Skip to main content

Advertisement

SpringerLink
Log in

Current use of hepatitis B immune globulin for prevention of de novo hepatitis B in recipients receiving anti-HBc-positive livers

  • Review Article
  • Published:
Hepatology International Aims and scope Submit manuscript

Abstract

Livers from donors positive for antibody against anti-HBc can potentially transmit de novo hepatitis B (DNH) to their recipients. Despite a good outcome, prophylaxis is usually offered to such recipients. There is no consensus on the standard prophylactic regimen and hence prophylaxis varies among different transplant centres. Nonetheless, hepatitis B immune globulin (HBIG) is considered the mainstay of such prophylaxis, either alone or in combination with an oral antiviral treatment. We aim to provide a concise review of the current use of HBIG in prevention of DNH. We also address a few important questions regarding HBIG use.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Wolfe RA, Merion RM, Roys EC, Port FK. Trends in organ donation and transplantation in the United States, 1998–2007. Am J Transpl 2009;9(4 Pt 2):869–878

    Article  CAS  Google Scholar 

  2. Chazouilleres O, Mamish D, Kim M, Carey K, Ferrell L, Roberts JP, et al. “Occult” hepatitis B virus as source of infection in liver transplant recipients. Lancet 1994;343(8890):142–146

    Article  PubMed  CAS  Google Scholar 

  3. Lowell JA, Howard TK, White HM, Shenoy S, Huettner PC, Brennan DC, et al. Serological evidence of past hepatitis B infection in liver donor and hepatitis B infection in liver allograft. Lancet 1995;345(8957):1084–1085

    Article  PubMed  CAS  Google Scholar 

  4. Wachs ME, Amend WJ, Ascher NL, Bretan PN, Emond J, Lake JR, et al. The risk of transmission of hepatitis B from HBsAg(−), HBcAb(+), HBIgM(−) organ donors. Transplantation 1995;59(2):230–234

    PubMed  CAS  Google Scholar 

  5. Dodson SF, Issa S, Araya V, Gayowski T, Pinna A, Eghtesad B, et al. Infectivity of hepatic allografts with antibodies to hepatitis B virus. Transplantation 1997;64(11):1582–1584

    Article  PubMed  CAS  Google Scholar 

  6. Dickson RC, Everhart JE, Lake JR, Wei Y, Seaberg EC, Wiesner RH, et al. Transmission of hepatitis B by transplantation of livers from donors positive for antibody to hepatitis B core antigen. The National Institute of Diabetes and Digestive and Kidney Diseases Liver Transplantation Database. Gastroenterology 1997;113(5):1668–1674

    Article  PubMed  CAS  Google Scholar 

  7. Prieto M, Gomez MD, Berenguer M, Cordoba J, Rayon JM, Pastor M, et al. De novo hepatitis B after liver transplantation from hepatitis B core antibody-positive donors in an area with high prevalence of anti-HBc positivity in the donor population. Liver Transpl 2001;7(1):51–58

    Article  PubMed  CAS  Google Scholar 

  8. Michalak TI, Pasquinelli C, Guilhot S, Chisari FV. Hepatitis B virus persistence after recovery from acute viral hepatitis. J Clin Invest 1994;94(2):907

    Article  PubMed  CAS  Google Scholar 

  9. Blackberg J, Kidd-Ljunggren K. Occult hepatitis B virus after acute self-limited infection persisting for 30 years without sequence variation. J Hepatol 2000;33(6):992–997

    Article  PubMed  CAS  Google Scholar 

  10. Knoll A, Hartmann A, Hamoshi H, Weislmaier K, Jilg W. Serological pattern “anti-HBc alone”: characterization of 552 individuals and clinical significance. World J Gastroenterol 2006;12(8):1255–1260

    PubMed  Google Scholar 

  11. Raimondo G, Navarra G, Mondello S, Costantino L, Colloredo G, Cucinotta E, et al. Occult hepatitis B virus in liver tissue of individuals without hepatic disease. J Hepatol 2008;48(5):743–746

    Article  PubMed  Google Scholar 

  12. de Villa VH, Chen YS, Chen CL. Hepatitis B core antibody-positive grafts: recipient’s risk. Transplantation 2003;75(3 Suppl):S49–S53

