Skip to main content

Studying the Treatment of Chronic Hepatitis B Viral Infection in Special Populations

  • Protocol
Hepatitis B and D Protocols

Part of the book series: Methods in Molecular Medicine™ ((MIMM,volume 96))

  • 545 Accesses

Abstract

There are estimated to be more than 400 million people chronically infected with the hepatitis B virus (HBV) worldwide (Fig. 1) (1). At least 20–30% of those chronically infected will die of complications of chronic liver disease including cirrhosis and liver cancer (2,3). The World Health Organization (WHO) places HBV in the top 10 causes of death worldwide (4). The estimated viral burden in the United States is 1.5 million people, with disease concentrated in ethnic subgroups and populations with high-risk behavior, and health care costs to the North American economy that exceed $350 million per year. Although the United States is considered an area of low-prevalence hepatitis B infection, the incidence of new cases, the prevalence of carriers, and the burden of acute and chronic disease maintain hepatitis B high among the important communicable diseases. It is estimated that 300,000 new cases of hepatitis B infection occurred each year in the United States in the 1970s and 1980s. Currently about 125,000 new cases occur each year in North America. These acute infections have led to at least 27,000–42,000 chronic carriers, 17,000 hospitalizations, 300 cases of fulminant liver failure, and ultimately 4000–5500 deaths per year in the United States from cirrhosis and primary liver cancer as well as the morbidity and cost of liver transplantation in approx 350 patients per year (511). The age-specific incidence of acute HBV infection is shown in Fig. 2. The risk of developing chronic HBV infection after acute exposure ranges from 1% to 5% for adults and 90% for infants born to infected mothers (Fig. 3). Once chronic infection has occurred, a heterogeneous group of patients or clinical profiles is evident based on a combination of viral replication, fibrosis progression, host immune response, and presence or evolution of viral mutants.

The 350 million chronic carriers of HBV worldwide account for more than 5% of the world’s population. Although widely distributed, the prevalence of HBV varies from a highly endemic disease (>8%) in China, Southeast Asia, and Africa to a disease of low endemicity (>2%) in North America, western Europe, and Australia. Areas with intermediate levels of prevalence (2–7%) are also noted. In most developed countries, the prevalence of chronic HBV infection is >2%. Within these areas reside ethnic groups with HBV infection rates that are significantly higher than those of the general population, for example, Eskimo populations in Alaska and Canada and the Maoris in New Zealand. (WHO Statistics [166].)

Age-specific incidence of acute hepatitis B in the United States from 1982 to 1998. The median age increased from 27 to 32 yr, with 61% males. Age groups: gray line, 10–19 yr; dashed line, 20–29 yrs; dotted line, 30–39 yr; solid line, 40’49 yr. (Centers for Disease Control, Sentinel Counties Study.)

Carrier state and recovery.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Protocol
USD 49.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 89.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 119.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Maynard, J. E. (1990) Hepatitis B: global importance and need for control. Vaccine 8(Suppl), S18–S20.

    Article  PubMed  Google Scholar 

  2. Dodd, R. Y. and Nath, N. (1987) Increased risk for lethal forms of liver disease among HBsAg-positive blood donors in the United States. J. Virol. Methods 17, 81–94.

    Article  PubMed  CAS  Google Scholar 

  3. Lee, W. M. (1997) Hepatitis B virus infection. N. Engl. J. Med. 337, 1733–1745.

    Article  PubMed  CAS  Google Scholar 

  4. Hoofnagle, J. H. (1990) Chronic hepatitis B. N. Engl. J. Med. 323, 337–339.

    Article  PubMed  CAS  Google Scholar 

  5. Moyer, L.A. and Mast, E.E. (1994) Hepatitis B: virology, epidemiology, disease, and prevention, and an overview of viral hepatitis. Am. J. Prev. Med. 10(Suppl), 45–55.

    PubMed  Google Scholar 

  6. Kane, M. (1995) Epidemiology of hepatitis B infection in North America. Vaccine 13(Suppl 1), S16–S17.

    PubMed  Google Scholar 

  7. McMahon, B. J., Lanier, A. P., and Wainwright, R. B. (1998) Hepatitis B and hepatocellular carcinoma in Eskimo/Inuit population. Int. J. Circumpolar. Health 57(Suppl 1), 414–419.

    PubMed  Google Scholar 

  8. Chu, C. M. (2000) Natural history of chronic hepatitis B virus infection in adults with emphasis on the occurrence of cirrhosis and hepatocellular carcinoma. J. Gastroenterol. Hepatol. 15(Suppl), E25–E30.

    Article  PubMed  Google Scholar 

  9. de Franchis, R., Meucci, G., Vecchi, M., et al. (1993) The natural history of asymptomatic hepatitis B surface antigen carriers. Ann. Intern. Med. 118, 191–194.

    PubMed  Google Scholar 

  10. Fattovich, G., Brollo, L., Giustina, G., et al. (1991) Natural history and prognostic factors for chronic hepatitis type B. Gut 32, 294–298.

    Article  PubMed  CAS  Google Scholar 

  11. Lok, A. S. (1992) Natural history and control of perinatally acquired hepatitis B virus infection. Dig. Dis. 10, 46–52.

    Article  PubMed  CAS  Google Scholar 

  12. Angus, P.W. (1997) Review: hepatitis B and liver transplantation. J. Gastroenterol. Hepatol. 12, 217–223.

    Article  PubMed  CAS  Google Scholar 

  13. Arevalo, J. A. and Washington, A. E. (1988) Cost-effectiveness of prenatal screening and immunization for hepatitis B virus. JAMA 259, 365–369.

    Article  PubMed  CAS  Google Scholar 

  14. Blumberg, B. S. (1977) Australia antigen and the biology of hepatitis B. Science 197, 17–25.

    Article  PubMed  CAS  Google Scholar 

  15. Perrault, J., McGill, D.B., Ott, B.J., and Taylor, W. F. (1978) Liver biopsy: complications in 1000 inpatients and outpatients. Gastroenterology 74, 103–106.

    PubMed  CAS  Google Scholar 

  16. Younossi, Z. M., Teran, J.C., Ganiats, T.G., and Carey, W.D. (1998) Ultrasound-guided liver biopsy for parenchymal liver disease: an economic analysis. Dig. Dis. Sci. 43, 46–50.

