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Hepatitis-B- und -C-Reinfektion: Prophylaxe und Therapie

Hepatitis B and C re-infection: prophylaxis and therapy

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Zusammenfassung

Die orthotope Lebertransplantation (OLT) hat die Behandlung der terminalen Leberinsuffizienz fundamental verändert, Zehnjahreslangzeitüberlebensraten liegen inzwischen bei etwa 70%. Die Langzeitergebnisse für Patienten mit OLT aufgrund Hepatitis-B/C-bedingter Zirrhose werden wesentlich durch die Rezidivgefahr beeinflusst. Referiert werden aktuelle Strategien und Perspektiven für das Management des Virushepatitisrezidivs. Besprochen werden zudem das Monitoring vor und nach OLT (routinemäßig entnommene Biopsien nach Transplantation auch bei ausbleibendem Transaminasenanstieg, Vakzinierungsstrategien, Probleme der Resistenzentwicklung und der antiviralen Therapie (wie Umstellung der Therapie bei ausbleibender/nicht anhaltender virologischer Response, Modifikation durch Mycophenolatmofetil) – auch vor einer Transplantation. Eigenen Untersuchungen zufolge ist die effektive, Synergismen nutzende antivirale Therapie der wichtigste Faktor zur Verhinderung von mit Hepatitis-C-Reinfektion assoziierten Transplantatverlusten.

Abstract

Orthotopic liver transplants (OLT) have fundamentally changed the treatment of terminal liver failure and the 10-year survival rates are now approximately 70%. The long-term results for patients with OLT due to cirrhosis caused by hepatitis B and C are mostly influenced by the danger of recurrence. This article gives a review of the current strategies and perspectives for the management of recurrent viral hepatitis. In addition monitoring before and after OLT will be discussed (routinely taken biopsies following transplantation even when transaminase levels do not increase, vaccination strategies, problems of resistance development and antiviral therapy, such as modifying therapy by lack of or non-persisting viral response and modification by mycophenolatmofetil), even before transplantation. According to our investigations the effective synergistic antiviral therapy is the most important factor for avoidance of transplant loss due to hepatitis-associated re-infection.

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Literatur

  1. Samuel D, Muller R, Alexander G et al (1993) Liver transplantation in European patients with the hepatitis B surface antigen. N Engl J Med 329:1842–1847

    Article  CAS  PubMed  Google Scholar 

  2. Yao FY, Terrault NA, Freise C et al (2001) Lamivudine treatment is beneficial in patients with severely decompensated cirrhosis and actively replicating hepatitis B infection awaiting liver transplantation: a comparative study using a matched, untreated cohort. Hepatology 34:411–416

    Article  CAS  PubMed  Google Scholar 

  3. Cornberg M, Protzer U, Dollinger MM et al (2007) Prophylaxis, diagnosis and therapy of hepatitis B virus (HBV) infection: the German guidelines for the management of HBV infection. Z Gastroenterol 45:1281–1328

    Article  CAS  PubMed  Google Scholar 

  4. Lange C, Bonjunga J, Wunder K et al (2009) Laktatazidosen unter antiviraler Therapie mit Entecavir bei Patenten mit chronischer Hepatitis B und fortgeschrittenener Lebercirrhose. Z Gastroenterol 47:947

    Article  Google Scholar 

  5. Liaw YF (2005) Prevention and surveillance of hepatitis B virus-related hepatocellular carcinoma. Semin Liver Dis 25(Suppl 1):40–47

    Article  PubMed  Google Scholar 

  6. Roche B, Feray C, Gigou M et al (2003) HBV DNA persistence 10 years after liver transplantation despite successful anti-HBS passive immunoprophylaxis. Hepatology 38:86–95

    Article  PubMed  Google Scholar 

  7. Seehofer D, Rayes N, Neuhaus P (2003) Prophylaxis and treatment of Hepatitis B recurrence after liver Transplantation in the antiviral era. Expert Rev Anti Infect Ther 1:307–318