    Article  PubMed  Google Scholar 

  13. Burton JR Jr, Shaw-Stiffel TA. Use of hepatitis B core antibody-positive donors in recipients without evidence of hepatitis B infection: a survey of current practice in the United States. Liver Transpl 2003;9(8):837–842

    Article  PubMed  Google Scholar 

  14. Perrillo R. Hepatitis B virus prevention strategies for antibody to hepatitis B core antigen-positive liver donation: a survey of North American, European, and Asian-Pacific transplant programs. Liver Transpl 2009;15(2):223–232

    Article  PubMed  Google Scholar 

  15. Lee KW, Lee DS, Lee HH, Kim SJ, Joh JW, Seo JM, et al. Prevention of de novo hepatitis B infection from HbcAb-positive donors in living donor liver transplantation. Transpl Proc 2004;36(8):2311–2312

    Article  CAS  Google Scholar 

  16. Chen YS, Wang CC, de Villa VH, Wang SH, Cheng YF, Huang TL, et al. Prevention of de novo hepatitis B virus infection in living donor liver transplantation using hepatitis B core antibody positive donors. Clin Transpl 2002;16(6):405–409

    Article  Google Scholar 

  17. Douglas DD, Rakela J, Wright TL, Krom RA, Wiesner RH. The clinical course of transplantation-associated de novo hepatitis B infection in the liver transplant recipient. Liver Transpl Surg 1997;3(2):105–111

    Article  PubMed  CAS  Google Scholar 

  18. Uemoto S, Sugiyama K, Marusawa H, Inomata Y, Asonuma K, Egawa H, et al. Transmission of hepatitis B virus from hepatitis B core antibody-positive donors in living related liver transplants. Transplantation 1998;65(4):494–499

    Article  PubMed  CAS  Google Scholar 

  19. Rokuhara A, Tanaka E, Yagi S, Mizokami M, Hashikura Y, Kawasaki S, et al. De novo infection of hepatitis B virus in patients with orthotopic liver transplantation: analysis by determining complete sequence of the genome. J Med Virol 2000;62(4):471–478

    Article  PubMed  CAS  Google Scholar 

  20. Roque-Afonso AM, Feray C, Samuel D, Simoneau D, Roche B, Emile JF, et al. Antibodies to hepatitis B surface antigen prevent viral reactivation in recipients of liver grafts from anti-HBC positive donors. Gut 2002;50(1):95–99

    Article  PubMed  CAS  Google Scholar 

  21. Manzarbeitia C, Reich DJ, Ortiz JA, Rothstein KD, Araya VR, Munoz SJ. Safe use of livers from donors with positive hepatitis B core antibody. Liver Transpl 2002;8(6):556–561

    Article  PubMed  Google Scholar 

  22. Castells L, Vargas V, Rodriguez F, Allende H, Buti M, Sanchez-Avila JF, et al. Clinical impact and efficacy of lamivudine therapy in de novo hepatitis B infection after liver transplantation. Liver Transplant 2002;8(10):892–900

    Article  Google Scholar 

  23. De Feo TM, Poli F, Mozzi F, Moretti MP, Scalamogna M. Risk of transmission of hepatitis B virus from anti-HBC positive cadaveric organ donors: a collaborative study. Transpl Proc 2005;37(2):1238–1239

    Article  Google Scholar 

  24. Donataccio D, Roggen F, De Reyck C, Verbaandert C, Bodeus M, Lerut J. Use of anti-HBc positive allografts in adult liver transplantation: toward a safer way to expand the donor pool. Transpl Int 2006;19(1):38–43

    Article  PubMed  Google Scholar 

  25. Su WJ, Ho MC, Ni YH, Chen HL, Hu RH, Wu YM, et al. High-titer antibody to hepatitis B surface antigen before liver transplantation can prevent de novo hepatitis B infection. J Pediatr Gastroenterol Nutr 2009;48(2):203–208

    Article  PubMed  CAS  Google Scholar 

  26. Pan JJ, Oh SH, Soldevila-Pico C, Nelson DR, Liu C (2010) Low prevalence of HBV DNA in the liver allograft from anti-HBc-positive donors: a single-center experience. Clin Transplant (Epub ahead of print)

