Journal of Hepatology
Volume 45, Issue 1 , Pages 127-143 , July 2006

Report of the Monothematic EASL Conference on Liver Transplantation for Viral Hepatitis: (Paris, France, January 12–14, 2006)

  • Didier Samuel

      Affiliations

    • HepatoBiliary Centre, Inserm-Paris XI U 785, Paul Brousse Hospital, APHP, Villejuif, France
    • Corresponding Author InformationCorresponding author. Tel.: +33 1 45 59 34 03; fax: +33 1 45 59 38 57.
  • ,
  • Xavier Forns

      Affiliations

    • Liver Unit, Hospital Clinic, Barcelona, Spain
  • ,
  • Marina Berenguer

      Affiliations

    • Liver Unit, La Fe Hospital, Valencia, Spain
  • ,
  • Christian Trautwein

      Affiliations

    • Medizinische Klinik III, University Hospital RWTH Aachen, Germany
  • ,
  • Andrew Burroughs

      Affiliations

    • Liver Unit, Royal Free Hospital, London, United Kingdom
  • ,
  • Mario Rizzetto

      Affiliations

    • Department of Gastroenterology and Hepatology, Hospital Molinette, Torino, Italy
  • ,
  • Christian Trepo

      Affiliations

    • Department of Hepatology – Inserm U271, Hospital Hotel Dieu, Lyon, France

References 

  1. Liaw YF, Sung JY, Chow WC, Farrell G, Lee C-Z, Yuen H, et al. Lamivudine for patients with chronic hepatitis B and advanced liver disease. N Engl J Med. 2004;315:1521–1531
  2. Fontana R, Han H, Perrillo R, Vierling JM, Wright T, Rakela J, et al. Determinants of early mortality in patients with decompensated chronic hepatitis B treated with antiviral therapy. Gastroenterology. 2002;123:719–727
  3. Schiff ER, Lai CL, Hadziyannis S, Neuhaus P, Terrault N, Colombo M, et al. Adefovir dipivoxil therapy for lamivudine-resistant hepatitis B in pre- and post-liver transplantation patients. Hepatology. 2003;38:1419–1427
  4. Samuel D, Muller R, Alexander G, Fassati L, Ducot B, Benhamou JP, et al. Liver transplantation in European patients with the hepatitis B surface antigen. N Engl J Med. 1993;329:1842–1847
  5. Shouval D, Samuel D. Hepatitis B immune globulin to prevent HBV graft reinfection following liver transplantation: a concise review. Hepatology. 2000;32:1189–1195
  6. Terrrault N, Roche B, Samuel D. Management of the hepatitis B virus in the liver transplantation setting: a European and an American perspective. Liver Transpl. 2005;11:716–732
  7. Marzano A, Gaia S, Ghisetti V, Carensi S, Premoli A, Debernardi-Venon W, et al. Viral load at the time of liver transplantation and risk of hepatitis B virus recurrence. Liver Transpl. 2005;11:402–409
  8. Tur-Kaspa R, Burk RD, Shaul Y, Shafritz DA. Hepatitis B virus DNA contains a glucocorticoid-responsive element. Proc Natl Acad Sci USA. 1986;83:1627–1631
  9. Bock CT, Tillmann HL, Maschek HJ, Manns MP, Trautwein C. A preS mutation isolated from a patient with chronic hepatitis B infection leads to virus retention and misassembly. Gastroenterology. 1997;113:1976–1982
  10. Trautwein C, Schrem H, Tillmann HL, Kubicka S, Walker D, Boker KH, et al. Hepatitis B virus mutations in the pre-S genome before and after liver transplantation. Hepatology. 1996;24:482–488
  11. Roche B, Feray C, Gigou M, Roque-Afonso AM, Arulnaden JL, Delvart V, et al. HBV DNA persistence 10 years after liver transplantation despite successful anti-HBs passive immunoprophylaxis. Hepatology. 2003;38:86–95
  12. Perrillo RP, Wright T, Rakela J, Levy G, Schiff E, Gish R, et al. A multicenter United States-Canadian trial to assess lamivudine monotherapy before and after transplantation for chronic hepatitis B. Hepatology. 2001;33:424–432
  13. Steinmuller T, Seehofer D, Rayes N, Muller AR, Settmacher U, Jonas S, et al. Increasing applicability of liver transplantation for patients with hepatitis B-related liver disease. Hepatology. 2002;35:1528–1535
  14. Kim WR, Poterucha JJ, Kremers WK, Ishitani MB, Dickson ER. Outcome of liver transplantation for hepatitis B in the United States. Liver Transpl. 2004;10:968–974
