Skip to main content
SpringerLink
Log in

Intravenous Interferon Administered During Liver Transplantation Is Not Effective in Preventing Hepatitis C Reinfection

  • Original Article
  • Published:
Digestive Diseases and Sciences Aims and scope Submit manuscript

Abstract

Background

Post-transplant hepatitis C is a major challenge after liver transplantation (LT). Antiviral therapy is associated with lower efficacy in the post-transplant setting.

Aims

The purpose of this study was to determine the safety and effect of intravenous interferon (IFN) during the anhepatic phase of LT on hepatitis C viral load.

Methods

Fifteen consecutive subjects undergoing liver transplant for hepatitis C cirrhosis were enrolled in the study, ten of which received study drug and five subjects served as controls. Cases received weight-based ribavirin and subcutaneous IFN at time of incision followed by intravenous IFN at the start of the anhepatic phase. Adverse events and viral levels were recorded. Repeated measures ANOVA was employed to test for differences over time, between the groups, and time by group interaction.

Results

All subjects had genotype 1 virus. Hepatitis C viral load was lower at week 4 in cases compared to controls (769,004 ± 924,082 IU/ml and 2,329,896 ± 3,731,749 IU/ml, respectively), but did not reach statistical significance (p = 0.50). Three subjects developed adverse events related to IFN including pulmonary edema, rejection, and neutropenia.

Conclusions

Intravenous IFN administered during the anhepatic phase of liver transplant did not prevent graft reinfection and was associated with manageable adverse events. This regimen could be further studied if direct acting antiviral agents alone are insufficient for treating post-transplant hepatitis C.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

Abbreviations

TAC:

Tacrolimus

ANC:

Absolute neutrophil count

IFN:

Interferon

FCH:

Fibrosing cholestatic hepatitis C

RBV:

Ribavirin

SVR:

Sustained virologic response

LT:

Liver transplantation

NS:

Not significant

MELD:

Model for end stage liver disease

IL:

Interleukin

HCV:

Hepatitis C virus

ALT:

Alanine aminotransferase

References

  1. Alonso O, Loinaz C, Abradelo M, et al. Changes in the incidence and severity of recurrent hepatitis C after liver transplantation over 1990–1999. Transplant Proc. 2003;35:1836–1837.

    Article  PubMed  CAS  Google Scholar 

  2. Sanchez-Fueyo A, Restrepo JC, Quintó L, et al. Impact of the recurrence of hepatitis C virus infection after liver transplantation on the long-term viability of the graft. Transplantation. 2002;73:56–63.

    Article  PubMed  Google Scholar 

  3. Prieto M, Berenguer M, Rayón J, 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 

  4. Berenguer M, Lopez F, Wright T. Hepatitis C and liver transplantation. J Hepatol. 2001;35:666–678.

    Article  PubMed  CAS  Google Scholar 

  5. Berenguer M, Crippin J, Gish R, Bass N, et al. A model to predict severe HCV related disease following liver transplantation. Hepatology. 2003;38:34–41.

    Article  PubMed  Google Scholar 

  6. Berenguer M, Prieto M, San-Juan F, Rayon J. Contribution of donor age to the recent decrease in patient survival among HCV infected liver transplant recipients. Hepatology. 2002;36:202–210.

    Article  PubMed  Google Scholar 

  7. Garcia-Retortillo M, Forns X, Feliu A, et al. Hepatitis C virus kinetics during and immediately after liver transplantation. Hepatology. 2002;35:680–687.

    Article  PubMed  Google Scholar 

  8. Testa G, Crippen JS, Netto GJ, et al. Liver transplantation for hepatitis C: recurrence and disease progression in 300 patients. Liver Transpl. 2000;6:553–561.

    Article  PubMed  CAS  Google Scholar 

  9. Berenguer M, Ferrell L, Watson J, et al. HCV related fibrosis progression after liver transplantation: increase in recent years. J Hepatol. 2000;32:673–684.

    Article  PubMed  CAS  Google Scholar 

  10. Rosen HR, Gretch DR, Oehlke M, et al. Timing and severity of hepatitis C recurrence after liver transplantation as predictors of long term allograft injury. Transplantation. 1998;65:1178–1182.

    Article  PubMed  CAS  Google Scholar 

  11. Forman LM, Lewis JD, Berlin JA, Feldman HI, Lucey MR. The association between hepatitis C infection and survival after orthotopic liver transplantation. Gastroenterology. 2002;122:889–896.

    Article  PubMed  Google Scholar 

  12. Feray C, Gigou M, Samuel D, et al. Influence of the genotypes of hepatitis C virus on the severity of recurrent liver disease after liver transplantation. Gastroenterology. 1995;108:1088–1096.

    Article  PubMed  CAS  Google Scholar 

  13. Charlton M, Seaberg E. Impact of immunosuppression and acute rejection on recurrence of hepatitis C: results of the National Institute of Diabetes and Digestive and Kidney Disease Liver Transplantation Database. Liver Transpl Surg. 1999;5:S107–S114.