    Article  CAS  PubMed  Google Scholar 

  8. Rosenau J, Bahr MJ, Tillmann HL et al (2001) Lamivudine and low-dose hepatitis B immune globulin for prophylaxis of hepatitis B reinfection after liver transplantation possible role of mutations in the YMDD motif prior to transplantation as a risk factor for reinfection. J Hepatol 34:895–902

    Article  CAS  PubMed  Google Scholar 

  9. Seehofer D, Rayes N, Steinmüller T et al (2002) Combination prophylaxis with Hepatitis B immunoglobulin and lamivudine after liver transplantation minimizes HBV recurrence rates unless evolution of pretransplant lamivudine resistance. Z Gastroenterol 40:795–799

    Article  CAS  PubMed  Google Scholar 

  10. Markowitz JS, Martin P, Conrad AJ et al (1998) Prophylaxis against hepatitis B recurrence following liver transplantation using combination lamivudine and hepatitis B immune globulin. Hepatology 28:585–589

    Article  CAS  PubMed  Google Scholar 

  11. Seehofer D, Berg T (2005) Prevention of hepatitis B virus recurrence after liver transplantation. Transplantation 80(1S Suppl):120–S124

    Article  Google Scholar 

  12. Angus PW, McCaughan GW, Gane EJ et al (2000) Combination low-dose hepatitis B immune globulin and lamivudine therapy provides effective prophylaxis against posttransplantation hepatitis B. Liver Transpl 6:429–433

    Article  CAS  PubMed  Google Scholar 

  13. Steinmüller T, Seehofer D, Rayes N et al (2002) Increasing applicability of liver transplantation for patients with hepatitis B related liver disease. Hepatology 35:1528–1535

    Article  PubMed  Google Scholar 

  14. Kim WR, Poterucha JJ, Kremers WK et al (2004) Outcome of liver transplantation for hepatitis B in the United States. Liver Transpl 10:968–974

    Article  PubMed  Google Scholar 

  15. Sanchez-Fueyo A, Rimola A, Grande L et al (2000) 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 31:496–501

    Article  CAS  PubMed  Google Scholar 

  16. Bienzle U, Gunther M, Neuhaus R et al (2003) Immunization with an adjuvant hepatitis B vaccine after liver transplantation for hepatitis B-related disease. Hepatology 38:811–819

    CAS  PubMed  Google Scholar 

  17. Schiff ER, Lai CL, Hadziyannis S et al (2003) Adefovir dipivoxil therapy for lamivudine-resistant hepatitis B in pre- and post-liver transplantation patients. Hepatology 38:1419–1427

    CAS  PubMed  Google Scholar 

  18. Lo CM, Liu CL, Lau GK et al (2005) Liver transplantation for chronic hepatitis B with lamivudine-resistant YMDD mutant using add-on adefovir dipivoxil plus lamivudine. Liver Transpl 11:807–813

    Article  PubMed  Google Scholar 

  19. Lampertico P, Marzano A, Levrero M et al (2006) Adefovir and lamivudine combination therapy is superior to adefovir monotherapy for lamivudine-resistant patients with HBeAg-negative chronic hepatitis B. Hepatology 44:693A–694A

    Google Scholar 

  20. Peters MG, Andersen J, Lynch P et al (2006b) Randomized controlled study of tenofovir and adefovir in chronic hepatitis B virus and HIV infection: ACTG A5127. Hepatology 44:1110–1116

    Article  CAS  PubMed  Google Scholar 

  21. Bommel van F, Wunsche T, Mauss S et al (2004) Comparison of adefovir and tenofovir in the treatment of lamivudine-resistant hepatitis B virus infection. Hepatology 40:1421–1425

    Article  PubMed  Google Scholar 

  22. Neff GW, Nery J, Lau DT et al (2004) Tenofovir therapy for lamivudine resistance following liver transplantation. Ann Pharmacother 38:1999–2004