    Article  PubMed  CAS  Google Scholar 

  17. Piton, A., Poynard, T., Imbert-Bismut, F., et al. (1998) Factors associated with serum alanine transaminase activity in healthy subjects: consequences for the definition of normal values, for selection of blood donors, and for patients with chronic hepatitis C. MULTIVIRC Group. Hepatology 27, 1213–1219.

    Article  PubMed  CAS  Google Scholar 

  18. Knodell, R. G., Ishak, K.G., Black, W. C., et al. (1981) Formulation and application of a numerical scoring system for assessing histological activity in asymptomatic chronic active hepatitis. Hepatology 1, 431–435.

    Article  PubMed  CAS  Google Scholar 

  19. Hruska, J.F. and Robinson, W. S. (1977) The proteins of hepatitis B Dane particle cores. J. Med. Virol. 1, 119–131.

    Article  PubMed  CAS  Google Scholar 

  20. Summers, J., O’Connell, A., and Millman, I. (1975) Genome of hepatitis B virus: restriction enzyme cleavage and structure of DNA extracted from Dane particles. Proc. Natl. Acad. Sci. U.S.A 72, 4597–4601.

    Article  PubMed  CAS  Google Scholar 

  21. Albin, C. and Robinson, W.S. (1980) Protein kinase activity in hepatitis B virus. J. Virol. 34, 297–302.

    PubMed  CAS  Google Scholar 

  22. Nassal, M. (1999) Hepatitis B virus replication: novel roles for virus-host interactions. Intervirology 42, 100–116.

    Article  PubMed  CAS  Google Scholar 

  23. Spandau, D.F. and Lee, C. H. (1988) Trans-activation of viral enhancers by the hepatitis B virus X protein. J. Virol. 62, 427–434.

    PubMed  CAS  Google Scholar 

  24. Twu, J. S. and Robinson, W. S. (1989) Hepatitis B virus X gene can transactivate heterologous viral sequences. Proc. Natl. Acad. Sci. USA 86, 2046–2050.

    Article  PubMed  CAS  Google Scholar 

  25. Twu, J.S., Chu, K., and Robinson, W.S. (1989) Hepatitis B virus X gene activates kappa B-like enhancer sequences in the long terminal repeat of human immunodeficiency virus 1. Proc. Natl. Acad. Sci. USA 86, 5168–5172.

    Article  PubMed  CAS  Google Scholar 

  26. Chen, H.S., Kaneko, S., Girones, R., et al. (1993) The woodchuck hepatitis virus X gene is important for establishment of virus infection in woodchucks. J. Virol. 67, 1218–1226.

    PubMed  CAS  Google Scholar 

  27. Zoulim, F., Saputelli, J., and Seeger, C. (1994) Woodchuck hepatitis virus X protein is required for viral infection in vivo. J. Virol. 68, 2026–2030.

    PubMed  CAS  Google Scholar 

  28. Ganem, D. (1996). Hepadnaviridae and their replication. In: “Virology,” 3rd Ed. (Fields, B.N., Eds.). New York: Lippincott-Raven Publishers, pp. 2703–2737

    Google Scholar 

  29. Raney, A. K., Milich, D.R., Easton, A. J., and McLachlan, A. (1990) Differentiation-specific transcriptional regulation of the hepatitis B virus large surface antigen gene in human hepatoma cell lines. J. Virol. 64, 2360–2368.

    PubMed  CAS  Google Scholar 

  30. Cattaneo, R., Will, H., Hernandez, N., and Schaller, H. (1983) Signals regulating hepatitis B surface antigen transcription. Nature 305, 336–338.

    Article  PubMed  CAS  Google Scholar 

  31. Standring, D.N., Rutter, W.J., Varmus, H.E., and Ganem, D. (1984) Transcription of the hepatitis B surface antigen gene in cultured murine cells initiates within the presurface region. J. Virol. 50, 563–571.

    PubMed  CAS  Google Scholar 

  32. Siddiqui, A., Jameel, S., and Mapoles, J. (1987) Expression of the hepatitis B virus X gene in mammalian cells. Proc. Natl. Acad. Sci. USA 84, 2513–2517.

    Article  PubMed  CAS  Google Scholar 

  33. Shaul, Y., Rutter, W. J., and Laub, O. (1985) A human hepatitis B viral enhancer element. EMBO J. 4, 427–430.

    PubMed  CAS  Google Scholar 

  34. Yee, J. K. (1989) A liver-specific enhancer in the core promoter region of human hepatitis B virus. Science 246, 658–661.

    Article  PubMed  CAS  Google Scholar 

  35. Bock, C., Malek, N.P., Tillmann, H.L., Manns, M.P., and Trautwein, C. (2000) The enhancer I core region contributes to the replication level of hepatitis B virus In vivo and In vitro. J. Virol. 74, 2193–2202.

    Article  PubMed  CAS  Google Scholar 

  36. Tur-Kaspa, R., Burk, R.D., Shaul, Y., and Shafritz, D.A. (1986) Hepatitis B virus DNA contains a glucocorticoid-responsive element. Proc. Natl. Acad. Sci. USA 83, 1627–1631.

    Article  PubMed  CAS  Google Scholar 

  37. Tur-Kaspa, R., Shaul, Y., Moore, D. D., et al. (1988) The glucocorticoid receptor recognizes a specific nucleotide sequence in hepatitis B virus DNA causing increased activity of the HBV enhancer. Virology 167, 630–633.

    PubMed  CAS  Google Scholar 

  38. Neurath, A. R., Kent, S. B., Parker, K., et al. (1986) Antibodies to a synthetic peptide from the preS 120–145 region of the hepatitis B virus envelope are virus neutralizing. Vaccine 4, 35–37.

    Article  PubMed  CAS  Google Scholar 

  39. Le Seyec, J., Chouteau, P., Cannie, I., Guguen-Guillouzo, C., and Gripon, P. (1999) Infection process of the hepatitis B virus depends on the presence of a defined sequence in the pre-S1 domain. J. Virol. 73, 2052–2057.

