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Pre- and Posttransplant Management of Hepatitis C

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Liver Transplantation

Part of the book series: Clinical Gastroenterology ((CG))

Abstract

Hepatitis C is the most common indication for liver transplantation in the United States. Reinfection is a universal occurrence in patients who are transplanted with viremia, and recurrent hepatitis results in higher rates of graft and patient loss compared to other indications for transplantation. The most important factors that predict poor transplant outcome are advanced donor age and treatment of acute rejection. Therapy may be given prior to transplantation to eradicate virus and prevent recurrent disease. Alternatively, posttransplantation therapy can be administered prior to the development of overt clinical disease (early or preemptive therapy) or delayed until histological progression is evident. However, posttransplantation therapy with interferon and ribavirin is problematic due to a high incidence of treatment complications and low sustained virologic response rate. New therapies that are more uniformly effective and better tolerated are needed to improve virologic response rates and ultimately reduce the rates of cirrhosis and graft loss.

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References

  1. 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(4):889–96.

    Article  PubMed  Google Scholar 

  2. Neumann UP, Berg T, Bahra M, Puhl G, Guckelberger O, Langrehr JM, et al. Long-term outcome of liver transplants for chronic hepatitis C: A 10-year follow-up. Transplantation 2004; 77(2):226–31.

    Article  PubMed  Google Scholar 

  3. Everhart J, Wei Y, Eng H, Charlton M, Persing D, Wiesner R, et al. Recurrent and new hepatitis C virus infection after liver transplantation. Hepatology 1999; 29:1220–6.

    Article  PubMed  CAS  Google Scholar 

  4. Prieto M, Berenguer M, Rayon J, 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; 29:250–6.

    Article  CAS  Google Scholar 

  5. Gane E, Portmann B, Naoumov N, Smith H, Underhill J, Donaldson P, et al. Long-term outcome of hepatitis C infection after liver transplantation. N Engl J Med 1996; 334:815–20.

    Article  PubMed  CAS  Google Scholar 

  6. Feray C, Caccamo L, Alexander GJ, Ducot B, Gugenheim J, Casanovas T, et al. European collaborative study on factors influencing outcome after liver transplantation for hepatitis C. European Concerted Action on Viral Hepatitis (EUROHEP) Group. Gastroenterology 1999; 117(3):619–25.

    Article  PubMed  CAS  Google Scholar 

  7. Neumann U, Berg T, Bahra M, Seehofer D, Langrehr J, Neuhaus R, et al. Fibrosis progression after liver transplantation in patients with recurrent hepatitis C. J Hepatol 2004; 41(5):830–6.

    Article  PubMed  CAS  Google Scholar 

  8. Wali M, Harrison RF, Gow PJ, Mutimer D. Advancing donor liver age and rapid fibrosis progression following transplantation for hepatitis C. Gut 2002; 51(2): 248–52.

    Article  PubMed  CAS  Google Scholar 

  9. 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(4 Pt 1):852–8.

    Article  PubMed  CAS  Google Scholar 

  10. Schluger L, Sheiner P, Thung S, Lau J, Min A, Wolf D, et al. Severe recurrent cholestatic hepatitis C following orthotopic liver transplantation. Hepatology 1996; 23:971–6.

    Article  PubMed  CAS  Google Scholar 

  11. Gaglio P, Malireddy S, Levitt B, Lapointe-Rudow D, Lefkowitch J, Kinkhabwala M, et al. Increased risk of cholestatic hepatitis C in recipients of grafts from living versus cadaveric liver donors. Liver Transpl 2003; 9(10): 1028–35.

    Article  PubMed  Google Scholar 

  12. Wali MH, Heydtmann M, Harrison RF, Gunson BK, Mutimer DJ. Outcome of liver transplantation for patients infected by hepatitis C, including those infected by genotype 4. Liver Transpl 2003; 9(8):796–804.

    Article  PubMed  Google Scholar 

  13. 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(4):673–84.