  15. Dickson R, Terrault N, Ishitani M, Reddy R, Sheiner P, Luketic V, et al. Protective antibody levels and dose requirements for IV 5% Nabi Hepatitis B immune globulin combined with lamivudine in liver transplantation for hepatitis B-induced end stage liver disease. Liver Transpl. 2006;12:124–133
  16. 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;9:182–187
  17. Naoumov NV, Lopes AR, Burra P, Caccamo L, Iemmolo RM, De Man RA, et al. Randomized trial of lamivudine versus hepatitis B immunoglobulin for long-term prophylaxis of hepatitis B recurrence after liver transplantation. J Hepatol. 2001;34:888–894
  18. Buti M, Mas A, Prieto M, Casafont F, Gonzalez A, Miras M, et al. A randomized study comparing lamivudine monotherapy after a short course of hepatitis B immune globulin (HBIg) and lamivudine with long-term lamivudine plus HBIg in the prevention of hepatitis B virus recurrence after liver transplantation. J Hepatol. 2003;38:811–817
  19. Sanchez-Fueyo A, Rimola A, Grande L, Costa J, Mas A, Navasa M, et al. Hepatitis B immunoglobulin discontinuation followed by hepatitis B virus vaccination: a new strategy in the prophylaxis of hepatitis B virus recurrence after liver transplantation. Hepatology. 2000;31:496–501
  20. Angelico M, Di Paolo D, Trinito M, Petrolati A, Araco A, Zazza S, et al. Failure of a reinforced triple course of hepatitis B vaccination in patients transplanted for HBV-related cirrhosis. Hepatology. 2002;35:176–181
  21. Bienzle U, Günther M, Neuhaus R, Vandepapeliere P, Vollmar J, Lun A, et al. Immunization with an adjuvant hepatitis B vaccine after liver transplantation for hepatitis B-related disease. Hepatology. 2003;38:811–819
  22. Fontana RJ, Hann HW, Wright T, Everson G, Baker A, Schiff ER, et al. A multicenter study of lamivudine treatment in 33 patients with hepatitis B after liver transplantation. Liver Transpl. 2001;6:504–510
  23. Mutimer D, Feraz-Neto BH, Harrison R, O’Donnell K, Shaw J, Cane P, et al. Acute liver graft failure due to emergence of lamivudine resistant hepatitis B virus: rapid resolution during treatment with adefovir. Gut. 2001;49:860–863
  24. Lavillette D, Morice Y, Germanidis G, Donot P, Soulier A, Pagkalos E, et al. Human serum facilitates hepatitis C virus infection, and neutralizing responses inversely correlate with viral replication kinetics at the acute phase of hepatitis C virus infection. J Virol. 2005;79:6023–6034
  25. Takaki A, Wiese M, Maertens G, Depla E, Seifert U, Liebetrau A, et al. Cellular immune responses persist and humoral responses decrease two decades after recovery from a single-source outbreak of hepatitis C. Nat Med. 2000;6:578–582
  26. Wedemeyer H, He XS, Nascimbeni M, Davis AR, Greenberg HB, Hoofnagle JH, et al. Impaired effector function of hepatitis C virus-specific CD8+ T cells in chronic hepatitis C virus infection. J Immunol. 2002;169:3447–3458
  27. Everson GT, Trotter J, Forman L, Kugelmas M, Halprin A, Fey B, et al. Treatment of advanced hepatitis C with a low accelerating dosage regimen of antiviral therapy. Hepatology. 2005;42:255–262
  28. Forns X, Garcia-Retortillo M, Serrano T, Feliu A, Suarez F, de la Mata M, et al. Antiviral therapy of patients with decompensated cirrhosis to prevent recurrence of hepatitis C after liver transplantation. J Hepatol. 2003;39:389–396
  29. Gane EJ, Portmann BC, Naoumov NV, Smith HM, Underhill JA, Donaldson PT, et al. Long-term outcome of hepatitis C infection after liver transplantation. N Engl J Med. 1996;334:815–820
  30. Feray C, Caccamo L, Alexander GJM, Ducot B, Gugenheim J, Casanovas T, et al. European collaborative study on factors influencing outcome after liver transplantation for hepatitis C. Gastroenterology. 1999;117:619–625
  31. Prieto M, Berenguer M, Rayon JM, Cordoba J, Arguello L, Carrasco D, et al. High incidence of allograft cirrhosis in hepatitis C virus genotype 1b infection following transplantation: relationship with rejection episodes. Hepatology. 1999;29:250–256