    PubMed  Google Scholar 

  40. Jung, M. C., Diepolder, H.M., Spengler, U., et al. (1995) Activation of a heterogeneous hepatitis B (HB) core and e antigen-specific CD4+ T-cell population during seroconversion to anti-HBe and anti-HBs in hepatitis B virus infection. J. Virol. 69, 3358–3368.

    PubMed  CAS  Google Scholar 

  41. Chiang, P. W., Jeng, K.S., Hu, C. P., and Chang, C.M. (1992) Characterization of a cis element required for packaging and replication of the human hepatitis B virus. Virology 186, 701–711.

    Article  PubMed  CAS  Google Scholar 

  42. Junker-Niepmann, M., Bartenschlager, R., and Schaller, H. (1990) A short cis-acting sequence is required for hepatitis B virus pregenome encapsidation and sufficient for packaging of foreign RNA. EMBO J. 9, 3389–3396.

    PubMed  CAS  Google Scholar 

  43. Pollack, J. R. and Ganem, D. (1993) An RNA stem-loop structure directs hepatitis B virus genomic RNA encapsidation. J. Virol. 67, 3254–3263.

    PubMed  CAS  Google Scholar 

  44. Pollack, J.R. and Ganem, D. (1994) Site-specific RNA binding by a hepatitis B virus reverse transcriptase initiates two distinct reactions: RNA packaging and DNA synthesis. J. Virol. 68, 5579–5587.

    PubMed  CAS  Google Scholar 

  45. Hirsch, R. C., Loeb, D. D., Pollack, J. R., and Ganem, D. (1991) cis-acting sequences required for encapsidation of duck hepatitis B virus pregenomic RNA. J. Virol. 65, 3309–3316.

    PubMed  CAS  Google Scholar 

  46. Bartenschlager, R. and Schaller, H. (1992) Hepadnaviral assembly is initiated by polymerase binding to the encapsidation signal in the viral RNA genome. EMBO J. 11, 3413–3420.

    PubMed  CAS  Google Scholar 

  47. Nassal, M. and Schaller, H. (1993) Hepatitis B virus replication. Trends Microbiol. 1, 221–228.

    Article  PubMed  CAS  Google Scholar 

  48. Tavis, J. E., Perri, S., and Ganem, D. (1994) Hepadnavirus reverse transcription initiates within the stem-loop of the RNA packaging signal and employs a novel strand transfer. J. Virol. 68, 3536–3543.

    PubMed  CAS  Google Scholar 

  49. Summers, J. and Mason, W.S. (1982) Replication of the genome of a hepatitis B—like virus by reverse transcription of an RNA intermediate. Cell 29, 403–415.

    Article  PubMed  CAS  Google Scholar 

  50. Oberhaus, S.M. and Newbold, J.E. (1995) Detection of an RNase H activity associated with hepadnaviruses. J. Virol. 69, 5697–5704.

    PubMed  CAS  Google Scholar 

  51. Lien, J. M., Aldrich, C.E., and Mason, W. S. (1986) Evidence that a capped oligoribonu-cleotide is the primer for duck hepatitis B virus plus-strand DNA synthesis. J. Virol. 57, 229–236.

    PubMed  CAS  Google Scholar 

  52. Loeb, D.D., Hirsch, R.C., and Ganem, D. (1991) Sequence-independent RNA cleavages generate the primers for plus strand DNA synthesis in hepatitis B viruses: implications for other reverse transcribing elements. EMBO J. 10, 3533–3540.

    PubMed  CAS  Google Scholar 

  53. Tuttleman, J. S., Pourcel, C., and Summers, J. (1986) Formation of the pool of covalently closed circular viral DNA in hepadnavirus-infected cells. Cell 47, 451–460.

    Article  PubMed  CAS  Google Scholar 

  54. Wu, T.T., Coates, L., Aldrich, C.E., Summers, J., and Mason, W.S. (1990) In hepatocytes infected with duck hepatitis B virus, the template for viral RNA synthesis is amplified by an intracellular pathway. Virology 175, 255–261.

    Article  PubMed  CAS  Google Scholar 

  55. Gauthier, J., Bourne, E. J., Lutz, M.W., et al. (1999) Quantitation of hepatitis B viremia and emergence of YMDD variants in patients with chronic hepatitis B treated with lamivudine. J. Infect. Dis. 180, 1757–1762.

    Article  PubMed  CAS  Google Scholar 

  56. Ishak, K. G. (1994) Chronic hepatitis: morphology and nomenclature. Mod. Pathol. 7, 690–713.

    PubMed  CAS  Google Scholar 

  57. Bedossa, P. and Poynard, T. (1996) An algorithm for the grading of activity in chronic hepatitis C. The METAVIR Cooperative Study Group. Hepatology 24, 289–293.

    Article  PubMed  CAS  Google Scholar 

  58. Eddleston, A. (1986) Interferons in the treatment of chronic hepatitis B virus infection. Med. Clin. North Am. Suppl, 25–30.

    Google Scholar 

  59. Di Bisceglie, A. M. (1995) Long-term outcome of interferon-alpha therapy for chronic hepatitis B. J. Hepatol. 22, 65–67.

    Article  PubMed  Google Scholar 

  60. Korenman, J., Baker, B., Waggoner, J., Everhart, J.E., Di Bisceglie, A.M., and Hoofnagle, J. H. (1991) Long-term remission of chronic hepatitis B after alpha-interferon therapy. Ann. Intern. Med. 114, 629–634.

    PubMed  CAS  Google Scholar 

  61. Hadziyannis, S. (1995) Hepatitis Be Antigen Negative Chronic Hepatitis B: from Clinical Recognition to Pathogenesis and Treatment. Viral Hepat. Rev. 1, 7–36.

    Google Scholar 

  62. Brunetto, M.R., Oliveri, F., Rocca, G., et al. (1989) Natural course and response to interferon of chronic hepatitis B accompanied by antibody to hepatitis B e antigen. Hepatology 10, 198–202.

    Article  PubMed  CAS  Google Scholar 

  63. Hadziyannis, S., Bramou, T., Makris, A., Moussoulis, G., Zignego, L., and Papaioannou, C. (1990) Interferon alfa-2b treatment of HBeAg negative/serum HBV DNA positive chronic active hepatitis type B. J. Hepatol. 11Suppl 1(S133-136).

