Skip to main content

Advertisement

Log in

Antiviral therapy of chronic hepatitis C in patients with advanced liver disease and after liver transplantation

  • Review
  • Published:
Medical Microbiology and Immunology Aims and scope Submit manuscript

Abstract

Chronic infection with the hepatitis C virus (HCV) represents one of the major causes for end-stage liver disease worldwide. Although liver transplantation offers an effective treatment, HCV reinfection of the transplanted graft is a critical and almost inevitable complication with major influence on graft- and patient survival. Pre-transplant antiviral therapy in advanced liver disease is limited by poor tolerance and only applicable to mildly decompensated patients but was able to show promising results in patients reaching negative viral load when undergoing transplantation. Prophylactic therapy with HCV antibodies during the anhepatic phase has not been shown to be effective in studies to date. Antiviral therapy after transplantation but before evidence of reinfection, so called pre-emptive treatment, is limited by frequent complications and a high rate of side effects. The mainstay of management represents directed antiviral therapy after evidence of recurrence of chronic Hepatitis C. With a combination therapy of pegylated interferon and ribavirin, sustained virologic response rates of 25–45% are achieved. However, tolerability is often poor, and the need of dose reduction is frequent. To date, there is no general consensus on modality, timing and dosing of antiviral treatment of HCV in patients with advanced liver disease and after liver transplantation. More randomised, controlled trials are needed. Moreover, upcoming new treatment approaches, e.g. specifically targeted antiviral therapy for hepatitis C (STAT-C) with HCV-specific polymerase and protease inhibitors, may represent a therapeutic alternative.

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

Access this article

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

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Brown RS (2005) Hepatitis C and liver transplantation. Nature 436:973–978. doi:10.1038/nature04083 nature04083 [pii]

    Article  PubMed  CAS  Google Scholar 

  2. Lavanchy D (2009) The global burden of hepatitis C. Liver Int 29(Suppl 1):74–81. doi:10.1111/j.1478-3231.2008.01934.x LIV1934 [pii]

    Article  PubMed  Google Scholar 

  3. Muhlberger N, Schwarzer R, Lettmeier B, Sroczynski G, Zeuzem S, Siebert U (2009) HCV-related burden of disease in Europe: a systematic assessment of incidence, prevalence, morbidity, and mortality. BMC Public Health 9:34. doi:10.1186/1471-2458-9-34 1471-2458-9-34 [pii]

    Article  PubMed  Google Scholar 

  4. Berenguer M, Prieto M, Rayon JM, Mora J, Pastor M, Ortiz V, Carrasco D, San Juan F, Burgueno MD, Mir J, Berenguer J (2000) Natural history of clinically compensated hepatitis C virus-related graft cirrhosis after liver transplantation. Hepatology 32:852–858. doi:10.1053/jhep.2000.17924 S0270913900860425 [pii]

    Article  PubMed  CAS  Google Scholar 

  5. Ghobrial RM, Steadman R, Gornbein J, Lassman C, Holt CD, Chen P, Farmer DG, Yersiz H, Danino N, Collisson E, Baquarizo A, Han SS, Saab S, Goldstein LI, Donovan JA, Esrason K, Busuttil RW (2001) A 10-year experience of liver transplantation for hepatitis C: analysis of factors determining outcome in over 500 patients. Ann Surg 234:384–393 discussion 393–384

    Article  PubMed  CAS  Google Scholar 

  6. Neumann UP, Berg T, Bahra M, Puhl G, Guckelberger O, Langrehr JM, Neuhaus P (2004) Long-term outcome of liver transplants for chronic hepatitis C: a 10-year follow-up. Transplantation 77:226–231. doi:10.1097/01.TP.0000101738.27552.9D 00007890-200401270-00012 [pii]

    Article  PubMed  Google Scholar 

  7. Rowe IA, Webb K, Gunson BK, Mehta N, Haque S, Neuberger J (2008) The impact of disease recurrence on graft survival following liver transplantation: a single centre experience. Transpl Int 21:459–465. doi:10.1111/j.1432-2277.2007.00628.x TRI628 [pii]

    Article  PubMed  Google Scholar 

  8. Chalasani N, Manzarbeitia C, Ferenci P, Vogel W, Fontana RJ, Voigt M, Riely C, Martin P, Teperman L, Jiao J, Lopez-Talavera JC (2005) Peginterferon alfa-2a for hepatitis C after liver transplantation: two randomized, controlled trials. Hepatology 41:289–298. doi:10.1002/hep.20560

    Article  PubMed  CAS  Google Scholar 

  9. Everson GT, Trotter J, Forman L, Kugelmas M, Halprin A, Fey B, Ray C (2005) Treatment of advanced hepatitis C with a low accelerating dosage regimen of antiviral therapy. Hepatology 42:255–262. doi:10.1002/hep.20793

    Article  PubMed  CAS  Google Scholar 

  10. Forns X, Garcia-Retortillo M, Serrano T, Feliu A, Suarez F, de la Mata M, Garcia-Valdecasas JC, Navasa M, Rimola A, Rodes J (2003) Antiviral therapy of patients with decompensated cirrhosis to prevent recurrence of hepatitis C after liver transplantation. J Hepatol 39:389–396 S0168827803003106 [pii]

