霉酚酸酯不耐受的肝移植受者转归：杭州经验
|
摘要
背景：
肝移植是治疗终末期肝病的唯一有效手段。霉酚酸酯(Mycophenolate mofetil, MMF)作为无肾毒性的免疫抑制剂在肝移植术后广泛应用,但它存在骨髓抑制,胃肠道反应等副作用,使得临床上存在一部分肝移植受者不能耐受MMF治疗。本研究通过分析临床上因不耐受MMF而未使用MMF的肝移植受者术后并发症发生及转归情况,总结出MMF不耐受病人的免疫抑制方案使用经验。
方法：
我院从2008年1月至2009年12月间共施行肝移植手术188例,其中采用他克莫司(FK506)联合激素或不联合激素免疫抑制方案的病例24例为无MMF组；对照组选择同期手术并与实验组在年龄、性别、随访时间等相匹配的48例病例,为MMF组,均采用他克莫司+MMF+激素三联或他克莫司+MMF二联方案。比较两组间肝移植术前资料及术后并发症的发生情况。
结果：
无MMF组和MMF组肝移植受者术后平均随访时间分别为12.4月和14.0月。无MMF组病人术前白细胞、血红蛋白、血小板水平显著低于MMF组病人,分别为(2.1±0.9)*109/L vs.(5.5±3.3)*109/L,P<0.01；93±23g/L vs.106±27g/L,P=0.041；(38±21)*109/L vs.(84±66)*109/L,P<0.01)。无MMF组的FK506血药浓度在移植术后2d、1周、2周、3周、4周与MMF组相比无明显统计学差异(P>0.05)。发生急性排斥时无MMF组FK506血药浓度与MMF组相比无显著性差异(5.54±1.96 ng／ml vs.6.76±1.84 ng／ml,P>0.05)。在急性排斥反应发生率上,无MMF组显著高于MMF组(45.8% vs.14.6%,P=0.004)；在经肝穿证实的急性排斥反应发生率上,无MMF组与MMF组相比在统计学上无显著性差异(25%vs.10.6%,P=0.105),且无MMF组63.6%为轻型容易控制的急性排斥反应。无MMF组和MMF组在移植术后感染发生率(62.5% vs.43.8%,P=0.134)高血压病发生率(8.3%vs.8.7%,P=0.959),糖尿病发生率(13% vs.4.5%,P=0.209),肝癌复发率(27.3% vs.38.5%,P=0.562),乙肝复发率(0%vs.4.2%,P>0.05)及患者生存率(100% vs.93.8%,P>0.05)在统计学上并无显著差异。
结论：
对于MMF不耐受的肝移植受者,无MMF免疫抑制方案可增加轻型急性排斥反应的发生,但不影响肝移植受者术后感染、代谢并发症、肝癌复发、乙肝复发的发生及患者生存率,因而是安全可行的。
Background:
Liver transplantation is the only effective method to treat end-stage liver disease. As a non-nephrotoxic immunosuppressant following liver transplantation, mycophenolate mofetil(MMF) possesses side effects such as bone marrow suppression, and gastrointestinal disorders, resulting in the existence of patients who are intolerant of MMF. This study aims to explore the complications and outcome of MMF-intolerant patients treated with MMF-free immunosuppressive regimens after liver transplantation, and summarizes a single center experience in application of immunosuppressive regimens in MMF-intolerant liver transplant recipients.
Methods:
Altogether 188 patients undergoing liver transplantation from January 2008 to December 2009 were reviewed. The preoperative data and postoperative complication rates were compared between MMF-free group (24 cases, tacrolimus(FK506)+steroid or FK506 regimen without steroid) and MMF group (48 cases, FK506+MMF+steroid or FK506+MMF regimen) as a control.
Results:
The mean follow-up time for liver transplant recipients in MMF-free group and MMF group was 12.4 and 14.0 months, respectively. Preoperative levels of white blood cell, hemoglobin and platelet in MMF-free group were significantly lower than that in the MMF group, respectively (2.1±0.9)*109/Lvs.(5.5±3.3)*109/L,P<0.01; 93±23g/L vs.106±27g/L, P=0.041; (38±21)*109/L vs.(84±66)*109/L, P<0.01). There was no significant difference between MMF-free group and MMF group in blood concentration of FK506 at 2nd day,1st week,2nd week,3rd week and 4th week after liver transplantation (P> 0.05). When acute rejection occurs, there was no significant difference in the blood concentration of FK506 between MMF-free group and MMF group (5.54±1.96 ng/ml vs.6.76±1.84 ng/ml, P>0.05). The incidence of acute rejection in MMF-free group was significantly higher than that in MMF group (45.8% vs.14.6%, P=0.004). The incidence of biopsy-proven acute rejection in MMF-free group was higher than that in MMF group (25% vs.10.6%), but the difference was not statistically significant (P=0.105), and about 63.6% acute rejection types in MMF-free group are considered to be mild rejection easy to be controlled. There was no significant difference between MMF-free group and MMF group in the rates of infection (62.5% vs. 43.8%, P=0.134), hypertension (8.3% vs.8.7%, P=0.959), diabetes (13% vs.4.5%, P=0.209), tumor recurrence (27.3% vs.38.5%, P=0.562), hepatitis B recurrence (0% vs.4.2%, P> 0.05) and patient survival (100% vs.93.8%, P> 0.05).
Conclusion:
For liver transplant recipients who are intolerant of MMF, MMF-free immunosuppressive regimen may increase the incidence of mild acute rejection,but does not affect infection, metabolic complications, tumor recurrence, HBV recurrence and patient survival after liver transplantation, so it is considered to be safe and feasible.
肝移植是治疗终末期肝病的唯一有效手段。霉酚酸酯(Mycophenolate mofetil, MMF)作为无肾毒性的免疫抑制剂在肝移植术后广泛应用,但它存在骨髓抑制,胃肠道反应等副作用,使得临床上存在一部分肝移植受者不能耐受MMF治疗。本研究通过分析临床上因不耐受MMF而未使用MMF的肝移植受者术后并发症发生及转归情况,总结出MMF不耐受病人的免疫抑制方案使用经验。
方法：
我院从2008年1月至2009年12月间共施行肝移植手术188例,其中采用他克莫司(FK506)联合激素或不联合激素免疫抑制方案的病例24例为无MMF组；对照组选择同期手术并与实验组在年龄、性别、随访时间等相匹配的48例病例,为MMF组,均采用他克莫司+MMF+激素三联或他克莫司+MMF二联方案。比较两组间肝移植术前资料及术后并发症的发生情况。
结果：
无MMF组和MMF组肝移植受者术后平均随访时间分别为12.4月和14.0月。无MMF组病人术前白细胞、血红蛋白、血小板水平显著低于MMF组病人,分别为(2.1±0.9)*109/L vs.(5.5±3.3)*109/L,P<0.01；93±23g/L vs.106±27g/L,P=0.041；(38±21)*109/L vs.(84±66)*109/L,P<0.01)。无MMF组的FK506血药浓度在移植术后2d、1周、2周、3周、4周与MMF组相比无明显统计学差异(P>0.05)。发生急性排斥时无MMF组FK506血药浓度与MMF组相比无显著性差异(5.54±1.96 ng／ml vs.6.76±1.84 ng／ml,P>0.05)。在急性排斥反应发生率上,无MMF组显著高于MMF组(45.8% vs.14.6%,P=0.004)；在经肝穿证实的急性排斥反应发生率上,无MMF组与MMF组相比在统计学上无显著性差异(25%vs.10.6%,P=0.105),且无MMF组63.6%为轻型容易控制的急性排斥反应。无MMF组和MMF组在移植术后感染发生率(62.5% vs.43.8%,P=0.134)高血压病发生率(8.3%vs.8.7%,P=0.959),糖尿病发生率(13% vs.4.5%,P=0.209),肝癌复发率(27.3% vs.38.5%,P=0.562),乙肝复发率(0%vs.4.2%,P>0.05)及患者生存率(100% vs.93.8%,P>0.05)在统计学上并无显著差异。
结论：
对于MMF不耐受的肝移植受者,无MMF免疫抑制方案可增加轻型急性排斥反应的发生,但不影响肝移植受者术后感染、代谢并发症、肝癌复发、乙肝复发的发生及患者生存率,因而是安全可行的。
Background:
Liver transplantation is the only effective method to treat end-stage liver disease. As a non-nephrotoxic immunosuppressant following liver transplantation, mycophenolate mofetil(MMF) possesses side effects such as bone marrow suppression, and gastrointestinal disorders, resulting in the existence of patients who are intolerant of MMF. This study aims to explore the complications and outcome of MMF-intolerant patients treated with MMF-free immunosuppressive regimens after liver transplantation, and summarizes a single center experience in application of immunosuppressive regimens in MMF-intolerant liver transplant recipients.
Methods:
Altogether 188 patients undergoing liver transplantation from January 2008 to December 2009 were reviewed. The preoperative data and postoperative complication rates were compared between MMF-free group (24 cases, tacrolimus(FK506)+steroid or FK506 regimen without steroid) and MMF group (48 cases, FK506+MMF+steroid or FK506+MMF regimen) as a control.