    Google Scholar 

  64. Santantonio, T., Mazzola, M., Iacovazzi, T., Miglietta, A., Guastadisegni, A., and Pastore, G. (2000) Long-term follow-up of patients with anti-HBe/HBV DNA-positive chronic hepatitis B treated for 12 months with lamivudine. J. Hepatol. 32, 300–306.

    Article  PubMed  CAS  Google Scholar 

  65. Dusheiko, G. (1999) Lamivudine therapy for hepatitis B infection. Scand. J. Gastroenterol. 230(Suppl), 76–81.

    Article  CAS  Google Scholar 

  66. Dienstag, J.L. (1997) Sexual and perinatal transmission of hepatitis C. Hepatology 26, 66S–70S.

    Article  PubMed  CAS  Google Scholar 

  67. Dienstag, J. L., Schiff, E. R., Mitchell, M., et al. (1999) Extended lamivudine retreatment for chronic hepatitis B: maintenance of viral suppression after discontinuation of therapy. Hepatology 30, 1082–1087.

    Article  PubMed  CAS  Google Scholar 

  68. Liaw, Y. F., Leung, N.W., Chang, T.T., et al. (2000) Effects of extended lamivudine therapy in Asian patients with chronic hepatitis B. Asia Hepatitis Lamivudine Study Group. Gastroenterology 119, 172–180.

    Article  PubMed  CAS  Google Scholar 

  69. Hadziyannis, S. J., Papatheodoridis, G. V., Dimou, E., Laras, A., and Papaioannou, C. (2000) Efficacy of long-term Lamivudine monotherapy in patients with hepatitis B e antigen-negative chronic hepatitis B. Hepatology 32, 847–851.

    Article  PubMed  CAS  Google Scholar 

  70. Fischer, K.P., Gutfreund, K. S., and Tyrrell, D.L. (2001) Lamivudine resistance in hepatitis B: mechanisms and clinical implications. Drug Resist. Updat. 4, 118–128.

    Article  PubMed  CAS  Google Scholar 

  71. Gutfreund, K. S., Williams, M., George, R., et al. (2000) Genotypic succession of mutations of the hepatitis B virus polymerase associated with lamivudine resistance. J. Hepatol. 33, 469–475.

    Article  PubMed  CAS  Google Scholar 

  72. Kobayashi, S., Ide, T., and Sata, M. (2001) Detection of YMDD motif mutations in some lamivudine-untreated asymptomatic hepatitis B virus carriers. J. Hepatol. 34, 584–586.

    Article  PubMed  CAS  Google Scholar 

  73. Leung, N. W., Lai, C. L., Chang, T. T., et al. (2001) Extended lamivudine treatment in patients with chronic hepatitis B enhances hepatitis B e antigen seroconversion rates: results after 3 years of therapy. Hepatology 33, 1527–1532.

    Article  PubMed  CAS  Google Scholar 

  74. Perrillo, R., Rakela, J., Dienstag, J., et al. (1999) Multicenter study of lamivudine therapy for hepatitis B after liver transplantation.Lamivudine Transplant Group. Hepatology 29, 1581–1586.

    Article  PubMed  CAS  Google Scholar 

  75. De Man, R.A., Heijtink, R.A., Niesters, H.G., and Schalm, S.W. (1995) New developments in antiviral therapy for chronic hepatitis B infection. Scand. J. Gastroenterol. 212(Suppl), 100–104.

    Article  Google Scholar 

  76. Bridges, E.G. and Cheng, Y.C. (1995) Use of novel beta-L(−)-nucleoside analogues for treatment and prevention of chronic hepatitis B virus infection and hepatocellular carcinoma. Prog. Liver Dis. 13, 231–245.

    PubMed  CAS  Google Scholar 

  77. Cossart, Y. E. (1972) Australia antigen and hepatitis in renal units. Proc. Eur. Dial. Transplant. Assoc. 9, 235–242.

    PubMed  CAS  Google Scholar 

  78. Davis, H. L. (1999) DNA vaccines for prophylactic or therapeutic immunization against hepatitis B virus. Mt. Sinai J. Med. 66, 84–90.

    PubMed  CAS  Google Scholar 

  79. Tiollais, P., Pourcel, C., and Dejean, A. (1985) The hepatitis B virus. Nature 317, 489–495.

    Article  PubMed  CAS  Google Scholar 

  80. Carman, W.F. (1997) The clinical significance of surface antigen variants of hepatitis B virus. J. Viral Hepat. 4(Suppl 1), 11–20.

    Article  PubMed  Google Scholar 

  81. Yoshida, E. M., Ramji, A., Erb, S.R., et al. (2000) De novo acute hepatitis B infection in a previously vaccinated liver transplant recipient due to a strain of HBV with a Met 133 Thr mutation in the “a” determinant. Liver 20, 411–414.

    Article  PubMed  CAS  Google Scholar 

  82. Ijaz, S., Torre, F., Tedder, R.S., Williams, R., and Naoumov, N.V. (2001). Novel immunoassay for the detection of hepatitis B surface ‘escape’ mutants and its application in liver transplant recipients. J.Med.Virol. 63, 210–216.

    Article  PubMed  CAS  Google Scholar 

  83. Rossner, M. T. (1992). Review: hepatitis B virus X-gene product: a promiscuous transcriptional activator. J.Med.Virol. 36, 101–117.

    Article  PubMed  CAS  Google Scholar 

  84. Jean-Jean, O., Weimer, T., de Recondo, A. M., Will, H., and Rossignol, J. M. (1989). Internal entry of ribosomes and ribosomal scanning involved in hepatitis B virus P gene expression. J.Virol. 63, 5451–5454.

    PubMed  CAS  Google Scholar 

  85. Lin, C.G. and Lo, S.J. (1992). Evidence for involvement of a ribosomal leaky scanning mechanism in the translation of the hepatitis B virus pol gene from the viral pregenome RNA. Virology 188, 342–352.