  32. Forman LM, Lewis JD, Berlin JA, Feldman HI, Lucey MR. The association between hepatitis C infection and survival after orthotopic liver transplantation. Gastroenterology. 2002;122:889–896
  33. Berenguer M, Prieto M, Rayon JM, Mora J, Pastor M, Ortiz V, et al. Natural history of clinically compensated hepatitis C virus-related graft cirrhosis after liver transplantation. Hepatology. 2000;32:852–858
  34. Berenguer M, Ferrell L, Watson J, Prieto M, Kim M, Rayon M, et al. HCV-related fibrosis progression following liver transplantation increase in recent years. J Hepatol. 2000;32:673–684
  35. Berenguer M, Aguilera V, Prieto M, San Juan F, Rayon JM, Benlloch S, et al. Significant improvement in the outcome of HCV-infected transplant recipients by avoiding rapid steroid tapering and potent induction immunosuppression. J Hepatol. 2006;44:717–722
  36. McCaughan GW, Zekry A. Mechanisms of HCV infection and allograft damage after liver transplantation. J Hepatol. 2004;40:368–374
  37. Samonakis DN, Triantos CK, Talheimer U, Quaglia A, Leandro G, Teixera R, et al. Immunosuppression and donor age with respect to severity of HCV recurrence after liver transplantation. Liver Transpl. 2005;11:386–395
  38. Marcos A, Eghtesad B, Fung JJ, Fontes P, Patel K, De Vera M, et al. Use of alemtuzumab and tacrolimus monotherapy for cadveric liver transplantation with particular reference to hepatitis C virus. Transplantation. 2004;78:966–971
  39. Watashi K, Hijikata M, Hosaka M, Yamagi M, Shimotohno K. Cyclosporin A suppresses replication of hepatitis C virus genome in cultured hepatocytes. Hepatology. 2003;38:1282–1288
  40. Zekry A, Gleeson M, Guney S, McCaughan GW. Prospective cross-over study comparing the effect of mycophenolate versus azathioprine on allograft function and viral load in liver transplant recipients with recurrent chronic HCV infection. Liver Transpl. 2004;10:52–57
  41. Sheiner PA, Schwartz ME, Mor E, Schluger LK, Theise N, Kiishikawa K, et al. Severe or multiple rejection episodes are associated with early recurrence of hepatitis C after orthotopic liver transplantation. Hepatology. 1995;21:30–34
  42. Berenguer M, Prieto M, Cordoba J, Rayon JM, Carrasco D, Olaso V, et al. Early development of chronic active hepatitis in recurrent hepatitis C virus infection after liver transplantation: association with treatment of rejection. J Hepatol. 1998;28:756–763
  43. Rosen HR, Shackleton CR, Higa L, Gralnek IM, Farmer DA, McDiarmid SV, et al. Use of OKT3 is associated with early and severe recurrence of hepatitis C after liver transplantation. Am J Gastroenterol. 1997;92:14453–14457
  44. Brillanti S, Vivarelli M, De Ruvo N, Aden A, Camaggi V, D’Errico A, et al. Slowly tapering off steroids protects the graft against hepatitis C virus recurrence after liver transplantation. Liver Transpl. 2002;8:884–888
  45. Neumann UP, Berg T, Bahra M, Seehofer D, Langrehr JM, Neuhaus R, et al. Fibrosis progression after liver transplantation in patients with recurrent hepatitis C. J Hepatol. 2004;41:830–836
  46. Berenguer M, Prieto M, San Juan F, Rayon JM, Martinez F, Cararsco D, et al. Contribution of donor age to the recent decrease in patient survival among HCV-infected liver transplant recipients. Hepatology. 2002;36:202–210
  47. Wali M, Harrison RF, Gow PJ, Mutimer D. Advancing donor liver age and rapid fibrosis progression following transplantation for hepatitis C. Gut. 2002;51:248–252
  48. Demetris AT, Eghtesad B, Marcos A, Ruppert K, Nalesnik MA, Randhawa P, et al. Recurrent hepatitis C in liver allografts: prospective assessment of diagnostic accuracy, identification of pitfalls and observations about pathogenesis. Am J Surg Pathol. 2004;28:658–699
  49. Monto A, Patel K, Bostrom A, Pianko S, Pockros P, McHutchinson JG, et al. Risk of a range of alcohol intake on hepatitis C-related fibrosis. Hepatology. 2004;39:826–834
  50. Burra P, Mioni D, Cecchetto A, Cillo U, Zanus G, Fagiuoli S, et al. Histological features after liver transplantation in alcoholic cirrhotics. J Hepatol. 2001;34:716–722