Results:
The mean follow-up time for liver transplant recipients in MMF-free group and MMF group was 12.4 and 14.0 months, respectively. Preoperative levels of white blood cell, hemoglobin and platelet in MMF-free group were significantly lower than that in the MMF group, respectively (2.1±0.9)*109/Lvs.(5.5±3.3)*109/L,P<0.01; 93±23g/L vs.106±27g/L, P=0.041; (38±21)*109/L vs.(84±66)*109/L, P<0.01). There was no significant difference between MMF-free group and MMF group in blood concentration of FK506 at 2nd day,1st week,2nd week,3rd week and 4th week after liver transplantation (P> 0.05). When acute rejection occurs, there was no significant difference in the blood concentration of FK506 between MMF-free group and MMF group (5.54±1.96 ng/ml vs.6.76±1.84 ng/ml, P>0.05). The incidence of acute rejection in MMF-free group was significantly higher than that in MMF group (45.8% vs.14.6%, P=0.004). The incidence of biopsy-proven acute rejection in MMF-free group was higher than that in MMF group (25% vs.10.6%), but the difference was not statistically significant (P=0.105), and about 63.6% acute rejection types in MMF-free group are considered to be mild rejection easy to be controlled. There was no significant difference between MMF-free group and MMF group in the rates of infection (62.5% vs. 43.8%, P=0.134), hypertension (8.3% vs.8.7%, P=0.959), diabetes (13% vs.4.5%, P=0.209), tumor recurrence (27.3% vs.38.5%, P=0.562), hepatitis B recurrence (0% vs.4.2%, P> 0.05) and patient survival (100% vs.93.8%, P> 0.05).
Conclusion:
For liver transplant recipients who are intolerant of MMF, MMF-free immunosuppressive regimen may increase the incidence of mild acute rejection,but does not affect infection, metabolic complications, tumor recurrence, HBV recurrence and patient survival after liver transplantation, so it is considered to be safe and feasible.
引文
1 Shapiro R, Young JB, Milford EL, et al. Immunosuppression:evolution in practice and trends,1993-2003. Am J Transplant 2005;5(pt 2):874-886.
2 Perry I, Neuberger J. Immunosuppression:towards a logical approach in liver transplantation. Clin Exp Immunol 2005; 139:2-10.
3 Padbury RT, Toogood GJ, McMaster P. Withdrawal of immunosuppression in liver allograft recipients. Liver Transpl Surg 1998;4:242-248.
4. Stegall MD, Wachs ME, Everson G, et al. Prednisone withdrawal 14 days after liver transplantation with mycophenolate:a prospective trial of cyclosporine and tacrolimus. Transplantation 1997;64:1755-1760.
5 Grinyo JM, Campistol JM, Paul J,et al. Pilot randomized study of early tacrolimus withdrawal from a regimen with sirolimus plus tacrolimus in kidney transplantation. Am J Transplant 2004;4:1308-1314
6 Klupp J, Pfitzmann R, Langrehr JM, et al. Indications of mycophenolate mofetil in liver transplantation.Transplantation 2005;80:S142-S146.
7 Wiesner RH, Shorr JS, Steffen BJ,et al. Mycophenolate mofetil combination therapy imp roves long-term outcomes after liver transplantation in patients with and without hepatitis C. Liver Transpl 2005,11(7):750-759.
8 Pfitzmann R, Klup PJ, Langrehr JM, et al. Mycophenolatemofetil for immunosupp ression after liver transp lantation:a follow-up study of 191 patients. Transplantation 2003,76 (1):130-136.
9 Sato K, Sekiguchi S, Kawagishi N, et al.Unique histopathological features of graft biopsies with liver function abnormalities in living donor liver transplant patients receiving basiliximab induction therapy.Clin Transplant 2010. [Epub ahead of print]
10 Fisher RA, Ham JM, Marcos A, et al. A prospective randomized trial of mycophenolate mofetil with neoral or tacrolimus after orthotopic liver transplantation. Transplantation 1998; 66:1616-1621.
11 Barkmann A, Nashan B, Schmidt HH, et al. Improvement of acute and chronic renal dysfunction in liver transplant patients after substitution of calcineurin inhibitors by mycophenolate mofetil. Transplantation 2000; 69:1886-1890.
12 S. Dharancy, A. Iannelli, A. Hulin. Mycophenolate Mofetil Monotherapy for Severe Side Effects of Calcineurin Inhibitors Following Liver Transplantation. American Journal of Transplantation 2009; 9:610-613.
13 Shipkova M, Armstrong VW, Oellerich M, et al. Mycophenolate mofetil in organ transplantation:focus on metabolism, safety and tolerability. Expert Opin Drug Metab Toxicol 2005;1:505-526.
14 Allison AC, Almquist SJ, Muller CD, et al. In vitro immunosuppressive effects of mycophenolic acid and an ester pro-drug, RS-61443. Transplant Proc 1991;23(2 Suppl2):10-14
15 Klupp J, Glanemann M, Bechstein WO, et al. Mycophenolate mofetil in combinati on with tacrolimus versus Neoral after liver transplantation.Transplant Proc 1999;31:1113-1114
16 Platz KP, Mueller AR, Neuhaus P. Indications for mycofenolate mofetil therapy after liver transplantation. Transplant Proc,1997;29:2880-2881
17 Aw MM, Verma A, Rela M, et al. Long-term outcome of mycophenolate mofetil rescue therapy for resistant acute allograft rejection in pediatric liver transplant recipients.Liver Transpl.2008;14(9):1303-1308.
18 Wietzke-Braun P, Braun F, Sattler B, et al. Initial steroid-free immunosuppression after liver transplantation in recipients with hepatitis c virus related cirrhosis.World J Gastroenterol 2004;10(15):2213-2217.
19 Hebert MF, Ascher NL, Lake JR, et al. Four-year follow-up of mycophenolate mofetil for graft rescue in liver allograft recipients. Transplantation1999;67(5):707-712.
20 Robaeys G, Cassiman D, Verslype C, et al. Successful conversion from.mycophenolate mofetil to enteric-coated mycophenolate sodium (myfortic) in liver transplant patients with gastrointestinal side effects. Transplant Proc.2009;41(2):610-613.
21 Stegal MD, Wachs ME, Everson G, et al. Prednisone withdrawal 14 days after liver transplantation with mycophenolate:a prospective trial of cyclosporine and tacrolimus. Transplantation 1997; 64:1755-1760.
22 Boucher A, Lord H, Collette S, et al. Cytomegalovirus infection in kidney transplant recipients:Evolution of approach through three eras. Transplant Proc 2006; 38:3506-3508.
23 Jorge S, Guerra J, Santana A, et al. Mycophenolate mofetil:ten years' experience of a renal transplant unit. Transplant Proc 2008; 81:700-704.
24 Sarmiento JM, Dockrell DH, Schwab TR, et al. Mycophenolate mofetil increases cytomegalovirus invasive organ disease in renal transplant patients. Clin Transplant 2000; 14:136-138.
25 Smak Gregoor PJ, van Gelder T, van Riemsdijk-van Overbeeke IC, et al. Unusual presentation of herpes virus infections in renal transplant recipients exposed to high mycophenolic acid plasma concentrations. Transpl Infect Dis 2003; 5:79-83.
26 Herrero JI, Quiroga J, Sangro B, et al. Herpes zoster after liver transplantation: incidence, risk factors, and complications. Liver Transpl 2004; 10:1140-1143
27 Neff RT, Hurst FP, Falta EM, et al. Progressive multifocal leukoencephalopathy and use of mycophenolate mofetil after kidney transplantation. Transplantation 2008; 86:1474-1478.
28 Engl T, Makarevic J,Relja B,et al.Mycophenolate mofetil modulates adhesion receptors of the betal integrin family on tumor cells:impact on tumor recurrence and malignancy. BMC Cancer.2005;5(4):1-11
29 Engl T, Relja B, Natsheh I. Modulation of the CXC-chemokine expression profile on tumor cells by the immunosuppressive drug mycophenolate mofetil. Int J Mol Med.2005;15(4):641-647.
30 Gnatta D, Keitel E, Heineck I, et al. Use of tacrolimus and the development of posttransplant diabetes mellitus:a Brazilian single-center, observational study. Transplant Proc 2010;42(2):475-478.
31 Xiao Xu, Qi Ling, Zeng-Lei He, et al. Post-transplant diabetes mellitus in liver transplantation:Hangzhou experience. Hepatobiliary Pancreat Dis Int 2008,7(5):465-470.
32 Li L, Chang A, Naesens M, et al. Steroid-free immunosuppression since 1999: 129 pediatric renal transplants with sustained graft and patient benefits. Am J Transplant 2009;9(6):1362-1372.
33 Humar A, Crotteau S, Gruessner A, et al. Steroid minimization in liver transplant recipients:impact on hepatitis C recurrence and post-transplant diabetes. Clin Transplant.2007;21(4):526-531.
1. Waki K. UNOS Liver Registry:ten year survivals. Clin Transpl 2006; 29-39.
2. El-Serag HB, Mason AC. Rising incidence of hepatocellular carcinoma in the United States. N Engl J Med 1999; 340:745-750.
3. Deuffic S, Poynard T, Buffat L, et al. Trends in primary liver cancer. Lancet 1998; 351:214-215.
4. Taylor-Robinson SD, Foster GR, Arora S, et al. Increase in primary liver cancer in the UK,1979-94. Lancet 1997; 350:1142-1143
5. Zimmerman M, Busuttil RW. Long-term efficacy of percutaneous thermal ablation for patients with recurrent hepatocellular carcinoma. Nat Clin Pract Gastroenterol Hepatol 2006;3:250-251
6. Zimmerman MA, Ghobrial RM, TongMJ, et al. Recurrence of hepatocellular carcinoma following liver transplantation:A review of preoperative and postoperative prognostic indicators. Arch Surg 2008; 143(2):182-188.
7. Mazzaferro V, Regalia E, Doci R, et al. Liver transplantation for the treatment of small hepatocellular carcinoma in patients with cirrhosis.N Engl J Med 1996; 334(11):693-699.
8. Mazzaferro V. Results of liver transplantation:With or without Milan criteria? Liver Transpl 2007; 13:S44.
9. Vivarelli M, Cucchetti A, Piscaglia F, et al. Analysis of risk factors for tumor recurrence after liver transplantation for hepatocellular carcinoma: Key role of immunosuppression. Liver Transpl 2005; 11(5):497-503.
