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Impact of Anti-Thymocyte Globulin During Immunosuppression Induction in Patients with Hepatitis C After Liver Transplantation

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Abstract

Background

Induction immunosuppression with anti-thymocyte globulin (ATG) provides potential benefits after liver transplantation (LT). However, its use in patients with LT and hepatitis C (HCV) is controversial.

Aim

To evaluate the 1- and 2-year patient survival and HCV recurrence rate in patients receiving ATG during the induction phase of immunosuppression (IPI) after LT.

Methods

A total of 49 patients undergoing their first LT for HCV were randomized to receive ATG during IPI. Patient survival and HCV recurrence were determined at 1 and 2 years. The frequency of acute cellular rejection (ACR), infections, and neoplasms was also evaluated.

Results

Twenty-six patients were randomized to receive ATG (Arm-1) and 23 to standard induction therapy (Arm-2). Those given ATG had lower HCV recurrence (26.9 vs 73.9 %, p = 0.001). The 1- and 2-year patient survival rates were similar for both arms (p = 0.33). Infections occurred in 46.1 % subjects in Arm-1 and 34.7 % in Arm-2 (p = 0.562). There was a greater proportion of fungal infections in Arm-1 (19.2 vs 0 %, p = 0.032).

Conclusions

ATG during the IPI was associated with lower frequency of recurrence of HCV in patients undergoing LT. This, however, did not affect the 1- and 2-year survival and the frequency of ACR, infections, or neoplasms.

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References

  1. Te HS, Jensen DM. Epidemiology of hepatitis B and C viruses: a global overview. Clin Liver Dis. 2010;14:1–21.

    Article  PubMed  Google Scholar 

  2. Trotter JF. Hot-topic debate on hepatitis C virus: the type of immunosuppression matters. Liver Transpl. 2011;17:S20–S23.

    Article  PubMed  Google Scholar 

  3. Rosen HR. Clinical practice. Chronic hepatitis C infection. N Engl J Med. 2011;364:2429–2438.

    Article  PubMed  CAS  Google Scholar 

  4. 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;13:122–129.

    Article  PubMed  PubMed Central  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  6. Berenguer M, Prieto M, Rayon JM, et al. Natural history of clinically compensated hepatitis C virus-related graft cirrhosis after liver transplantation. Hepatology. 2000;32:852–858.

    Article  PubMed  CAS  Google Scholar 

  7. Ciesek S, Wedemeyer H. Immunosuppression, liver injury and post-transplant HCV recurrence. J Viral Hepat. 2012;19:1–8.

    Article  PubMed  CAS  Google Scholar 

  8. Kamar N, Ribes D, Sandres-Saune K, et al. Efficacy and safety of induction therapy with rabbit antithymocyte globulins in liver transplantation for hepatitis C. Transplant Proc. 2004;36:2757–2761.

    Article  PubMed  CAS  Google Scholar 

  9. Uemura T, Schaefer E, Hollenbeak CS, Khan A, Kadry Z. Outcome of induction immunosuppression for liver transplantation comparing anti-thymocyte globulin, daclizumab, and corticosteroid. Transpl Int. 2011;24:640–650.

    Article  PubMed  CAS  Google Scholar 

  10. Soliman T, Hetz H, Burghuber C, et al. Short-term induction therapy with anti-thymocyte globulin and delayed use of calcineurin inhibitors in orthotopic liver transplantation. Liver Transpl. 2007;13:1039–1044.

    Article  PubMed  Google Scholar 

  11. Neuberger JM, Mamelok RD, Neuhaus P, et al. Delayed introduction of reduced-dose tacrolimus, and renal function in liver transplantation: the ‘ReSpECT’ study. Am J Transplant. 2009;9:327–336.

    Article  PubMed  CAS  Google Scholar 

  12. 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;75:1396–1399.

    Article  PubMed  CAS  Google Scholar 

  13. Opelz G, Naujokat C, Daniel V, Terness P, Dohler B. Disassociation between risk of graft loss and risk of non-Hodgkin lymphoma with induction agents in renal transplant recipients. Transplantation. 2006;81:1227–1233.

    Article  PubMed  CAS  Google Scholar 

  14. Bajjoka I, Hsaiky L, Brown K, Abouljoud M. Preserving renal function in liver transplant recipients with rabbit anti-thymocyte globulin and delayed initiation of calcineurin inhibitors. Liver Transpl. 2008;14:66–72.