    Article  PubMed  CAS  Google Scholar 

  14. Burak KW, Kremers WK, Batts KP, Wiesner RH, Rosen CB, Razonable RR, et al. Impact of cytomegalovirus infection, year of transplantation, and donor age on outcomes after liver transplantation for hepatitis C. Liver Transpl 2002; 8(4): 362–9.

    Article  PubMed  Google Scholar 

  15. Lake JR, Shorr JS, Steffen BJ, Chu AH, Gordon RD, Wiesner RH. Differential effects of donor age in liver transplant recipients infected with hepatitis B, hepatitis C and without viral hepatitis. Am J Transpl 2005; 5(3):549–57.

    Article  Google Scholar 

  16. Sheiner P, Schwartz M, Mor E, Schluger L, Theise N, Kishikawa K, et al. Severe and multiple rejection episodes are associated with early recurrence of hepatitis C after orthotopic liver transplantation. Hepatology 1995; 21(1):30–4.

    Article  PubMed  CAS  Google Scholar 

  17. Rosen HR, Chou S, Corless CL, Gretch DR, Flora KD, Boudousquie A, et al. Cytomegalovirus viremia: Risk factor for allograft cirrhosis after liver transplantation for hepatitis C. Transplantation 1997; 64(5):721–6.

    Article  PubMed  CAS  Google Scholar 

  18. Charlton M, Seaberg E, Wiesner R, Everhart J, Zetterman R, Lake J, et al. Predictors of patient and graft survival following liver transplantation for hepatitis C. Hepatology 1998; 28:823–30.

    Article  PubMed  CAS  Google Scholar 

  19. Wiesner R, Sorrell M, Villamil F, International Liver Transplantation Society Expert Panel. Report of the First International Liver Transplantation Society Expert Panel Consensus Conference on liver transplantation and hepatitis C. Liver Transpl 2003; 9(11):S1–S9.

    Google Scholar 

  20. Terrault NA, Berenguer M. Treating hepatitis C infection in liver transplant recipients. Liver Transpl 2006; 12(8):1192–204.

    Article  PubMed  Google Scholar 

  21. Terrault NA, Shiffman ML, Lok AS, et al. Outcomes in hepatitis C virus-infected recipients of living donor vs. deceased donor liver transplantation. Liver Transpl 2007; 13(1):122–9.

    Google Scholar 

  22. Garcia-Retortillo M, Forns X, Llovet J, 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(3):699–707.

    Article  PubMed  Google Scholar 

  23. Shiffman M, Stravitz R, Contos M, Mills A, Sterling R, Luketic V, et al. Histologic recurrence of chronic hepatitis C virus in patients after living donor and deceased donor liver transplantation. Liver Transpl 2004; 10:1248–55.

    Article  PubMed  Google Scholar 

  24. Watashi K, Hijikata M, Hosaka M, Yamaji M, Shimotohno K. Cyclosporin A suppresses replication of hepatitis C virus genome in cultured hepatocytes. Hepatology 2003; 38(5):1282–8.

    Article  PubMed  CAS  Google Scholar 

  25. Levy G, Villamil F, Samuel D, Sanjuan F, Grazi GL, Wu Y, et al. Results of LIS2T, a multicenter, randomized study comparing cyclosporine microemulsion with C2 monitoring and tacrolimus with C0 monitoring in de novo liver transplantation. Transplantation 2004; 77(11):1632–8.

    Article  PubMed  CAS  Google Scholar 

  26. Martin P, Busuttil RW, Goldstein RM, Crippin JS, Klintmalm GB, Fitzsimmons WE, et al. Impact of tacrolimus versus cyclosporine in hepatitis C virus-infected liver transplant recipients on recurrent hepatitis: A prospective, randomized trial. Liver Transpl 2004; 10(10):1258–62.

    Article  PubMed  Google Scholar 

  27. Fisher RA, Stone JJ, Wolfe LG, Rodgers CM, Anderson ML, Sterling RK, et al. Four-year follow-up of a prospective randomized trial of mycophenolate mofetil with cyclosporine microemulsion or tacrolimus following liver transplantation. Clin Transpl 2004; 18(4):463–72.

    Article  Google Scholar 

  28. 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(4):717–22.