  51. Miguet JP, Monnet E, Vanlemmens C, Gache P, Messner M, Hruskosky S, et al. Predictive factors of alcohol relapse after orthotopic liver transplantation for alcoholic liver disease. Gastroenterol Clin Biol. 2004;28:845–851
  52. Davis GL, Nelson DR, Terrault N, Pruett TL, Schiano TD, Fletcher CV, et al. A randomized, open-label study to evaluate the safety ad pharmacokinetics of human hepatitis C immune globulin (Cicavir) in liver transplant recipients. Liver Transpl. 2005;11:941–949
  53. Bizollon T, Pradat P, Mabrut JY, Chevallier M, Adham M, Radenne S, et al. Benefit of sustained virological response to combination therapy on graft survival of liver transplanted patients with recurrent chronic hepatitis C. Am J Transplant. 2005;5:1909–1913
  54. Bizollon T, Ahmed SNS, Radenne S, Chevallier M, Chevallier P, Parvaz P, et al. Long-term histological improvement and clearance of intrahepatic hepatitis C virus RNA following sustained response to interferon-ribavirin combination therapy in liver transplanted patients with hepatitis C virus recurrence. Gut. 2003;52:283–287
  55. Garcia-Retortillo M, Forns X, Feliu A, Moitinho E, Costa J, Navasa M, et al. Hepatitis C virus kinetics during and immediately after liver transplantation. Hepatology. 2002;35:680–687
  56. Shergill A, Khalili M, Straley S, Bollinger K, Roberts JP, Ascher NA, et al. Applicability, tolerability and efficacy of preemptive antiviral therapy in hepatitis C-infected patients undergoing liver transplantation. Am J Transplant. 2005;5:118–124
  57. Sheiner PA, Boros P, Klion FM, Thung SN, Schluger LK, Lau JY, et al. The efficacy of prophylactic interferon alfa-2b in preventing recurrent hepatitis C after liver transplantation. Hepatology. 1998;28:831–838
  58. Singh N, Gayowski T, Wannstedt CF, Shakil AO, Wagener MM, Fung JJ, et al. Interferon alfa for prophylaxis of recurrent viral hepatitis C in liver transplant recipients: a prospective, randomized, controlled trial. Transplantation. 1998;65:82–86
  59. Mazzaferro V, Tagger A, Schiavo M, Regalia E, Pulvirenti A, Ribero ML, et al. Prevention of recurrent hepatitis C after liver transplantation with early interferon and ribavirin treatment. Transplant Proc. 2001;33:1355–1357
  60. Chalasani N, Manzarbeita C, Ferenci P, Vogel W, Fontana RJ, Voigt M, et al. Peginterferon alfa-2a for hepatitis C after liver transplantation: two randomized, controlled trials. Hepatology. 2005;41:289–298
  61. Feray C, Samuel D, Gigou M, Paradis V, David MF, Lemonnier C, et al. An open trial of Interferon alfa recombinant for hepatitis C after liver transplantation: antiviral effects and risk of rejection. Hepatology. 1995;22:1084–1089
  62. Samuel D, Bizollon T, Feray C, Roche B, Si Ahmed SN, Lemonnier C, et al. Interferon-alfa 2b plus ribavirin in patients with chronic hepatitis C after liver transplantation: a randomized study. Gastroenterology. 2003;124:642–650
  63. Castells L, Vargas V, Allende H, Bilbao I, Luis-Lazaro J, Margarit C, et al. Combined treatment with pegylated interferon (alpha-2b) and ribavirin in the acute phase of hepatitis C virus recurrence after liver transplantation. J Hepatol. 2005;43:53–59
  64. Dumortier J, Scoazec JY, Chevallier P, Boillot O. Treatment of recurrent hepatitis C after liver transplantation: a pilot study of peginterferon alfa-2b and ribavirin combination. J Hepatol. 2004;40:669–674
  65. Saab S, Kalmaz D, Gajjar NA, Hiatt J, Durazo F, Han S, et al. Outcomes of acute rejection after interferon therapy in Liver Transplant recipients. Liver Transpl. 2004;10:859–867
  66. Rosen HR, Madden JP, Martin P. A model to predict survival following liver retransplantation. Hepatology. 1999;29:365–370
  67. Pelletier SJ, Schaubel DE, Punch JD, Wolfe RA, Port FK, Merion RM. Hepatitis C is a risk factor for death after liver retransplantation. Liver Transpl. 2005;11:434–440