    Article  PubMed  CAS  Google Scholar 

  11. Davis GL, Nelson DR, Terrault N, Pruett TL, Schiano TD, Fletcher CV, Sapan CV, Riser LN, Li Y, Whitley RJ, Gnann JW Jr (2005) A randomized, open-label study to evaluate the safety and pharmacokinetics of human hepatitis C immune globulin (Civacir) in liver transplant recipients. Liver Transpl 11:941–949. doi:10.1002/lt.20405

    Article  PubMed  Google Scholar 

  12. Schiano TD, Charlton M, Younossi Z, Galun E, Pruett T, Tur-Kaspa R, Eren R, Dagan S, Graham N, Williams PV, Andrews J (2006) Monoclonal antibody HCV-AbXTL68 in patients undergoing liver transplantation for HCV: results of a phase 2 randomized study. Liver Transpl 12:1381–1389. doi:10.1002/lt.20876

    Article  PubMed  Google Scholar 

  13. Hezode C, Forestier N, Dusheiko G, Ferenci P, Pol S, Goeser T, Bronowicki JP, Bourliere M, Gharakhanian S, Bengtsson L, McNair L, George S, Kieffer T, Kwong A, Kauffman RS, Alam J, Pawlotsky JM, Zeuzem S (2009) Telaprevir and peginterferon with or without ribavirin for chronic HCV infection. N Engl J Med 360:1839–1850. doi:10.1056/NEJMoa0807650 360/18/1839 [pii]

    Article  PubMed  CAS  Google Scholar 

  14. Kronenberger B, Welsch C, Forestier N, Zeuzem S (2008) Novel hepatitis C drugs in current trials. Clin Liver Dis 12(3):529–555. doi:10.1016/j.cld.2008.03.001 S1089-3261(08)00042-1 [pii]

    Article  PubMed  Google Scholar 

  15. Kwo P, Lawitz E, McCone J, Schiff E, Vierling J, Pound D, Davis M, Galati J, Gordon S, Ravendhran N, Rossaro L, Anderson F, Jacobson I, Rubin R, Koury K, Brass C, Chaudhri E, Albrecht J (2009) HCV SPRINT-1 final results: SVR 24 from a phase 2 study of Boceprevir plus PEGINTRON (TM) (peginterferon alfa-2b)/ribavirin in treatment-naive subjects with genotype-1 chronic hepatitis C—44th annual meeting of the European-association-for-the-Study-of-the-Liver, APR 22–26, 2009; Copenhagen, DENMARK. J Hepatol 50:4

    Article  Google Scholar 

  16. Garcia-Retortillo M, Forns X, Feliu A, Moitinho E, Costa J, Navasa M, Rimola A, Rodes J (2002) Hepatitis C virus kinetics during and immediately after liver transplantation. Hepatology 35:680–687. doi:10.1053/jhep.2002.31773 S0270913902950949 [pii]

    Article  PubMed  Google Scholar 

  17. Feray C, Gigou M, Samuel D, Paradis V, Wilber J, David MF, Urdea M, Reynes M, Brechot C, Bismuth H (1994) The course of hepatitis C virus infection after liver transplantation. Hepatology 20:1137–1143 S0270913994003332 [pii]

    PubMed  CAS  Google Scholar 

  18. Feray C, Caccamo L, Alexander GJ, Ducot B, Gugenheim J, Casanovas T, Loinaz C, Gigou M, Burra P, Barkholt L, Esteban R, Bizollon T, Lerut J, Minello-Franza A, Bernard PH, Nachbaur K, Botta-Fridlund D, Bismuth H, Schalm SW, Samuel D (1999) European collaborative study on factors influencing outcome after liver transplantation for hepatitis C. European Concerted Action on Viral Hepatitis (EUROHEP) Group. Gastroenterology 117:619–625 S0016508599002528 [pii]

    Article  PubMed  CAS  Google Scholar 

  19. Forman LM, Lewis JD, Berlin JA, Feldman HI, Lucey MR (2002) The association between hepatitis C infection and survival after orthotopic liver transplantation. Gastroenterology 122:889–896 S0016508502603853 [pii]

    Article  PubMed  Google Scholar 

  20. Prieto M, Berenguer M, Rayon JM, Cordoba J, Arguello L, Carrasco D, Garcia-Herola A, Olaso V, De Juan M, Gobernado M, Mir J, Berenguer J (1999) High incidence of allograft cirrhosis in hepatitis C virus genotype 1b infection following transplantation: relationship with rejection episodes. Hepatology 29:250–256. doi:10.1002/hep.510290122 S0270913999000336 [pii]

    Article  PubMed  CAS  Google Scholar 

  21. Yosephy A, Gallegos-Orozco JF, Byrne TJ, Noble B, Aqel B, Carey E, Douglas DD, Mulligan D, Rakela J, Vargas HE (2009) Natural history of fibrosing cholestatic Hepatitis (FHC) after liver transplantation: a single center experience—44th Annual Meeting of the European-Association-for-the-Study-of-the-Liver, APR 22–26, 2009; Copenhagen, DENMARK. J Hepatol 50:498