    Article  CAS  PubMed  Google Scholar 

  23. Rayes N, Seehofer D, Hopf U et al (2001) Comparison of lamivudine and famciclovir in the long term treatment of hepatitis B infection following liver transplantation. Transplantation 71:96–101

    Article  CAS  PubMed  Google Scholar 

  24. Charest AF, McDougall J, Goldstein MB (2000) A randomized comparison of intradermal and intramuscular vaccination against hepatitis B virus in incident chronic hemodialysis patients. Am J Kidney Dis 36:976–982

    Article  CAS  PubMed  Google Scholar 

  25. Arslan M, Wiesner RH, Sievers C et al (2001) Double-dose accelerated hepatitis B vaccine in patients with end-stage liver disease. Liver Transpl 7:314–320

    Article  CAS  PubMed  Google Scholar 

  26. Douglas DD, Rakela J, Wright TL et al (1997) The clinical course of transplantation-associated de novo hepatitis B infection in the liver transplant recipient. Liver Transpl Surg 3:105–111

    Article  CAS  PubMed  Google Scholar 

  27. Prieto M, Gomez MD, Berenguer M et al (2001) 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 7:51–58

    Article  CAS  PubMed  Google Scholar 

  28. Prakoso E, Strasser SI, Koorey DJ et al (2006) 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 Transplant 20:369–373

    Article  PubMed  Google Scholar 

  29. Hartwig MG, Patel V, Palmer SM et al (2005) Hepatitis B core antibody positive donors as a safe and effective therapeutic option to increase available organs for lung transplantation. Transplantation 80:320–325

    Article  PubMed  Google Scholar 

  30. De Feo TM, Poli F, Mozzi F et al (2005) Risk of transmission of hepatitis B virus from anti-HBC positive cadaveric organ donors: a collaborative study. Transplant Proc 37:1238–1239

    Article  Google Scholar 

  31. Berg T et al (1998) Pretransplant virological markers hepatitis C virus genotype and viremia level are not helpful in predicting individual outcome after orthotopic liver transplantation. Transplantation 66(2):225–228

    Article  CAS  PubMed  Google Scholar 

  32. Wright TL et al (1992) Recurrent and acquired hepatitis C viral infection in liver transplant recipients. Gastroenterology 103(1):317–322

    CAS  PubMed  Google Scholar 

  33. Fukumoto T et al (1996) Viral dynamics of hepatitis C early after orthotopic liver transplantation: evidence for rapid turnover of serum virions. Hepatology 24(6):1351–1354

    Article  CAS  PubMed  Google Scholar 

  34. Berenguer M, Lopez-Labrador FX, Wright TL (2001) Hepatitis C and liver transplantation. J Hepatol 35(5):666–678

    Article  CAS  PubMed  Google Scholar 

  35. Neumann UP, Berg T, Bahra M et al (2004) Fibrosis progression after liver transplantation in patients with recurrent hepatitis C. J Hepatol 41(5):830–836

    Article  CAS  PubMed  Google Scholar 

  36. Neumann UP, Berg T, Bahra M et al (2004) Long-term outcome of liver transplants for chronic hepatitis C: A ten years follow-up. Transplantation 77:226–231

    Article  PubMed  Google Scholar 

  37. Berenguer M (2002) Natural history of recurrent hepatitis C. Liver Transpl 8(10 Suppl 1):S14–S18

    Article  PubMed  Google Scholar 

  38. Di Martino V et al (1997) Long-term longitudinal study of intrahepatic hepatitis C virus replication after liver transplantation. Hepatology 26(5):1343–1350

    Google Scholar 

  39. Taga SA et al (1998) Cholestatic hepatitis C in liver allografts. Liver Transpl Surg 4(4):304–310

    Article  CAS  PubMed  Google Scholar 

  40. Wiesner RH, Sorrell M, Villamil F (2003) Report of the first International Liver Transplantation Society expert panel consensus conference on liver transplantation and hepatitis C. Liver Transpl 9(11):S1–S9