10. Vivarelli M, Cucchetti A, La Barba G, et al. Liver transplantation for hepatocellular carcinoma under calcineurin inhibitors. Reassessment of risk factors for tumor recurrence. Ann Surg 2008; 248 (5):857-862.
11. Yokoyama I, Carr B, Saitsu H, et al. Accelerated growth rates of recurrent hepatocellular carcinoma after liver transplantation. Cancer.1991;68:2095-2100.
12. Freise CE, Ferrell L, Liu T, et al. Effect of systemic cyclosporine on tumor recurrence after liver transplantation in a model of hepatocellular carcinoma. Transplantation.1999;67:510-513.
13. Guba M, Graeb C, Jauch KW, et al. Pro-and anti-cancer effects of immunosuppressive agents used in organ transplantation. Transplantation. 2004;77:1777-1782.
14. Geissler EK, Schlitt HJ. Immunosuppression for liver transplantation. Gut 2009; 58: 452-463.
15. Tisone G, Orlando G, Angelico M. Operational tolerance in clinical liver transplantation: emerging developments. Transpl Immunol 2007; 17:108-113.
16. Mazariegos GV, Reyes J, Marino IR, et al. Weaning of immunosuppression in liver transplant recipients. Transplantation 1997; 63:243-249.
17. Girlanda R, Rela M, Williams R, et al. Long-term outcome of immunosuppression withdrawal after liver transplantation. Transplant Proc 2005; 37:1708-1709.
18. Takatsuki M, Uemoto S, Inomata Y, et al. Weaning of immunosuppression in living donor liver transplant recipients. Transplantation 2001; 72:449-454
19. Eason JD, Cohen AJ, Nair S, et al. Tolerance:is it worth the risk? Transplantation 2005;79:1157-1159
20. Gonwa TA, Mai ML, Melton LB, et al. End-stage renal disease (ESRD) after orthotopic liver transplantation (OLTX) using calcineurin-based immunotherapy: risk of development and treatment. Transplantation 2001; 72:1934-1939.
21. Ojo AO, Held PJ, Port FK, et al. Chronic renal failure after transplantation of a nonrenal organ. N Engl J Med 2003; 349:931-940
22. Mannon RB. Therapeutic management of posttransplant diabetes mellitus. Transplant Rev 2008;22:116-124.
23. Jain A, Marcos A, Reyes J, et al. Tacrolimus for primary liver transplantation:12 to 15 years actual follow-up with safety profile. Transplant Proc 2005; 37: 1207-1210.
24. Foroncewicz B, Mucha K, Ryszkowska E,et al. Safety and efficacy of steroid-free immunosuppression with tacrolimus and daclizumab in liver transplant recipients: 6-year follow-up in a single center. Transplant Proc.2009;41 (8):3103-3106.
25. Carr B, Saitsu H, Iwatsuki S, Starzl TE. Accelerated growth rates of recurrent hepatocellular carcinoma after liver transplantation. Cancer 1991; 68: 2095-2100.
26. Ceriello A, Mezza F, Cozzolino S,et al. Role of immunosuppression in recurrence after liver transplantation for diethylnitrosamine-induced tumors in rats. Transpl Int 1994; 7 Suppll:S204-S207
27. Vivarelli M, Bellusci R, Cucchetti A, et al. Low recurrence rate of hepatocellular carcinoma after liver transplantation:better patient selection or lower immunosuppression? Transplantation 2002; 74:1746-1751.
28. Hojo M, Morimoto T, Maluccio M, et al. Cyclosporine induces cancer progression by a cell-autonomous mechanism. Nature 1999; 397:530-534
29. Levy G, Villamil F, Samuel D, et al. Results of lis2t, a multicenter, randomized study comparing cyclosporine microemulsion with C2 monitoring and tacrolimus with CO monitoring in de novo liver transplantation. Transplantation 2004;77:1632-1638.
30. Firpi RJ, Zhu H, Morelli G, et al. Cyclosporine suppresses hepatitis C virus in vitro and increases the chance of a sustained virological response after liver transplantation. Liver Transpl 2006; 12:51-57.
31. Henry SD, Metselaar HJ, Lonsdale RC, et al. Mycophenolic acid inhibits hepatitis C virus replication and acts in synergy with cyclosporin A and interferon-alpha. Gastroenterology,2006; 131:1452-1462.
32. Watashi K, Hijikata M, Hosaka M, et al. Cyclosporin A suppresses replication of hepatitis C virus genome in cultured hepatocytes. Hepatology 2003;38:1282-1288.
33. Guba M, von Breitenbuch P, Steinbauer M, et al. Rapamycin inhibits primary and metastatic tumor growth by antiangiogenesis:involvement of vascular endothelial growth factor. Nat Med 2002;8:128-135.
34. Koehl G, Andrassy J, Guba M, et al. Rapamycin protects allografts from rejection while simultaneously attacking tumors in immunosuppressed mice. Transplantation 2004;77:1319-1326.
35. Kneteman NM, Oberholzer J, Al Saghier M, et al. Sirolimus-based immunosuppression for liver transplantation in the presence of extended criteria for hepatocellular carcinoma. Liver Transpl.2004;10:1301-1311.
36. Pescovitz MD, Conti D, Dunn J, et al. Intravenous mycophenolate mofetil:safety, tolerability, and pharmacokinetics. Clin Transplant 2000; 14:179-188.
37. Fisher RA, Ham JM, Marcos A, et al. A prospective randomized trial of mycophenolate mofetil with neoral or tacrolimus after orthotopic liver transplantation. Transplantation 1998; 66:1616-1621.
38. Barkmann A, Nashan B, Schmidt HH, et al. Improvement of acute and chronic renal dysfunction in liver transplant patients after substitution of calcineurin inhibitors by mycophenolate mofetil. Transplantation 2000; 69:1886-1890.
39. Gao R, Lu Y, Xin YP, et al. The effects of different immunosuppressants on chronic allograft nephropathy by affecting the transforming growth factor-beta and Smads signal pathways. Transplant Proc 2006; 38:2154-2157.
40. Shihab FS, Bennet t WM, Yi H, et al. Combination therapy with sirolimus and mycophenolate mofetil:effects on the kidney and on transforming growth factor-betal. Transplantation 2004; 77:683-686.
41. Shihab FS, Bennet t WM, Yi H, et al. Mycophenolate mofetil ameliorates arteriolopathy and decreases transforming growth factor-betal in chronic cyclosporine nephrotoxicity. Am J Transplant 2003; 3:1550-1559.
42. Fairbanks KD, Thuluvath PJ. Mycophenolate mofetil monotherapy in liver transplant recipients:A single center experience. Liver Transpl 2004; 10: 1189-1194.
43. Schlitt HJ, Barkmann A, Boker KH, et al. Replacement of calcineurin inhibitors with mycophenolate mofetil in liver-transplant patients with renal dysfunction:A randomised controlled study. Lancet 2001; 357:587-591.
44. Stewart SF, Hudson M, Talbot D, et al. Mycophenolate mofetil monotherapy in liver transplantation. Lancet 2001; 357:609-610.
45. Orlando G, Baiocchi L, Cardillo A, et al. Switch to 1.5 grams MMF monotherapy for CNI-related toxicity in liver transplantation is safe and improves renal function, dyslipidemia, and hypertension. Liver Transpl 2007; 13:46-54.
46. Schmeding M, Neumann UP, Neuhaus R, Neuhaus P. Mycophenolate mofetil in liver transplantation—Is monotherapy safe? Clin Transplant 2006; 20(Suppl 17): 75-79.
47. S. Dharancy, A. Iannelli, A. Hulin. Mycophenolate Mofetil Monotherapy for Severe Side Effects of Calcineurin Inhibitors Following Liver Transplantation. American Journal of Transplantation 2009; 9:610-613
48. Stegal MD, Wachs ME, Everson G, et al. Prednisone withdrawal 14 days after liver transplantation with mycophenolate:a prospective trial of cyclosporine and tacrolimus. Transplantation.1997; 64:1755-1760.
49. Boucher A, Lord H, Collette S, et al. Cytomegalovirus infection in kidney transplant recipients:Evolution of approach through three eras. Transplant Proc 2006; 38:3506-3508.
50. Jorge S, Guerra J, Santana A, et al. Mycophenolate mofetil:ten years'experience of a renal transplant unit. Transplant Proc 2008; 81:700-704.
51. Sarmiento JM, Dockrell DH, Schwab TR, et al. Mycophenolate mofetil increases cytomegalovirus invasive organ disease in renal transplant patients. Clin Transplant 2000; 14:136-138.
52. Smak Gregoor PJ, van Gelder T, van Riemsdijk-van Overbeeke IC, et al. Unusual presentation of herpes virus infections in renal transplant recipients exposed to high mycophenolic acid plasma concentrations. Transpl Infect Dis 2003; 5:79-83.
53. Herrero JI, Quiroga J, Sangro B, et al. Herpes zoster after liver transplantation: incidence, risk factors, and complications. Liver Transpl 2004; 10:1140-1143
54. Neff RT, Hurst FP, Falta EM, et al. Progressive multifocal leukoencephalopathy and use of mycophenolate mofetil after kidney transplantation. Transplantation 2008; 86:1474-1478.
55. Jain A, Kashyap R, Demetris AJ, et al. A prospectively randomized trial of mycophenolate mofetil in liver transplant recipients with recurrent HCV. Liver Transpl 2002; 8:40-46.
56. Engl T, Makarevic J, Relja B,et al. Mycophenolate mofetil modulates adhesion receptors of the betal integrin family on tumor cells:impact on tumor recurrence and malignancy. BMC Cancer.2005(11):1-11
57. Engl T, Relja B, Natsheh I. Modulation of the CXC-chemokine expression profile on tumor cells by the immunosuppressive drug mycophenolate mofetil. Int J Mol Med.2005 Apr; 15(4):641-647.