    Article  Google Scholar 

  22. McCaughan GW, Zekry A (2004) Mechanisms of HCV reinfection and allograft damage after liver transplantation. J Hepatol 40:368–374. doi:10.1016/j.jhep.2004.01.014 S016882780400025X [pii]

    Article  PubMed  Google Scholar 

  23. Berenguer M, Prieto M, San Juan F, Rayon JM, Martinez F, Carrasco D, Moya A, Orbis F, Mir J, Berenguer J (2002) Contribution of donor age to the recent decrease in patient survival among HCV-infected liver transplant recipients. Hepatology 36:202–210. doi:10.1053/jhep.2002.33993 S027091390200023X [pii]

    Article  PubMed  Google Scholar 

  24. Neumann UP, Berg T, Bahra M, Seehofer D, Langrehr JM, Neuhaus R, Radke C, Neuhaus P (2004) Fibrosis progression after liver transplantation in patients with recurrent hepatitis C. J Hepatol 41:830–836. doi:10.1016/j.jhep.2004.06.029 S0168-8278(04)00322-8 [pii]

    Article  PubMed  CAS  Google Scholar 

  25. Charlton M, Seaberg E, Wiesner R, Everhart J, Zetterman R, Lake J, Detre K, Hoofnagle J (1998) Predictors of patient and graft survival following liver transplantation for hepatitis C. Hepatology 28:823–830. doi:10.1002/hep.510280333 S0270913998003814 [pii]

    Article  PubMed  CAS  Google Scholar 

  26. Roche B, Samuel D (2007) Risk factors for hepatitis C recurrence after liver transplantation. J Viral Hepat 14(Suppl 1):89–96. doi:10.1111/j.1365-2893.2007.00920.x JVH920 [pii]

    Article  PubMed  Google Scholar 

  27. Sheiner PA, Schwartz ME, Mor E, Schluger LK, Theise N, Kishikawa K, Kolesnikov V, Bodenheimer H, Emre S, Miller CM (1995) Severe or multiple rejection episodes are associated with early recurrence of hepatitis C after orthotopic liver transplantation. Hepatology 21:30–34 S0270913995000267 [pii]

    Article  PubMed  CAS  Google Scholar 

  28. Carrion JA, Navasa M, Garcia-Retortillo M, Garcia-Pagan JC, Crespo G, Bruguera M, Bosch J, Forns X (2007) Efficacy of antiviral therapy on hepatitis C recurrence after liver transplantation: a randomized controlled study. Gastroenterology 132:1746–1756. doi:10.1053/j.gastro.2007.03.041 S0016-5085(07)00565-3 [pii]

    Article  PubMed  CAS  Google Scholar 

  29. Russo MW, Firpi RJ, Nelson DR, Schoonhoven R, Shrestha R, Fried MW (2005) Early hepatic stellate cell activation is associated with advanced fibrosis after liver transplantation in recipients with hepatitis C. Liver Transpl 11:1235–1241. doi:10.1002/lt.20432

    Article  PubMed  Google Scholar 

  30. Burak KW, Kremers WK, Batts KP, Wiesner RH, Rosen CB, Razonable RR, Paya CV, Charlton MR (2002) Impact of cytomegalovirus infection, year of transplantation, and donor age on outcomes after liver transplantation for hepatitis C. Liver Transpl 8:362–369. doi:10.1053/jlts.2002.32282 S1527646502046816 [pii]

    Article  PubMed  Google Scholar 

  31. Duclos-Vallee JC, Feray C, Sebagh M, Teicher E, Roque-Afonso AM, Roche B, Azoulay D, Adam R, Bismuth H, Castaing D, Vittecoq D, Samuel D (2008) Survival and recurrence of hepatitis C after liver transplantation in patients coinfected with human immunodeficiency virus and hepatitis C virus. Hepatology 47:407–417. doi:10.1002/hep.21990

    Article  PubMed  CAS  Google Scholar 

  32. Sabharwal S, Delgado-Borrego A, Chung RT (2008) Extrahepatic hepatitis C virus after transplantation: diabetes and renal dysfunction. Liver Transpl 14(Suppl 2):S51–S57. doi:10.1002/lt.21613

    Article  PubMed  Google Scholar 

  33. Veldt BJ, Poterucha JJ, Watt KD, Wiesner RH, Hay JE, Rosen CB, Heimbach JK, Janssen HL, Charlton MR (2009) Insulin resistance, serum adipokines and risk of fibrosis progression in patients transplanted for hepatitis C. Am J Transplant 9(6):1406–1413. doi:10.1111/j.1600-6143.2009.02642.x (AJT2642 [pii])

    Article  PubMed  CAS  Google Scholar 

  34. Berenguer M, Royuela A, Zamora J (2007) Immunosuppression with calcineurin inhibitors with respect to the outcome of HCV recurrence after liver transplantation: results of a meta-analysis. Liver Transpl 13:21–29. doi:10.1002/lt.21035

    Article  PubMed  Google Scholar 

  35. Segev DL, Sozio SM, Shin EJ, Nazarian SM, Nathan H, Thuluvath PJ, Montgomery RA, Cameron AM, Maley WR (2008) Steroid avoidance in liver transplantation: meta-analysis and meta-regression of randomized trials. Liver Transpl 14:512–525. doi:10.1002/lt.21396