    Article  PubMed  CAS  Google Scholar 

  86. Lanford, R.E., Kim, Y.H., Lee, H., Notvall, L., and Beames, B. (1999). Mapping of the hepatitis B virus reverse transcriptase TP and RT domains by transcomplementation for nucleotide priming and by protein-protein interaction. J.Virol. 73, 1885–1893.

    PubMed  CAS  Google Scholar 

  87. Bartenschlager, R. and Schaller, H. (1988). The amino-terminal domain of the hepadnaviral P-gene encodes the terminal protein (genome-linked protein) believed to prime reverse transcription. EMBO J. 7, 4185–4192.

    PubMed  CAS  Google Scholar 

  88. Jacobo-Molina, A., Ding, J., Clark, A.D., Jr., Lu, X., Williams, R.L., Williams, R. L., Kamer, G., Ferria, A.L., and Clark, P. (1993). Crystal structure of human immunodeficiency virus type 1 reverse transcriptase complexed with double-stranded DNA at 3.0 A resolution shows bent DNA. Proc.Natl.Acad.Sci.U.S.A 90, 6320–6324.

    Article  PubMed  CAS  Google Scholar 

  89. Bartholomeusz, A. and Thompson, P. (1999). Flaviviridae polymerase and RNA replication. J.Viral Hepat. 6, 261–270.

    Article  PubMed  CAS  Google Scholar 

  90. Locarnini, S. and Birch, C. (1999). Antiviral chemotherapy for chronic hepatitis B infection: lessons learned from treating HIV-infected patients. J.Hepatol. 30, 536–550.

    Article  PubMed  CAS  Google Scholar 

  91. Stuyver, L.J., Locarnini, S. A., Lok, A., Richman, D. D., Carman, W. F., Dienstag, J.L., and Schinazi, R. F. (2001). Nomenclature for antiviral-resistant human hepatitis B virus mutations in the polymerase region. Hepatology 33, 751–757.

    Article  PubMed  CAS  Google Scholar 

  92. Das, K., Xiong, X., Yang, H., Westland, C. E., Gibbs, C. S., Sarafianos, S. G., and Arnold, E. (2001). Molecular modeling and biochemical characterization reveal the mechanism of hepatitis B virus polymerase resistance to lamivudine (3TC) and emtricitabine (FTC). J.Virol. 75, 4771–4779.

    Article  PubMed  CAS  Google Scholar 

  93. Hunt, C.M., McGill, J. M., Allen, M. I., and Condreay, L.D. (2000). Clinical relevance of hepatitis B viral mutations. Hepatology 31, 1037–1044.

    Article  PubMed  CAS  Google Scholar 

  94. Lok, A. S., Akarca, U., and Greene, S. (1994). Mutations in the pre-core region of hepatitis B virus serve to enhance the stability of the secondary structure of the pre-genome encapsidation signal. Proc.Natl.Acad.Sci.U.S.A 91, 4077–4081.

    Article  PubMed  CAS  Google Scholar 

  95. Gunther, S., Fischer, L., Pult, I., Sterneck, M., and Will, H. (1999). Naturally occurring variants of hepatitis B virus. Adv.Virus Res. 52, 125–137.

    Google Scholar 

  96. Cabrerizo, M., Bartolome, J., Ruiz-Moreno, M., Otero, M., Lopez-Alcorocho, J.M., and Carreno, V. (1996). Distribution of the predominant hepatitis B virus precore variants in hepatitis B e antigen-positive children and their effect on treatment response. Pediatr.Res. 39, 980–984.

    Article  PubMed  CAS  Google Scholar 

  97. Lampertico, P., Manzin, A., Rumi, M.G., Paolucci, S., Del Ninno, E., Clementi, M., and Colombo, M. (1995). Hepatitis B virus precore mutants in HBeAg carriers with chronic hepatitis treated with interferon. J.Viral Hepat. 2, 251–256.

    Article  PubMed  CAS  Google Scholar 

  98. Lopez-Alcorocho, J. M., Cabrerizo, M., Bartolome, J., Cotonat, T., and Carreno, V. (1995). Analysis of hepatitis B virus precore variants in hepatitis B e antibody-positive patients treated with prednisone plus interferon. J.Viral Hepat. 2, 279–284.

    Article  PubMed  CAS  Google Scholar 

  99. Alberti, A., Pontisso, P., Chemello, L., Fattovich, G., Benvegnu, L., Belussi, F., and De Mitri, M. S. (1995). The interaction between hepatitis B virus and hepatitis C virus in acute and chronic liver disease. J.Hepatol. 22, 38–41.

    PubMed  CAS  Google Scholar 

  100. Benhamou, Y., Bochet, M., Thibault, V., Di, M., V, Caumes, E., Bricaire, F., Opolon, P., Katlama, C., and Poynard, T. (1999). Long-term incidence of hepatitis B virus resistance to lamivudine in human immunodeficiency virus-infected patients. Hepatology 30, 1302–1306.

    Article  PubMed  CAS  Google Scholar 

  101. Bessesen, M., Ives, D., Condreay, L., Lawrence, S., and Sherman, K.E. (1999) Chronic active hepatitis B exacerbations in human immunodeficiency virus-infected patients following development of resistance to or withdrawal of lamivudine. Clin. Infect. Dis. 28, 1032–1035.

    Article  PubMed  CAS  Google Scholar 

  102. Thibault, V., Benhamou, Y., Seguret, C., et al. (1999) Hepatitis B virus (HBV) mutations associated with resistance to lamivudine in patients coinfected with HBV and human immunodeficiency virus. J. Clin. Microbiol. 37, 3013–3016.

    PubMed  CAS  Google Scholar 

  103. Bonino, F. and Smedile, A. (1986) Delta agent (type D) hepatitis. Semin. Liver Dis. 6, 28–33.

    Article  PubMed  CAS  Google Scholar 

  104. Hadziyannis, S.J. (1983) Delta antigen positive chronic liver disease in Greece: clinical aspects and natural course. Prog. Clin. Biol. Res. 143, 209–217.

    PubMed  CAS  Google Scholar 

  105. Rizzetto, M., Shih, J.W., Gocke, D. J., Purcell, R. H., Verme, G., and Gerin, J.L. (1979) Incidence and significance of antibodies to delta antigen in hepatitis B virus infection. Lancet 2, 986–990.

