Skip to main content
Log in

Variability of the hepatitis B surface protein in HBV-infected liver transplant recipients

  • Original Paper
  • Published:
Journal of Biomedical Science

Abstract

Variations in the major surface proteins (HBsAg) of hepatitis B virus (HBV) have been implicated in the high rate of reinfection in HBV-infected recipients of orthotopic liver transplantations (OLT). Sera from 6 OLT patients positive for HBsAg and from 3 recipients negative for it prior to transplantation were analyzed over several years, and 39 HBsAg sequences were compared. Despite anti-HBs immunoprophylaxis resulting in the disappearance of HBsAg, HBV DNA was detectable by a sensitive nested PCR in almost all sera. In 1 patient, a significant temporary shift in HBV subtypes was observed, indicating a mixed infection or the presence of multiple HBV populations in this patient; this was also true for other patients. Amino acid substitutions compared to wild-type HBV subtypes in 7 patients and variations within patients in 5 patients were detectable over time; the ‘escape mutation’ at amino acid position 145 was detected in 2 patients. Our data suggest that the high rate of reinfection in OLT recipients seems not to be associated with specific sequence variations in the major HBs gene, but shows a remarkable inter- and intraindividual variability. Obviously, no correlation between heterogeneity in this gene and clinical outcome was present.

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

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Barnaba V, Balsano S. Immunologic and molecular basis of viral persistence. The hepatitis B virus model. J Hepatol 14:391–397;1992.

    Google Scholar 

  2. Beasley RP, Hwang LY, Lin CC, Chien CS. Hepatocellular carcinoma and hepatitis B virus: A prospective study of 22,707 men in Taiwan. Lancet ii: 1129–1133;1981.

    Google Scholar 

  3. Brown JL, Carman WF, Thomas HC. The clinical significance of molecular variation within the hepatitis B virus genome. Hepatology 15:144–148;1992.

    Google Scholar 

  4. Brunetto MR, Giarin MM, Oliveri F, Chiaberge E, Baldi M, Alfarano A, Serra A, Saracco G, Verme G, Will H, Bonino F: Wild-type and e antigen-minus hepatitis B viruses and course of chronic hepatitis. Proc Natl Acad Sci USA 88:4186–4190;1991.

    Google Scholar 

  5. Carman WF, Zanetti R, Karayiannis P, Waters J, Manzillo G, Tanzi E, Zuckerman AJ, Thomas HC. Vaccine-induced escape mutant of hepatitis B virus. Lancet 336:325–329;1990.

    Google Scholar 

  6. Carman WF, Thomas HC. Genetically defined variants of hepatitis B virus. Rev Med Virol 1:29–39;1991.

    Google Scholar 

  7. Carman WF, Thomas HC, Domingo E. Viral genetic variation: Hepatitis B virus as a clinical example. Lancet 341:349–353;1993.

    Google Scholar 

  8. Chazouilleres O, Mamish D, Kim M, Carey K, Ferrell L, Roberts JP, Ascher NL, Wright TL. ‘Occult’ hepatitis B virus as source of infection in liver transplant recipients. Lancet 343:142–146;1994.

    Google Scholar 

  9. Chuang WL, Omata M, Ehata T, Yokosuka O, Ito Y, Imazeki F, Lu SN, Chang WY, Ohto M. Precore mutations and core clustering mutations in chronic hepatitis B virus infection. Gastroenterology 104;263–271;1993.

    Google Scholar 

  10. Domingo E, Martinez-Salas E, Sobrino F, de la Torre JC, Portela A, Ortin J, Lopez-Galindez C, Perez-Brena P, Villanueva N, Najera R, et al. The quasispecies (extremely heterogenous) nature of viral RNA genome populations: Biological relevance — A review. Gene 40:1–8;1985.

    Google Scholar 

  11. Douglas DD, Rakela J, Taswell HF, Krom RA, Wiesner RH. Hepatitis B virus replication patterns after orthotopic liver transplantation: De novo versus recurrent infection. Transplant Proc 25:1755–1757;1993.

    Google Scholar 

  12. Girones R, Miller RH. Mutation rate of theHepadnavirus genome. Virology 170:595–597;1989.

    Google Scholar 

  13. Hoofnagle JH. Chronic hepatitis B. N Engl J Med 323:337–339;1990.

    Google Scholar 

  14. Jilg W, Sieger E, Zachoval R, Schätzl H. Individuals with antibodies against hepatitis B core antigen as the only serological marker for hepatitis B infection: High percentage of carriers of hepatitis B and C virus. J Hepatol 23:14–20;1995.

    Google Scholar 

  15. Korenman J, Baker B, Waggoner J, Everhart JE, Di Bisceglie AM, Hoofnagle JH. Long-term remission of chronic hepatitis B after alpha-interferon therapy. Ann Med 114:629–633;1991.

    Google Scholar 

  16. Kwok S, Higuchi R. Avoiding false positives with PCR. Nature 339:237–238;1989.

    Google Scholar 

  17. Lake JR, Wright TL. Liver transplantation for patients with hepatitis B: What have we learned from our results? Hepatology 13:796–799;1991.

