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Treatment of hepatitis B and C following liver transplantation

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Abstract

Advanced liver disease from hepatitis B virus (HBV) and hepatitis C virus (HCV) is the leading indication for orthotopic liver transplantation (OLT) worldwide. Our understanding of recurrent liver disease related to HBV and HCV in the setting of OLT has evolved rapidly in the past decade. Recurrent viral hepatitis may lead to graft failure, death, or the need for retransplantation. Until about a decade ago, HBV was considered a contraindication to OLT due to its frequent recurrence and development of associated liver disease. Medical therapy with hepatitis B immune globulin and nucleoside analogues has diminished the risk of HBV recurrence and led to improvement in patient and graft survival. Consequently, OLT is now considered to be the standard of care in patients with end-stage liver disease related to HBV. HCV recurrence after OLT is almost universal. Although short-term survival in patients undergoing OLT for HCV is similar to survival for those transplanted for other indications, recurrent HCV may have an impact on long-term patient and graft survival. A specific and effective therapy has not been defined for recurrent HCV following transplantation, but the combination of interferon and ribavirin appears promising. Optimal strategies to eradicate these viruses or to slow disease progression are continually being investigated in light of the disparity between supply and demand in a diminishing organ pool for OLT candidates.

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References and Recommended Reading

  1. Belle SH, Beringer KC, Detre KM: An up-date on liver transplantation in the United States: recipient characteristics and outcome. Clin Transpl 1995, 1:19–33.

    Google Scholar 

  2. Samuel D, Muller R, Alexander G, et al.: Liver transplantation in European patients with the hepatitis B antigen. N Engl J Med 1993, 329:1842–1847. This large retrospective analysis of long-term administration of HBIg in 372 patients conclusively showed reduction in HBV recurrence and improved survival and identified factors associated with low and high risk for recurrent HBV infection.

    Article  PubMed  CAS  Google Scholar 

  3. Seaberg E, Belle S, Beringer K, et al.: Liver transplantation in the United States from 1987–1998: updated results from the Pitt-UNOS Liver Transplant Registry. Clin Transpl 1998, 17–37.

  4. Wright TL, Donegan E, Hsu H, et al.: Recurrent and acquired hepatitis C viral infection in liver transplant recipients. Gastroenterology 1992, 103:317–322.

    PubMed  CAS  Google Scholar 

  5. Todo S, Demetris AJ, Van Thiel D, et al.: Orthotopic liver transplantation for patients with hepatitis B virus-related liver disease. Hepatology 1991, 13:619–626.

    PubMed  CAS  Google Scholar 

  6. Terrault NA: Hepatitis B virus and liver transplantation. Clin Liver Dis 1999, 3:389–415.

    Article  Google Scholar 

  7. Mora NP, Klintmalm GB, Poplawski SS, et al.: Recurrence of hepatitis B after liver transplantation: does hepatitis B immunoglobulin modify the recurrent disease? Transplant Proc 1990, 22:1549–1550.

    PubMed  CAS  Google Scholar 

  8. de Jongh FE, Janssen HL, de Man RA, et al.: Survival and prognostic indicators in hepatitis B surface antigen-positive cirrhosis of the liver. Gastroenterology 1992, 103:1630–1635.

    PubMed  Google Scholar 

  9. Muller R, Gubernatis G, Farle M, et al.: Liver transplantation in HBs antigen (HBsAg) carriers: prevention of hepatitis B virus (HBV) recurrence by passive immunization. J Hepatol 1991, 13:90–96.

    Article  PubMed  CAS  Google Scholar 

  10. Samuel D, Bismuth A, Mathieau D, et al.: Passive immunoprophylaxis after liver transplantation in HBsAg-positive patients. Lancet 1991, 337:813–815.

    Article  PubMed  CAS  Google Scholar 

  11. Rimoldi P, Belli LS, Rondinara GF, et al.: Recurrent HBV/HDV infections under different immunoprophylaxis protocols. Transplant Proc 1993, 25:2675–2676.

    PubMed  CAS  Google Scholar 

  12. Gugenheim J, Baldini E, Ouzan D, et al.: Absence of initial viral replication and long-term high dose immunoglobulin administration improve results of hepatitis B virus recurrence prophylaxis after liver transplant. Transplant Proc 1997, 29:517–518.

