Patterns and mechanisms of hepatitis B/hepatitis D reinfection after liver transplantation

  • Anna Linda Zignego
  • D. Samuel
  • P. Gentilini
  • H. Bismuth
Conference paper
Part of the Archives of Virology Supplementum book series (ARCHIVES SUPPL, volume 8)


Viral recurrence is the limiting factor in orthotopic liver transplantation (OLT) for hepatitis B virus (HBV) related liver disease. In fact, high rates of HBV infection of the transplanted liver are reported, followed by the recurrence of liver disease in a high percentage of cases. The importance of reinfection stimulates the study of its modalities and mechanisms in order to better identify preventive measures and better select patients for OLT. In HBV and HDV positive patients, the outcome of liver transplantation appears significantly better than in patients that are solely HBV positive, in spite of a high rate of HDV reinfection. Long-term analysis (5 years) of HBV and HDV infection, using the PCR technique, in 15 patients transplanted for an HBV/HDV positive liver disease and treated with anti-HBs immunoglobulin (HBIG), revealed that all patients experienced an HDV reinfection, but only about 7 were still harboring the virus after four years of follow- up. HDV reinfection was either associated to HBV reinfection or isolated whereas no cases of HBV isolated reinfection was observed. Isolated HDV reinfection was frequent and transient in all but one case that was superinfected by HBV. Infected peripheral blood mononuclear cells seem to be implicated in HBV superinfection of HDV infected liver. Liver damage was observed only in cases of HBV/HDV co-infection, suggesting that, in vivo, HBV is necessary to produce liver damage although it is not essential for HDV absorption to target cells, HDV penetration of these cells or HDV genomic replication. In addition, in isolated HDV infection, transient HDV viraemia and its low levels suggest that, perhaps in these patients HDV uses a very limited presence of HBV or alternative ways which are not efficient enough for envelope production. These data suggest that, particularly in HDV positive patients, antiHBs Ig administration, which has previously been proven to significantly reduce HBV reinfection in HBsAg-positive patients, may be useful in changing the natural history of repetition of the original viral infection and liver disease after OLT.


Orthotopic Liver Transplantation Hepatitis Delta Virus Hepatitis Delta Virus Infection Envelope Production Positive Liver Disease 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Bismuth H (1989) Hepatic transplantation in Europe: improved survival. Eur J Gastroenterol Hepatol 1: 79–82Google Scholar
  2. 2.
    Lauchart W, Muller R, Pichlayr R (1987) Immunoprophylaxis of hepatitis B virus reinfection in recipients of human liver allografts. Transplant Proc 19: 2387–2389PubMedGoogle Scholar
  3. 3.
    Starzl TE, Demetris AJ, Van Thiel D (1989) Liver transplantation. N Engl J Med 321: 1092–1099PubMedCrossRefGoogle Scholar
  4. 4.
    Zignego AL, Samuel D, Gugenheim J, Chardan B, Bismuth H (1988) Hepatitis B virus replication and mononuclear blood cell infection after liver transplantation. In: Zuckerman (ed) Viral hepatitis and liver disease. Williams and Wilkins, Baltimore, pp 808–809Google Scholar
  5. 5.
    Feray C, Zignego AL, Samuel D, Bismuth A, Reynes M, Tiollais P, Bismuth H, Brechot C (1990) Persistent hepatitis B virus infection of mononuclear cells without concomitant liver infection. Transplantation 49: 1155–1158PubMedCrossRefGoogle Scholar
  6. 6.
    Samuel D, Zignego AL, Bismuth A, Serres C, Feray C, Benhamou J-P, Brechot C, Bismuth H (1990) Outcome of HBV infection after liver transplantation for HBsAg positive patients: experience with long term prophylaxis: In: Hollinger FB, Lemon SM, Margolis H (eds) Viral hepatitis and liver disease. Williams and Wilkins, Baltimore, pp 648–650Google Scholar
  7. 7.
    Samuel D, Bismuth A, Mathieu D, Arulnaden J-L, Reynes M, Benhamou J-P, Brechot C, Bismuth H (1991) Passive immunoprophylaxis after liver transplantation in HBsAg-positive patients. Lancet 337: 813–815PubMedCrossRefGoogle Scholar
  8. 8.
    Ottobrelli A, Marzano A, Smedile A, Recchia S, Salizzoni M, Cornu C, Lamy ME, Otte JB, De Hemptinne B, Geubel A, Grendele M, Colledan M, Galmarini D, Marinucci G, Di Giacomo C, Agnes S, Bonino F, Rizzetto M (1991) Patterns of hepatitis delta virus reinfection and disease in liver tranplantation. Gastroenterology 101: 1649–1655PubMedGoogle Scholar
  9. 9.
    Rizzetto M, Macagno S, Chiaberge E, Verme G, Negro F, Marinucci G, Di Giacomo C, Alfani D, Cortesini R, Milazzo F, Doglia M, Fassati LR, Galmarini D (1987) Liver transplantation in hepatitis delta virus disease. Lancet ii: 469–471Google Scholar
  10. 10.
    Reynes M, Zignego AL, Samuel D, Fabiani B, Gugenheim J, Tricottet Y, Brechot C, Bismuth H (1989) Graft hepatitis delta virus reinfection after orthotopic liver transplantation in HDV cirrhosis. Transplant Proc 21: 2424–2426PubMedGoogle Scholar
  11. 11.
    Grendele M, Colledan M, Gridelli B (1990) Does the experience with liver transplantation suggest that hepatitis Delta virus is not cytopathic, Transplant Proc 22: 1551–1553PubMedGoogle Scholar
  12. 12.
    Zignego AL, Dubois F, Samuel D, Georgopoulou U, Reynes M, Gentilini P, Bismuth A, Benhamou J-P, Hadziyannis SJ, Bismuth H, Brechot C (1990) Serum hepatitis delta virus RNA in pattients with delta hepatitis and in liver graft recipients. J Hepatol 11: 102–110PubMedCrossRefGoogle Scholar
  13. 13.
    Taylor J, Mason W, Summers J, Goldberg J, Aldrich C, Coates L, Gerin J, Gowans E (1987) Replication of human hepatitis delta virus in primary cultures of woodchuck hepatocytes. J Virol 61: 2891–2895PubMedGoogle Scholar
  14. 14.
    Mason WS, Taylor JM (1989) Experimental systems for the study of hepadna- viruses and hepatitis delta virus infections. Hepatology 9: 635–645PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 1993

Authors and Affiliations

  • Anna Linda Zignego
    • 1
  • D. Samuel
    • 2
  • P. Gentilini
    • 1
  • H. Bismuth
    • 2
  1. 1.Istituto di Clinica Medica IIUniversity of FlorenceFlorenceItaly
  2. 2.Hepatobiliary Surgery and Liver Transplantation Research UnitHopital Paul BrousseVillejuifFrance

Personalised recommendations