  27. Roche B, Roque-Afonso AM, Sebagh M, Delvart V, Duclos-Vallee JC, Castaing D, et al. Escape hepatitis B virus mutations in recipients of antibody to hepatitis B core antigen-positive liver grafts receiving hepatitis B immunoglobulins. Liver Transpl 2010;16(7):885–894

    Article  PubMed  Google Scholar 

  28. Yoshida EM, Ramji A, Erb SR, Davis JE, Steinbrecher UP, Sherlock CH, et al. 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 2000;20(5):411–414

    Article  PubMed  CAS  Google Scholar 

  29. Nery JR, Nery-Avila C, Reddy KR, Cirocco R, Weppler D, Levi DM, et al. Use of liver grafts from donors positive for antihepatitis B-core antibody (anti-HBc) in the era of prophylaxis with hepatitis-B immunoglobulin and lamivudine. Transplantation 2003;75(8):1179–1186

    Article  PubMed  CAS  Google Scholar 

  30. Moraleda G, Barcena R, Del Campo S, Oton E, Moreno J, Foruni JR. De novo HBV infection caused by an anti-HBc positive donor in a vaccinated liver transplant recipient in spite of anti-HBs response. Am J Transpl 2006;6(2):438–440

    Article  CAS  Google Scholar 

  31. Prakoso E, Strasser SI, Koorey DJ, Verran D, McCaughan GW. Long-term lamivudine monotherapy prevents development of hepatitis B virus infection in hepatitis B surface-antigen negative liver transplant recipients from hepatitis B core-antibody-positive donors. Clin Transpl 2006;20(3):369–373

    Article  Google Scholar 

  32. Barcena R, Moraleda G, Moreno J, Martin MD, de Vicente E, Nuno J, et al. Prevention of de novo HBV infection by the presence of anti-HBs in transplanted patients receiving core antibody-positive livers. World J Gastroenterol 2006;12(13):2070–2074

    PubMed  Google Scholar 

  33. Takemura N, Sugawara Y, Tamura S, Makuuchi M. Liver transplantation using hepatitis B core antibody-positive grafts: review and university of Tokyo experience. Dig Dis Sci 2007;52(10):2472–2477

    Article  PubMed  Google Scholar 

  34. Dodson SF, Bonham CA, Geller DA, Cacciarelli TV, Rakela J, Fung JJ. Prevention of de novo hepatitis B infection in recipients of hepatic allografts from anti-HBc positive donors. Transplantation 1999;68(7):1058–1061

    Article  PubMed  CAS  Google Scholar 

  35. Loss GE, Mason AL, Blazek J, Dick D, Lipscomb J, Guo L, et al. Transplantation of livers from hbc Ab positive donors into HBc Ab negative recipients: a strategy and preliminary results. Clin Transplant 2001;15(Suppl 6):55–58

    Article  PubMed  Google Scholar 

  36. Holt D, Thomas R, Van Thiel D, Brems JJ. Use of hepatitis B core antibody-positive donors in orthotopic liver transplantation. Arch Surg 2002;137(5):572–575

    Article  PubMed  CAS  Google Scholar 

  37. Chang SH, Suh KS, Yi NJ, Choi SH, Lee HJ, Seo JK, et al. Active immunization against de novo hepatitis B virus infection in pediatric patients after liver transplantation. Hepatology 2003;37(6):1329–1334

    Article  PubMed  Google Scholar 

  38. Fabrega E, Garcia-Suarez C, Guerra A, Orive A, Casafont F, Crespo J, et al. Liver transplantation with allografts from hepatitis B core antibody-positive donors: a new approach. Liver Transpl 2003;9(9):916–920

    Article  PubMed  Google Scholar 

  39. Suehiro T, Shimada M, Kishikawa K, Shimura T, Soejima Y, Yoshizumi T, et al. Prevention of hepatitis B virus infection from hepatitis B core antibody-positive donor graft using hepatitis B immune globulin and lamivudine in living donor liver transplantation. Liver Int 2005;25(6):1169–1174