    Article  PubMed  CAS  Google Scholar 

  13. Nymann T, Shokouh-Amiri MH, Vera SR, et al.: Prevention of hepatitis B recurrence with indefinite hepatitis B immune globulin (HBIg) prophylaxis after transplantation. Clin Transplantation 1996, 10:663–667.

    CAS  Google Scholar 

  14. Terrault NA, Zhou S, Combs C, et al.: Prophylaxis in liver transplant recipients using a fixed dosing schedule of hepatitis B immunoglobulin. Hepatology 1996, 24:1327–1333.

    Article  PubMed  CAS  Google Scholar 

  15. Sawyer RG, McGory RW, Gaffey MJ, et al.: Improved clinical outcomes with liver transplantation for hepatitis B-induced chronic liver failure using passive immunization. Ann Surg 1998, 227:841–850.

    Article  PubMed  CAS  Google Scholar 

  16. Samuel D, Zignego A, Reynes M, et al.: Long-term clinical and virological outcome after liver transplantation for cirrhosis caused by chronic delta hepatitis. Hepatology 1995, 21:333–339.

    Article  PubMed  CAS  Google Scholar 

  17. Ho BM, So SK, Esquivel CO, et al.: Liver transplantation in Asian patients with chronic hepatitis B. Hepatology 1997, 25:223–225.

    Article  PubMed  CAS  Google Scholar 

  18. Loss GE Jr, Mason AL, Nair S, et al.: Transplantation of livers from anti-HBc positive donors into anti-HBc negative recipients: maintenance lamivudine therapy prevents de novo hepatitis B. Paper presented at the American Association for the Study of Liver Disease Annual Meeting. Dallas, TX. November 9–13, 2001.

  19. Ghany MG, Ayola B, Villamil FG, et al.: Hepatitis B virus S mutants in liver transplant recipients who were reinfected despite hepatitis B immune globulin prophylaxis. Hepatology 1998, 27:213–222.

    Article  PubMed  CAS  Google Scholar 

  20. Stirk HJ, Thornton JM, Howard CR: A topological model for hepatitis B surface antigen. Intervirology 1992, 33:148–158.

    PubMed  CAS  Google Scholar 

  21. Terrault NA, Zhou S, McGory RW, et al.: Incidence and clinical consequences of surface and polymerase gene mutations in liver transplant recipients on hepatitis B immunoglobulin. Hepatology 1998, 28:555–561.

    Article  PubMed  CAS  Google Scholar 

  22. Terrault NA, Holland CC, Ferrell L, et al.: Interferon alfa for recurrent hepatitis B infection after liver transplantation. Liver Transplant Surg 1996, 2:132–138.

    Article  CAS  Google Scholar 

  23. Perrillo RP: Interferon in the management of chronic hepatitis B. Dig Dis Sci 1993, 38:577–593.

    Article  PubMed  CAS  Google Scholar 

  24. Gish RG, Lao JYN, Brooks L, et al.: Gancyclovir treatment of hepatitis B virus infection in liver transplant recipients. Hepatology 1996, 23:1–7.

    Article  PubMed  CAS  Google Scholar 

  25. Kruger M, Tillmann HL, Trautwein C, et al.: Famcyclovir treatment of hepatitis B virus recurrence after liver transplantation: a pilot study. Liver Transplant Surg 1996, 2:253–262.

    Article  CAS  Google Scholar 

  26. Nery JR, Weppler D, Rodriguez M, et al.: Efficacy of lamivudine in controlling hepatitis B virus recurrence after liver transplantation. Transplantation 1998, 65:1615–1621.

    Article  PubMed  CAS  Google Scholar 

  27. Andreone P, Caraceni P, Grazi GL, et al.: Lamivudine treatment for acute hepatitis B after liver transplantation. J Hepatology 1998, 29:985–989.

    Article  CAS  Google Scholar 

  28. Perrillo R, Rakela J, Deinstag J, et al.: Multicenter study of lamivudine therapy for hepatitis B after liver transplantation. Lamivudine Transplant Group. Hepatology 1999, 29:1581–1586.

    Article  PubMed  CAS  Google Scholar 

  29. Sponseller CA, Bacon BR, DiBisceglie AM: Clinical improvement in patients with decompensated liver disease caused by hepatitis B after treatment with lamivudine. Liver Transplantation 2000, 6:715–720.

    Article  PubMed  CAS  Google Scholar 

  30. Villeneuve JP, Condreay LD, Willems B. et al.: Lamivudine treatment for decompensated cirrhosis resulting from chronic hepatitis B. Hepatology 2000, 31:207–210.