    Article  PubMed  Google Scholar 

  36. Firpi RJ, Zhu H, Morelli G, Abdelmalek MF, Soldevila-Pico C, Machicao VI, Cabrera R, Reed AI, Liu C, Nelson DR (2006) Cyclosporine suppresses hepatitis C virus in vitro and increases the chance of a sustained virological response after liver transplantation. Liver Transpl 12:51–57. doi:10.1002/lt.20532

    Article  PubMed  Google Scholar 

  37. Henry SD, Metselaar HJ, Lonsdale RC, Kok A, Haagmans BL, Tilanus HW, van der Laan LJ (2006) Mycophenolic acid inhibits hepatitis C virus replication and acts in synergy with cyclosporin A and interferon-alpha. Gastroenterology 131:1452–1462. doi:10.1053/j.gastro.2006.08.027 S0016-5085(06)01786-0 [pii]

    Article  PubMed  CAS  Google Scholar 

  38. Ghany MG, Strader DB, Thomas DL, Seeff LB (2009) Diagnosis, management, and treatment of hepatitis C: an update. Hepatology 49:1335–1374. doi:10.1002/hep.22759

    Article  PubMed  CAS  Google Scholar 

  39. McCaughan GW, Omata M, Amarapurkar D, Bowden S, Chow WC, Chutaputti A, Dore G, Gane E, Guan R, Hamid SS, Hardikar W, Hui CK, Jafri W, Jia JD, Lai MY, Wei L, Leung N, Piratvisuth T, Sarin S, Sollano J, Tateishi R (2007) Asian pacific association for the study of the liver consensus statements on the diagnosis, management and treatment of hepatitis C virus infection. J Gastroenterol Hepatol 22:615–633. doi:10.1111/j.1440-1746.2007.04883.x JGH4883 [pii]

    PubMed  CAS  Google Scholar 

  40. Mallet V, Gilgenkrantz H, Serpaggi J, Verkarre V, Vallet-Pichard A, Fontaine H, Pol S (2008) Brief communication: the relationship of regression of cirrhosis to outcome in chronic hepatitis C. Ann Intern Med 149:399–403 149/6/399 [pii]

    PubMed  Google Scholar 

  41. Poynard T, McHutchison J, Manns M, Trepo C, Lindsay K, Goodman Z, Ling MH, Albrecht J (2002) Impact of pegylated interferon alfa-2b and ribavirin on liver fibrosis in patients with chronic hepatitis C. Gastroenterology 122:1303–1313 S001650850234959X [pii]

    Article  PubMed  CAS  Google Scholar 

  42. Veldt BJ, Heathcote EJ, Wedemeyer H, Reichen J, Hofmann WP, Zeuzem S, Manns MP, Hansen BE, Schalm SW, Janssen HL (2007) Sustained virologic response and clinical outcomes in patients with chronic hepatitis C and advanced fibrosis. Ann Intern Med 147:677–684 147/10/677 [pii]

    PubMed  Google Scholar 

  43. Poynard T, Colombo M, Bruix J, Schiff E, Terg R, Flamm S, Moreno-Otero R, Carrilho F, Schmidt W, Berg T, McGarrity T, Heathcote EJ, Goncales F, Diago M, Craxi A, Silva M, Bedossa P, Mukhopadhyay P, Griffel L, Burroughs M, Brass C, Albrecht J (2009) Peginterferon alfa-2b and ribavirin: effective in patients with hepatitis C who failed interferon alfa/ribavirin therapy. Gastroenterology 136:1618–1628. doi:10.1053/j.gastro.2009.01.039 (e1612) S0016-5085(09)00102-4 [pii]

    Article  PubMed  CAS  Google Scholar 

  44. Di Bisceglie AM, Shiffman ML, Everson GT, Lindsay KL, Everhart JE, Wright EC, Lee WM, Lok AS, Bonkovsky HL, Morgan TR, Ghany MG, Morishima C, Snow KK, Dienstag JL (2008) Prolonged therapy of advanced chronic hepatitis C with low-dose peginterferon. N Engl J Med 359:2429–2441. doi:10.1056/NEJMoa0707615 359/23/2429 [pii]

    Article  PubMed  CAS  Google Scholar 

  45. Bruix J, Poynard T, Colombo M, Schiff E, Reichen J, Burak K, Heathcote EJL, Berg T, Poo-Ramirez JL, Mello CB, Guenther R, Niederau C, Terg R, Bopari N, Harvey J, Griffel LH, Burroughs M, Brass CA, Albrecht JK (2009) PegIntron maintenance therapy in cirrhotic (METAVIR F4) HCV patients, who failed to respond to interferon/ribavirin (IR) therapy: final results of the EPIC3 cirrhosis maintenance trial—44th Annual Meeting of the European-Association-for-the-Study-of-the-Liver, APR 22–26, 2009; Copenhagen, DENMARK. J Hepatol 50:49

    Article  CAS  Google Scholar 

  46. Afdhal NH, Levine R, Brown R, Freilich B, O’Brien M, Brass C (2008) Colchicine versus PEG-interferon alfa 2b long term therapy: results of the 4 year copilot trial. J Hepatol 48:3