    Article  PubMed  Google Scholar 

  15. Nair S, Loss GE, Cohen AJ, Eason JD. Induction with rabbit antithymocyte globulin versus induction with corticosteroids in liver transplantation: impact on recurrent hepatitis C virus infection. Transplantation. 2006;81:620–622.

    Article  PubMed  CAS  Google Scholar 

  16. De Ruvo N, Cucchetti A, Lauro A, et al. Preliminary results of a “prope” tolerogenic regimen with thymoglobulin pretreatment and hepatitis C virus recurrence in liver transplantation. Transplantation. 2005;80:8–12.

    Article  PubMed  Google Scholar 

  17. Kamar N, Borde JS, Sandres-Saune K, et al. Induction therapy with either anti-CD25 monoclonal antibodies or rabbit antithymocyte globulins in liver transplantation for hepatitis C. Clin Transplant. 2005;19:83–89.

    Article  PubMed  Google Scholar 

  18. Moonka DK, Kim D, Kapke A, Brown KA, Yoshida A. The influence of induction therapy on graft and patient survival in patients with and without hepatitis C after liver transplantation. Am J Transplant. 2010;10:590–601.

    Article  PubMed  CAS  Google Scholar 

  19. Schmitt TM, Phillips M, Sawyer RG, et al. Anti-thymocyte globulin for the treatment of acute cellular rejection following liver transplantation. Dig Dis Sci. 2010;55:3224–3234.

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  Google Scholar 

  21. Iacob S, Cicinnati VR, Hilgard P, et al. Predictors of graft and patient survival in hepatitis C virus (HCV) recipients: model to predict HCV cirrhosis after liver transplantation. Transplantation. 2007;84:56–63.

    Article  PubMed  Google Scholar 

  22. Belli LS, Burroughs AK, Burra P, et al. Liver transplantation for HCV cirrhosis: improved survival in recent years and increased severity of recurrent disease in female recipients: results of a long term retrospective study. Liver Transpl. 2007;13:733–740.

    Article  PubMed  Google Scholar 

  23. Batts KP, Ludwig J. Chronic hepatitis. An update on terminology and reporting. Am J Surg Pathol. 1995;19:1409–1417.

    Article  PubMed  CAS  Google Scholar 

  24. Ghany MG, Strader DB, Thomas DL, Seeff LB. Diagnosis, management, and treatment of hepatitis C: an update. Hepatology. 2009;49:1335–1374.

    Article  PubMed  CAS  Google Scholar 

  25. Demetris A, Batts K, Dhillon A, Wight D, Williams J, Yamabe H. Banff schema for grading liver allograft rejection: an international consensus document. Hepatology. 1997;25:658–663.

  26. Cisneros E, Banos I, Citores MJ, et al. Increased risk of severe hepatitis C virus recurrence after liver transplantation in patients with a T allele of IL28B rs12979860. Transplantation. 2012;94:275–280.

    Article  PubMed  CAS  Google Scholar 

  27. De Ruvo N, Cucchetti A, Lauro A, et al. Preliminary results of immunosuppression with thymoglobuline pretreatment and hepatitis C virus recurrence in liver transplantation. Transplant Proc. 2005;37:2607–2608.

    Article  PubMed  Google Scholar 

  28. De Ruvo N, Cucchetti A, Lauro A, et al. Minimization of immunosuppression with thymoglobuline pre-treatment and HCV recurrence in liver transplantation. Clin Transplant. 2005;19:255–258.

    Article  PubMed  Google Scholar 

  29. Eason JD, Loss GE, Blazek J, Nair S, Mason AL. Steroid-free liver transplantation using rabbit antithymocyte globulin induction: results of a prospective randomized trial. Liver Transpl. 2001;7:693–697.

    Article  PubMed  CAS  Google Scholar 

  30. Eason JD, Blazek J, Mason A, Nair S, Loss GE. Steroid-free immunosuppression through thymoglobulin induction in liver transplantation. Transplant Proc. 2001;33:1470–1471.

    Article  PubMed  CAS  Google Scholar 

  31. Tector AJ, Fridell JA, Mangus RS, et al. Promising early results with immunosuppression using rabbit anti-thymocyte globulin and steroids with delayed introduction of tacrolimus in adult liver transplant recipients. Liver Transpl. 2004;10:404–407.