    Article  PubMed  CAS  Google Scholar 

  106. Rizzetto, M., Purcell, R.H., and Gerin, J. L. (1980) Epidemiology of HBV-associated delta agent: geographical distribution of anti-delta and prevalence in polytransfused HBsAg carriers. Lancet 1, 1215–1218.

    Article  PubMed  CAS  Google Scholar 

  107. Rizzetto, M. (1993) Hepatitis delta virus disease: an overview. Prog. Clin. Biol. Res. 382, 425–430.

    PubMed  CAS  Google Scholar 

  108. Cenac, A., Pedroso, M. L., Djibo, A., et al. (1995) Hepatitis B, C, and D virus infections in patients with chronic hepatitis, cirrhosis, and hepatocellular carcinoma: a comparative study in Niger. Am. J. Trop. Med. Hyg. 52, 293–296.

    PubMed  CAS  Google Scholar 

  109. Mion, F., Boillot, O., Gille, D., Chevallier, P., and Paliard, P. (1993) Liver transplantation for posthepatic B-delta cirrhosis: prevention of recurrence with high-dose anti-HBs immunoglobulins. Transplant. Proc. 25, 2638–2639.

    PubMed  CAS  Google Scholar 

  110. Alvarez, F. (1996) Therapy for chronic viral hepatitis. Clin. Invest Med. 19, 381–388.

    PubMed  CAS  Google Scholar 

  111. Bortolotti, F., Jara, P., Barbera, C., et al. (2000) Long term effect of alpha interferon in children with chronic hepatitis B [see comments]. Gut 46, 715–718.

    Article  PubMed  CAS  Google Scholar 

  112. Carreno, V., Porres, J. C., Ruiz-Moreno, M., Gutiez, J., and Bartolome, F. J. (1991) [A controlled study of treatment with recombinant interferon alpha of chronic hepatitis due to the B virus in childhood]. Rev. Esp. Enferm. Dig. 79, 24–28.

    PubMed  CAS  Google Scholar 

  113. Castaneda, G.C., Sotto, E. A., and Lopez, S. P. (1990) Antiviral effect of interferon: the interferon in viral hepatitis. Rev. Roum. Virol. 41, 171–179.

    Google Scholar 

  114. Jara, P. and Bortolotti, F. (1999) Interferon-alpha treatment of chronic hepatitis B in childhood: a consensus advice based on experience in European children. J. Pediatr. Gastroenterol. Nutr. 29, 163–170.

    Article  PubMed  CAS  Google Scholar 

  115. (1996) Hepatitis B immunization/prophylaxis: recommendations for adults/older adults. Nurse Pract. 21, 64,67–64,70.

    Google Scholar 

  116. Mahon, M. M. and James, O.F. (1994) Liver disease in the elderly. J. Clin. Gastroenterol. 18, 330–334.

    Article  PubMed  CAS  Google Scholar 

  117. Malaguarnera, M., Restuccia, S., Ferlito, L., Mazzoleni, G., Giugno, I., and Pistone, G. (2001) Antiviral drugs in chronic hepatitis B: review and meta-analysis. Int. J. Clin. Pharmacol. Ther. 39, 4–11.

    PubMed  CAS  Google Scholar 

  118. Chiaramonte, M., Floreani, A., and Naccarato, R. (1987) Hepatitis B virus (HBV) in the elderly: an underestimated problem? Biomed. Pharmacother. 41, 121–123.

    PubMed  CAS  Google Scholar 

  119. Dienstag, J.L., Perrillo, R.P., Schiff, E.R., Bartholomew, M., Vicary, C., and Rubin, M. (1995) A preliminary trial of lamivudine for chronic hepatitis B infection. N. Engl. J. Med. 333, 1657–1661.

    Article  PubMed  CAS  Google Scholar 

  120. Lai, C.L., Ching, C. K., Tung, A.K., et al. (1997) Lamivudine is effective in suppressing hepatitis B virus DNA in Chinese hepatitis B surface antigen carriers: a placebo-controlled trial. Hepatology 25, 241–244.

    Article  PubMed  CAS  Google Scholar 

  121. Nevens, F., Main, J., Honkoop, P., et al. (1997) Lamivudine therapy for chronic hepatitis B: a six-month randomized dose-ranging study. Gastroenterology 113, 1258–1263.

    Article  PubMed  CAS  Google Scholar 

  122. Honkoop, P., De Man, R. A., Niesters, H.G., et al. (1998). Quantitative hepatitis B virus DNA assessment by the limiting-dilution polymerase chain reaction in chronic hepatitis B patients: evidence of continuing viral suppression with longer duration and higher dose of lamivudine therapy. J. Viral Hepat. 5, 307–312.

    Article  PubMed  CAS  Google Scholar 

  123. Xiong, X., Flores, C., Yang, H., Toole, J.J., and Gibbs, C. S. (1998) Mutations in hepatitis B DNA polymerase associated with resistance to lamivudine do not confer resistance to adefovir in vitro. Hepatology 28, 1669–1673.

    Article  PubMed  CAS  Google Scholar 

  124. Xiong, X., Yang, H., Westland, C. E., Zou, R., and Gibbs, C.S. (2000) In vitro evaluation of hepatitis B virus polymerase mutations associated with famciclovir resistance. Hepatology 31, 219–224.

    Article  PubMed  CAS  Google Scholar 

  125. Perrillo, R., Schiff, E., Yoshida, E., et al. (2000) Adefovir dipivoxil for the treatment of lamivudine-resistant hepatitis B mutants. Hepatology 32, 129–134.

    Article  PubMed  CAS  Google Scholar 

  126. Peters, M.G., Singer, G., Howard, T., et al. (1999) Fulminant hepatic failure resulting from lamivudine-resistant hepatitis B virus in a renal transplant recipient: durable response after orthotopic liver transplantation on adefovir dipivoxil and hepatitis B immune globulin. Transplantation 68, 1912–1914.

    Article  PubMed  CAS  Google Scholar 

  127. Brechot, C., Nalpas, B., and Feitelson, M.A. (1996) Interactions between alcohol and hepatitis viruses in the liver. Clin. Lab. Med. 16, 273–287.