58. Fulton B, Markham A. Mycophenolate mofetil. A review of its pharmacodynamic and pharmacokinetic properties and clinical efficacy in renal transplantation. Drugs 1996; 51:278-298.
59. Stangl JR, Carroll KL, Illichmann M, et al. Effect of antimetabolite immunosuppressants on Flaviviridae, including hepatitis C virus. Transplantation 2004; 77:562-567.
60. Nebbia G, Mattes FM, Sabin CA, et al. Differential effects of prednisolone and azathioprine on the development of human cytomegalovirus replication post liver transplantation. Transplantation 2007;84:605-610.
61. G.Germania, M.Pleguezueloa, F. Villamilb. Azathioprine in Liver Transplantation: A Reevaluation of Its Use and a Comparison with Mycophenolate Mofetil. American Journal of Transplantation 2009; 9:1725-1731.
62. Mita MM, Mita A, Rowinsky EK. The molecular target of rapamycin (mTOR) as a therapeutic target against cancer. Cancer Biol Ther 2003; 2:S169-S177.
63. Diekmann F, Gutierrez-Dalmau A, Lopez S, et al. Influence of sirolimus on proteinuria in de novo kidney transplantation with expanded criteria donors: comparison of two CNI-free protocols. Nephrol Dial Transpl 2007;22:2316-2321.
64. Bumbea V, Kamar N, Ribes D, et al. Long-term results in renal transplant patients with allograft dysfunction after switching from calcineurin inhibitors to sirolimus. Nephrol Dial Transplant 2005;20:2517-2523.
65. Letavernier E, Pe'raldi MN, Pariente A, et al. Proteinuria following a switch from calcineurin inhibitors to sirolimus. Transplantation 2005;80:1198-1203.
66. Kniepeiss D, Iberer F, Grasser B, et al. Sirolimus and mycophenolate mofetil after liver transplantation. Transpl Int 2003; 16:504-509.
67. Fairbanks KD, Eustace JA, Fine D, et al. Renal function improves in liver transplant recipients when switched from a calcineurin inhibitor to sirolimus. Liver Transpl 2003; 9:1079-1085.
68. Nair S, Eason J, Loss G. Sirolimus monotherapy in nephrotoxicity due to calcineurin inhibitors in liver transplant recipients. Liver Transpl 2003; 9: 126-129
69. D. Dubay, R. J. Smith, K. G Qiu,et al.Sirolimus in liver transplant recipients with renal dysfunction offers no advantage over low-dose calcineurin inhibitor regimens. Liver Transplantation,2008; 14(5):651-659.
70. Dean PG, Lund WJ, Larson TS, et al. Wound-healing complications after kidney transplantation:a prospective, randomized comparison of sirolimus and tacrolimus. Transplantation 2004; 77:1555-1561.
71. Guba M, Yezhelyev M, Eichhorn ME, et al. Rapamycin induces tumor-specific thrombosis via tissue factor in the presence of VEGF. Blood 2005;105:4463-4469.
72. Schumacher G, Oidtmann M, Rueggeberg A, et al. Sirolimus inhibits growth of human hepatoma cells alone or combined with tacrolimus, while tacrolimus promotes cell growth. World J Gastroenterol 2005;11:1420-1425.
73. Piguet AC, Semela D, Keogh A, et al. Inhibition of mTOR in combination with doxorubicin in an experimental model of hepatocellular carcinoma. J Hepatol 2008;49:78-87.
74. Wang Z, Zhou J, Fan J, et al. Effect of rapamycin alone and in combination with sorafenib in an orthotopic model of human hepatocellular carcinoma. Clin Cancer Res 2008;14:5124-5130.
75. Guertin DA, Sabatini DM. Defining the role of mTOR in cancer. Cancer Cell 2007;12:9-22.
76. Luan FL, Hojo M, Maluccio M, et al. Rapamycin blocks tumor progression: unlinking immunosuppression from antitumor efficacy. Transplantation 2002;73:1565-1572.
77. Zhou J, Wulfkuhle J, Zhang H, et al. Activation of the PTEN/mTOR/STAT3 pathway in breast cancer stem-like cells is required for viability and maintenance. Proc Natl Acad Sci U S A 2007;104:16158-16163.
78. Hudes G, Carducci M, Tomczak P, et al. Temsirolimus, interferon alfa, or both for advanced renal-cell carcinoma. N Engl J Med 2007;356:2271-2281.
79. Motzer RJ, Escudier B, Oudard S, et al. Efficacy of everolimus in advanced renal cell carcinoma: a double-blind, randomised, placebo-controlled phase III trial. Lancet 2008;372:449-456.
80. Zimmerman MA, Trotter JF, Wachs M, et al. Sirolimus-based immunosuppression following liver transplantation for hepatocellular carcinoma. Liver Transpl 2008; 14:633-638
81. Toso C, Meeberg GA, Bigam DL, et al. De novo sirolimus-based immunosuppression after liver transplantation for hepatocellular carcinoma: long-term outcomes and side effects. Transplantation 2007; 83:1162-1168,
82. Jian Zhou, Jia Fan, Zheng Wang, et al. Conversion to sirolimus immunosuppression in liver transplantation recipients with hepatocellular carcinoma: Report of an initial experience. World J Gastroenterol 2006; 12(19): 3114-3118.
83. J. Zhou, Z. Wang, Z.-Q. Wu, et al. Sirolimus-based immunosuppression therapy in liver transplantation for patients with hepatocellular carcinoma exceeding the Milan Criteria. Transplantation Proceedings,2008,40:3548-3553
84. Marco Vivarelli, Alessandro Dazzi, Matteo Zanello, et al. Effect of different immunosuppressive schedules on recurrence-free survival after liver transplantation for hepatocellular carcinoma. Transplantation 2010;89:227-231
85. Christian Toso, Shaheed Merani, David L. Bigam, et al. Sirolimus-Based Immunosuppression Is Associated with Increased Survival After Liver Transplantation for Hepatocellular Carcinoma. HEPATOLOGY,2010; 51(2):1-7.
86. Chinnakotla S, Davis GL, Vasani S, et al. Impact of sirolimus on the recurrence of hepatocellular carcinoma after liver transplantation. Liver Transpl. 2009;15(12):1834-1842.
87. Schlitt HJ, Barkmann A, Boker KH, et al. Replacement of calcineurin inhibitors with mycophenolate mofetil in liver-transplant patients with renal dysfunction: a randomised controlled study. Lancet 2001; 357:587-591.
88. Taylor AL, Watson CJ, Bradley JA. Immunosuppressive agents in solid organ transplantation:Mechanisms of action and therapeutic efficacy. Crit Rev Oncol Hematol 2005; 56:23-46.
89. Greig P, Lilly L, Scudamore C, et al. Early steroid withdrawal after liver transplantation: the Canadian tacrolimu versus microemulsion cyclosporin A trial:1-year follow-up. Liver Transpl 2003; 9:587-595
90. Vivarelli M, Burra P, La Barba G, et al. Influence of steroids on HCV recurrence after liver transplantation:A prospective study. J Hepatol 2007;47:793-798.
91. Segev DL, Sozio SM, Shin EJ, et al. Steroid avoidance in liver transplantation: meta-analysis and meta-regression of randomized trials. Liver Transpl 2008;14:512-525.
92. Hong JC, Kahan BD. Immunosuppressive agents in organ transplantation:past, present, and future. Semin Nephrol 2000; 20:108-125
93. Wilde MI, Goa KL. Muromonab CD3:a reappraisal of its pharmacology and use as prophylaxis of solid organ transplant rejection. Drugs 1996; 51:865-894
94. Caillat-Zucman S, Blumenfeld N, Legendre C, et al. The OKT3 immunosuppressive effect. In situ antigenic modulation of human graft-infiltrating T cells. Transplantation 1990; 49:156-160
95. Colonna JO 2nd, Goldstein LI, Brems JJ, et al. A prospective study on the use of monoclonal anti-T3-cell antibody (OKT3) to treat steroid-resistant liver transplant rejection. Arch Surg 1987; 122:1120-1123.
96. Solomon H, Gonwa TA, Mor E, et al. OKT3 rescue for steroid-resistant rejection in adult liver transplantation. Transplantation 1993; 55:87-91.
97. 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.
98. Everson GT. Impact of immunosuppressive therapy on recurrence of hepatitis C. Liver Transpl 2002; 8:S19-S27.
99. Thomas Decaens, Francoise Roudot-Thoraval,et al. Role of immunosuppression and tumor differentiation in predicting recurrence after liver transplantation for hepatocellular carcinoma:A multicenter study of 412 patients.World J Gastroenterol.2006;12(45):7319-7325.
100. Zimmerman MA, Kelly MA, Campsen J,et al. The influence of OKT3 therapy on hepatocellular carcinoma recurrence following liver transplantation.Clin Transplant.2009. [Epub ahead of print]
101. Neuhaus P, Clavien PA, Kittur D, et al. Improved treatment response with basiliximab immunoprophylaxis after liver transplantation:results from a double-blind randomized placebo-controlled trial. Liver Transpl 2002;8:132-142.
102. Liu CL, Fan ST, Lo CM, et al. Interleukin-2 receptor antibody (basiliximab) for immunosuppressive induction therapy after liver transplantation:a protocol with early elimination of steroids and reduction of tacrolimus dosage. Liver Transpl 2004; 10:728-733.
103. Ramirez CB, Doria C, Di Francesco F, et al. Anti-IL2 induction in liver transplantation with 93% rejection-free patient and graft survival at 18 months. J Surg Res 2007; 138:198-204.
104. Christian Toso, Shaheed Merani, David L. Bigam, et al. Sirolimus-Based Immunosuppression Is Associated with Increased Survival After Liver Transplantation for Hepatocellular Carcinoma. HEPATOLOGY,2010; 51(2):1-7.