    Article  PubMed  Google Scholar 

  41. Samuel D et al (2006) Report of the monothematic EASL conference on liver transplantation for viral hepatitis (Paris, France, January 12–14, 2006). J Hepatol 45(1):127–143

    Article  PubMed  Google Scholar 

  42. Forns X et al (2003) Antiviral therapy of patients with decompensated cirrhosis to prevent recurrence of hepatitis C after liver transplantation. J Hepatol 39(3):389–396

    Article  CAS  PubMed  Google Scholar 

  43. Thomas RM et al (2003) Infection with chronic hepatitis C virus and liver transplantation: a role for interferon therapy before transplantation. Liver Transpl 9(9):905–915

    Article  PubMed  Google Scholar 

  44. Everson GT et al (2005) Treatment of advanced hepatitis C with a low accelerating dosage regimen of antiviral therapy. Hepatology 42(2):255–262

    Article  CAS  PubMed  Google Scholar 

  45. Mazzaferro V et al (1997) Prophylaxis against HCV recurrence after liver transplantation: effect of interferon and ribavirin combination. Transplant Proc 29(1–2):519–521

    Google Scholar 

  46. Nakagawa M et al (2003) Cyclosporin A suppresses replication of hepatitis C virus genome in cultured hepatocytes. Hepatology 38(5):1282–1288

    Article  Google Scholar 

  47. Watashi K et al (2003) Cyclosporin A suppresses replication of hepatitis C virus genome in cultured hepatocytes. Hepatology 38(5):1282–1288

    Article  CAS  PubMed  Google Scholar 

  48. Nakagawa M et al (2004) Specific inhibition of hepatitis C virus replication by cyclosporin A. Biochem Biophys Res Commun 313(1):42–47

    Article  CAS  PubMed  Google Scholar 

  49. Kakumu S et al (1997) Cyclosporine therapy affects aminotransferase activity but not hepatitis C virus RNA levels in chronic hepatitis C. J Gastroenterol Hepatol 12(1):62–66

    Article  CAS  PubMed  Google Scholar 

  50. Zervos XA et al (1998) Comparison of tacrolimus with neoral as primary immunosuppression in hepatitis C patients after liver transplantation. Transplant Proc 30(4):1405–1406

    Article  CAS  PubMed  Google Scholar 

  51. Neyts J, Andrei G, De Clercq E (1998) The novel immunosuppressive agent mycophenolate mofetil markedly potentiates the antiherpesvirus activities of acyclovir, ganciclovir and penciclovir in vitro and in vivo. Antimicrob Agents Chemother 42(2):216–222

    CAS  PubMed  Google Scholar 

  52. Lau JY et al (2002) Mechanism of action of ribavirin in the combination treatment of chronic HCV infection. Hepatology 35(5):1002–1009

    Article  CAS  PubMed  Google Scholar 

  53. Bahra M et al (2005) MMF and calcineurin taper in recurrent hepatitis C after liver transplantation: impact on histological course. Am J Transplant 5(2):406–411

    Article  CAS  PubMed  Google Scholar 

  54. Wiesner RH et al (2005) Mycophenolate mofetil combination therapy improves long-term outcomes after liver transplantation in patients with and without hepatitis C. Liver Transpl 11(7):750–759

    Article  PubMed  Google Scholar 

  55. Klintmalm GB et al (2007) Corticosteroid-free immunosuppression with daclizumab in HCV(+) liver transplant recipients: 1-year interim results of the HCV-3 study. Liver Transpl 13(11):1521–1531

    Article  PubMed  Google Scholar 

  56. Neuhaus P, Clavien PA, Kittur D et al (2002) Improved treatment response with basiliximab immunoprophylaxis after liver transplantation: results from a double-blind randomized placebo-controlled trial. Liver Transpl 8:132–142