    Article  CAS  Google Scholar 

  47. Hofmann WP, Zeuzem S (2009) Hepatitis C new therapeutic strategies needed for advanced disease. Nat Rev Gastroenterol Hepatol 6:325–327. doi:10.1038/nrgastro.2009.63

    Article  PubMed  CAS  Google Scholar 

  48. Freeman RB (2005) MELD: the holy grail of organ allocation? J Hepatol 42:16–20. doi:10.1016/j.jhep.2004.11.002 S0168-8278(04)00516-1 [pii]

    Article  PubMed  Google Scholar 

  49. Everson GT (2003) Treatment of patients with hepatitis C virus on the waiting list. Liver Transpl 9:S90–S94. doi:10.1053/jlts.2003.50247 S1527646503504853 [pii]

    Article  PubMed  Google Scholar 

  50. Forns X, Navasa M, Rodes J (2004) Treatment of HCV infection in patients with advanced cirrhosis. Hepatology 40:498. doi:10.1002/hep.20345

    Article  PubMed  Google Scholar 

  51. Crippin JS, McCashland T, Terrault N, Sheiner P, Charlton MR (2002) A pilot study of the tolerability and efficacy of antiviral therapy in hepatitis C virus-infected patients awaiting liver transplantation. Liver Transpl 8:350–355. doi:10.1053/jlts.2002.31748 S152764650275140X [pii]

    Article  PubMed  Google Scholar 

  52. 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:S1–S9. doi:10.1053/jlts.2003.50268 S1527646503504713 [pii]

    Article  PubMed  Google Scholar 

  53. Smallwood GA, Devine R, Fasola C, Stieber AC, Heffron TG (2008) Does interferon use prior to liver transplant influence hepatitis C outcomes following transplantation? Transplantation 86:1795–1798. doi:10.1097/TP.0b013e3181914188 00007890-200812270-00031 [pii]

    Article  PubMed  CAS  Google Scholar 

  54. Terrault NA, Zhou S, Combs C, Hahn JA, Lake JR, Roberts JP, Ascher NL, Wright TL (1996) Prophylaxis in liver transplant recipients using a fixed dosing schedule of hepatitis B immunoglobulin. Hepatology 24:1327–1333. doi:10.1002/hep.510240601 S0270913996005058 [pii]

    Article  PubMed  CAS  Google Scholar 

  55. Krawczynski K, Alter MJ, Tankersley DL, Beach M, Robertson BH, Lambert S, Kuo G, Spelbring JE, Meeks E, Sinha S, Carson DA (1996) Effect of immune globulin on the prevention of experimental hepatitis C virus infection. J Infect Dis 173:822–828

    PubMed  CAS  Google Scholar 

  56. Yu MY, Bartosch B, Zhang P, Guo ZP, Renzi PM, Shen LM, Granier C, Feinstone SM, Cosset FL, Purcell RH (2004) Neutralizing antibodies to hepatitis C virus (HCV) in immune globulins derived from anti-HCV-positive plasma. Proc Natl Acad Sci USA 101:7705–7710. doi:10.1073/pnas.0402458101 0402458101 [pii]

    Article  PubMed  CAS  Google Scholar 

  57. Santantonio T, Wiegand J, Gerlach JT (2008) Acute hepatitis C: current status and remaining challenges. J Hepatol 49:625–633. doi:10.1016/j.jhep.2008.07.005 S0168-8278(08)00434-0 [pii]

    Article  PubMed  CAS  Google Scholar 

  58. Castells L, Esteban JI, Bilbao I, Vargas V, Allende H, Ribera E, Piron M, Sauleda S, Len O, Pahissa A, Esteban R, Guardia J, Margarit C (2006) Early antiviral treatment of hepatitis C virus recurrence after liver transplantation in HIV-infected patients. Antivir Ther 11:1061–1070

    PubMed  CAS  Google Scholar 

  59. Zimmermann T, Bocher WO, Biesterfeld S, Zimmermann A, Kanzler S, Greif-Higer G, Barreiros AP, Sprinzl MF, Worns MA, Lohse AW, Monch C, Otto G, Galle PR, Schuchmann M (2007) Efficacy of an escalating dose regimen of pegylated interferon alpha-2a plus ribavirin in the early phase of HCV reinfection after liver transplantation. Transpl Int 20:583–590. doi:10.1111/j.1432-2277.2007.00481.x TRI481 [pii]

    Article  PubMed  CAS  Google Scholar 

  60. Mazzaferro V, Tagger A, Schiavo M, Regalia E, Pulvirenti A, Ribero ML, Coppa J, Romito R, Burgoa L, Zucchini N, Urbanek T, Bonino F (2001) Prevention of recurrent hepatitis C after liver transplantation with early interferon and ribavirin treatment. Transplant Proc 33:1355–1357 S0041-1345(00)02508-2 [pii]

    Article  PubMed  CAS  Google Scholar 

  61. Shergill AK, Khalili M, Straley S, Bollinger K, Roberts JP, Ascher NA, Terrault NA (2005) Applicability, tolerability and efficacy of preemptive antiviral therapy in hepatitis C-infected patients undergoing liver transplantation. Am J Transplant 5:118–124. doi:10.1111/j.1600-6143.2004.00648.x AJT648 [pii]