    Article  PubMed  CAS  Google Scholar 

  31. Perrillo R, Wright T, Rakela J, et al.: A multicenter United States-Canadian trial to assess lamivudine monotherapy before and after transplantation for chronic hepatitis B. The Lamivudine Transplant Group. Hepatology 2001, 33:424–432.

    Article  PubMed  CAS  Google Scholar 

  32. Mutimer D, Pillay D, Shields P, et al.: Outcome of lamivudine resistant hepatitis B virus infection in liver transplant recipients. Gut 2000, 46:110–113.

    Article  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  34. Yao FY, Osorio RW, Roberts JP, et al.: Intramuscular hepatitis B immune globulin combined with lamivudine for prophylaxis against hepatitis B recurrence after liver transplantation. Liver Transpl Surg 1999, 5:491–496.

    Article  PubMed  CAS  Google Scholar 

  35. Terrault NA, Wright TL, Roberts JP, et al.: Combined short-term hepatitis B immune globulin (HBIg) and long-term Lamivudine versus HBIg therapy as hepatitis B prophylaxis in liver transplant recipients [abstract]. Hepatology 1998, 28:389A.

    Article  Google Scholar 

  36. Rosenau J, Bahr MJ, Tillmann HL, et al.: Lamivudine and low-dose hepatitis 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 2001, 34:895–902.

    Article  PubMed  CAS  Google Scholar 

  37. Locarnini SA: Hepatitis B virus surface antigen and polymerase gene variants: potential virological and clinical significance. Hepatology 1998, 27:294–297.

    Article  PubMed  CAS  Google Scholar 

  38. Naoumov NV, Ross Lopes A, Burra P, et al.: Randomized trial of lamivudine versus hepatitis B immunoglobulin for longterm prophylaxis of hepatitis B recurrence after liver transplantation. J Hepatol 2001, 34:888–894.

    Article  PubMed  CAS  Google Scholar 

  39. Machicao VI, Devarbhavi HC, Soldevilla-Pico C, et al.: Replication status does not predict one-year outcome in hepatitis B patients in combined prophylaxis after liver transplantation. Paper presented at the American Association for the Study of Liver Disease Annual Meeting. Dallas, TX. November 9–13, 2001.

  40. Xiong X, Yang H, Westland CE, et al.: Human hepatitis B virus DNA polymerases which contain mutations arising during famcyclovir treatment remain sensitive to adefovir [abstract]. Hepatology 1998, 28:491A.

    Article  Google Scholar 

  41. Perrillo R, Schiff E, Yoshida E, et al.: Adefovir dipivoxil for the treatment of lamivudine-resistant hepatitis B mutants. Hepatology 2000, 32:129–134.

    Article  PubMed  CAS  Google Scholar 

  42. Westland C, Yang H, Lamy P, et al.: Genotypic analysis of lamivudine (LAM)-resistant HBV and their sensitivities to adefovir (ADV) in vitro and in liver transplant patients. Paper presented at the 36th European Association for the Study of Liver Meeting. Prague, Czech Republic. April 18–22, 2001.

  43. Ahmad J, Dodson SF, Balan V, et al.: Adefovir dipivoxil suppresses lamivudine-resistant hepatitis B virus in liver transplant recipients. Paper presented at the American Association for the Study of Liver Disease Annual Meeting. Dallas, TX. October 27–31, 2000.

  44. Dickson RC, Terrault NA, Ishitani MB, et al.: Protective antibody levels and dose requirements of IV 5% NABI hepatitis B immune globulin combined with lamivudine in liver transplantation for hepatitis B induced end stage liver disease. Paper presented at the American Association for the Study of Liver Disease Annual Meeting. Dallas, TX. November 9–13, 2001.

  45. Gretch D, Bacchi C, Corey L, et al.: Persistent hepatitis C virus infection after liver transplantation: clinical and virological features. Hepatology 1995, 22:1–9. This study highlights the natural virologic properties of recurrent HCV infection in the liver allograft and transplant recipients by histologic and serum biochemical analysis.

    PubMed  CAS  Google Scholar 

  46. Gane EJ, Portmann BC, Naoumov NV, et al.: Long-term outcome of hepatitis C infection after liver transplantation. N Engl J Med 1996, 334:815–820.