    Article  PubMed  Google Scholar 

  57. Rosen HR et al (1997) Use of OKT3 is associated with early and severe recurrence of hepatitis C after liver transplantation. Am J Gastroenterol 92(9):1453–1457

    CAS  PubMed  Google Scholar 

  58. Marcos A, Eghtesad B, Fung JJ et al (2004) Use of alemtuzumab and tacrolimus monotherapy for cadaveric liver transplantation: with particular reference to hepatitis C virus. Transplantation 78:966–971

    Article  CAS  PubMed  Google Scholar 

  59. Hoffmann RM, Gunther C, Diepolder HM et al (1995) Hepatitis C virus infection as a possible risk factor for ductopenic rejection (vanishing bile duct syndrome) after liver transplantation. Transpl Int 8(5):353–359

    Article  CAS  PubMed  Google Scholar 

  60. Regev A, Molina E, Moura R et al (2004) Reliability of histopathologic assessment for the differentiation of recurrent hepatitis C from acute rejection after liver transplantation. Liver Transpl 10:1233–1239

    Article  PubMed  Google Scholar 

  61. Bahra M, Neumann UP, Jacob D et al (2005) Repeated steroid pulse therapies in HCV-positive liver recipients: significant risk factor for HCV-related graft loss. Transplant Proc 37:1700–1702

    Article  CAS  PubMed  Google Scholar 

  62. Nakagawa M et al (2004) Specific inhibition of hepatitis C virus replication by cyclosporin A. Biochem Biophys Res Commun 313(1): 42–47

    Article  CAS  PubMed  Google Scholar 

  63. Filipponi F, Salizzoni M, Grazi G et al. (2001) Study of simulect-based, steroid-free immunosuppressive regimen in HCV+ de novo liver transplant patients: preliminary results. Transplant Proc 33:3211–3212

    Article  CAS  PubMed  Google Scholar 

  64. Samuel D, Bizollon T, Feray C et al (2003) Interferon-alpha 2b plus ribavirin in patients with chronic hepatitis C after liver transplantation: a randomized study. Gastroenterology 124(3):642–650

    Article  CAS  PubMed  Google Scholar 

  65. Neumann U, Puhl G, Bahra M et al (2006) Treatment of patients with recurrent hepatitis C after liver transplantation with peginterferon alfa-2B plus ribavirin. Transplantation 82(1):43–47

    Article  CAS  PubMed  Google Scholar 

  66. Schmidt SC, Bahra M, Bayraktar S et al (2009) Antiviral rreatment of patients with recurrent hepatitis C after liver transplantation with pegylated interferon. Dig Dis Sci

  67. Berenguer M, Palau A, Fernandez A et al (2006) Efficacy, predictors of response, and potential risks associated with antiviral therapy in liver transplant recipients with recurrent hepatitis C. Liver Transpl 12:1067–1076

    Article  PubMed  Google Scholar 

  68. Bahra M, Neumann UP, Jacob D et al (2007) Fibrosis progression in hepatitis C positive liver recipients after sustained virologic response to antiviral combination therapy (interferon-ribavirin therapy). Transplantation 83:351–353

    Article  CAS  PubMed  Google Scholar 

  69. Berenguer M (2006) Management of hepatitis C virus infection in liver transplantation. Gastroenterol Hepatol 29:422–427

    Article  PubMed  Google Scholar 

  70. Carrion JA, Navasa M, Garcia-Retortillo M et al (2007) Efficacy of antiviral therapy on hepatitis C recurrence after liver transplantation: a randomized controlled study. Gastroenterology 132:1746–1756.