    Google Scholar 

  18. Lauchart W, Müller R, Pichlmayr R. Immunoprophylaxis of hepatitis B virus reinfection in recipients of human liver allografts. Transplant Proc 19:2387–2389;1987.

    Google Scholar 

  19. Lauder IJ, Lin HJ, Lau JYN, Siu TS, Lai CL. The variability of the hepatitis B virus genome: Statistical analysis and biological implications. Mol Biol Evol 10:457–470;1993.

    Google Scholar 

  20. Liang TJ, Hasegawa K, Rimon N, Wands JR, Ben Porath E. Hepatitis B virus mutant associated with an epidemic of fulminant hepatitis. N Engl J Med 324:1705–1709;1991.

    Google Scholar 

  21. Martell M, Esteban JI, Quer J, Genesca J, Weiner A, Esteban R, Guardia J, Gomez J. Hepatitis C virus (HCV) circulates as a population of different but closely related genomes: Quasispecies nature of HCV genome distribution. J Virol 66:3225–3229;1992.

    Google Scholar 

  22. McMahon G, Ehrlich PH, Moustafa ZA, McCarthy LA, Dottavio D, Tolpin MD, Nadler PI, Ostberg L. Genetic alterations in the gene encoding the major HBsAg: DNA and immunological analysis of recurrent HBsAg derived from monoclonal antibody-treated liver transplant patients. Hepatology 15:757–766;1992.

    Google Scholar 

  23. Norder H, Couroucé AM, Magnius LO. Molecular basis of hepatitis B virus serotype variations within the four major subtypes. J Gen Virol 73:3141–3145;1992.

    Google Scholar 

  24. Ono Y, Onda H, Sasada R, Igarashi K, Sugino Y, Nishioka K. The complete nucleotide sequences of the cloned hepatitis B virus DNA; Subtype adr and adw. Nucleic Acids Res 11:1747–1757;1983.

    Google Scholar 

  25. Ranki M, Schätzl H, Zachoval R, Uusi Oukari M, Lehtovaara P. Quantification of hepatitis B virus DNA over a wide range from serum for studying viral replicative activity in response to treatment and in recurrent infection. Hepatology 21:1492–1499;1995.

    Google Scholar 

  26. Repp R, Mance A, Bertram U, Niemann H, Gerlich WH, Lampert F. Persistent hepatitis B virus replication in mononuclear blood cells as a source of reinfection of liver transplants. Transplantation 52:933–935;1991.

    Google Scholar 

  27. Rizzetto M, Recchia S, Salizzoni M. Liver transplantation in carriers of the HBsAg. J Hepatol 13:5–7;1991.

    Google Scholar 

  28. Samuel D, Muller R, Graeme A, Fassati L, Ducot B, Benhamou JP, Bismuth H. Liver transplantation in European patients with the hepatitis B surface antigen. N Engl J Med 16:1842–1847;1993.

    Google Scholar 

  29. Santantonio T, Jung MC, Miska S, Pastore G, Pape GR, Will H. Prevalence and type of pre-C mutants in anti-HBe positive carriers with chronic liver disease in a highly endemic area. Virology 183:840–844;1991.

    Google Scholar 

  30. Schätzl H, Sieger E, Jäger G, Nitschko H, Bader L, Ruckdeschel G. Detection by PCR of humanPolyomaviruses BK and JC in immunocompromised individuals and partial sequencing of control regions. J Med Virol 42:138–145;1994.

    Google Scholar 

  31. Schätzl H, DaCosta M, Taylor L, Cohen FE, Prusiner SB. Prion protein gene variation among primates. J Mol Biol 245:362–374;1995.

    Google Scholar 

  32. Tiollais P, Pourcel C, Dejean A. The hepatitis B virus. Nature 317:489–495;1985.

    Google Scholar 

  33. Vyas GN, Rao DR, Ibrahim AB. Australia antigen (hepatitis B antigen). A conformational antigen dependent on disulfide bonds. Science 178:1300–1301;1972.

    Google Scholar 

  34. Wright TL, Lau JYN. Clinical aspects of hepatitis B virus infection. Lancet 342:1340–1344;1993.

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Additional information

The following investigators and institutions were members of the Liver Transplantation Group: U. Beuers, M. Bilzer, W. Caselmann, A. Gerbes, R. Hoffmann, C. Jung, G.R. Pape (Medical Department II), J. Briegel, J. Groh, M. Haller (Institute of Anesthesiology), H.J. Krämling, H. Rauh and M. Stangl (Department of Surgery).

Rights and permissions

Reprints and permissions

About this article

Cite this article

Schätzl, H.M., Sieger, E., Jilg, W. et al. Variability of the hepatitis B surface protein in HBV-infected liver transplant recipients. J Biomed Sci 4, 146–154 (1997). https://doi.org/10.1007/BF02255643

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02255643

Key Words

Navigation