    Article  PubMed  CAS  Google Scholar 

  47. Feray C, Gigou M, Samuel D, et al.: The course of hepatitis C virus infection after liver transplantation. Hepatology 1994, 20:1137–1143.

    PubMed  CAS  Google Scholar 

  48. Taga SA, Washington MK, Terrault N, et al.: Cholestatic hepatitis C in liver allografts. Liver Transpl Surg 1998, 4:304–310.

    Article  PubMed  CAS  Google Scholar 

  49. Schluger LK, Sheiner PA, Thung SN, et al.: Severe recurrent cholestatic hepatitis C following orthotopic liver transplantation. Hepatology 1996, 23:971–976.

    Article  PubMed  CAS  Google Scholar 

  50. Prieto M, Berenguer M, Rayon JM, 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.

    Article  PubMed  CAS  Google Scholar 

  51. Martinez MF, Berenguer MF, Prieto MM, et al.: Recent decrease in patient survival among HCV-infected liver transplant recipients. Paper presented at the American Association for the Study of Liver Disease. Dallas, TX. November 9–13, 2001.

  52. Zhou S, Terrault NA, Ferrell L, et al.: Severity of liver disease in liver transplantation recipients with hepatitis C virus infection: relationship to genotype and level of viremia. Hepatology 1996, 24:1041–1046.

    Article  PubMed  CAS  Google Scholar 

  53. Gane E: Hepatitis C virus infection following liver transplantation. Viral Hepat Rev 1998, 4:97–125.

    Google Scholar 

  54. Feray C, Caccamo L, Graeme JMA, et al.: European collaborative study on factors influencing outcome after liver transplantation for hepatitis C. Gastroenterology 1999, 117:619–625.

    Article  PubMed  CAS  Google Scholar 

  55. Rosen HR, Chou S, Cordless CL, et al.: Cytomegalovirus viremia. Risk factor for allograft cirrhosis after liver transplantation for hepatitis C. Transplantation 1997, 64:721–726.

    Article  PubMed  CAS  Google Scholar 

  56. Teixeira R, Pastacaldi S, Dagher L, et al.: Cytomegalovirus viremia after liver transplantation: is it a risk factor for acute allograft rejection of cirrhosis [abstract]? Hepatology 1999, 30:244A.

    Article  Google Scholar 

  57. Deschenes M, Barkun J, Cantarovich M, et al.: Corticosteroid treatment of late acute cellular rejection is associated with worst recurrent hepatitis C virus hepatitis after liver transplantation than treatment of early cellular rejection. Paper presented at the American Association for the Study of Liver Disease Annual Meeting. Dallas, TX. October 27–31, 2000.

  58. Berenguer M, Watson J, Crippin J, et al.: A model to predict HCV-related fibrosis progression following liver transplantation OLT. Paper presented at the American Association of the Study of Liver Disease Annual Meeting. Dallas, TX. October 27–31, 2000.

  59. Berenguer M, Crippin J, Bass N, et al.: Proposed strategy to reduce post-transplantation HCV-related disease progression. Paper presented at the American Association for the Study of Liver Disease. Dallas, TX. November 9–13, 2001.

  60. Wright T, Combs C, Kim M, et al.: Interferon-alfa therapy for hepatitis C virus infection after liver transplantation. Hepatology 1994, 20:773–779.

    Article  PubMed  CAS  Google Scholar 

  61. Feray C, Samuel D, Gigou M, et al.: An open trial of interferon alfa recombinant for hepatitis C after liver transplantation: anti-viral effects and risk of rejection. Hepatology 1995, 22:1084–1089.

    Article  PubMed  CAS  Google Scholar 

  62. DiBisceglie AM, Shindo M, Fong TL, et al.: A pilot study of ribavirin therapy for chronic hepatitis C. Hepatology 1992, 16:649–654.

    Article  CAS  Google Scholar 

  63. Cattral MS, Krajden M, Wanless IR, et al.: A pilot study of ribavirin therapy for chronic hepatitis C virus infection after liver transplantation. Transplantation 1999, 61:1483–1488.

    Article  Google Scholar 

  64. Pham HP, Feray C, Samuel D, et al.: Effects of ribavirin on hepatitis C-associated nephrotic syndrome in four liver transplant recipients. Kidney Intl 1998, 54:1311–1319.

    Article  CAS  Google Scholar 

  65. Bizollon T, Pallazo U, Ducerf C, et al.: Pilot study of the combination of interferon alfa and ribavirin as therapy of recurrent hepatitis C after liver transplantation. Hepatology 1997, 26:500–504.

