

Citation: Smedile A, Ciancio A, Rizzetto M. 2009. Hepatitis D Virus, p 1291-1306. In Richman D, Whitley R, Hayden F (ed), Clinical Virology, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815981.ch56
Generic image for table

Progression from chronic HDV hepatitis to cirrhosis and liver dysfunction

Citation: Smedile A, Ciancio A, Rizzetto M. 2009. Hepatitis D Virus, p 1291-1306. In Richman D, Whitley R, Hayden F (ed), Clinical Virology, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815981.ch56
Generic image for table

Death (free of transplantation) from HDV cirrhosis

Citation: Smedile A, Ciancio A, Rizzetto M. 2009. Hepatitis D Virus, p 1291-1306. In Richman D, Whitley R, Hayden F (ed), Clinical Virology, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815981.ch56

This is a required field
Please enter a valid email address
Please check the format of the address you have entered.
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error