    Article  PubMed  CAS  Google Scholar 

  40. Kwon CH, Suh KS, Cho JY, Yi NJ, Jang JJ, Lee KU. Change of hepatitis B virus DNA status in anti-HBc positive liver graft. Korean J Hepatol 2006;12(2):191–200

    PubMed  Google Scholar 

  41. Umeda M, Marusawa H, Ueda M, Takada Y, Egawa H, Uemoto S, et al. Beneficial effects of short-term lamivudine treatment for de novo hepatitis B virus reactivation after liver transplantation. Am J Transplant 2006;6(11):2680–2685

    Article  PubMed  CAS  Google Scholar 

  42. Yen RD, Bonatti H, Mendez J, Aranda-Michel J, Satyanarayana R, Dickson RC. Case report of lamivudine-resistant hepatitis B virus infection post liver transplantation from a hepatitis B core antibody donor. Am J Transplant 2006;6(5 Pt 1):1077–1083

    Article  PubMed  CAS  Google Scholar 

  43. Park JB, Kwon CH, Lee KW, Choi GS, Kim DJ, Seo JM, et al. Hepatitis B virus vaccine switch program for prevention of de novo hepatitis B virus infection in pediatric patients. Transpl Int 2008;21(4):346–352

    Article  PubMed  Google Scholar 

  44. Loss GE Jr, Mason AL, Nair S, Blazek J, Farr G, Guo L, et al. Does lamivudine prophylaxis eradicate persistent HBV DNA from allografts derived from anti-HBc-positive donors? Liver Transpl 2003;9(12):1258–1264

    Article  PubMed  Google Scholar 

  45. Yu AS, Vierling JM, Colquhoun SD, Arnaout WS, Chan CK, Khanafshar E, et al. Transmission of hepatitis B infection from hepatitis B core antibody—positive liver allografts is prevented by lamivudine therapy. Liver Transpl 2001;7(6):513–7

    Article  PubMed  CAS  Google Scholar 

  46. Celebi Kobak A, Karasu Z, Kilic M, Ozacar T, Tekin F, Gunsar F, et al. Living donor liver transplantation from hepatitis B core antibody positive donors. Transplant Proc 2007;39(5):1488–1490

    Article  PubMed  CAS  Google Scholar 

  47. Saab S, Waterman B, Chi AC, Tong MJ. Comparison of different immunoprophylaxis regimens after liver transplantation with hepatitis B core antibody-positive donors: a systemic review. Liver Transpl 2010;16(3):300–307

    PubMed  Google Scholar 

  48. Cholongitas E, Papatheodoridis GV, Burroughs AK. Liver grafts from anti-hepatitis B core positive donors: a systemic review. J Hepatol 2010;52(2):272–279

    Article  PubMed  CAS  Google Scholar 

  49. Powell JJ, Apiratpracha W, Partovi N, Erb SR, Scudamore CH, Steinbrecher UP, et al. Subcutaneous administration of hepatitis B immune globulin in combination with lamivudine following orthotopic liver transplantation: effective prophylaxis against recurrence. Clin Transplant 2006;20(4):524–525

    Article  PubMed  Google Scholar 

  50. Singham J, Greanya ED, Lau K, Erb SR, Partovi N, Yoshida EM. Efficacy of maintenance subcutaneous hepatitis B immune globulin (HBIG) post-transplant for prophylaxis against hepatitis B recurrence. Ann Hepatol 2010;9(2):166–171

    PubMed  Google Scholar 

  51. Yoshida EM, Erb SR, Partovi N, Scudamore CH, Chung SW, Frighetto L, et al. Liver transplantation for chronic hepatitis B infection with the use of combination lamivudine and low-dose hepatitis B immune globulin Liver Transpl Surg 1999;5(6):520–525

    Article  PubMed  CAS  Google Scholar 

  52. Yao FY, Osorio RW, Roberts JP, Poordad FF, Briceno MN, Garcia-Kennedy R, et al. Intramuscular hepatitis B immune globulin combined with lamivudine for prophylaxis against hepatitis B recurrence after liver transplantation. Liver Transpl Surg 1999;5(6):491–496