    Article  PubMed  Google Scholar 

  62. Sugawara Y, Makuuchi M, Matsui Y, Kishi Y, Akamatsu N, Kaneko J, Kokudo N (2004) Preemptive therapy for hepatitis C virus after living-donor liver transplantation. Transplantation 78:1308–1311 00007890-200411150-00011 [pii]

    Article  PubMed  CAS  Google Scholar 

  63. Kuo A, Tan V, Lan B, Khalili M, Feng S, Roberts JP, Terrault NA (2008) Long-term histological effects of preemptive antiviral therapy in liver transplant recipients with hepatitis C virus infection. Liver Transpl 14:1491–1497. doi:10.1002/lt.21548

    Article  PubMed  Google Scholar 

  64. Sheiner PA, Boros P, Klion FM, Thung SN, Schluger LK, Lau JY, Mor E, Bodian C, Guy SR, Schwartz ME, Emre S, Bodenheimer HC Jr, Miller CM (1998) The efficacy of prophylactic interferon alfa-2b in preventing recurrent hepatitis C after liver transplantation. Hepatology 28:831–838. doi:10.1002/hep.510280334 S0270913998003826 [pii]

    Article  PubMed  CAS  Google Scholar 

  65. Singh N, Gayowski T, Wannstedt CF, Shakil AO, Wagener MM, Fung JJ, Marino IR (1998) Interferon-alpha for prophylaxis of recurrent viral hepatitis C in liver transplant recipients: a prospective, randomized, controlled trial. Transplantation 65:82–86

    Article  PubMed  CAS  Google Scholar 

  66. Cattral MS, Hemming AW, Wanless IR, Al Ashgar H, Krajden M, Lilly L, Greig PD, Levy GA (1999) Outcome of long-term ribavirin therapy for recurrent hepatitis C after liver transplantation. Transplantation 67:1277–1280

    Article  PubMed  CAS  Google Scholar 

  67. Feray C, Samuel D, Gigou M, Paradis V, David MF, Lemonnier C, Reynes M, Bismuth H (1995) An open trial of interferon alfa recombinant for hepatitis C after liver transplantation: antiviral effects and risk of rejection. Hepatology 22:1084–1089 S0270913995003478 [pii]

    Article  PubMed  CAS  Google Scholar 

  68. Gane EJ, Lo SK, Riordan SM, Portmann BC, Lau JY, Naoumov NV, Williams R (1998) A randomized study comparing ribavirin and interferon alfa monotherapy for hepatitis C recurrence after liver transplantation. Hepatology 27:1403–1407. doi:10.1002/hep.510270530 S0270913998002055 [pii]

    Article  PubMed  CAS  Google Scholar 

  69. Gane EJ, Tibbs CJ, Ramage JK, Portmann BC, Williams R (1995) Ribavirin therapy for hepatitis C infection following liver transplantation. Transpl Int 8:61–64

    Article  PubMed  CAS  Google Scholar 

  70. Wright TL, Combs C, Kim M, Ferrell L, Bacchetti P, Ascher N, Roberts J, Wilber J, Sheridan P, Urdea M (1994) Interferon-alpha therapy for hepatitis C virus infection after liver transplantation. Hepatology 20:773–779 S0270913994003009 [pii]

    Article  PubMed  CAS  Google Scholar 

  71. Firpi RJ, Abdelmalek MF, Soldevila-Pico C, Reed A, Hemming A, Howard R, Van Der Werf W, Lauwers G, Liu C, Crawford JM, Davis GL, Nelson DR (2002) Combination of interferon alfa-2b and ribavirin in liver transplant recipients with histological recurrent hepatitis C. Liver Transpl 8:1000–1006. doi:10.1053/jlts.2002.34968 S1527646502001466 [pii]

    Article  PubMed  Google Scholar 

  72. Lavezzo B, Franchello A, Smedile A, David E, Barbui A, Torrani M, Ottobrelli A, Zamboni F, Fadda M, Bobbio A, Salizzoni M, Rizzetto M (2002) Treatment of recurrent hepatitis C in liver transplants: efficacy of a six versus a twelve month course of interferon alfa 2b with ribavirin. J Hepatol 37:247–252 S0168827802001095 [pii]

    Article  PubMed  CAS  Google Scholar 

  73. Samuel D, Bizollon T, Feray C, Roche B, Ahmed SN, Lemonnier C, Cohard M, Reynes M, Chevallier M, Ducerf C, Baulieux J, Geffner M, Albrecht JK, Bismuth H, Trepo C (2003) Interferon-alpha 2b plus ribavirin in patients with chronic hepatitis C after liver transplantation: a randomized study. Gastroenterology 124:642–650. doi:10.1053/gast.2003.50095 S0016508502159737 [pii]

    Article  PubMed  CAS  Google Scholar 

  74. Berenguer M, Palau A, Fernandez A, Benlloch S, Aguilera V, Prieto M, Rayon JM, Berenguer J (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. doi:10.1002/lt.20737

    Article  PubMed  Google Scholar 

  75. 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. doi:10.1016/j.jhep.2003.12.015 S0168827804000030 [pii]