    Article  CAS  PubMed  Google Scholar 

  71. Watt K, Veldt B, Charlton M (2009) A practical guide to the management of HCV infection following liver transplantation. Am J Transplant 9:1707–1713

    Article  CAS  PubMed  Google Scholar 

  72. Mukherjee S, Rogge J, Weaver L et al (2003) Pilot study of pegylated interferon alfa-2b and ribavirin for recurrent hepatitis C after liver transplantation. Transplant Proc 35:3042–3044

    Article  CAS  PubMed  Google Scholar 

  73. Dumortier J, Scoazec JY, Chevallier P, Boillot O (2004) Treatment of recurrent hepatitis C after liver transplantation: a pilot study of peginterferon alfa-2b and ribavirin combination. J Hepatol 40:669–674

    Article  CAS  PubMed  Google Scholar 

  74. Rodriguez-Luna H, Khatib A, Sharma P et al (2004) Treatment of recurrent hepatitis C infection after liver transplantation with combination of pegylated interferon alpha2b and ribavirin: an open-label series. Transplantation 77:190–194

    Article  CAS  PubMed  Google Scholar 

  75. Neff GW, Montalbano M, O’Brien CB et al (2004) Treatment of established recurrent hepatitis C in liver-transplant recipients with pegylated interferon-alfa-2b and ribavirin therapy. Transplantation 78:1303–1307

    Article  CAS  PubMed  Google Scholar 

  76. Oton E, Barcena R, Moreno-Planas JM et al (2006) Hepatitis C recurrence after liver transplantation: Viral and histologic response to full-dose PEG-interferon and ribavirin. Am J Transplant 6:2348–2355

    Article  CAS  PubMed  Google Scholar 

  77. Fernandez I, Meneu JC, Colina F et al (2006) Clinical and histological efficacy of pegylated interferon and ribavirin therapy of recurrent hepatitis C after liver transplantation. Liver Transpl 12:1805–1812

    Article  PubMed  Google Scholar 

  78. Ross AS, Bhan AK, Pascual M et al (2004) Pegylated interferon alpha-2b plus ribavirin in the treatment of post-liver transplant recurrent hepatitis C. Clin Transplant 18:166–173

    Article  PubMed  Google Scholar 

  79. Castells L, Vargas V, Allende H et al (2005) Combined treatment with pegylated interferon (alpha-2b) and ribavirin in the acute phase of hepatitis C virus recurrence after liver transplantation. J Hepatol 43:53–59

    Article  CAS  PubMed  Google Scholar 

  80. Mukherjee S (2005) Pegylated interferon alfa-2a and ribavirin for recurrent hepatitis C after liver transplantation. Transplant Proc 37:4403–4405

    Article  CAS  PubMed  Google Scholar 

  81. Angelico M, Koehler-Horst B, Piccolo P et al (2008) Peginterferon alpha-2a and ribavirin versus peginterferon alpha-2a monotherapy in early virological responders and peginterferon alpha-2a and ribavirin versus peginterferon alpha-2a, ribavirin and amantadine triple therapy in early virological nonresponders: the SMIEC II trial in naive patients with chronic hepatitis C. Eur J Gastroenterol Hepatol 20:680–687

    Article  CAS  PubMed  Google Scholar 

  82. European Association For The Study Of The Liver, EASL (2009) Clinical practice guidelines: management of chronic hepatitis B. J Hepatol 50:227–242

    Article  Google Scholar 

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  1. Klinik für Allgemein-, Viszeral- und Transplantationschirurgie, Berlin, Deutschland

    M. Bahra, D. Seehofer & U.P. Neumann

  2. Medizinische Klinik mit Schwerpunkt Hepatologie und Gastroenterologie, Charité, Campus Virchow-Klinikum, Universitätsmedizin Berlin, Augustenburger Platz 1, 13353, Berlin, Deutschland

    T. Berg

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  1. M. Bahra
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Bahra, M., Seehofer, D., Neumann, U. et al. Hepatitis-B- und -C-Reinfektion: Prophylaxe und Therapie. Gastroenterologe 4, 526–539 (2009). https://doi.org/10.1007/s11377-009-0335-x

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