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Erschienen in: Digestive Diseases and Sciences 11/2010

01.11.2010 | Original Article

Anti-thymocyte Globulin for the Treatment of Acute Cellular Rejection Following Liver Transplantation

verfasst von: Timothy M. Schmitt, Melissa Phillips, Robert G. Sawyer, Patrick Northup, Klaus D. Hagspiel, Timothy L. Pruett, Hugo J. R. Bonatti

Erschienen in: Digestive Diseases and Sciences | Ausgabe 11/2010

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Abstract

Introduction

Acute cellular rejection (ACR) post-liver transplantation (LT) can usually be reversed with pulse dose steroids. Anti-thymocyte globulin (ATG) is used to treat steroid-resistant rejection (SRR).

Patients and Methods

We report 15 male and five female LT recipients with a median age of 48.3 (range 14.3–71.7) years, who received ATG for biopsy-proven steroid-resistant rejection (n = 13), severe rejection (6), and severe rejection/recurrent autoimmune hepatitis (n = 1) median 42 (range 6–2,456) days following LT.

Results

Underlying liver diseases included HCV (n = 7), alcoholic cirrhosis (n = 3), NASH (n = 2), HBV (n = 2), autoimmune hepatitis (n = 1), PSC (n = 1), miscellaneous (n = 4) including three re LTs. All patients responded to treatment (median AST declined from 172 to 34U/l, median total bilirubin from 9.1 to 1.3 mg/dl; p < 0.001). Three patients developed recurrent ACR, and none chronic rejection. All HCV patients developed recurrence with significant rises in HCV RNA levels. Infections included pneumonia, sepsis, intraabdominal infection, chronic diarrhea, wound infection, EBV, and CMV disease. After a median follow-up of 65.5 (range 4.3–101.7) months post-ATG and median 67.7 (range 9.3–306.3) months post-LT, 17 patients are alive, two died from sepsis/multi-organ failure and one from HCV recurrence.