    Article  PubMed  CAS  Google Scholar 

  76. Neff GW, Montalbano M, O’Brien CB, Nishida S, Safdar K, Bejarano PA, Khaled AS, Ruiz P, Slapak-Green G, Lee M, Nery J, De Medina M, Tzakis A, Schiff ER (2004) Treatment of established recurrent hepatitis C in liver-transplant recipients with pegylated interferon-alfa-2b and ribavirin therapy. Transplantation 78:1303–1307 00007890-200411150-00010 [pii]

    Article  PubMed  CAS  Google Scholar 

  77. Oton E, Barcena R, Moreno-Planas JM, Cuervas-Mons V, Moreno-Zamora A, Barrios C, Garcia-Garzon S, Moreno A, Boullosa-Grana E, Rubio-Gonzalez EE, Garcia-Gonzalez M, Blesa C, Mateos ML (2006) Hepatitis C recurrence after liver transplantation: viral and histologic response to full-dose PEG-interferon and ribavirin. Am J Transplant 6:2348–2355. doi:10.1111/j.1600-6143.2006.01470.x AJT1470 [pii]

    Article  PubMed  CAS  Google Scholar 

  78. Roche B, Sebagh M, Canfora ML, Antonini T, Roque-Afonso AM, Delvart V, Saliba F, Duclos-Vallee JC, Castaing D, Samuel D (2008) Hepatitis C virus therapy in liver transplant recipients: response predictors, effect on fibrosis progression, and importance of the initial stage of fibrosis. Liver Transpl 14:1766–1777. doi:10.1002/lt.21635

    Article  PubMed  Google Scholar 

  79. Sharma P, Marrero JA, Fontana RJ, Greenson JK, Conjeevaram H, Su GL, Askari F, Sullivan P, Lok AS (2007) Sustained virologic response to therapy of recurrent hepatitis C after liver transplantation is related to early virologic response and dose adherence. Liver Transpl 13:1100–1108. doi:10.1002/lt.21121

    Article  PubMed  Google Scholar 

  80. Wang CS, Ko HH, Yoshida EM, Marra CA, Richardson K (2006) Interferon-based combination anti-viral therapy for hepatitis C virus after liver transplantation: a review and quantitative analysis. Am J Transplant 6:1586–1599. doi:10.1111/j.1600-6143.2006.01362.x AJT1362 [pii]

    Article  PubMed  CAS  Google Scholar 

  81. Berenguer M (2008) Systematic review of the treatment of established recurrent hepatitis C with pegylated interferon in combination with ribavirin. J Hepatol 49:274–287. doi:10.1016/j.jhep.2008.05.002 S0168-8278(08)00309-7 [pii]

    Article  PubMed  CAS  Google Scholar 

  82. Lodato F, Berardi S, Gramenzi A, Mazzella G, Lenzi M, Morelli MC, Tame MR, Piscaglia F, Andreone P, Ballardini G, Bernardi M, Bianchi FB, Biselli M, Bolondi L, Cescon M, Colecchia A, D’Errico A, Del Gaudio M, Ercolani G, Grazi GL, Grigioni W, Lorenzini S, Pinna AD, Ravaioli M, Roda E, Sama C, Vivarelli M (2008) Clinical trial: peg-interferon alfa-2b and ribavirin for the treatment of genotype-1 hepatitis C recurrence after liver transplantation. Aliment Pharmacol Ther 28:450–457. doi:10.1111/j.1365-2036.2008.03761.x APT3761 [pii]

    Article  PubMed  CAS  Google Scholar 

  83. Shiffman ML, Salvatore J, Hubbard S, Price A, Sterling RK, Stravitz RT, Luketic VA, Sanyal AJ (2007) Treatment of chronic hepatitis C virus genotype 1 with peginterferon, ribavirin, and epoetin alpha. Hepatology 46:371–379. doi:10.1002/hep.21712

    Article  PubMed  CAS  Google Scholar 

  84. Berardi S, Lodato F, Gramenzi A, D’Errico A, Lenzi M, Bontadini A, Morelli MC, Tame MR, Piscaglia F, Biselli M, Sama C, Mazzella G, Pinna AD, Grazi G, Bernardi M, Andreone P (2007) High incidence of allograft dysfunction in liver transplanted patients treated with pegylated-interferon alpha-2b and ribavirin for hepatitis C recurrence: possible de novo autoimmune hepatitis? Gut 56:237–242. doi:10.1136/gut.2006.092064 gut.2006.092064 [pii]

    Article  PubMed  CAS  Google Scholar 

  85. Cholongitas E, Samonakis D, Patch D, Senzolo M, Burroughs AK, Quaglia A, Dhillon A (2006) Induction of autoimmune hepatitis by pegylated interferon in a liver transplant patient with recurrent hepatitis C virus. Transplantation 81:488–490. doi:10.1097/01.tp.0000196716.07188.c4 00007890-200602150-00033 [pii]

    Article  PubMed  Google Scholar 

  86. Kontorinis N, Agarwal K, Elhajj N, Fiel MI, Schiano TD (2006) Pegylated interferon-induced immune-mediated hepatitis post-liver transplantation. Liver Transpl 12:827–830. doi:10.1002/lt.20706

    Article  PubMed  Google Scholar 

  87. Berenguer M, Palau A, Aguilera V, Rayon JM, Juan FS, Prieto M (2008) Clinical benefits of antiviral therapy in patients with recurrent hepatitis C following liver transplantation. Am J Transplant 8:679–687. doi:10.1111/j.1600-6143.2007.02126.x AJT2126 [pii]