105. 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.
106. Magliocca JF, Knechtle SJ. The evolving role of alemtuzumab (Campath-1H) for immunosuppressive therapy in organ transplantation. Transpl Int 2006;19:705-714.
107. Pascual J, Bloom D, Torrealba J, et al. Calcineurin inhibitor withdrawal after renal transplantation with alemtuzumab:clinical outcomes and effect on T-regulatory cells. Am J Transplant 2008;8:1529-1536.
108. Barth RN, Janus CA, Lillesand CA, et al. Outcomes at 3 years of a prospective pilot study of Campath-1H and sirolimus immunosuppression for renal transplantation. Transpl Int 2006;19:885-892.
109. Bloom DD, Chang Z, Fechner JH, et al. CD4+CD25+FOXP3+regulatory T cells increase de novo in kidney transplant patients after immunodepletion with Campath-1H. Am J Transplant 2008;8:793-802.
110. Tzakis AG, Tryphonopoulos P, Kato T, et al. Preliminary experience with alemtuzumab (Campath-1H) and low-dose tacrolimus immunosuppression in adult liver transplantation.Transplantation 2004; 77:1209-1214.
111. Marcos A, Eghtesad B, Fung JJ, et al. Use of alemtuzumab and tacrolimus monotherapy for cadaveric liver transplantation:with particular reference to hepatitis C virus. Transplantation 2004; 78:966-971.
112. Mueller TM. Thymoglobulin:an immunologic overview. Curr Opin Organ Transplant 2003; 8:305-12.
113. Feng X, Kajigaya S, Solomou EE, et al. Rabbit ATG but not horse ATG promotes expansion of functional CD4+CD25highFOXP3+ regulatory T cells in vitro. Blood 2008; 111:3675-3683.
114. Lopez M, Clarkson MR, Albin M, et al. A novel mechanism of action for anti-thymocyte globulin: induction of CD4+CD25+Foxp3+ regulatory T cells. J Am Soc Nephrol 2006; 17:2844-2853.
115. Lytton SD, Denton CP, Nutzenberger AM. Treatment of autoimmune disease with rabbit anti-T lymphocyte globulin:clinical efficacy and potential mechanisms of action. Ann N Y Acad Sci 2007; 1110:285-296
116. 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.
117. 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.
118. 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.
119. Eason JD, Loss GE, Blazek J,et al. Steroid-free liver transplantation using rabbit antithymocyte globulin induction:results of a prospective randomized trial. Liver Transpl 2001; 7:693-697.
120. Eason JD, Nair S, Cohen AJ, et al. Steroid-free liver transplantation using rabbit antithymocyte globulin and early tacrolimus monotherapy. Transplantation 2003; 75:1396-1399.
121. Oettinger CW, D'Souza M, Milton GV. In vitro comparison of cytokine release from antithymocyte serum and OKT3. Inhibition with soluble and microencapsulated neutralizing antibodies. Transplantation 1996; 62:1690-1693.
122. Guttmann RD, Caudrelier P, Alberici G, Touraine JL. Pharmacokinetics, foreign protein immune response, cytokine release, and lymphocyte subsets in patients receiving thymoglobuline and immunosuppression. Transplant Proc 1997; 29: 24S-26S
123. Buchler M, Hurault de Ligny B, Madec C, Lebranchu Y.Induction therapy by anti-thymocyte globulin (rabbit) in renal transplantation: a 1-yr follow-up of safety and efficacy. Clin Transplant 2003; 17:539-545.
124. Ducloux D, Kazory A, Challier B, et al. Long-term toxicity of antithymocyte globulin induction may vary with choice of agent:a single-center retrospective study. Transplantation 2004; 77:1029-1033.
125. Lundquist AL, Chari RS, Wood JH, et al. Serum sickness following rabbit antithymocyte-globulin induction in a liver transplant recipient: case report and literature review. Liver Transpl 2007; 13:647-650.
126. Larsen CP, Pearson TC, Adams AB, et al. Rational development of LEA29Y (belatacept), a high affinity variant of CTLA4-Ig with potent immunosuppressive properties. Am J Transplant 2005; 5:443-453.
127. Vincenti F, Larsen C, Durrbach A, et al. Co-stimulation blockade with belatacept in renal transplantation.. N Eng J Med 2005; 353:770-781.
128. Pribila JT, Quale AC, Mueller KL, Shimizu Y. Integrins and T cell-mediated immunity. Annu Rev Immunol 2004; 22:157-180.
129. Dedrick RL, Walicke P, Garovoy M. Anti-adhesion antibodies efalizumab, a humanized anti-CDlla monoclonal antibody. Transpl Immunol 2002; 9:181-186.
130. Vincenti F, Mendez R, Pescovitz M, et al. A phase I/II randomized open-label multicenter trial of efalizumab, a humanized anti-CDlla, anti-LFA-1 in renal transplantation. Am J Transplant 2007;7:1770-1777.
131. O'Shea JJ. Jaks. STATs, cytokine signal transduction and immunoregulation:are we there yet? Immunity 1997; 7:1-11.
132. Ozaki K, Spolski R, Feng CG, et al. A critical role for IL-21 in regulating immunoglobulin production..Science 2002; 298:1630-1634.
133. Vincenti F, Kirk AD. What's next in the pipeline. Am J Transplant 2008; 8: 1972-1981.
134. Krueger GG. Clinical response to alefacept:results of a phase 3 study of intravenous administration of alefacept in patients with chronic plaque psoriasis. J Eur Acad Dermatol Venereol 2003; 17 Suppl 2:17-24.
2 Perry I, Neuberger J. Immunosuppression:towards a logical approach in liver transplantation. Clin Exp Immunol 2005; 139:2-10.
3 Padbury RT, Toogood GJ, McMaster P. Withdrawal of immunosuppression in liver allograft recipients. Liver Transpl Surg 1998;4:242-248.
4. Stegall MD, Wachs ME, Everson G, et al. Prednisone withdrawal 14 days after liver transplantation with mycophenolate:a prospective trial of cyclosporine and tacrolimus. Transplantation 1997;64:1755-1760.
5 Grinyo JM, Campistol JM, Paul J,et al. Pilot randomized study of early tacrolimus withdrawal from a regimen with sirolimus plus tacrolimus in kidney transplantation. Am J Transplant 2004;4:1308-1314
6 Klupp J, Pfitzmann R, Langrehr JM, et al. Indications of mycophenolate mofetil in liver transplantation.Transplantation 2005;80:S142-S146.
7 Wiesner RH, Shorr JS, Steffen BJ,et al. Mycophenolate mofetil combination therapy imp roves long-term outcomes after liver transplantation in patients with and without hepatitis C. Liver Transpl 2005,11(7):750-759.
8 Pfitzmann R, Klup PJ, Langrehr JM, et al. Mycophenolatemofetil for immunosupp ression after liver transp lantation:a follow-up study of 191 patients. Transplantation 2003,76 (1):130-136.
9 Sato K, Sekiguchi S, Kawagishi N, et al.Unique histopathological features of graft biopsies with liver function abnormalities in living donor liver transplant patients receiving basiliximab induction therapy.Clin Transplant 2010. [Epub ahead of print]
10 Fisher RA, Ham JM, Marcos A, et al. A prospective randomized trial of mycophenolate mofetil with neoral or tacrolimus after orthotopic liver transplantation. Transplantation 1998; 66:1616-1621.
11 Barkmann A, Nashan B, Schmidt HH, et al. Improvement of acute and chronic renal dysfunction in liver transplant patients after substitution of calcineurin inhibitors by mycophenolate mofetil. Transplantation 2000; 69:1886-1890.
12 S. Dharancy, A. Iannelli, A. Hulin. Mycophenolate Mofetil Monotherapy for Severe Side Effects of Calcineurin Inhibitors Following Liver Transplantation. American Journal of Transplantation 2009; 9:610-613.
13 Shipkova M, Armstrong VW, Oellerich M, et al. Mycophenolate mofetil in organ transplantation:focus on metabolism, safety and tolerability. Expert Opin Drug Metab Toxicol 2005;1:505-526.
14 Allison AC, Almquist SJ, Muller CD, et al. In vitro immunosuppressive effects of mycophenolic acid and an ester pro-drug, RS-61443. Transplant Proc 1991;23(2 Suppl2):10-14
15 Klupp J, Glanemann M, Bechstein WO, et al. Mycophenolate mofetil in combinati on with tacrolimus versus Neoral after liver transplantation.Transplant Proc 1999;31:1113-1114
16 Platz KP, Mueller AR, Neuhaus P. Indications for mycofenolate mofetil therapy after liver transplantation. Transplant Proc,1997;29:2880-2881
17 Aw MM, Verma A, Rela M, et al. Long-term outcome of mycophenolate mofetil rescue therapy for resistant acute allograft rejection in pediatric liver transplant recipients.Liver Transpl.2008;14(9):1303-1308.
18 Wietzke-Braun P, Braun F, Sattler B, et al. Initial steroid-free immunosuppression after liver transplantation in recipients with hepatitis c virus related cirrhosis.World J Gastroenterol 2004;10(15):2213-2217.
19 Hebert MF, Ascher NL, Lake JR, et al. Four-year follow-up of mycophenolate mofetil for graft rescue in liver allograft recipients. Transplantation1999;67(5):707-712.
20 Robaeys G, Cassiman D, Verslype C, et al. Successful conversion from.mycophenolate mofetil to enteric-coated mycophenolate sodium (myfortic) in liver transplant patients with gastrointestinal side effects. Transplant Proc.2009;41(2):610-613.
21 Stegal MD, Wachs ME, Everson G, et al. Prednisone withdrawal 14 days after liver transplantation with mycophenolate:a prospective trial of cyclosporine and tacrolimus. Transplantation 1997; 64:1755-1760.