    PubMed  CAS  Google Scholar 

  128. Abou-Saif, A. and Lewis, J. H. (2000) Gastrointestinal and hepatic disorders in end-stage renal disease and renal transplant recipients [In Process Citation]. Adv. Ren. Replace. Ther. 7, 220–230.

    Article  PubMed  CAS  Google Scholar 

  129. Samuel, D., Zignego, A.L., Reynes, M., et al. (1995) Long-term clinical and virological outcome after liver transplantation for cirrhosis caused by chronic delta hepatitis. Hepatology 21, 333–339.

    Article  PubMed  CAS  Google Scholar 

  130. Gish, R.G., Lau, J. Y., Brooks, L., et al. (1996) Ganciclovir treatment of hepatitis B virus infection in liver transplant recipients. Hepatology 23, 1–7.

    Article  PubMed  CAS  Google Scholar 

  131. Al, F.K., Yoshida, E. M., Davis, J. E., Vartanian, R.K., Anderson, F. H., and Steinbrecher, U. P. (1997) Alteration of the dismal natural history of fibrosing cholestatic hepatitis secondary to hepatitis B virus with the use of lamivudine. Transplantation 64, 926–928.

    Article  Google Scholar 

  132. Andreone, P., Caraceni, P., Grazi, G.L., et al. (1998) Lamivudine treatment for acute hepatitis B after liver transplantation. J. Hepatol. 29, 985–989.

    Article  PubMed  CAS  Google Scholar 

  133. Ben-Ari, Z., Shmueli, D., Mor, E., et al. (1997) Beneficial effect of lamivudine pre-and post-liver transplantation for hepatitis B infection. Transplant. Proc. 29, 2687–2688.

    Article  PubMed  CAS  Google Scholar 

  134. Ben-Ari, Z., Shmueli, D., Mor, E., Shapira, Z., and Tur-Kaspa, R. (1997) Beneficial effect of lamivudine in recurrent hepatitis B after liver transplantation. Transplantation 63, 393–396.

    Article  PubMed  CAS  Google Scholar 

  135. Ben Ari, Z., Zemel, R., Kazetsker, A., Fraser, G., and Tur-Kaspa, R. (1999) Efficacy of lamivudine in patients with hepatitis B virus precore mutant infection before and after liver transplantation. Am. J. Gastroenterol. 94, 663–667.

    Google Scholar 

  136. De Man, R.A., Bartholomeusz, A. I., Niesters, H. G., Zondervan, P.E., and Locarnini, S. A. (1998) The sequential occurrence of viral mutations in a liver transplant recipient re-infected with hepatitis B: hepatitis B immune globulin escape, famciclovir non-response, followed by lamivudine resistance resulting in graft loss. J. Hepatol. 29, 669–675.

    Article  PubMed  Google Scholar 

  137. Dodson, S.F., Bonham, C.A., Geller, D. A., Cacciarelli, T.V., Rakela, J., and Fung, J.J. (1999) Prevention of de novo hepatitis B infection in recipients of hepatic allografts from anti-HBc positive donors. Transplantation 68, 1058–1061.

    Article  PubMed  CAS  Google Scholar 

  138. Dodson, S. F. (2000) Prevention of de novo hepatitis B infection after liver transplantation with allografts from hepatitis B core antibody positive donors. Clin. Transplant. 14(Suppl 2), 20–24.

    PubMed  Google Scholar 

  139. Grellier, L., Mutimer, D., Ahmed, M., et al. (1996) Lamivudine prophylaxis against reinfection in liver transplantation for hepatitis B cirrhosis. Lancet 348, 1212–1215.

    Article  PubMed  CAS  Google Scholar 

  140. Gugenheim, J., Baldini, E., Ouzan, D., Sowka, P., and Mouiel, J. (1999) Good results of lamivudine in hepatitis B surface antigen-positive patients with active viral replication before liver transplantation. Transplant. Proc. 31, 554–555.

    Article  PubMed  CAS  Google Scholar 

  141. McCaughan, G. W., Spencer, J., Koorey, D., et al. (1999) Lamivudine therapy in patients undergoing liver transplantation for hepatitis B virus precore mutant-associated infection: high resistance rates in treatment of recurrence but universal prevention if used as prophylaxis with very low dose hepatitis B immune globulin. Liver Transplant Surg. 5, 512–519.

    Article  CAS  Google Scholar 

  142. Mutimer, D., Dusheiko, G., Barrett, C., et al. (2000) Lamivudine without HBIg for prevention of graft reinfection by hepatitis B: long-term follow-up. Transplantation 70, 809–815.

    Article  PubMed  CAS  Google Scholar 

  143. Perrillo, R. P. (1997) Treatment of posttransplantation hepatitis B. Liver Transplant. Surg. 3, S8–12.

    Google Scholar 

  144. Perrillo, R.P., Rakela, J., Dienstag, J., et al. (1999) Multicenter study of lamivudine therapy for hepatitis B after liver transplantation.Lamivudine Transplant Group. Hepatology 29, 1581–1586.

    Article  PubMed  CAS  Google Scholar 

  145. Terrault, N.A., Holland, C. C., Ferrell, L., et al. (1996) Interferon alfa for recurrent hepatitis B infection after liver transplantation. Liver Transplant. Surg. 2, 132–138.

    Article  CAS  Google Scholar 

  146. Bartholomew, M.M., Jansen, R. W., Jeffers, L. J., et al. (1997) Hepatitis-B-virus resistance to lamivudine given for recurrent infection after orthotopic liver transplantation. Lancet 349, 20–22.

    Article  PubMed  CAS  Google Scholar 

  147. Ling, R., Mutimer, D., Ahmed, M., et al. (1996) Selection of mutations in the hepatitis B virus polymerase during therapy of transplant recipients with lamivudine. Hepatology 24, 711–713.

    Article  PubMed  CAS  Google Scholar 

  148. Tipples, G. A., Ma, M. M., Fischer, K.P., Bain, V. G., Kneteman, N.M., and Tyrrell, D. L. (1996) Mutation in HBV RNA-dependent DNA polymerase confers resistance to lamivu-dine in vivo. Hepatology 24, 714–717.