Conclusion

ATG effectively reversed severe and SSR; HCV recurrence and infections remain significant complications.
Literatur
1.
Zurück zum Zitat Andreu H, Rimola A, Bruguera M, et al. Acute cellular rejection in liver transplant recipients under cyclosporine immunosuppression: predictive factors of response to antirejection therapy. Transplantation. 2002;73:1936–1943.CrossRefPubMed Andreu H, Rimola A, Bruguera M, et al. Acute cellular rejection in liver transplant recipients under cyclosporine immunosuppression: predictive factors of response to antirejection therapy. Transplantation. 2002;73:1936–1943.CrossRefPubMed
2.
Zurück zum Zitat Kaufman DB, Shapiro R, Lucey MR, Cherikh WSRTB, Dyke DB. Immunosuppression: practice and trends. Am J Transplant. 2004;4(9):38–53.CrossRefPubMed Kaufman DB, Shapiro R, Lucey MR, Cherikh WSRTB, Dyke DB. Immunosuppression: practice and trends. Am J Transplant. 2004;4(9):38–53.CrossRefPubMed
3.
Zurück zum Zitat Shapiro R, Young JB, Milford EL, Trotter JF, Bustami RT, Leichtman AB. Immunosuppression: evolution in practice and trends, 1993–2003. Am J Transplant. 2005;5:874–886.CrossRefPubMed Shapiro R, Young JB, Milford EL, Trotter JF, Bustami RT, Leichtman AB. Immunosuppression: evolution in practice and trends, 1993–2003. Am J Transplant. 2005;5:874–886.CrossRefPubMed
4.
Zurück zum Zitat Ramirez CB, Doria C, di Francesco F, Iaria M, Kang Y, Marino IR. Anti-IL2 induction in liver transplantation with 93% rejection-free patient and graft survival at 18 months. J Surg Res. 2007;138:198–204.CrossRefPubMed Ramirez CB, Doria C, di Francesco F, Iaria M, Kang Y, Marino IR. Anti-IL2 induction in liver transplantation with 93% rejection-free patient and graft survival at 18 months. J Surg Res. 2007;138:198–204.CrossRefPubMed
5.
Zurück zum Zitat Bathgate AJ, Hynd P, Sommerville D, Hayes PC. The prediction of acute cellular rejection in orthotopic liver transplantation. Liver Transpl Surg. 1999;5:475–479.CrossRefPubMed Bathgate AJ, Hynd P, Sommerville D, Hayes PC. The prediction of acute cellular rejection in orthotopic liver transplantation. Liver Transpl Surg. 1999;5:475–479.CrossRefPubMed
6.
Zurück zum Zitat Berlakovich GA, Rockenschaub S, Taucher S, Kaserer K, Muhlbacher F, Steiniger R. Underlying disease as a predictor for rejection after liver transplantation. Arch Surg. 1998;133:167–172.CrossRefPubMed Berlakovich GA, Rockenschaub S, Taucher S, Kaserer K, Muhlbacher F, Steiniger R. Underlying disease as a predictor for rejection after liver transplantation. Arch Surg. 1998;133:167–172.CrossRefPubMed
7.
Zurück zum Zitat Conti F, Dousset B, Archambeau D, Louvel A, Houssin D, Calmus Y. Enhanced risk of steroid-resistant acute rejection following pretransplant steroid therapy in liver graft recipients. Transplantation. 1995;60:1104–1108.CrossRefPubMed Conti F, Dousset B, Archambeau D, Louvel A, Houssin D, Calmus Y. Enhanced risk of steroid-resistant acute rejection following pretransplant steroid therapy in liver graft recipients. Transplantation. 1995;60:1104–1108.CrossRefPubMed
8.
Zurück zum Zitat Farges O, Saliba F, Farhamant H, et al. Incidence of rejection and infection after liver transplantation as a function of the primary disease: possible influence of alcohol and polyclonal immunoglobulins. Hepatology. 1996;23:240–248.CrossRefPubMed Farges O, Saliba F, Farhamant H, et al. Incidence of rejection and infection after liver transplantation as a function of the primary disease: possible influence of alcohol and polyclonal immunoglobulins. Hepatology. 1996;23:240–248.CrossRefPubMed
9.
Zurück zum Zitat Fisher LR, Henley KS, Lucey MR. Acute cellular rejection after liver transplantation: variability, morbidity, and mortality. Liver Transpl Surg. 1995;1:10–15.CrossRefPubMed Fisher LR, Henley KS, Lucey MR. Acute cellular rejection after liver transplantation: variability, morbidity, and mortality. Liver Transpl Surg. 1995;1:10–15.CrossRefPubMed
10.
Zurück zum Zitat Mirza DF, Gunson BK, Soonawalla Z, et al. Reduced acute rejection after liver transplantation with Neoral-based triple immunosuppression. Lancet. 1997;349:701–702.CrossRefPubMed Mirza DF, Gunson BK, Soonawalla Z, et al. Reduced acute rejection after liver transplantation with Neoral-based triple immunosuppression. Lancet. 1997;349:701–702.CrossRefPubMed
11.
Zurück zum Zitat Seiler CA, Dufour JF, Renner EL, et al. Primary liver disease as a determinant for acute rejection after liver transplantation. Langenbecks Arch Surg. 1999;384:259–263.CrossRefPubMed Seiler CA, Dufour JF, Renner EL, et al. Primary liver disease as a determinant for acute rejection after liver transplantation. Langenbecks Arch Surg. 1999;384:259–263.CrossRefPubMed
12.