22 Boucher A, Lord H, Collette S, et al. Cytomegalovirus infection in kidney transplant recipients:Evolution of approach through three eras. Transplant Proc 2006; 38:3506-3508.
23 Jorge S, Guerra J, Santana A, et al. Mycophenolate mofetil:ten years' experience of a renal transplant unit. Transplant Proc 2008; 81:700-704.
24 Sarmiento JM, Dockrell DH, Schwab TR, et al. Mycophenolate mofetil increases cytomegalovirus invasive organ disease in renal transplant patients. Clin Transplant 2000; 14:136-138.
25 Smak Gregoor PJ, van Gelder T, van Riemsdijk-van Overbeeke IC, et al. Unusual presentation of herpes virus infections in renal transplant recipients exposed to high mycophenolic acid plasma concentrations. Transpl Infect Dis 2003; 5:79-83.
26 Herrero JI, Quiroga J, Sangro B, et al. Herpes zoster after liver transplantation: incidence, risk factors, and complications. Liver Transpl 2004; 10:1140-1143
27 Neff RT, Hurst FP, Falta EM, et al. Progressive multifocal leukoencephalopathy and use of mycophenolate mofetil after kidney transplantation. Transplantation 2008; 86:1474-1478.
28 Engl T, Makarevic J,Relja B,et al.Mycophenolate mofetil modulates adhesion receptors of the betal integrin family on tumor cells:impact on tumor recurrence and malignancy. BMC Cancer.2005;5(4):1-11
29 Engl T, Relja B, Natsheh I. Modulation of the CXC-chemokine expression profile on tumor cells by the immunosuppressive drug mycophenolate mofetil. Int J Mol Med.2005;15(4):641-647.
30 Gnatta D, Keitel E, Heineck I, et al. Use of tacrolimus and the development of posttransplant diabetes mellitus:a Brazilian single-center, observational study. Transplant Proc 2010;42(2):475-478.
31 Xiao Xu, Qi Ling, Zeng-Lei He, et al. Post-transplant diabetes mellitus in liver transplantation:Hangzhou experience. Hepatobiliary Pancreat Dis Int 2008,7(5):465-470.
32 Li L, Chang A, Naesens M, et al. Steroid-free immunosuppression since 1999: 129 pediatric renal transplants with sustained graft and patient benefits. Am J Transplant 2009;9(6):1362-1372.
33 Humar A, Crotteau S, Gruessner A, et al. Steroid minimization in liver transplant recipients:impact on hepatitis C recurrence and post-transplant diabetes. Clin Transplant.2007;21(4):526-531.
1. Waki K. UNOS Liver Registry:ten year survivals. Clin Transpl 2006; 29-39.
2. El-Serag HB, Mason AC. Rising incidence of hepatocellular carcinoma in the United States. N Engl J Med 1999; 340:745-750.
3. Deuffic S, Poynard T, Buffat L, et al. Trends in primary liver cancer. Lancet 1998; 351:214-215.
4. Taylor-Robinson SD, Foster GR, Arora S, et al. Increase in primary liver cancer in the UK,1979-94. Lancet 1997; 350:1142-1143
5. Zimmerman M, Busuttil RW. Long-term efficacy of percutaneous thermal ablation for patients with recurrent hepatocellular carcinoma. Nat Clin Pract Gastroenterol Hepatol 2006;3:250-251
6. Zimmerman MA, Ghobrial RM, TongMJ, et al. Recurrence of hepatocellular carcinoma following liver transplantation:A review of preoperative and postoperative prognostic indicators. Arch Surg 2008; 143(2):182-188.
7. Mazzaferro V, Regalia E, Doci R, et al. Liver transplantation for the treatment of small hepatocellular carcinoma in patients with cirrhosis.N Engl J Med 1996; 334(11):693-699.
8. Mazzaferro V. Results of liver transplantation:With or without Milan criteria? Liver Transpl 2007; 13:S44.
9. Vivarelli M, Cucchetti A, Piscaglia F, et al. Analysis of risk factors for tumor recurrence after liver transplantation for hepatocellular carcinoma: Key role of immunosuppression. Liver Transpl 2005; 11(5):497-503.
10. Vivarelli M, Cucchetti A, La Barba G, et al. Liver transplantation for hepatocellular carcinoma under calcineurin inhibitors. Reassessment of risk factors for tumor recurrence. Ann Surg 2008; 248 (5):857-862.
11. Yokoyama I, Carr B, Saitsu H, et al. Accelerated growth rates of recurrent hepatocellular carcinoma after liver transplantation. Cancer.1991;68:2095-2100.
12. Freise CE, Ferrell L, Liu T, et al. Effect of systemic cyclosporine on tumor recurrence after liver transplantation in a model of hepatocellular carcinoma. Transplantation.1999;67:510-513.
13. Guba M, Graeb C, Jauch KW, et al. Pro-and anti-cancer effects of immunosuppressive agents used in organ transplantation. Transplantation. 2004;77:1777-1782.
14. Geissler EK, Schlitt HJ. Immunosuppression for liver transplantation. Gut 2009; 58: 452-463.
15. Tisone G, Orlando G, Angelico M. Operational tolerance in clinical liver transplantation: emerging developments. Transpl Immunol 2007; 17:108-113.
16. Mazariegos GV, Reyes J, Marino IR, et al. Weaning of immunosuppression in liver transplant recipients. Transplantation 1997; 63:243-249.
17. Girlanda R, Rela M, Williams R, et al. Long-term outcome of immunosuppression withdrawal after liver transplantation. Transplant Proc 2005; 37:1708-1709.
18. Takatsuki M, Uemoto S, Inomata Y, et al. Weaning of immunosuppression in living donor liver transplant recipients. Transplantation 2001; 72:449-454
19. Eason JD, Cohen AJ, Nair S, et al. Tolerance:is it worth the risk? Transplantation 2005;79:1157-1159
20. Gonwa TA, Mai ML, Melton LB, et al. End-stage renal disease (ESRD) after orthotopic liver transplantation (OLTX) using calcineurin-based immunotherapy: risk of development and treatment. Transplantation 2001; 72:1934-1939.
21. Ojo AO, Held PJ, Port FK, et al. Chronic renal failure after transplantation of a nonrenal organ. N Engl J Med 2003; 349:931-940
22. Mannon RB. Therapeutic management of posttransplant diabetes mellitus. Transplant Rev 2008;22:116-124.
23. Jain A, Marcos A, Reyes J, et al. Tacrolimus for primary liver transplantation:12 to 15 years actual follow-up with safety profile. Transplant Proc 2005; 37: 1207-1210.
24. Foroncewicz B, Mucha K, Ryszkowska E,et al. Safety and efficacy of steroid-free immunosuppression with tacrolimus and daclizumab in liver transplant recipients: 6-year follow-up in a single center. Transplant Proc.2009;41 (8):3103-3106.
25. Carr B, Saitsu H, Iwatsuki S, Starzl TE. Accelerated growth rates of recurrent hepatocellular carcinoma after liver transplantation. Cancer 1991; 68: 2095-2100.
26. Ceriello A, Mezza F, Cozzolino S,et al. Role of immunosuppression in recurrence after liver transplantation for diethylnitrosamine-induced tumors in rats. Transpl Int 1994; 7 Suppll:S204-S207
27. Vivarelli M, Bellusci R, Cucchetti A, et al. Low recurrence rate of hepatocellular carcinoma after liver transplantation:better patient selection or lower immunosuppression? Transplantation 2002; 74:1746-1751.
28. Hojo M, Morimoto T, Maluccio M, et al. Cyclosporine induces cancer progression by a cell-autonomous mechanism. Nature 1999; 397:530-534
29. Levy G, Villamil F, Samuel D, et al. Results of lis2t, a multicenter, randomized study comparing cyclosporine microemulsion with C2 monitoring and tacrolimus with CO monitoring in de novo liver transplantation. Transplantation 2004;77:1632-1638.
30. Firpi RJ, Zhu H, Morelli G, et al. Cyclosporine suppresses hepatitis C virus in vitro and increases the chance of a sustained virological response after liver transplantation. Liver Transpl 2006; 12:51-57.
31. Henry SD, Metselaar HJ, Lonsdale RC, et al. Mycophenolic acid inhibits hepatitis C virus replication and acts in synergy with cyclosporin A and interferon-alpha. Gastroenterology,2006; 131:1452-1462.
32. Watashi K, Hijikata M, Hosaka M, et al. Cyclosporin A suppresses replication of hepatitis C virus genome in cultured hepatocytes. Hepatology 2003;38:1282-1288.
33. Guba M, von Breitenbuch P, Steinbauer M, et al. Rapamycin inhibits primary and metastatic tumor growth by antiangiogenesis:involvement of vascular endothelial growth factor. Nat Med 2002;8:128-135.
34. Koehl G, Andrassy J, Guba M, et al. Rapamycin protects allografts from rejection while simultaneously attacking tumors in immunosuppressed mice. Transplantation 2004;77:1319-1326.
35. Kneteman NM, Oberholzer J, Al Saghier M, et al. Sirolimus-based immunosuppression for liver transplantation in the presence of extended criteria for hepatocellular carcinoma. Liver Transpl.2004;10:1301-1311.
36. Pescovitz MD, Conti D, Dunn J, et al. Intravenous mycophenolate mofetil:safety, tolerability, and pharmacokinetics. Clin Transplant 2000; 14:179-188.
37. Fisher RA, Ham JM, Marcos A, et al. A prospective randomized trial of mycophenolate mofetil with neoral or tacrolimus after orthotopic liver transplantation. Transplantation 1998; 66:1616-1621.