    Article  PubMed  CAS  Google Scholar 

  29. Hilgard P, Kahraman A, Lehmann N, Seltmann C, Beckebaum S, Ross RS, et al. Cyclosporine versus tacrolimus in patients with HCV infection after liver transplantation: Effects on virus replication and recurrent hepatitis. World J Gastroenterol 2006; 12(5):697–702.

    PubMed  CAS  Google Scholar 

  30. Bahra M, Neumann UI, Jacob D, Puhl G, Klupp J, Langrehr JM, et al. MMF and calcineurin taper in recurrent hepatitis C after liver transplantation: Impact on histological course. Am J Transpl 2005; 5(2):406–11.

    Article  CAS  Google Scholar 

  31. Zekry A, Gleeson M, Guney S, McCaughan GW. A 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(1):52–7.

    Article  PubMed  Google Scholar 

  32. Wiesner RH, Shorr JS, Steffen BJ, Chu AH, Gordon RD, Lake JR. Mycophenolate mofetil combination therapy improves long-term outcomes after liver transplantation in patients with and without hepatitis C. Liver Transpl 2005; 11(7):750–9.

    Google Scholar 

  33. Filipponi F, Callea F, Salizzoni M, Grazi GL, Fassati LR, Rossi M, et al. Double-blind comparison of hepatitis C histological recurrence rate in HCV+ liver transplant recipients given basiliximab + steroids or basiliximab + placebo, in addition to cyclosporine and azathioprine. Transplantation 2004; 78(10):1488–95.

    Article  PubMed  CAS  Google Scholar 

  34. Eason JD, Nair S, Cohen AJ, Blazek JL, Loss GE, Jr. Steroid-free liver transplantation using rabbit antithymocyte globulin and early tacrolimus monotherapy. Transplantation 2003; 75(8):1396–9.

    Article  PubMed  CAS  Google Scholar 

  35. Brillanti S, Vivarelli M, De Ruvo N, Aden AA, Camaggi V, D'Errico A, et al. Slowly tapering off steroids protects the graft against hepatitis C recurrence after liver transplantation. Liver Transpl 2002; 8(10):884–8.

    Google Scholar 

  36. Belli L, Alberti A, Vangeli M, Airoldi A, Pinzello G. Tapering off steroids three months after liver transplantation is not detrimental for hepatitis C virus disease recurrence. Liver Transpl 2003; 9(2):201–2.

    Article  PubMed  Google Scholar 

  37. Papatheodoridis GV, Davies S, Dhillon AP, Teixeira R, Goulis J, Davidson B, et al. The role of different immunosuppression in the long-term histological outcome of HCV reinfection after liver transplantation for HCV cirrhosis. Transplantation 2001; 72(3):412–8.

    Article  PubMed  CAS  Google Scholar 

  38. Gonzalez MG, Madrazo CP, Rodriguez AB, Gutierrez MG, Herrero JI, Pallardo JM, et al. An open, randomized, multicenter clinical trial of oral tacrolimus in liver allograft transplantation: A comparison of dual vs. triple drug therapy. Liver Transpl 2005; 11(5):515–24.

    Article  PubMed  Google Scholar 

  39. Tisone G, Orlando G, Cardillo A, Palmieri G, Manzia TM, Baiocchi L, et al. Complete weaning off immunosuppression in HCV liver transplant recipients is feasible and favourably impacts on the progression of disease recurrence. J Hepatol 2006; 44:702–9.

    Google Scholar 

  40. Everson G. Treatment of patients with hepatitis C virus on the waiting list. Hepatology 2005; in press.

    Google Scholar 

  41. Forns X, Navasa M, Rodes J. Treatment of HCV infection in patients with advanced cirrhosis. Hepatology 2004; 40(2):498.

    Article  PubMed  Google Scholar 

  42. Davis G, Nelson D, Terrault N, Pruett T, Schiano T, Fletcher C, et al. A randomized, open-label study to evaluate the safety and pharmacokinetics of human hepatitis C immune globulin (Civacir) in liver transplant recipients. Liver Transpl 2005; in press.