Zurück zum Zitat Wiesner RH, Demetris AJ, Belle SH, et al. Acute hepatic allograft rejection: incidence, risk factors, and impact on outcome. Hepatology. 1998;28:638–645.CrossRefPubMed Wiesner RH, Demetris AJ, Belle SH, et al. Acute hepatic allograft rejection: incidence, risk factors, and impact on outcome. Hepatology. 1998;28:638–645.CrossRefPubMed
13.
Zurück zum Zitat Assy N, Adams PC, Myers P, et al. Randomized controlled trial of total immunosuppression withdrawal in liver transplant recipients: role of ursodeoxycholic acid. Transplantation. 2007;83:1571–1576.CrossRefPubMed Assy N, Adams PC, Myers P, et al. Randomized controlled trial of total immunosuppression withdrawal in liver transplant recipients: role of ursodeoxycholic acid. Transplantation. 2007;83:1571–1576.CrossRefPubMed
14.
Zurück zum Zitat 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.CrossRefPubMed 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.CrossRefPubMed
15.
Zurück zum Zitat Bahra M, Neumann UP, Jacob D, Langrehr JM, Neuhaus P. Repeated steroid pulse therapies in HCV-positive liver recipients: significant risk factor for HCV-related graft loss. Transplant Proc. 2005;37:1700–1702.CrossRefPubMed Bahra M, Neumann UP, Jacob D, Langrehr JM, Neuhaus P. Repeated steroid pulse therapies in HCV-positive liver recipients: significant risk factor for HCV-related graft loss. Transplant Proc. 2005;37:1700–1702.CrossRefPubMed
16.
Zurück zum Zitat Razonable RR. Cytomegalovirus infection after liver transplantation: current concepts and challenges. World J Gastroenterol. 2008;14:4849–4860.CrossRefPubMed Razonable RR. Cytomegalovirus infection after liver transplantation: current concepts and challenges. World J Gastroenterol. 2008;14:4849–4860.CrossRefPubMed
17.
Zurück zum Zitat Rosen HR, Shackleton CR, Higa L, et al. Use of OKT3 is associated with early and severe recurrence of hepatitis C after liver transplantation. Am J Gastroenterol. 1997;92:1453–1457.PubMed Rosen HR, Shackleton CR, Higa L, et al. Use of OKT3 is associated with early and severe recurrence of hepatitis C after liver transplantation. Am J Gastroenterol. 1997;92:1453–1457.PubMed
18.
Zurück zum Zitat Fernandes ML, Lee YM, Sutedja D, et al. Treatment of steroid-resistant acute liver transplant rejection with basiliximab. Transplant Proc. 2005;37:2179–2180.CrossRefPubMed Fernandes ML, Lee YM, Sutedja D, et al. Treatment of steroid-resistant acute liver transplant rejection with basiliximab. Transplant Proc. 2005;37:2179–2180.CrossRefPubMed
19.
Zurück zum Zitat Orr DW, Portmann BC, Knisely AS, et al. Anti-interleukin 2 receptor antibodies and mycophenolate mofetil for treatment of steroid-resistant rejection in adult liver transplantation. Transplant Proc. 2005;37:4373–4379.CrossRefPubMed Orr DW, Portmann BC, Knisely AS, et al. Anti-interleukin 2 receptor antibodies and mycophenolate mofetil for treatment of steroid-resistant rejection in adult liver transplantation. Transplant Proc. 2005;37:4373–4379.CrossRefPubMed
20.
Zurück zum Zitat 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.CrossRefPubMed 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.CrossRefPubMed
21.
Zurück zum Zitat 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.CrossRefPubMed 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.CrossRefPubMed
22.
Zurück zum Zitat 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.CrossRefPubMed 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.CrossRefPubMed
23.
Zurück zum Zitat Kato T, Gaynor JJ, Yoshida H, et al. Randomized trial of steroid-free induction versus corticosteroid maintenance among orthotopic liver transplant recipients with hepatitis C virus: impact on hepatic fibrosis progression at one year. Transplantation. 2007;84:829–835.CrossRefPubMed Kato T, Gaynor JJ, Yoshida H, et al. Randomized trial of steroid-free induction versus corticosteroid maintenance among orthotopic liver transplant recipients with hepatitis C virus: impact on hepatic fibrosis progression at one year. Transplantation. 2007;84:829–835.CrossRefPubMed
24.
Zurück zum Zitat 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.CrossRefPubMed 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.CrossRefPubMed
25.
Zurück zum Zitat 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.CrossRefPubMed 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.CrossRefPubMed
26.
Zurück zum Zitat Bijleveld CG, Klompmaker IJ, van den Berg AP, et al. Incidence, risk factors, and outcome of antithymocyte globulin treatment of steroid-resistant rejection after liver transplantation. Transpl Int. 1996;9:570–575.PubMed Bijleveld CG, Klompmaker IJ, van den Berg AP, et al. Incidence, risk factors, and outcome of antithymocyte globulin treatment of steroid-resistant rejection after liver transplantation. Transpl Int. 1996;9:570–575.PubMed
27.