38. Barkmann A, Nashan B, Schmidt HH, et al. Improvement of acute and chronic renal dysfunction in liver transplant patients after substitution of calcineurin inhibitors by mycophenolate mofetil. Transplantation 2000; 69:1886-1890.
39. Gao R, Lu Y, Xin YP, et al. The effects of different immunosuppressants on chronic allograft nephropathy by affecting the transforming growth factor-beta and Smads signal pathways. Transplant Proc 2006; 38:2154-2157.
40. Shihab FS, Bennet t WM, Yi H, et al. Combination therapy with sirolimus and mycophenolate mofetil:effects on the kidney and on transforming growth factor-betal. Transplantation 2004; 77:683-686.
41. Shihab FS, Bennet t WM, Yi H, et al. Mycophenolate mofetil ameliorates arteriolopathy and decreases transforming growth factor-betal in chronic cyclosporine nephrotoxicity. Am J Transplant 2003; 3:1550-1559.
42. Fairbanks KD, Thuluvath PJ. Mycophenolate mofetil monotherapy in liver transplant recipients:A single center experience. Liver Transpl 2004; 10: 1189-1194.
43. Schlitt HJ, Barkmann A, Boker KH, et al. Replacement of calcineurin inhibitors with mycophenolate mofetil in liver-transplant patients with renal dysfunction:A randomised controlled study. Lancet 2001; 357:587-591.
44. Stewart SF, Hudson M, Talbot D, et al. Mycophenolate mofetil monotherapy in liver transplantation. Lancet 2001; 357:609-610.
45. Orlando G, Baiocchi L, Cardillo A, et al. Switch to 1.5 grams MMF monotherapy for CNI-related toxicity in liver transplantation is safe and improves renal function, dyslipidemia, and hypertension. Liver Transpl 2007; 13:46-54.
46. Schmeding M, Neumann UP, Neuhaus R, Neuhaus P. Mycophenolate mofetil in liver transplantation—Is monotherapy safe? Clin Transplant 2006; 20(Suppl 17): 75-79.
47. S. Dharancy, A. Iannelli, A. Hulin. Mycophenolate Mofetil Monotherapy for Severe Side Effects of Calcineurin Inhibitors Following Liver Transplantation. American Journal of Transplantation 2009; 9:610-613
48. Stegal MD, Wachs ME, Everson G, et al. Prednisone withdrawal 14 days after liver transplantation with mycophenolate:a prospective trial of cyclosporine and tacrolimus. Transplantation.1997; 64:1755-1760.
49. Boucher A, Lord H, Collette S, et al. Cytomegalovirus infection in kidney transplant recipients:Evolution of approach through three eras. Transplant Proc 2006; 38:3506-3508.
50. Jorge S, Guerra J, Santana A, et al. Mycophenolate mofetil:ten years'experience of a renal transplant unit. Transplant Proc 2008; 81:700-704.
51. Sarmiento JM, Dockrell DH, Schwab TR, et al. Mycophenolate mofetil increases cytomegalovirus invasive organ disease in renal transplant patients. Clin Transplant 2000; 14:136-138.
52. Smak Gregoor PJ, van Gelder T, van Riemsdijk-van Overbeeke IC, et al. Unusual presentation of herpes virus infections in renal transplant recipients exposed to high mycophenolic acid plasma concentrations. Transpl Infect Dis 2003; 5:79-83.
53. Herrero JI, Quiroga J, Sangro B, et al. Herpes zoster after liver transplantation: incidence, risk factors, and complications. Liver Transpl 2004; 10:1140-1143
54. Neff RT, Hurst FP, Falta EM, et al. Progressive multifocal leukoencephalopathy and use of mycophenolate mofetil after kidney transplantation. Transplantation 2008; 86:1474-1478.
55. Jain A, Kashyap R, Demetris AJ, et al. A prospectively randomized trial of mycophenolate mofetil in liver transplant recipients with recurrent HCV. Liver Transpl 2002; 8:40-46.
56. Engl T, Makarevic J, Relja B,et al. Mycophenolate mofetil modulates adhesion receptors of the betal integrin family on tumor cells:impact on tumor recurrence and malignancy. BMC Cancer.2005(11):1-11
57. Engl T, Relja B, Natsheh I. Modulation of the CXC-chemokine expression profile on tumor cells by the immunosuppressive drug mycophenolate mofetil. Int J Mol Med.2005 Apr; 15(4):641-647.
58. Fulton B, Markham A. Mycophenolate mofetil. A review of its pharmacodynamic and pharmacokinetic properties and clinical efficacy in renal transplantation. Drugs 1996; 51:278-298.
59. Stangl JR, Carroll KL, Illichmann M, et al. Effect of antimetabolite immunosuppressants on Flaviviridae, including hepatitis C virus. Transplantation 2004; 77:562-567.
60. Nebbia G, Mattes FM, Sabin CA, et al. Differential effects of prednisolone and azathioprine on the development of human cytomegalovirus replication post liver transplantation. Transplantation 2007;84:605-610.
61. G.Germania, M.Pleguezueloa, F. Villamilb. Azathioprine in Liver Transplantation: A Reevaluation of Its Use and a Comparison with Mycophenolate Mofetil. American Journal of Transplantation 2009; 9:1725-1731.
62. Mita MM, Mita A, Rowinsky EK. The molecular target of rapamycin (mTOR) as a therapeutic target against cancer. Cancer Biol Ther 2003; 2:S169-S177.
63. Diekmann F, Gutierrez-Dalmau A, Lopez S, et al. Influence of sirolimus on proteinuria in de novo kidney transplantation with expanded criteria donors: comparison of two CNI-free protocols. Nephrol Dial Transpl 2007;22:2316-2321.
64. Bumbea V, Kamar N, Ribes D, et al. Long-term results in renal transplant patients with allograft dysfunction after switching from calcineurin inhibitors to sirolimus. Nephrol Dial Transplant 2005;20:2517-2523.
65. Letavernier E, Pe'raldi MN, Pariente A, et al. Proteinuria following a switch from calcineurin inhibitors to sirolimus. Transplantation 2005;80:1198-1203.
66. Kniepeiss D, Iberer F, Grasser B, et al. Sirolimus and mycophenolate mofetil after liver transplantation. Transpl Int 2003; 16:504-509.
67. Fairbanks KD, Eustace JA, Fine D, et al. Renal function improves in liver transplant recipients when switched from a calcineurin inhibitor to sirolimus. Liver Transpl 2003; 9:1079-1085.
68. Nair S, Eason J, Loss G. Sirolimus monotherapy in nephrotoxicity due to calcineurin inhibitors in liver transplant recipients. Liver Transpl 2003; 9: 126-129
69. D. Dubay, R. J. Smith, K. G Qiu,et al.Sirolimus in liver transplant recipients with renal dysfunction offers no advantage over low-dose calcineurin inhibitor regimens. Liver Transplantation,2008; 14(5):651-659.
70. Dean PG, Lund WJ, Larson TS, et al. Wound-healing complications after kidney transplantation:a prospective, randomized comparison of sirolimus and tacrolimus. Transplantation 2004; 77:1555-1561.
71. Guba M, Yezhelyev M, Eichhorn ME, et al. Rapamycin induces tumor-specific thrombosis via tissue factor in the presence of VEGF. Blood 2005;105:4463-4469.
72. Schumacher G, Oidtmann M, Rueggeberg A, et al. Sirolimus inhibits growth of human hepatoma cells alone or combined with tacrolimus, while tacrolimus promotes cell growth. World J Gastroenterol 2005;11:1420-1425.
73. Piguet AC, Semela D, Keogh A, et al. Inhibition of mTOR in combination with doxorubicin in an experimental model of hepatocellular carcinoma. J Hepatol 2008;49:78-87.
74. Wang Z, Zhou J, Fan J, et al. Effect of rapamycin alone and in combination with sorafenib in an orthotopic model of human hepatocellular carcinoma. Clin Cancer Res 2008;14:5124-5130.
75. Guertin DA, Sabatini DM. Defining the role of mTOR in cancer. Cancer Cell 2007;12:9-22.
76. Luan FL, Hojo M, Maluccio M, et al. Rapamycin blocks tumor progression: unlinking immunosuppression from antitumor efficacy. Transplantation 2002;73:1565-1572.
77. Zhou J, Wulfkuhle J, Zhang H, et al. Activation of the PTEN/mTOR/STAT3 pathway in breast cancer stem-like cells is required for viability and maintenance. Proc Natl Acad Sci U S A 2007;104:16158-16163.
78. Hudes G, Carducci M, Tomczak P, et al. Temsirolimus, interferon alfa, or both for advanced renal-cell carcinoma. N Engl J Med 2007;356:2271-2281.
79. Motzer RJ, Escudier B, Oudard S, et al. Efficacy of everolimus in advanced renal cell carcinoma: a double-blind, randomised, placebo-controlled phase III trial. Lancet 2008;372:449-456.
80. Zimmerman MA, Trotter JF, Wachs M, et al. Sirolimus-based immunosuppression following liver transplantation for hepatocellular carcinoma. Liver Transpl 2008; 14:633-638
81. Toso C, Meeberg GA, Bigam DL, et al. De novo sirolimus-based immunosuppression after liver transplantation for hepatocellular carcinoma: long-term outcomes and side effects. Transplantation 2007; 83:1162-1168,
82. Jian Zhou, Jia Fan, Zheng Wang, et al. Conversion to sirolimus immunosuppression in liver transplantation recipients with hepatocellular carcinoma: Report of an initial experience. World J Gastroenterol 2006; 12(19): 3114-3118.