    Google Scholar 

  43. Schiano TD, Charlton M, Younassi Z, et al. A phase III study of monoclonal antibody HCV-ABXTL-68 in patients requiring liver transplant for HCV disease. Hepatology 2005; 42:A701.

    Article  Google Scholar 

  44. Khalili M, Vardanian AJ, Hamerski CM, Wang R, Bacchetti P, Roberts JP, et al. Management of hepatitis C-infected liver transplant recipients at large North American centres: Changes in recent years. Clin Transpl 2006; 20(1):1–9.

    Article  Google Scholar 

  45. Regev A, Molina E, Moura R, Bejarano PA, Khaled A, Ruiz P, et al. Reliability of histopathologic assessment for the differentiation of recurrent hepatitis C from acute rejection after liver transplantation. Liver Transpl 2004; 10(10):1233–9.

    Article  PubMed  Google Scholar 

  46. Netto GJ, Watkins DL, Williams JW, Colby TV, dePetris G, Sharkey FE, et al. Interobserver agreement in hepatitis C grading and staging and in the Banff grading schema for acute cellular rejection: The “Hepatitis C 3” Multi-Institutional Trial experience. Arch Pathol Lab Med 2006; 130(8):1157–62.

    PubMed  Google Scholar 

  47. Crippin JS, McCashland T, Terrault N, Sheiner P, Charlton MR. A pilot study of the tolerability and efficacy of antiviral therapy in hepatitis C virus-infected patients awaiting liver transplantation. Liver Transpl 2002; 8(4):350–5.

    Article  PubMed  Google Scholar 

  48. Singh N, Gayowski T, Wannstedt CF, Shakil AO, Wagener MM, Fung JJ, et al. Interferon-alpha for prophylaxis of recurrent viral hepatitis C in liver transplant recipients: A prospective, randomized, controlled trial. Transplantation 1998; 65(1):82–6.

    Article  PubMed  CAS  Google Scholar 

  49. Sheiner P, Boros P, Klion F, Thung S, Schluger L, Lau J, et al. The efficacy of prophylactic interferon alfa-2b in preventing recurrent hepatitis C after liver transplantation. Hepatology 1998; 28:831–8.

    Article  PubMed  CAS  Google Scholar 

  50. Chalasani N, Manzarbeitia 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(2):289–98.

    Article  PubMed  CAS  Google Scholar 

  51. Shergill A, Khalili M, Straley S, Bollinger K, Roberts J, Ascher N, et al. Applicability, tolerability and efficacy of preemptive antiviral therapy in hepatitis C infected patients undergoing liver transplantation. Am J Transpl 2005; 5(1):118–24.

    Article  Google Scholar 

  52. Sugawara Y, Makuuchi M, Matsui Y, Kishi Y, Akamatsu N, Kaneko J, et al. Preemptive therapy for hepatitis C virus after living-donor liver transplantation. Transplantation 2004; 78(9):1308–11.

    Article  PubMed  CAS  Google Scholar 

  53. 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. Transpl Proc 2001; 33(1–2):1355–7.

    Article  CAS  Google Scholar 

  54. Terrault NA. Treatment of recurrent hepatitis C in liver transplant recipients. Clin Gastroenterol Hepatol 2005; 3(10 Suppl 2):S125–S131.

    Article  PubMed  CAS  Google Scholar 

  55. Gane E, Lo S, Portmann B, Lau J, Naoumov N, Williams R. A randomized study of the safety and efficacy of ribavirin versus interferon monotherapy for recurrent HCV infection in liver transplant recipients. Hepatology 1998; 24(4 Pt 2):293A.

    Google Scholar 

  56. Wright T, Combs C, Kim M, Ferrell L, Bacchetti P, Ascher N, et al. Interferon-alpha therapy for hepatitis C virus infection after liver transplantation. Hepatology 1994; 20(4):773–9.

    Article  PubMed  CAS  Google Scholar 

  57. Giostra E, Kullak-Ublick G, Keller W, Fried R, Vanlemmens C, Kraehenbuhl S, et al. Ribavirin/interferon-alpha sequential treatment of recurrent hepatitis C after liver transplantation. Transpl Int 2004; 17(4):169–76.