Zurück zum Zitat Demetris AJ, Ruppert K, Dvorchik I, et al. Real-time monitoring of acute liver-allograft rejection using the Banff schema. Transplantation. 2002;74:1290–1296.CrossRefPubMed Demetris AJ, Ruppert K, Dvorchik I, et al. Real-time monitoring of acute liver-allograft rejection using the Banff schema. Transplantation. 2002;74:1290–1296.CrossRefPubMed
28.
Zurück zum Zitat Demetris A, Adams D, Bellamy C, et al. Update of the international Banff schema for liver allograft rejection: working recommendations for the histopathologic staging and reporting of chronic rejection. An international panel. Hepatology. 2000;31:792–799.CrossRefPubMed Demetris A, Adams D, Bellamy C, et al. Update of the international Banff schema for liver allograft rejection: working recommendations for the histopathologic staging and reporting of chronic rejection. An international panel. Hepatology. 2000;31:792–799.CrossRefPubMed
29.
Zurück zum Zitat Demetris AJ, Seaberg EC, Batts KP, et al. Chronic liver allograft rejection: a National Institute of Diabetes and Digestive and Kidney Diseases interinstitutional study analyzing the reliability of current criteria and proposal of an expanded definition. National Institute of Diabetes and Digestive and Kidney Diseases liver transplantation database. Am J Surg Pathol. 1998;22:28–39.CrossRefPubMed Demetris AJ, Seaberg EC, Batts KP, et al. Chronic liver allograft rejection: a National Institute of Diabetes and Digestive and Kidney Diseases interinstitutional study analyzing the reliability of current criteria and proposal of an expanded definition. National Institute of Diabetes and Digestive and Kidney Diseases liver transplantation database. Am J Surg Pathol. 1998;22:28–39.CrossRefPubMed
30.
Zurück zum Zitat Batts KP, Ludwig J. Chronic hepatitis. An update on terminology and reporting. Am J Surg Pathol. 1995;19:1409–1417.CrossRefPubMed Batts KP, Ludwig J. Chronic hepatitis. An update on terminology and reporting. Am J Surg Pathol. 1995;19:1409–1417.CrossRefPubMed
31.
Zurück zum Zitat De P, Bechstein WO, Blumhardt G, Lange D, Schattenfroh N, Neuhaus P. Early steroid-resistant rejection following orthotopic liver transplantation: new aspects of treatment with FK 506 instead of OKT3? Transplant Proc. 1993;25:2693–2694.PubMed De P, Bechstein WO, Blumhardt G, Lange D, Schattenfroh N, Neuhaus P. Early steroid-resistant rejection following orthotopic liver transplantation: new aspects of treatment with FK 506 instead of OKT3? Transplant Proc. 1993;25:2693–2694.PubMed
32.
Zurück zum Zitat Hirose R, Roberts JP, Quan D, et al. Experience with daclizumab in liver transplantation: renal transplant dosing without calcineurin inhibitors is insufficient to prevent acute rejection in liver transplantation. Transplantation. 2000;69:307–311.CrossRefPubMed Hirose R, Roberts JP, Quan D, et al. Experience with daclizumab in liver transplantation: renal transplant dosing without calcineurin inhibitors is insufficient to prevent acute rejection in liver transplantation. Transplantation. 2000;69:307–311.CrossRefPubMed
33.
Zurück zum Zitat Neumann UP, Berg T, Bahra M, et al. Long-term outcome of liver transplants for chronic hepatitis C: a 10-year follow-up. Transplantation. 2004;77:226–231.CrossRefPubMed Neumann UP, Berg T, Bahra M, et al. Long-term outcome of liver transplants for chronic hepatitis C: a 10-year follow-up. Transplantation. 2004;77:226–231.CrossRefPubMed
34.
Zurück zum Zitat Berenguer M, Prieto M, Cordoba J, et al. Early development of chronic active hepatitis in recurrent hepatitis C virus infection after liver transplantation: association with treatment of rejection. J Hepatol. 1998;28:756–763.CrossRefPubMed Berenguer M, Prieto M, Cordoba J, et al. Early development of chronic active hepatitis in recurrent hepatitis C virus infection after liver transplantation: association with treatment of rejection. J Hepatol. 1998;28:756–763.CrossRefPubMed
35.
Zurück zum Zitat Burton JR Jr, Rosen HR. Acute rejection in HCV-infected liver transplant recipients: The great conundrum. Liver Transpl. 2006;12:S38–S47.CrossRefPubMed Burton JR Jr, Rosen HR. Acute rejection in HCV-infected liver transplant recipients: The great conundrum. Liver Transpl. 2006;12:S38–S47.CrossRefPubMed
Metadaten
Titel
Anti-thymocyte Globulin for the Treatment of Acute Cellular Rejection Following Liver Transplantation
verfasst von
Timothy M. Schmitt
Melissa Phillips
Robert G. Sawyer
Patrick Northup
Klaus D. Hagspiel
Timothy L. Pruett
Hugo J. R. Bonatti
Publikationsdatum
01.11.2010
Verlag
Springer US
Erschienen in
Digestive Diseases and Sciences / Ausgabe 11/2010
Print ISSN: 0163-2116
Elektronische ISSN: 1573-2568
DOI
https://doi.org/10.1007/s10620-010-1149-x

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