    Article  PubMed  CAS  Google Scholar 

  88. Gurusamy KS, Osmani B, Xirouchakis E, Burroughs AK, Davidson BR (2009) Antiviral therapy for recurrent liver graft infection with hepatitis C virus. Cochrane Database Syst Rev 21(1):CD006803. doi:10.1002/14651858.CD006803.pub2

    Google Scholar 

  89. Picciotto FP, Tritto G, Lanza AG, Addario L, De Luca M, Di Costanzo GG, Lampasi F, Tartaglione MT, Marsilia GM, Calise F, Cuomo O, Ascione A (2007) Sustained virological response to antiviral therapy reduces mortality in HCV reinfection after liver transplantation. J Hepatol 46:459–465. doi:10.1016/j.jhep.2006.10.017 S0168-8278(06)00622-2 [pii]

    Article  PubMed  CAS  Google Scholar 

  90. Saab S, Ly D, Han SB, Lin RK, Rojter SE, Ghobrial RM, Busuttil RW (2002) Is it cost-effective to treat recurrent hepatitis C infection in orthotopic liver transplantation patients? Liver Transpl 8:449–457. doi:10.1053/jlts.2002.32717 S152764650224558X [pii]

    Article  PubMed  Google Scholar 

  91. Thomas RM, Brems JJ, Guzman-Hartman G, Yong S, Cavaliere P, Van Thiel DH (2003) Infection with chronic hepatitis C virus and liver transplantation: a role for interferon therapy before transplantation. Liver Transpl 9:905–915. doi:10.1053/jlts.2003.50166 S152764650350377X [pii]

    Article  PubMed  Google Scholar 

  92. Iacobellis A, Siciliano M, Perri F, Annicchiarico BE, Leandro G, Caruso N, Accadia L, Bombardieri G, Andriulli A (2007) Peginterferon alfa-2b and ribavirin in patients with hepatitis C virus and decompensated cirrhosis: a controlled study. J Hepatol 46:206–212. doi:10.1016/j.jhep.2006.08.020 S0168-8278(06)00548-4 [pii]

    Article  PubMed  CAS  Google Scholar 

  93. Angelico M, Petrolati A, Lionetti R, Lenci I, Burra P, Donato MF, Merli M, Strazzabosco M, Tisone G (2007) A randomized study on Peg-interferon alfa-2a with or without ribavirin in liver transplant recipients with recurrent hepatitis C. J Hepatol 46:1009–1017. doi:10.1016/j.jhep.2006.12.017 S0168-8278(07)00059-1 [pii]

    Article  PubMed  CAS  Google Scholar 

  94. Castells L, Vargas V, Allende H, Bilbao I, Luis Lazaro J, Margarit C, Esteban R, Guardia J (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. doi:10.1016/j.jhep.2005.02.015 S0168-8278(05)00209-6 [pii]

    Article  PubMed  CAS  Google Scholar 

  95. Fernandez I, Meneu JC, Colina F, Garcia I, Munoz R, Castellano G, Fuertes A, Abradelo M, Lumbreras C, Moreno E, Solis-Herruzo JA (2006) Clinical and histological efficacy of pegylated interferon and ribavirin therapy of recurrent hepatitis C after liver transplantation. Liver Transpl 12:1805–1812. doi:10.1002/lt.20883

    Article  PubMed  Google Scholar 

  96. Mukherjee S, Lyden E (2006) Impact of pegylated interferon alfa-2a and ribavirin on hepatic fibrosis in liver transplant patients with recurrent hepatitis C: an open-label series. Hepatogastroenterology 53:561–565

    PubMed  CAS  Google Scholar 

  97. Mukherjee S, Lyden E (2006) Impact of pegylated interferon alpha-2B and ribavirin on hepatic fibrosis in liver transplant patients with recurrent hepatitis C: an open-label series. Liver Int 26:529–535. doi:10.1111/j.1478-3231.2006.01261.x LIV1261 [pii]

    Article  PubMed  CAS  Google Scholar 

  98. Neumann U, Puhl G, Bahra M, Berg T, Langrehr JM, Neuhaus R, Neuhaus P (2006) Treatment of patients with recurrent hepatitis C after liver transplantation with peginterferon alfa-2B plus ribavirin. Transplantation 82:43–47. doi:10.1097/01.tp.0000225827.18034.be 00007890-200607150-00008 [pii]

    Article  PubMed  CAS  Google Scholar 

  99. Rodriguez-Luna H, Khatib A, Sharma P, De Petris G, Williams JW, Ortiz J, Hansen K, Mulligan D, Moss A, Douglas DD, Balan V, Rakela J, Vargas HE (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. doi:10.1097/01.TP.0000100481.14514.BB

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Wolf Peter Hofmann.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Peveling-Oberhag, J., Zeuzem, S. & Hofmann, W.P. Antiviral therapy of chronic hepatitis C in patients with advanced liver disease and after liver transplantation. Med Microbiol Immunol 199, 1–10 (2010). https://doi.org/10.1007/s00430-009-0131-8

Download citation

  • Received:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00430-009-0131-8

Keywords

Navigation