  68. Rosen HR, Prieto M, Casanovas-Taltavull T, Cuervas-Mons V, Guckelberger O, Muiesan P, et al. Validation and refinement of survival models for liver retransplantation. Hepatology. 2003;38:460–469
  69. Burton JR, Rosen HR. Retransplantation for recurrent hepatitis C in the MELD era: maximizing utility. Liver Transpl. 2004;10:S59–S64
  70. Bruix J, Sherman M, Llovet JM, Beaugrand M, Lencioni R, Burroughs A, et al. Clinical management of hepatocellular carcinoma. Conclusions of the Barcelona-2000 EASL Conference. European Association for the Study of the Liver. J Hepatol. 2001;35:421–430
  71. Bruix J, Sherman M. Practice Guidelines Committee. American Association for the Study for Liver Diseases Management of hepatocellular carcinoma. Hepatology. 2005;42:1208–1236
  72. Garcia-Retortillo M, Forns X, Llovet JM, Navasa M, Feliu A, Massaguer A, et al. Hepatitis C recurrence is more severe after living donor compared to cadaveric liver transplantation. Hepatology. 2004;40:699–707
  73. Schiano TD, Gutierrez JA, Walewski JL, Fiel MI, Cheng B, Bodenheimer H, et al. Accelerated hepatitis C virus kinetics but similar survival rates in recipients of liver grafts from living versus deceased donors. Hepatology. 2005;42:1420–1428
  74. Pineda JA, Romero-Gomez M, Dfaz-Garcia F, Giron-Gonzalez JA, Montero JL, Torre-Cisneros J, et al. HIV Coinfection shortens the survival of patients with hepatitis C virus-related decompensated cirrhosis. Hepatology. 2005;41:779–789
  75. Vallet-Pichard A, Pol S. Hepatitis viruses and human immunodeficiency virus co-infection. Pathogenesis and treatment. J Hepatol. 2004;41:156–166
  76. Thio CL, Seaberg EC, Skolasky Jr R, Visscher B, Munoz A, Thomas DL, multicenter AIDS cohort study. HIV-1, Hepatitis B virus and risk of liver-related mortality in the multicenter cohort study (MACS). Lancet 2002;360:1921–1926.
  77. Alberti A, Clumeck N, Collins S, Gehrlich W, Lundgren J, Palu G, et al. Short statement of the first European consensus conference on the treatment of chronic hepatitis B and C in HIV co-infected patients. J Hepatol. 2005;42:615–624
  78. Stock PG, Roland ME, Carlson L, Freise CE, Roberts JP, Hirose R, et al. Kidney and liver transplantation in human immunodeficiency virus-infected patients: a pilot safety and efficacy study. Transplantation. 2003;76:370–375
  79. Fung J, Eghtesad B, Patel-Tom K, DeVera M, Chapman H, Ragni M. Liver transplantation in patients with HIV infection. Liver Transpl. 2004;10:S39–S53
  80. Duclos-Vallée JC, Vittecoq D, Teicher E, Feray C, Roque-Afonso AM, Lombes A, et al. Hepatitis C viral recurrence and liver mitochondrial damage after liver transplantation in HIV-HCV coinfected patients. J Hepatol. 2005;42:341–349
  81. Vargas H, Laskus T, Wang LF, Lee R, Radkowski M, Dodson F, et al. Outcome of liver transplantation in hepatitis C virus-infected patients who received hepatitis C virus-infected grafts. Gastroenterology. 1999;117:149–153
  82. Prieto M, Gomez MD, Berenguer M, Cordoba J, Rayon J, 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;7:51–58
  83. Dickson R, Everhart J, Lake JR, Wei Y, Seaberg E, Wiesner R, et al. Transmission of hepatitis B by transplantation of livers from donors positive for antibody to hepatitis B core antigen. Gastroenterology. 1997;113:1168–1174
  84. 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;50:95–99
  85. Dodson S, Bonham C, Geller D, Cacciarelli T, Rakela J, Fung J. Prevention of de novo hepatitis B infection in recipients of hepatic allografts from anti HBc-positive donors. Transplantation. 1999;68:1058–1061
  86. Nery JR, Weppler D, Rodriguez M, Ruiz P, Schiff ER, Tzakis AG. Efficacy of Lamivudine in controlling hepatitis B virus recurrence after liver transplantation. Transplantation. 1998;65:1615–1621

 This Conference was organized by the EASL. Authors of the paper were members of the organizing committee. Didier Samuel was the chairman of the conference.

PII: S0168-8278(06)00238-8

doi: 10.1016/j.jhep.2006.05.001

Journal of Hepatology
Volume 45, Issue 1 , Pages 127-143 , July 2006