    Article  PubMed  CAS  Google Scholar 

  53. Alonso I, Herreros de Tejada A, Moreno JM, Rubio E, Lucena JL, De la Revilla J, et al. Effectiveness of low-dose intramuscular anti-VHB immune globulin in the prophylaxis of viral B hepatitis reinfection after liver transplantation: preliminary report. Transplant Proc 2003;35(5):1850–1851

    Article  PubMed  CAS  Google Scholar 

  54. Han SH, Martin P, Edelstein M, Hu R, Kunder G, Holt C, et al. Conversion from intravenous to intramuscular hepatitis B immune globulin in combination with lamivudine is safe and cost-effective in patients receiving long-term prophylaxis to prevent hepatitis B recurrence after liver transplantation. Liver Transpl 2003;9(2):182–187

    Article  PubMed  Google Scholar 

  55. Ferretti G, Merli M, Ginanni Corradini S, Callejon V, Tanzilli P, Masini A, et al. Low-dose intramuscular hepatitis B immune globulin and lamivudine for long-term prophylaxis of hepatitis B recurrence after liver transplantation. Transplant Proc 2004;36(3):535–538

    Article  PubMed  CAS  Google Scholar 

  56. Yan ML, Yan LN, Li B, Zeng Y, Wen TF, Wang WT, et al. Intramuscular hepatitis B immune globulin combined with lamivudine in prevention of hepatitis B recurrence after liver transplantation. Hepatobiliary Pancreat Dis Int 2006;5(3):360–363

    PubMed  CAS  Google Scholar 

  57. Gane EJ, Angus PW, Strasser S, Crawford DH, Ring J, Jeffrey GP, et al. Lamivudine plus low-dose hepatitis B immunoglobulin to prevent recurrent hepatitis B following liver transplantation. Gastroenterology 2007;132(3):931–937

    Article  PubMed  CAS  Google Scholar 

  58. Anderson RD, Chinnakotla S, Guo L, Perrillo RP, Klintmalm GB, Davis GL. Intramuscular hepatitis B immunoglobulin (HBIG) and nucleosides for prevention of recurrent hepatitis B following liver transplantation: comparison with other HBIG regimens. Clin Transplant 2007;21(4):510–517

    Article  PubMed  Google Scholar 

  59. Filipponi F, Franchello A, Carrai P, Romagnoli R, De Simone P, Woodward MK, et al. Efficacy, safety, and pharmacokinetics of intramuscular hepatitis B immune globulin, Igantibe, for the prophylaxis of viral B hepatitis after liver transplantation. Dig Liver Dis 2009;42(7):509–514

    Article  PubMed  Google Scholar 

  60. Jiang L, Yan L, Li B, Wen T, Zhao J, Cheng N, et al. Prophylaxis against hepatitis B recurrence posttransplantation using lamivudine and individualized low-dose hepatitis B immunoglobulin. Am J Transplant 2010;10(8):1861–189

    Article  PubMed  CAS  Google Scholar 

  61. Degertekin B, Han SH, Keeffe EB, Schiff ER, Luketic VA, Brown RS Jr, et al. Impact of virologic breakthrough and HBIG regimen on hepatitis B recurrence after liver transplantation. Am J Transplant 2010;10(8):1823–1833

    Article  PubMed  CAS  Google Scholar 

  62. Faust D, Rabenau HF, Allwinn R, Caspary WF, Zeuzem S. Cost-effective and safe ambulatory long-term immunoprophylaxis with intramuscular instead of intravenous hepatitis B immunoglobulin to prevent reinfection after orthotopic liver transplantation. Clin Transplant 2003;17(3):254–258

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Gastroenterology, Hepatology and Nutrition, Department of Internal Medicine, The University of Texas Medical School at Houston, Houston, TX, USA

    Jen-Jung Pan, Nirav Thosani, Victor I. Machicao & Michael B. Fallon

Authors
  1. Jen-Jung Pan
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Nirav Thosani
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Victor I. Machicao
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Michael B. Fallon
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jen-Jung Pan.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Pan, JJ., Thosani, N., Machicao, V.I. et al. Current use of hepatitis B immune globulin for prevention of de novo hepatitis B in recipients receiving anti-HBc-positive livers. Hepatol Int 5, 635–643 (2011). https://doi.org/10.1007/s12072-010-9250-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12072-010-9250-y

Keywords

Search

Navigation