    Article  PubMed  Google Scholar 

  32. Mangus RS, Fridell JA, Vianna RM, Kwo PY, Chen J, Tector AJ. Immunosuppression induction with rabbit anti-thymocyte globulin with or without rituximab in 1000 liver transplant patients with long-term follow-up. Liver Transpl. 2012;18:786–795.

    Article  PubMed  Google Scholar 

  33. Hadley S, Samore MH, Lewis WD, Jenkins RL, Karchmer AW, Hammer SM. Major infectious complications after orthotopic liver transplantation and comparison of outcomes in patients receiving cyclosporine or FK506 as primary immunosuppression. Transplantation. 1995;59:851–859.

    Article  PubMed  CAS  Google Scholar 

  34. Biancofiore G, Bindi ML, Baldassarri R, et al. Antifungal prophylaxis in liver transplant recipients: a randomized placebo-controlled study. Transpl Int. 2002;15:341–347.

    Article  PubMed  CAS  Google Scholar 

  35. Saliba F, Delvart V, Ichai P, et al. Fungal infections after liver transplantation: outcomes and risk factors revisited in the MELD era. Clin Transplant 2013.

  36. Benitez CE, Puig-Pey I, Lopez M, et al. ATG-Fresenius treatment and low-dose tacrolimus: results of a randomized controlled trial in liver transplantation. Am J Transplant. 2010;10:2296–2304.

    Article  PubMed  CAS  Google Scholar 

  37. Bogetti D, Sankary HN, Jarzembowski TM, et al. Thymoglobulin induction protects liver allografts from ischemia/reperfusion injury. Clin Transplant. 2005;19:507–511.

    Article  PubMed  Google Scholar 

  38. Boillot O, Seket B, Dumortier J, et al. Thymoglobulin induction in liver transplant recipients with a tacrolimus, mycophenolate mofetil, and steroid immunosuppressive regimen: a five-year randomized prospective study. Liver Transpl. 2009;15:1426–1434.

    Article  PubMed  Google Scholar 

  39. Soliman T, Hetz H, Burghuber C, et al. Short-term versus long-term induction therapy with antithymocyte globulin in orthotopic liver transplantation. Transpl Int. 2007;20:447–452.

    Article  PubMed  CAS  Google Scholar 

  40. Rostaing L, Saliba F, Calmus Y, Dharancy S, Boillot O. Review article: use of induction therapy in liver transplantation. Transplant Rev (Orlando). 2012;26:246–260.

    Article  Google Scholar 

  41. Sharma P, Welch K, Hussain H, et al. Incidence and risk factors of hepatocellular carcinoma recurrence after liver transplantation in the MELD era. Dig Dis Sci. 2012;57:806–812.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

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Conflict of interest

The authors have no financial disclosures or conflict of interests.

Author information

Authors and Affiliations

  1. Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of Arkansas for Medical Sciences, 4301 W Markham St #567, Little Rock, AR, 72205, USA

    Mauricio Garcia-Saenz-de-Sicilia

  2. Section of Gastroenterology and Hepatology, Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE, USA

    Marco A. Olivera-Martinez & Timothy McCashland

  3. Adult Liver and Small Bowel Transplant Department, Department of Surgery, University of Nebraska Medical Center, Omaha, NE, USA

    Wendy J. Grant, David F. Mercer & Alan Langnas

  4. College of Public Health, University of Nebraska Medical Center, Omaha, NE, USA

    Chen Baojjang

Authors
  1. Mauricio Garcia-Saenz-de-Sicilia
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  2. Marco A. Olivera-Martinez
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  3. Wendy J. Grant
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  4. David F. Mercer
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  5. Chen Baojjang
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  6. Alan Langnas
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  7. Timothy McCashland
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Correspondence to Mauricio Garcia-Saenz-de-Sicilia.

Additional information

Clinicaltrials.gov NCT00564538.

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Garcia-Saenz-de-Sicilia, M., Olivera-Martinez, M.A., Grant, W.J. et al. Impact of Anti-Thymocyte Globulin During Immunosuppression Induction in Patients with Hepatitis C After Liver Transplantation. Dig Dis Sci 59, 2804–2812 (2014). https://doi.org/10.1007/s10620-014-3215-2

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  • DOI: https://doi.org/10.1007/s10620-014-3215-2

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