    PubMed  CAS  Google Scholar 

  58. Firpi R, Abdelmalek M, Soldevila-Pico C, Reed A, Hemming A, Howard R, et al. Combination of interferon alfa-2b and ribavirin in liver transplant recipients with histological recurrent hepatitis C. Liver Transpl 2002; 8(11):1000–6.

    Article  PubMed  Google Scholar 

  59. Mukherjee S, Lyden E, McCashland TM, Schafer DF. Interferon alpha 2b and ribavirin for the treatment of recurrent hepatitis C after liver transplantation: Cohort study of 38 patients. J Gastroenterol Hepatol 2005; 20(2):198–203.

    Article  PubMed  CAS  Google Scholar 

  60. Samuel D, Bizollon T, Feray C, Roche B, Ahmed S, Lemonnier C, et al. Interferon-alpha 2b plus ribavirin in patients with chronic hepatitis C after liver transplantation: A randomized study. Gastroenterology 2003; 124(3):642–50.

    Article  PubMed  CAS  Google Scholar 

  61. Bizollon T, Ahmed S, 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; 52:283–7.

    Article  PubMed  CAS  Google Scholar 

  62. Dumortier J, Scoazec J, 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(4):669–74.

    Article  PubMed  CAS  Google Scholar 

  63. Abdelmalek M, Firpi R, Soldevila-Pico C, Reed A, Hemming A, Liu C, et al. Sustained viral response to interferon and ribavirin in liver transplant recipients with recurrent hepatitis C. Liver Transpl 2004; 10(2):199–207.

    Article  PubMed  Google Scholar 

  64. Berenguer M, Prieto M, Palau A, Carrasco D, Rayon JM, Calvo F, et al. Recurrent hepatitis C genotype 1b following liver transplantation: Treatment with combination interferon-ribavirin therapy. Eur J Gastroenterol Hepatol 2004; 16(11):1207–12.

    Article  PubMed  CAS  Google Scholar 

  65. Oton E, Barcena R, Moreno-Planas JM, Cuervas-Mons V, Moreno-Zamora A, Barrios C, et al. Hepatitis C recurrence after liver transplantation: Viral and histologic response to full-dose peg-interferon and ribavirin. Am J Transpl 2006; 6:2348–55.

    Article  CAS  Google Scholar 

  66. Castells L, Vargas V, Allende H, Bilbao I, Luis Lázaro 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; 43:53–9.

    Google Scholar 

  67. Rodriguez-Luna H, Khatib A, Sharma P, De Petris G, Williams JW, Ortiz J, et al. Treatment of recurrent hepatitis C infection after liver transplantation with combination of pegylated interferon alpha2b and ribavirin: An open-label series. Transplantation 2004; 77(2):190–4.

    Article  PubMed  CAS  Google Scholar 

  68. Dumortier J, Ducos E, Scoazec JY, Chevallier P, Boillot O, Gagnieu MC. Plasma ribavirin concentrations during treatment of recurrent hepatitis C with peginterferon alpha-2b and ribavirin combination after liver transplantation. J Viral Hepat 2006; 13(8):538–43.

    Article  PubMed  CAS  Google Scholar 

  69. Biggins SW, Terrault NA. Treatment of recurrent hepatitis C after liver transplantation. Clin Liver Dis 2005; 9(3):505–23, ix.

    Article  PubMed  Google Scholar 

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  1. Division of Gastroenterology, University of California, San Francisco, San Francisco, CA

    Norah A. Terrault (MD, MPH)

  2. Sao Paulo, Brazil

    Mario G. Pessoa

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    © 2009 Humana Press, a part of Springer Science+Business Media, LLC

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    Terrault, N.A., Pessoa, M.G. (2009). Pre- and Posttransplant Management of Hepatitis C. In: Trotter, J., Everson, G. (eds) Liver Transplantation. Clinical Gastroenterology. Humana Press. https://doi.org/10.1007/978-1-60327-028-1_3

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    • DOI: https://doi.org/10.1007/978-1-60327-028-1_3

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