83. J. Zhou, Z. Wang, Z.-Q. Wu, et al. Sirolimus-based immunosuppression therapy in liver transplantation for patients with hepatocellular carcinoma exceeding the Milan Criteria. Transplantation Proceedings,2008,40:3548-3553
84. Marco Vivarelli, Alessandro Dazzi, Matteo Zanello, et al. Effect of different immunosuppressive schedules on recurrence-free survival after liver transplantation for hepatocellular carcinoma. Transplantation 2010;89:227-231
85. Christian Toso, Shaheed Merani, David L. Bigam, et al. Sirolimus-Based Immunosuppression Is Associated with Increased Survival After Liver Transplantation for Hepatocellular Carcinoma. HEPATOLOGY,2010; 51(2):1-7.
86. Chinnakotla S, Davis GL, Vasani S, et al. Impact of sirolimus on the recurrence of hepatocellular carcinoma after liver transplantation. Liver Transpl. 2009;15(12):1834-1842.
87. Schlitt HJ, Barkmann A, Boker KH, et al. Replacement of calcineurin inhibitors with mycophenolate mofetil in liver-transplant patients with renal dysfunction: a randomised controlled study. Lancet 2001; 357:587-591.
88. Taylor AL, Watson CJ, Bradley JA. Immunosuppressive agents in solid organ transplantation:Mechanisms of action and therapeutic efficacy. Crit Rev Oncol Hematol 2005; 56:23-46.
89. Greig P, Lilly L, Scudamore C, et al. Early steroid withdrawal after liver transplantation: the Canadian tacrolimu versus microemulsion cyclosporin A trial:1-year follow-up. Liver Transpl 2003; 9:587-595
90. Vivarelli M, Burra P, La Barba G, et al. Influence of steroids on HCV recurrence after liver transplantation:A prospective study. J Hepatol 2007;47:793-798.
91. Segev DL, Sozio SM, Shin EJ, et al. Steroid avoidance in liver transplantation: meta-analysis and meta-regression of randomized trials. Liver Transpl 2008;14:512-525.
92. Hong JC, Kahan BD. Immunosuppressive agents in organ transplantation:past, present, and future. Semin Nephrol 2000; 20:108-125
93. Wilde MI, Goa KL. Muromonab CD3:a reappraisal of its pharmacology and use as prophylaxis of solid organ transplant rejection. Drugs 1996; 51:865-894
94. Caillat-Zucman S, Blumenfeld N, Legendre C, et al. The OKT3 immunosuppressive effect. In situ antigenic modulation of human graft-infiltrating T cells. Transplantation 1990; 49:156-160
95. Colonna JO 2nd, Goldstein LI, Brems JJ, et al. A prospective study on the use of monoclonal anti-T3-cell antibody (OKT3) to treat steroid-resistant liver transplant rejection. Arch Surg 1987; 122:1120-1123.
96. Solomon H, Gonwa TA, Mor E, et al. OKT3 rescue for steroid-resistant rejection in adult liver transplantation. Transplantation 1993; 55:87-91.
97. 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.
98. Everson GT. Impact of immunosuppressive therapy on recurrence of hepatitis C. Liver Transpl 2002; 8:S19-S27.
99. Thomas Decaens, Francoise Roudot-Thoraval,et al. Role of immunosuppression and tumor differentiation in predicting recurrence after liver transplantation for hepatocellular carcinoma:A multicenter study of 412 patients.World J Gastroenterol.2006;12(45):7319-7325.
100. Zimmerman MA, Kelly MA, Campsen J,et al. The influence of OKT3 therapy on hepatocellular carcinoma recurrence following liver transplantation.Clin Transplant.2009. [Epub ahead of print]
101. Neuhaus P, Clavien PA, Kittur D, et al. Improved treatment response with basiliximab immunoprophylaxis after liver transplantation:results from a double-blind randomized placebo-controlled trial. Liver Transpl 2002;8:132-142.
102. Liu CL, Fan ST, Lo CM, et al. Interleukin-2 receptor antibody (basiliximab) for immunosuppressive induction therapy after liver transplantation:a protocol with early elimination of steroids and reduction of tacrolimus dosage. Liver Transpl 2004; 10:728-733.
103. Ramirez CB, Doria C, Di Francesco F, et al. Anti-IL2 induction in liver transplantation with 93% rejection-free patient and graft survival at 18 months. J Surg Res 2007; 138:198-204.
104. Christian Toso, Shaheed Merani, David L. Bigam, et al. Sirolimus-Based Immunosuppression Is Associated with Increased Survival After Liver Transplantation for Hepatocellular Carcinoma. HEPATOLOGY,2010; 51(2):1-7.
105. 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.
106. Magliocca JF, Knechtle SJ. The evolving role of alemtuzumab (Campath-1H) for immunosuppressive therapy in organ transplantation. Transpl Int 2006;19:705-714.
107. Pascual J, Bloom D, Torrealba J, et al. Calcineurin inhibitor withdrawal after renal transplantation with alemtuzumab:clinical outcomes and effect on T-regulatory cells. Am J Transplant 2008;8:1529-1536.
108. Barth RN, Janus CA, Lillesand CA, et al. Outcomes at 3 years of a prospective pilot study of Campath-1H and sirolimus immunosuppression for renal transplantation. Transpl Int 2006;19:885-892.
109. Bloom DD, Chang Z, Fechner JH, et al. CD4+CD25+FOXP3+regulatory T cells increase de novo in kidney transplant patients after immunodepletion with Campath-1H. Am J Transplant 2008;8:793-802.
110. Tzakis AG, Tryphonopoulos P, Kato T, et al. Preliminary experience with alemtuzumab (Campath-1H) and low-dose tacrolimus immunosuppression in adult liver transplantation.Transplantation 2004; 77:1209-1214.
111. Marcos A, Eghtesad B, Fung JJ, et al. Use of alemtuzumab and tacrolimus monotherapy for cadaveric liver transplantation:with particular reference to hepatitis C virus. Transplantation 2004; 78:966-971.
112. Mueller TM. Thymoglobulin:an immunologic overview. Curr Opin Organ Transplant 2003; 8:305-12.
113. Feng X, Kajigaya S, Solomou EE, et al. Rabbit ATG but not horse ATG promotes expansion of functional CD4+CD25highFOXP3+ regulatory T cells in vitro. Blood 2008; 111:3675-3683.
114. Lopez M, Clarkson MR, Albin M, et al. A novel mechanism of action for anti-thymocyte globulin: induction of CD4+CD25+Foxp3+ regulatory T cells. J Am Soc Nephrol 2006; 17:2844-2853.
115. Lytton SD, Denton CP, Nutzenberger AM. Treatment of autoimmune disease with rabbit anti-T lymphocyte globulin:clinical efficacy and potential mechanisms of action. Ann N Y Acad Sci 2007; 1110:285-296
116. 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.
117. 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.
118. 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.
119. Eason JD, Loss GE, Blazek J,et al. Steroid-free liver transplantation using rabbit antithymocyte globulin induction:results of a prospective randomized trial. Liver Transpl 2001; 7:693-697.
120. Eason JD, Nair S, Cohen AJ, et al. Steroid-free liver transplantation using rabbit antithymocyte globulin and early tacrolimus monotherapy. Transplantation 2003; 75:1396-1399.
121. Oettinger CW, D'Souza M, Milton GV. In vitro comparison of cytokine release from antithymocyte serum and OKT3. Inhibition with soluble and microencapsulated neutralizing antibodies. Transplantation 1996; 62:1690-1693.
122. Guttmann RD, Caudrelier P, Alberici G, Touraine JL. Pharmacokinetics, foreign protein immune response, cytokine release, and lymphocyte subsets in patients receiving thymoglobuline and immunosuppression. Transplant Proc 1997; 29: 24S-26S
123. Buchler M, Hurault de Ligny B, Madec C, Lebranchu Y.Induction therapy by anti-thymocyte globulin (rabbit) in renal transplantation: a 1-yr follow-up of safety and efficacy. Clin Transplant 2003; 17:539-545.
124. Ducloux D, Kazory A, Challier B, et al. Long-term toxicity of antithymocyte globulin induction may vary with choice of agent:a single-center retrospective study. Transplantation 2004; 77:1029-1033.
125. Lundquist AL, Chari RS, Wood JH, et al. Serum sickness following rabbit antithymocyte-globulin induction in a liver transplant recipient: case report and literature review. Liver Transpl 2007; 13:647-650.
126. Larsen CP, Pearson TC, Adams AB, et al. Rational development of LEA29Y (belatacept), a high affinity variant of CTLA4-Ig with potent immunosuppressive properties. Am J Transplant 2005; 5:443-453.
127. Vincenti F, Larsen C, Durrbach A, et al. Co-stimulation blockade with belatacept in renal transplantation.. N Eng J Med 2005; 353:770-781.
128. Pribila JT, Quale AC, Mueller KL, Shimizu Y. Integrins and T cell-mediated immunity. Annu Rev Immunol 2004; 22:157-180.
129. Dedrick RL, Walicke P, Garovoy M. Anti-adhesion antibodies efalizumab, a humanized anti-CDlla monoclonal antibody. Transpl Immunol 2002; 9:181-186.
130. Vincenti F, Mendez R, Pescovitz M, et al. A phase I/II randomized open-label multicenter trial of efalizumab, a humanized anti-CDlla, anti-LFA-1 in renal transplantation. Am J Transplant 2007;7:1770-1777.
131. O'Shea JJ. Jaks. STATs, cytokine signal transduction and immunoregulation:are we there yet? Immunity 1997; 7:1-11.
132. Ozaki K, Spolski R, Feng CG, et al. A critical role for IL-21 in regulating immunoglobulin production..Science 2002; 298:1630-1634.
133. Vincenti F, Kirk AD. What's next in the pipeline. Am J Transplant 2008; 8: 1972-1981.
134. Krueger GG. Clinical response to alefacept:results of a phase 3 study of intravenous administration of alefacept in patients with chronic plaque psoriasis. J Eur Acad Dermatol Venereol 2003; 17 Suppl 2:17-24.