    Article  PubMed  CAS  Google Scholar 

  14. Narang TK, Ahrens W, Russo MW. Post-liver transplant cholestatic hepatitis C. A systematic review of clinical and pathological findings and application of consensus criteria. Liver Transpl. 2010;16:1228–1235.

    Article  PubMed  Google Scholar 

  15. Chalasani N, Manzarbeitia C, Ferenci P, et al. Pegasys Transplant Study Group. Peginterferon alfa-2a for hepatitis C after liver transplantation: two randomized, controlled trials. Hepatology. 2005;41:289–298.

    Article  PubMed  CAS  Google Scholar 

  16. Kwo PY, Saxena R, Cummings OW, Tectar J. Intravenous interferon during the anhepatic phase of liver retransplantation and prevention of recurrence of cholestatic hepatitis C virus. Liver Transpl. 2007;13:1710–1713.

    Article  PubMed  Google Scholar 

  17. Levitsky J, Fiel MI, Norvell JP, et al. Risk for immune-mediated graft dysfunction in liver transplant recipients with recurrent HCV infection treated with pegylated interferon. Gastroenterology. 2012;142:1132–1139.

    Article  PubMed  CAS  Google Scholar 

  18. Weston SJ, Leistikow RL, Reddy KR, et al. Reconstitution of hepatitis C virus-specific T-cell mediated immunity after liver transplantation. Hepatology. 2005;41:72–81.

    Article  PubMed  Google Scholar 

  19. Powers KA, Ribeiro RM, Patel K, et al. Kinetics of hepatitis C virus reinfection after liver transplantation. Liver Transpl. 2006;12:207–216.

    Article  PubMed  Google Scholar 

  20. Schiano TD, Gutierrez JA, Walewski JL, et al. Accelerated hepatitis C virus kinetics but similar survival rates in recipients of liver grafts from living versus deceased donors. Hepatology. 2005;42:1420–1428.

    Article  PubMed  Google Scholar 

  21. Berenguer M, Aguilera V, Prieto M, et al. Worse recent efficacy of antiviral therapy in liver transplant recipients with recurrent hepatitis C: impact of donor age and baseline cirrhosis. Liver Transpl. 2009;15:738–746.

    Article  PubMed  Google Scholar 

  22. Neumann AU, Lam NP, Dahari H, et al. Hepatitis C viral dynamics in vivo and the antiviral efficacy of interferon-alpha therapy. Science. 1998;282:103–107.

    Article  PubMed  CAS  Google Scholar 

  23. Everson GT, Terrault NA, Lok AS, et al. A randomized controlled trial of pretransplant antiviral therapy to prevent recurrence of hepatitis C after liver transplantation. Hepatology; 2013;57:1752–1762. doi:10.1002/hep.25976.

    Google Scholar 

  24. Garg V, van Heeswijk R, Lee J, Alves K, Nadkarni P, Luo X. Effect of telaprevir on the pharmacokinetics of cyclosporine and tacrolimus. Hepatology. 2011;54:20–27.

    Article  PubMed  CAS  Google Scholar 

  25. Bitetto D, Fabris C, Falleti E, et al. Recipient interleukin-28B polymorphism and acute cellular rejection. Transplantation. 2012;93:1038–1044.

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

We would like to thank Gale Groseclose, RN for her tireless efforts on this study. This work was supported by an American College of Gastroenterology Clinical Research Award to Tarun Narang and a Clinical Research Award from Carolinas Medical Center.

Conflict of interest

None.

Author information

Authors and Affiliations

  1. Transplant Center, Department of Medicine, Carolinas Medical Center, 1000 Blythe Blvd, 3rd Floor Annex Building, Charlotte, NC, 28203, USA

    Mark W. Russo, Tarun Narang, Preston P. Purdum, John S. Hanson & Herbert Bonkovsky

  2. Department of Surgery, Carolinas Medical Center, Charlotte, NC, USA

    Lon Eskind, Daniel Hayes & Vincent Casingal

  3. Department of Pathology, Carolinas Medical Center, Charlotte, NC, USA

    Will Ahrens

  4. Cannon Research, Carolinas Medical Center, Charlotte, NC, USA

    James Norton & Herbert Bonkovsky

Authors
  1. Mark W. Russo
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Tarun Narang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Lon Eskind
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Daniel Hayes
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Vincent Casingal
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Preston P. Purdum
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. John S. Hanson
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Will Ahrens
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. James Norton
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Herbert Bonkovsky
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Mark W. Russo.

Additional information

ClinicalTrials.gov Identifier: NCT01192698.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Russo, M.W., Narang, T., Eskind, L. et al. Intravenous Interferon Administered During Liver Transplantation Is Not Effective in Preventing Hepatitis C Reinfection. Dig Dis Sci 58, 3010–3016 (2013). https://doi.org/10.1007/s10620-013-2749-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10620-013-2749-z

Keywords

Search

Navigation