    Article  PubMed  CAS  Google Scholar 

  66. Gopal DV, Rabkin JM, Berk BS, et al.: Treatment of progressive hepatitis C recurrence after liver transplantation with combination interferon plus ribavirin. Liver Transplantation 2001, 7:181–190.

    Article  PubMed  CAS  Google Scholar 

  67. Samuel D, Bizollon T, Feray C, et al.: Combination of interferon alfa 2B plus ribavirin for recurrent HCV infection after liver transplantation: a randomized controlled study. Paper presented at the American Association for the Study of Liver Disease Annual Meeting. Dallas, TX. October 27–31, 2000.

  68. Firpi RJ, Nelson DR, Soldevila C, et al.: Combination of interferon alfa 2B and ribavirin in liver transplant recipients with histologic recurrent hepatitis C. Paper presented at the Digestive Diseases Week Annual Meeting. Atlanta, GA. May 19–26, 2001.

  69. Casanovas T, Ramos E, Serrano T, et al.: Pilot study with the combination of interferon alfa and ribavirin for recurrent post-liver transplantation hepatitis C: causes of treatment failure in two different populations. Paper presented at the American Association for the Study of Liver Disease. Dallas, TX. November 9–13, 2001.

  70. Reddy K, Wippler D, Zervos X, et al.: Recurrent HCV infection following liver transplantation: the role of early posttransplant interferon treatment [abstract]. Hepatology 1996, 24:295A.

    Google Scholar 

  71. Sheiner P, Boros P, Klion F, et al.: The efficacy of prophylactic interferon alfa-2b in preventing recurrent hepatitis C after liver transplantation. Hepatology 1998, 28:831–838.

    Article  PubMed  CAS  Google Scholar 

  72. Mazzaferro V, Regalia E, Pulvirenti A, et al.: Prophylaxis against HCV recurrence after liver transplantation: effect of interferon and ribavirin combination. Transplant Proc 1997, 29:519–521.

    Article  PubMed  CAS  Google Scholar 

  73. Davis G, Lau J: Factors predictive of a beneficial response to therapy of hepatitis C. Hepatology 1997, 26:122s-127s.

    Article  PubMed  CAS  Google Scholar 

  74. Reily C, Ferenci P, Peck-Radosavljevic M, et al.: Pegylated (40kDa) interferon alfa-2a (Pegasys) in post-liver transplant recipients with established recurrent hepatitis C: a preliminary report. Am J Transplantation 2001, 1(suppl 1):S158A.

    Google Scholar 

  75. Krawczynski K, Fattom A, Culveer D, et al.: Passive transfer of anti-HCV in chronic and acute HCV infection in chimpanzees: Trials of experimental immune treatment [abstract]. Hepatology 1999, 30:423A.

    Google Scholar 

  76. Halprin A, Trotter JF, Everson GT, et al.: Post-transplant eradication of hepatitis C by pre-transplant treatment in living donor liver transplant recipients. Paper presented by the American Association for the Study of Liver Disease. Dallas, TX. November 9–13, 2001.

  77. Teixeira R, Pastacaldi, S, Papatheodoridis BV, Burroughs AK: Recurrent hepatitis after liver transplantation [review]. J Med Virol 2000, 61:443–454.

    Article  PubMed  CAS  Google Scholar 

  78. Boker KHW, Dalley G, Bahr MJ, et al.: Long-term outcome of hepatitis C virus infection after liver transplantation. Hepatology 1997, 25:203–210.

    PubMed  CAS  Google Scholar 

  79. Casavilla FA, Rakela J, Kapur S, et al.: Clinical Outcome of patients with hepatitis C virus infection and survival after primary liver transplantation under tacrolimus. Liver Transplant Surg 1998, 4:448–454.

    Article  CAS  Google Scholar 

  80. Ghobriel RM, Farmer DG, Baquerizo A, et al.: Orthotopic liver transplantation for hepatitis C: outcome, effects of immunosuppression, and causes of re-transplantation during an 8 year single-centre experience. Ann Surg 1999, 6:824–833.

    Article  Google Scholar 

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Sponseller, C.A., Ramrakhiani, S. Treatment of hepatitis B and C following liver transplantation. Curr Gastroenterol Rep 4, 52–62 (2002). https://doi.org/10.1007/s11894-002-0038-7

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