    PubMed  CAS  Google Scholar 

  149. Honkoop, P., Niesters, H.G., De Man, R.A., Osterhaus, A.D., and Schalm, S.W. (1997) Lamivudine resistance in immunocompetent chronic hepatitis B. Incidence and patterns. J. Hepatol. 26, 1393–1395.

    Article  PubMed  CAS  Google Scholar 

  150. Chayama, K., Suzuki, Y., Kobayashi, M., et al. (1998) Emergence and takeover of YMDD motif mutant hepatitis B virus during long-term lamivudine therapy and re-takeover by wild type after cessation of therapy. Hepatology 27, 1711–1716.

    Article  PubMed  CAS  Google Scholar 

  151. Liaw, Y. F., Chien, R. N., Yeh, C. T., Tsai, S. L., and Chu, C.M. (1999) Acute exacerbation and hepatitis B virus clearance after emergence of YMDD motif mutation during lamivudine therapy. Hepatology 30, 567–572.

    Article  PubMed  CAS  Google Scholar 

  152. Seta, T., Yokosuka, O., Imazeki, F., Tagawa, M., and Saisho, H. (2000) Emergence of YMDD motif mutants of hepatitis B virus during lamivudine treatment of immunocompetent type B hepatitis patients. J. Med. Virol. 60, 8–16.

    Article  PubMed  CAS  Google Scholar 

  153. Lai, C.L., Chien, R. N., Leung, N. W., et al. (1998) A one-year trial of lamivudine for chronic hepatitis B. Asia Hepatitis Lamivudine Study Group. N. Engl. J. Med. 339, 61–68.

    Article  PubMed  CAS  Google Scholar 

  154. Dienstag, J. L., Schiff, E. R., Wright, T. L., et al. (1999) Lamivudine as initial treatment for chronic hepatitis B in the United States. N. Engl. J. Med. 341, 1256–1263.

    Article  PubMed  CAS  Google Scholar 

  155. Tassopoulos, N. C., Volpes, R., Pastore, G., et al. (1999) Efficacy of lamivudine in patients with hepatitis B e antigen-negative/hepatitis B virus DNA-positive (precore mutant) chronic hepatitis B.Lamivudine Precore Mutant Study Group. Hepatology 29, 889–896.

    Article  PubMed  CAS  Google Scholar 

  156. Wedemeyer, H., Pethig, K., Wagner, D., et al. (1998) Long-term outcome of chronic hepatitis B in heart transplant recipients. Transplantation 66, 1347–1353.

    Article  PubMed  CAS  Google Scholar 

  157. Chen, P. M., Chiou, T.J., Fan, F.S., et al. (1999) Fulminant hepatitis is significantly increased in hepatitis B carriers after allogeneic bone marrow transplantation. Transplantation 67, 1425–1433.

    Article  PubMed  CAS  Google Scholar 

  158. Cooksley, W.G. and McIvor, C.A. (1995) Fibrosing cholestatic hepatitis and HBV after bone marrow transplantation. Biomed. Pharmacother. 49, 117–124.

    Article  PubMed  CAS  Google Scholar 

  159. Fan, F.S., Tzeng, C.H., Yeh, H.M., and Chen, P.M. (1992) Reverse seroconversion of hepatitis B virus infectious status after allogeneic bone marrow transplantation from a carrier donor. Bone Marrow Transplant. 10, 189–191.

    PubMed  CAS  Google Scholar 

  160. Fornairon, S., Pol, S., Legendre, C., et al. (1996) The long-term virologic and pathologic impact of renal transplantation on chronic hepatitis B virus infection. Transplantation 62, 297–299.

    Article  PubMed  CAS  Google Scholar 

  161. Uemoto, S., Inomata, Y., Sannomiya, A., et al. (1998) Posttransplant hepatitis B infection in liver transplantation with hepatitis B core antibody-positive donors. Transplant. Proc. 30, 134–135.

    Article  PubMed  CAS  Google Scholar 

  162. Wachs, M.E., Amend, W. J., Ascher, N. L., et al. (1995) The risk of transmission of hepatitis B from HBsAg(−), HBcAb(+), HBIgM(−) organ donors. Transplantation 59, 230–234.

    PubMed  CAS  Google Scholar 

  163. Fabia, R., Levy, M.F., Crippin, J., et al. (1998) De novo hepatitis B infection after liver transplantation: source of disease, incidence, and impact. Liver Transplant. Surg. 4, 119–127.

    Article  CAS  Google Scholar 

  164. Lau, G. K., Liang, R., Lee, C. K., et al. (1998) Clearance of persistent hepatitis B virus infection in Chinese bone marrow transplant recipients whose donors were anti-hepatitis B core-and anti-hepatitis B surface antibody-positive. J. Infect. Dis. 178, 1585–1591.

    Article  PubMed  CAS  Google Scholar 

  165. Lok, A.S.F. and McMahon, B.J. (2001) Chronic hepatitis B. Hepatology 34, 1225–1241.

    Article  PubMed  CAS  Google Scholar 

  166. Margolis, H. S., Alter, M.J., and Hadler, S. C. (1991) Hepatitis B: evolving epidemiology and implications for control. Semin. Liver Dis. 11, 84–92.

    Article  PubMed  CAS  Google Scholar 

  167. Angus, P., Vaughan, R., Xiong, S., et al. (2003) Resistance to adefovir dipivoxil therapy associated with the selection of a novel mutation in the HBV polymerase. Gastroenterology 125, 292–297.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2004 Humana Press Inc.

About this protocol

Cite this protocol

Gish, R.G., Locarnini, S. (2004). Studying the Treatment of Chronic Hepatitis B Viral Infection in Special Populations. In: Hamatake, R.K., Lau, J.Y.N. (eds) Hepatitis B and D Protocols. Methods in Molecular Medicine™, vol 96. Humana Press. https://doi.org/10.1385/1-59259-670-3:465

Download citation

  • DOI: https://doi.org/10.1385/1-59259-670-3:465

  • Publisher Name: Humana Press

  • Print ISBN: 978-1-58829-108-0

  • Online ISBN: 978-1-59259-670-6

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics