期刊首页 优先出版 当期阅读 过刊浏览 作者中心 关于期刊 English

《工程(英文)》 >> 2023年 第21卷 第2期 doi: 10.1016/j.eng.2022.07.007

免疫抑制和肝移植

a Institut de Recherche Expérimentale et Clinique, Université catholique de Louvain, Brussels 1200, Belgium
b General Surgery and Kidney Transplantation, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan 20122, Italy

收稿日期: 2022-03-23 修回日期: 2022-06-20 录用日期: 2022-07-10 发布日期: 2022-08-03

下一篇 上一篇

摘要

完美的手术技术和充分的免疫抑制是确保最佳移植物和患者存活的关键。不同药物的可用性导致了一些通常由行业驱动的不同类型的临床试验,以寻找理想的免疫抑制方案。然而,大量概念不同的研究设计未能明确定义最佳免疫抑制方案。基于钙调神经磷酸酶抑制剂他克莫司、抗代谢药物霉酚酸酯或硫唑嘌呤和短期类固醇(除了可能的诱导外)的三联免疫抑制方案仍然是目前公认的肝移植标准免疫抑制方案。然而,鉴于排斥定义的变化、免疫抑制负荷的定制以及由于慢性免疫抑制引起的长期副作用,未来的试验最好包括一个以上的终点,而不是急性T细胞介导的急性排斥(a-TCMR)或肾衰竭。相反,需要一个涵盖患者和移植物存活率以及急性和慢性排斥反应发生率的综合终点。这些免疫现象应根据一系列长期的生物学和组织学随访进行检查。临床相关α-TCMR的诊断和治疗应基于综合生物学、免疫学和组织病理学的发现。这两个要素对于朝着更谨慎的免疫抑制处理和有利于临床操作耐受性的方向发展至关重要。

图片

图1

图2

图3

参考文献

[ 1 ] Starzl TE. Experience in liver transplantation. Philadelphia: WB Saunders Company; 1969.

[ 2 ] Starzl TE, Demetris AJ. Liver transplantation: a 31-year perspective. Part I. Curr Probl Surg 1990;27(2):49‒116. 链接1

[ 3 ] Perry I, Neuberger J. Immunosuppression: towards a logical approach in liver transplantation. Clin Exp Immunol 2005;139(1):2‒10. 链接1

[ 4 ] Zhang W, Fung J. Limitations of current liver transplant immunosuppressive regimens: renal considerations. Hepatobiliary Pancreat Dis Int 2017;16(1):27‒32. 链接1

[ 5 ] Rodríguez-Perálvarez M, Guerrero-Misas M, Thorburn D, Davidson BR, Tsochatzis E, Gurusamy KS. Maintenance immunosuppression for adults undergoing liver transplantation: a network meta-analysis. Cochrane Database Syst Rev 2017;3(3):CD011639. 链接1

[ 6 ] Jadad AR, Enkin MW. Randomized controlled trials. Questions, answers and musings. 2nd ed. Hoboken: Wiley-Blackwell; 2007. 链接1

[ 7 ] Wiesner R, Rabkin J, Klintmalm G, McDiarmid S, Langnas A, Punch J, et al. A randomized double-blind comparative study of mycophenolate mofetil and azathioprine in combination with cyclosporine and corticosteroids in primary liver transplant recipients. Liver Transpl 2001;7(5):442‒50. 链接1

[ 8 ] Neuhaus P, Clavien PA, Kittur D, Salizzoni M, Rimola A, Abeywickrama K, et al. Improved treatment response with Basiliximab immunoprophylaxis after liver transplantation: results from a double-blind randomized placebo- controlled trial. Liver Transpl 2002;8(2):132‒42. 链接1

[ 9 ] Pageaux GP, Calmus Y, Boillot O, Ducerf C, Vanlemmens C, Boudjema K, et al. Steroid withdrawal at day 14 after liver transplantation: a double-blind, placebo-controlled study. Liver Transpl 2004;10(12):1454‒60. 链接1

[10] Moench C, Barreiros AP, Schuchmann M, Bittinger F, Thiesen J, Hommel G, et al. Tacrolimus monotherapy without steroids after liver transplantation—a prospective randomized double-blinded placebo-controlled trial. Am J Transplant 2007;7(6):1616‒23. 链接1

[11] Filipponi F, Callea F, Salizzoni M, Grazi GL, Fassati LR, Rossi M, et al. Double- blind comparison of hepatitis C histological recurrence rate in HCV+ Liver transplant recipients given Basiliximab + steroids or Basiliximab + placebo, in addition to cyclosporine and azathioprine. Transplantation 2004;78(10):1488‒95. 链接1

[12] Lerut J, Mathys J, Verbaandert C, Talpe S, Ciccarelli O, Lemaire J, et al. Tacrolimus monotherapy in liver transplantation: one-year results of a prospective, randomized, double-blind, placebo-controlled study. Ann Surg 2008;248(6):956‒67. 链接1

[13] Lerut JP, Pinheiro RS, Lai Q, Stouffs V, Orlando G, Juri JMR, et al. Is minimal, [almost] steroid-free immunosuppression a safe approach in adult liver transplantation? Long-term outcome of a prospective, blinddouble, controlledplacebo-, randomized, studyinvestigator-driven. Ann Surg 2014;260(5):886‒92. 链接1

[14] Iesari S, Ackenine K, Foguenne M, De Reyck C, Komuta M, Bonaccorsi Riani E, et al. Tacrolimus and single intraoperative high-dose of anti-T-lymphocyte globulins versus tacrolimus monotherapy in adult liver transplantation: one- year results of an investigator-driven randomized controlled trial. Ann Surg 2018;268(5):776‒83. 链接1

[15] Watt KD, Charlton MR. Metabolic syndrome and liver transplantation: a review and guide to management. J Hepatol 2010;53(1):199‒206. 链接1

[16] Åberg F, Gissler M, Karlsen TH, Ericzon BG, Foss A, Rasmussen A, et al. Differences in long-term survival among liver transplant recipients and the general population: a population-based Nordic study. Hepatology 2015;61(2):668‒77. 链接1

[17] Starzl TE, Koep LJ, Halgrimson CG, Hood J, Schroter GPJ, Porter KA, et al. Fifteen years of clinical liver transplantation. Gastroenterology 1979;77(2):375‒88. 链接1

[18] Starzl TE, Demetris AJ, Trucco M, Murase N, Ricordi C, Ildstad S, et al. Cell migration and chimerism after whole-organ transplantation: the basis of graft acceptance. Hepatology 1993;17(6):1127‒52. 链接1

[19] Calne RY, Rolles K, Thiru S, Mcmaster P, Craddock GN, Aziz S, et al. Cyclosporin a initially as the only immunosuppressant in 34 recipients of cadaveric organs: 32 kidneys, 2 pancreases, and 2 livers. Lancet 1979;314(8151):1033‒6. 链接1

[20] Starzl TE, Todo S, Fung J, Demetris AJ, Venkataramman R, Jain A. FK 506 for liver, kidney, and pancreas transplantation. Lancet 1989;2 (8670):1000‒4. 链接1

[21] Penninga L, Wettergren A, Wilson CH, Chan AW, Steinbrüchel DA, Gluud C. Antibody induction versus placebo, no induction, or another type of antibody induction for liver transplant recipients. Cochrane Database Syst Rev 2014;2014(6):CD010253. 链接1

[22] Farkas SA, Schnitzbauer AA, Kirchner G, Obed A, Banas B, Schlitt HJ. Calcineurin inhibitor minimization protocols in liver transplantation. Transpl Int 2009;22(1):49‒60. 链接1

[23] Wiesner RH, Demetris AJ, Belle SH, Seaberg EC, Lake JR, Zetterman RK, et al. Acute hepatic allograft rejection: incidence, risk factors, and impact on outcome. Hepatology 1998;28(3):638‒45. 链接1

[24] Neuberger J, Adams DH. What is the significance of acute liver allograft rejection? J Hepatol 1998;29(1):143‒50. 链接1

[25] Egawa H, Umeshita K, Uemoto S. Optimal dosage regimen for rituximab in ABO-incompatible living donor liver transplantation. J Hepatobiliary Pancreat Sci 2017;24(2):89‒94. 链接1

[26] Starzl TE, Demetris AJ, Murase N, Thomson AW, Trucco M, Ricordi C. Donor cell chimerism permitted by immunosuppressive drugs: a new view of organ transplantation. Immunol Today 1993;14(6):326‒32. 链接1

[27] Murase N, Starzl TE, Tanabe M, Fujisaki S, Miyazawa H, Ye Q, et al. Variable chimerism, graft-versus-host disease, and tolerance after different kinds of cell and whole organ transplantation from Lewis to brown Norway rats. Transplantation 1995;60(2):158‒70. 链接1

[28] Starzl TE. Immunosuppressive therapy and tolerance of organ allografts. N Engl J Med 2008;358(4):407‒11. 链接1

[29] Starzl TE, Murase N, Abu-Elmagd K, Gray EA, Shapiro R, Eghtesad B, et al. Tolerogenic immunosuppression for organ transplantation. Lancet 2003;361(9368):1502‒10. 链接1

[30] McAlister VC, Haddad E, Renouf E, Malthaner RA, Kjaer MS, Gluud LL. Cyclosporin versus tacrolimus as primary immunosuppressant after liver transplantation: a meta-analysis. Am J Transplant 2006;6(7):1578‒85. 链接1

[31] O’Grady JG, Burroughs A, Hardy P, Elbourne D, Truesdale A, UK and Republic of Ireland Liver Transplant Study Group. Tacrolimus versus microemulsified ciclosporin in liver transplantation: the TMC randomised controlled trial. Lancet 2002;360(9340):1119‒25. 链接1

[32] Lerut J, Sanchez-Fueyo A. An appraisal of tolerance in liver transplantation. Am J Transplant 2006;6(8):1774‒80. 链接1

[33] Appenzeller-Herzog C, Hartleif S, Vionnet J. Clinical parameters and biomarkers predicting spontaneous operational tolerance after liver transplantation: a scoping review. Am J Transplant 2021;21(10):3312‒23. 链接1

[34] Vionnet J, Sánchez-Fueyo A. Biomarkers of immune tolerance in liver transplantation. Hum Immunol 2018;79(5):388‒94. 链接1

[35] Demetris A; Banff Working Group on Liver Allograft Pathology. Importance of liver biopsy findings in immunosuppression management: biopsy monitoring and working criteria for patients with operational tolerance. Liver Transpl 2012;18(10):1154‒70. 链接1

[36] Yoshitomi M, Koshiba T, Haga H, Li Y, Zhao X, Cheng D, et al. Requirement of protocol biopsy before and after complete cessation of immunosuppression after liver transplantation. Transplantation 2009;87(4):606‒14. 链接1

[37] Feng S, Demetris AJ, Spain KM, Kanaparthi S, Burrell BE, Ekong UD, et al. Five- year histological and serological follow-up of operationally tolerant pediatric liver transplant recipients enrolled in WISP-R. Hepatology 2017;65(2):647‒60. 链接1

[38] Shaked A, DesMarais MR, Kopetskie H, Feng S, Punch JD, Levitsky J, et al. Outcomes of immunosuppression minimization and withdrawal early after liver transplantation. Am J Transplant 2019;19(5):1397‒409. 链接1

[39] Demetris AJ, Adeyi O, Bellamy CO, Clouston A, Charlotte F, Czaja A, et al. Liver biopsy interpretation for causes of late liver allograft dysfunction. Hepatology 2006;44(2):489‒501. 链接1

[40] Rodríguez-Perálvarez M, De Luca L, Crespo G, Rubin Á, Marín S, Benlloch S, et al. An objective definition for clinical suspicion of T-cell-mediated rejection after liver transplantation. Clin Transplant 2017;31(7):e13005. 链接1

[41] Rodríguez-Perálvarez M, Rico-Juri JM, Tsochatzis E, Burra P, De la Mata M, Lerut J. Biopsy-proven acute cellular rejection as an efficacy endpoint of randomized trials in liver transplantation: a systematic review and critical appraisal. Transpl Int 2016;29(9):961‒73. 链接1

[42] Ikegami T, Bekki Y, Imai D, Yoshizumi T, Ninomiya M, Hayashi H, et al. Clinical outcomes of living donor liver transplantation for patients 65 years old or older with preserved performance status. Liver Transpl 2014;20(4):408‒15. 链接1

[43] Heinbokel T, Hock K, Liu G, Edtinger K, Elkhal A, Tullius SG. Impact of immunosenescence on transplant outcome. Transpl Int 2013;26(3):242‒53. 链接1

[44] Wakabayashi T, Shinoda M, Obara H, Kitago M, Yagi H, Abe Y, et al. Decreased incidence of acute cellular rejection in low-muscle-mass recipients after living-donor liver transplantation. Transplant Proc 2018;50(10):3626‒34. 链接1

[45] Au KP, Chan SC, Chok KH, Sharr WW, Dai WC, Sin SL, et al. Clinical factors affecting rejection rates in liver transplantation. Hepatobiliary Pancreat Dis Int 2015;14(4):367‒73. 链接1

[46] Hann A, Osei-Bordom DC, Neil DAH, Ronca V, Warner S, Perera MTPR. The human immune response to cadaveric and living donor liver allografts. Front Immunol 2020;11:1227. 链接1

[47] Badawy A, Kaido T, Yoshizawa A, Yagi S, Fukumitsu K, Okajima H, et al. Human leukocyte antigen compatibility and lymphocyte cross-matching play no significant role in the current adult-to-adult living donor liver transplantation. Clin Transplant 2018;32(4):e13234. 链接1

[48] Sgourakis G, Dedemadi G. Corticosteroid-free immunosuppression in liver transplantation: an evidence-based review. World J Gastroenterol 2014;20(31):10703‒14. 链接1

[49] Volpin R, Angeli P, Galioto A, Fasolato S, Neri D, Barbazza F, et al. Comparison between two high-dose methylprednisolone schedules in the treatment of acute hepatic cellular rejection in liver transplant recipients: a controlled clinical trial. Liver Transpl 2002;8(6):527‒34. 链接1

[50] Demetris AJ. Longterm outcome of the liver graft: the pathologist’s perspective. Liver Transpl 2017;23(S1):S70‒5. 链接1

[51] Navez J, Iesari S, Kourta D, Baami-Mariza K, Nadiri M, Goffette P, et al. The real incidence of biliary tract complications after adult liver transplantation: the role of the prospective routine use of cholangiography during post-transplant follow-up. Transpl Int 2021;34(2):245‒58. 链接1

[52] Lerut J. Drug prescription after liver transplantation: immunosuppressive drugs and other drugs. In: Berenguer M, editor. Liver transplantation for non- specialists. Barcelona: Permanyer Publications; 2006. p. 121‒42. 链接1

[53] De Geest S, Burkhalter H, Bogert L, Berben L, Glass TR, Denhaerynck K, et al. Describing the evolution of medication nonadherence from pretransplant until 3 years post-transplant and determining pretransplant medication nonadherence as risk factor for post-transplant nonadherence to immunosuppressives: the Swiss Transplant Cohort Study. Transpl Int 2014;27(7):657‒66. 链接1

[54] Albano L. Review of clinical trials on minimization and interruption of calcineurin inhibitors (CNIs) and protocols without CNIs in the transplantation of different organs (kidney, heart, and liver). Nephrol Ther 2009;5(Suppl 6):S371‒8. French. 链接1

[55] Lan X, Liu MG, Chen HX, Liu HM, Zeng W, Wei D, et al. Efficacy of immunosuppression monotherapy after liver transplantation: a meta- analysis. World J Gastroenterol 2014;20(34):12330‒40. 链接1

[56] Memon MA, Karademir S, Shen J, Koukoulis G, Fabrega F, Williams JW, et al. Seventh day syndrome—acute hepatocyte apoptosis associated with a unique syndrome of graft loss following liver transplantation. Liver 2001;21(1):13‒7. 链接1

[57] Hwang S, Lee SG, Ahn CS, Kim KH, Moon DB, Ha TY. Reappraisal of seventh- day syndrome following living donor liver transplantation. Transplant Proc 2006;38(9):2961‒3. 链接1

[58] Demetris AJ, Bellamy C, Hübscher SG, O’Leary J, Randhawa PS, Feng S, et al. 2016 comprehensive update of the banff working group on liver allograft pathology: introduction of antibody-mediated rejection. Am J Transplant 2016;16(10):2816‒35.

[59] Song GW, Lee SG, Hwang S, Kim KH, Ahn CS, Moon DB, et al. ABO- incompatible adult living donor liver transplantation under the desensitization protocol with rituximab. Am J Transplant 2016;16(1):157‒70. 链接1

[60] Rodríguez-Perálvarez M, García-Caparrós C, Tsochatzis E, Germani G, Hogan B, Poyato-González A, et al. Lack of agreement for defining ‘clinical suspicion of rejection’ in liver transplantation: a model to select candidates for liver biopsy. Transpl Int 2015;28(4):455‒64. 链接1

[61] Lang M, Neumann UP, Müller AR, Bechstein WO, Neuhaus R, Neuhaus P. Complications of percutaneous liver biopsy in patients after liver transplantation. Z Gastroenterol 1999;37(3):205‒8. Germany.

[62] Perito ER, Martinez M, Turmelle YP, Mason K, Spain KM, Bucuvalas JC, et al. Posttransplant biopsy risk for stable long-term pediatric liver transplant recipients: 451 percutaneous biopsies from two multicenter immunosuppression withdrawal trials. Am J Transplant 2019;19(5):1545‒51. 链接1

[63] Saunders EA, Engel B, Höfer A, Hartleben B, Vondran FWR, Richter N, et al. Outcome and safety of a surveillance biopsy guided personalized immunosuppression program after liver transplantation. Am J Transplant 2022;22(2):519‒31. 链接1

[64] Levy G, Villamil F, Samuel D, Sanjuan F, Grazi GL, Wu Y, et al. Results of LIS2T, a multicenter, randomized study comparing cyclosporine microemulsion with C2 monitoring and tacrolimus with C0 monitoring in de novo liver transplantation. Transplantation 2004;77(11):1632‒8. 链接1

[65] Neuhaus P, Bechstein WO, Blumhardt G, Wiens M, Lemmens P, Langrehr JM, et al. Comparison of quadruple immunosuppression after liver transplantation with ATG or IL-2 receptor antibody. Transplantation 1993;55(6):1320‒7. 链接1

[66] Tzakis AG, Tryphonopoulos P, Kato T, Nishida S, Levi DM, Madariaga JR, et al. Preliminary experience with alemtuzumab (Campath-1H) and low-dose tacrolimus immunosuppression in adult liver transplantation. Transplantation 2004;77(8):1209‒14. 链接1

[67] Rodríguez-Perálvarez M, Germani G, Papastergiou V, Tsochatzis E, Thalassinos E, Luong TV, et al. Early tacrolimus exposure after liver transplantation: relationship with moderate/severe acute rejection and long-term outcome. J Hepatol 2013;58(2):262‒70. 链接1

[68] Verhelst XP, Troisi RI, Colle I, Geerts A, van Vlierberghe H. Biomarkers for the diagnosis of acute cellular rejection in liver transplant recipients: a review. Hepatol Res 2013;43(2):165‒78. 链接1

[69] Germani G, Rodriguez-Castro K, Russo FP, Senzolo M, Zanetto A, Ferrarese A, et al. Markers of acute rejection and graft acceptance in liver transplantation. World J Gastroenterol 2015;21(4):1061‒8. 链接1

[70] Bardhi E, McDaniels J, Rousselle T, Maluf DG, Mas VR. Nucleic acid biomarkers to assess graft injury after liver transplantation. J Hepatol 2022;4(3):100439. 链接1

[71] Perottino G, Harrington C, Levitsky J. Biomarkers of rejection in liver transplantation. Curr Opin Organ Transplant 2022;27(2):154‒8. 链接1

[72] Shaked A, Chang BL, Barnes MR, Sayre P, Li YR, Asare S, et al. An ectopically expressed serum miRNA signature is prognostic, diagnostic, and biologically related to liver allograft rejection. Hepatology 2017;65(1):269‒80. 链接1

[73] Rodríguez-Perálvarez M, Germani G, Tsochatzis E, Rolando N, Luong TV, Dhillon AP, et al. Predicting severity and clinical course of acute rejection after liver transplantation using blood eosinophil count. Transpl Int 2012;25(5):555‒63. 链接1

[74] Trull A, Steel L, Cornelissen J, Smith T, Sharples L, Cary N, et al. Association between blood eosinophil counts and acute cardiac and pulmonary allograft rejection. J Heart Lung Transplant 1998;17(5):517‒24.

[75] Trull AK, Steel LA, Sharples LD, Akhlaghi F, Parameshwar J, Cary N, et al. Randomized trial of blood eosinophil count monitoring as a guide to corticosteroid dosage adjustment after heart transplantation. Transplantation 2000;70(5):802‒9. 链接1

[76] Hughes VF, Trull AK, Joshi O, Alexander GJ. Monitoring eosinophil activation and liver function after liver transplantation. Transplantation 1998;65(10):1334‒9. 链接1

[77] McCaughan GW, Herkes R, Powers B, Rickard K, Gallagher ND, Thompson JF, et al. Thrombocytopenia post liver transplantation. Correlations with pre- operative platelet count, blood transfusion requirements, allograft function and outcome. J Hepatol 1992;16(1‒2):16‒22.

[78] Chatzipetrou MA, Tsaroucha AK, Weppler D, Pappas PA, Kenyon NS, Nery JR, et al. Thrombocytopenia after liver transplantation. Transplantation 1999;67(5):702‒6. 链接1

[79] Lesurtel M, Raptis DA, Melloul E, Schlegel A, Oberkofler C, El-Badry AM, et al. Low platelet counts after liver transplantation predict early posttransplant survival: the 60-5 criterion. Liver Transpl 2014;20(2):147‒55. 链接1

[80] Yamakuchi M, Kirkiles-Smith NC, Ferlito M, Cameron SJ, Bao C, Fox-Talbot K, et al. Antibody to human leukocyte antigen triggers endothelial exocytosis. Proc Natl Acad Sci USA 2007;104(4):1301‒6. 链接1

[81] Ekser B, Gridelli B, Veroux M, Cooper DK. Clinical pig liver xenotransplantation: how far do we have to go? Xenotransplantation 2011;18(3):158‒67. 链接1

[82] Rodríguez-Perálvarez M, Germani G, Darius T, Lerut J, Tsochatzis E, Burroughs AK. Tacrolimus trough levels, rejection and renal impairment in liver transplantation: a systematic review and meta-analysis. Am J Transplant 2012;12(10):2797‒814. 链接1

[83] Saliba F, Duvoux C, Gugenheim J, Kamar N, Dharancy S, Salamé E, et al. Efficacy and safety of everolimus and mycophenolic acid with early tacrolimus withdrawal after liver transplantation: a multicenter randomized trial. Am J Transplant 2017;17(7):1843‒52. 链接1

[84] Kwong AJ, Kim WR, Lake JR, Smith JM, Schladt DP, Skeans MA, et al. OPTN/SRTR 2019 annual data report: liver. Am J Transplant 2021;21(Suppl 2):208‒315. 链接1

[85] Ekberg H, Tedesco-Silva H, Demirbas A, Vítko Š, Nashan B, Gürkan A, et al. Reduced exposure to calcineurin inhibitors in renal transplantation. N Engl J Med 2007;357(25):2562‒75. 链接1

[86] Kwong AJ, Ebel NH, Kim WR, Lake JR, Smith JM, Schladt DP, et al. OPTN/SRTR 2020 annual data report: liver. Am J Transplant 2022;22(Suppl 2):204‒309. 链接1

[87] Neuberger JM, Bechstein WO, Kuypers DR, Burra P, Citterio F, De Geest S, et al. Practical recommendations for long-term management of modifiable risks in kidney and liver transplant recipients: a guidance report and clinical checklist by the Consensus On Managing Modifiable risk In Transplantation (COMMIT) group. Transplantation 2017;101(4S Suppl 2):S1‒56. 链接1

[88] Klintmalm GB, Feng S, Lake JR, Vargas HE, Wekerle T, Agnes S, et al. Belatacept-based immunosuppression in de novo liver transplant recipients: 1-year experience from a phase II randomized study. Am J Transplant 2014;14(8):1817‒27. 链接1

[89] Watt KDS, Pedersen RA, Kremers WK, Heimbach JK, Charlton MR. Evolution of causes and risk factors for mortality post-liver transplant: results of the NIDDK long-term follow-up study. Am J Transplant 2010;10(6):1420‒7. 链接1

[90] Padbury RT, Gunson BK, Dousset B, Hubscher SG, Buckels JA, Neuberger JM, et al. Steroid withdrawal from long-term immunosuppression in liver allograft recipients. Transplantation 1993;55(4):789‒94. 链接1

[91] Goralczyk AD, Hauke N, Bari N, Tsui TY, Lorf T, Obed A. Interleukin 2 receptor antagonists for liver transplant recipients: a systematic review and meta- analysis of controlled studies. Hepatology 2011;54(2):541‒54. 链接1

[92] Ali H, Mohamed MM, Sharma A, Fulop T, Halawa A. Outcomes of interleukin-2 receptor antagonist induction therapy in standard-risk renal transplant recipients maintained on tacrolimus: a systematic review and meta- analysis. Am J Nephrol 2021;52(4):279‒91. 链接1

[93] Germani G, Pleguezuelo M, Villamil F, Vaghjiani S, Tsochatzis E, Andreana L, et al. Azathioprine in liver transplantation: a reevaluation of its use and a comparison with mycophenolate mofetil. Am J Transplant 2009;9 (8):1725‒31. 链接1

[94] Björnsson ES, Gu J, Kleiner DE, Chalasani N, Hayashi PH, Hoofnagle JH, et al. Azathioprine and 6-mercaptopurine-induced liver injury: clinical features and outcomes. J Clin Gastroenterol 2017;51(1):63‒9. 链接1

[95] Meijer B, Simsek M, Blokzijl H, de Man RA, Coenraad MJ, Dijkstra G, et al. Nodular regenerative hyperplasia rarely leads to liver transplantation: a 20- year cohort study in all Dutch liver transplant units. United European Gastroenterol J 2017;5(5):658‒67. 链接1

[96] Ruggenenti P, Cravedi P, Gotti E, Plati A, Marasà M, Sandrini S, et al. Mycophenolate mofetil versus azathioprine in kidney transplant recipients on steroid-free, low-dose cyclosporine immunosuppression (ATHENA): a pragmatic randomized trial. PLoS Med 2021;18(6):e1003668. 链接1

[97] De Simone P, Nevens F, De Carlis L, Metselaar HJ, Beckebaum S, Saliba F, et al. Everolimus with reduced tacrolimus improves renal function in de novo liver transplant recipients: a randomized controlled trial. Am J Transplant 2012;12 (11):3008‒20. 链接1

[98] Geissler EK, Schnitzbauer AA, Zülke C, Lamby PE, Proneth A, Duvoux C, et al. Sirolimus use in liver transplant recipients with hepatocellular carcinoma: a randomized, multicenter, open-label phase 3 trial. Transplantation 2016;100(1):116‒25.

[99] Rodríguez-Perálvarez M, Colmenero J, González A, Gastaca M, Curell A, Caballero-Marcos A, et al. Cumulative exposure to tacrolimus and incidence of cancer after liver transplantation. Am J Transplant 2022;22 (6):1671‒82. 链接1

[100] Di Maira T, Sapisochin G, Lilly L, Fonés V, Berenguer M. Posttransplant calcineurin inhibitors levels and intrapatient variability are not associated with long-term outcomes following liver transplantation. Transplantation 2020;104(6):1201‒9. 链接1

[101] Schumacher L, Leino AD, Park JM. Tacrolimus intrapatient variability in solid organ transplantation: a multiorgan perspective. Pharmacotherapy 2021;41(1):103‒18. 链接1

[102] Schmeding M, Neumann UP, Neuhaus R, Neuhaus P. Mycophenolate mofetil in liver transplantation—is monotherapy safe? Clin Transplant 2006;20(Suppl 17):75‒9. 链接1

[103] Vivarelli M, Dazzi A, Zanello M, Cucchetti A, Cescon M, Ravaioli M, et al. Effect of different immunosuppressive schedules on recurrence-free survival after liver transplantation for hepatocellular carcinoma. Transplantation 2010;89(2):227‒31. 链接1

[104] Rodríguez-Perálvarez M, Tsochatzis E, Naveas MC, Pieri G, García-Caparrós C, O’Beirne J, et al. Reduced exposure to calcineurin inhibitors early after liver transplantation prevents recurrence of hepatocellular carcinoma. J Hepatol 2013;59(6):1193‒9. 链接1

[105] Rodríguez-Perálvarez M, De la Mata M, Burroughs AK. Liver transplantation: immunosuppression and oncology. Curr Opin Organ Transplant 2014;19(3):253‒60. 链接1

[106] Lerut J, Iesari S, Foguenne M, Lai Q. Hepatocellular cancer and recurrence after liver transplantation: what about the impact of immunosuppression? Transl Gastroenterol Hepatol 2017;2(10):80. 链接1

[107] Rodríguez-Perálvarez M, Guerrero M, De Luca L, Gros B, Thorburn D, Patch D, et al. Area under trough concentrations of tacrolimus as a predictor of progressive renal impairment after liver transplantation. Transplantation 2019;103(12):2539‒48. 链接1

[108] Coilly A, Calmus Y, Chermak F, Dumortier J, Duvoux C, Guillaud O, et al. Once- daily prolonged release tacrolimus in liver transplantation: experts’ literature review and recommendations. Liver Transpl 2015;21(10):1312‒21. 链接1

[109] Weiler N, Thrun I, Hoppe-Lotichius M, Zimmermann T, Kraemer I, Otto G. Early steroid-free immunosuppression with FK506 after liver transplantation: long-term results of a prospectively randomized double- blinded trial. Transplantation 2010;90(12):1562‒6. 链接1

[110] Baroja-Mazo A, Revilla-Nuin B, Parrilla P, Martínez-Alarcón L, Ramírez P, Pons JA. Tolerance in liver transplantation: biomarkers and clinical relevance. World J Gastroenterol 2016;22(34):7676‒91. 链接1

[111] Benítez CE, Puig-Pey I, López M, Martínez-Llordella M, Lozano JJ, Bohne F, et al. ATG-Fresenius treatment and low-dose tacrolimus: results of a randomized controlled trial in liver transplantation. Am J Transplant 2010;10(10):2296‒304. 链接1

[112] Neuberger J, Gunson B, Hubscher S, Nightingale P. Immunosuppression affects the rate of recurrent primary biliary cirrhosis after liver transplantation. Liver Transpl 2004;10(4):488‒91. 链接1

[113] Berenguer M, Aguilera V, Prieto M, San Juan F, Rayón JM, Benlloch S, et al. Significant improvement in the outcome of HCV-infected transplant recipients by avoiding rapid steroid tapering and potent induction immunosuppression. J Hepatol 2006;44(4):717‒22. 链接1

[114] Berenguer M, Royuela A, Zamora J. Immunosuppression with calcineurin inhibitors with respect to the outcome of HCV recurrence after liver transplantation: results of a meta-analysis. Liver Transpl 2007;13(1):21‒9. 链接1

[115] Lerut J, Foguenne M, Lai Q. Hepatocellular cancer selection systems and liver transplantation: from the tower of babel to an ideal comprehensive score. Updates Surg 2021;73(5):1599‒614. 链接1

[116] Lerut J, Iesari S, Vandeplas G, Fabbrizio T, Ackenine K, MEINúñez, et al. Secondary non-resectable liver tumors: a single-center living-donor and deceased-donor liver transplantation case series. Hepatobiliary Pancreat Dis Int 2019;18(5):412‒22. 链接1

[117] O’Leary JG, Demetris AJ, Friedman LS, Gebel HM, Halloran PF, Kirk AD, et al. The role of donor-specific HLA alloantibodies in liver transplantation. Am J Transplant 2014;14(4):779‒87. 链接1

[118] Jucaud V, Shaked A, DesMarais M, Sayre P, Feng S, Levitsky J, et al. Prevalence and impact of de novo donor-specific antibodies during a multicenter immunosuppression withdrawal trial in adult liver transplant recipients. Hepatology 2019;69(3):1273‒86. 链接1

[119] Kasiske BL, Vazquez MA, Harmon WE, Brown RS, Danovitch GM, Gaston RS, et al. Recommendations for the outpatient surveillance of renal transplant recipients. J Am Soc Nephrol 2000;11(Suppl 15):S1‒S86. 链接1

[120] Capron A, Lerut J, Verbaandert C, Mathys J, Ciccarelli O, Vanbinst R, et al. Validation of a liquid chromatography-mass spectrometric assay for tacrolimus in liver biopsies after hepatic transplantation: correlation with histopathologic staging of rejection. Ther Drug Monit 2007;29(3):340‒8. 链接1

[121] Capron A, Lerut J, Latinne D, Rahier J, Haufroid V, Wallemacq P. Correlation of tacrolimus levels in peripheral blood mononuclear cells with histological staging of rejection after liver transplantation: preliminary results of a prospective study. Transpl Int 2012;25(1):41‒7. 链接1

[122] Feng S, Bucuvalas JC, Demetris AJ, Burrell BE, Spain KM, Kanaparthi S, et al. Evidence of chronic allograft injury in liver biopsies from long-term pediatric recipients of liver transplants. Gastroenterology 2018;155(6):1838-51.e7. 链接1

[123] Feng S, Ekong UD, Lobritto SJ, Demetris AJ, Roberts JP, Rosenthal P, et al. Complete immunosuppression withdrawal and subsequent allograft function among pediatric recipients of parental living donor liver transplants. JAMA 2012;307(3):283‒93. 链接1

[124] Benítez C, Londoño MC, Miquel R, Manzia TM, Abraldes JG, Lozano JJ, et al. Prospective multicenter clinical trial of immunosuppressive drug withdrawal in stable adult liver transplant recipients. Hepatology 2013;58(5):1824‒35. 链接1

[125] Todo S, Yamashita K, Goto R, Zaitsu M, Nagatsu A, Oura T, et al. A pilot study of operational tolerance with a regulatory T-cell-based cell therapy in living donor liver transplantation. Hepatology 2016;64(2):632‒43. 链接1

[126] Sánchez-Fueyo A, Whitehouse G, Grageda N, Cramp ME, Lim TY, Romano M, et al. Applicability, safety, and biological activity of regulatory T cell therapy in liver transplantation. Am J Transplant 2020;20(4):1125‒36. 链接1

[127] Lascaris B, de Meijer VE, Porte RJ. Normothermic liver machine perfusion as a dynamic platform for regenerative purposes: what does the future have in store for us? J Hepatol 2022;6:S0168-8278(22)00269-0. 链接1

[128] Sawitzki B, Harden PN, Reinke P, Moreau A, Hutchinson JA, Game DS, et al. Regulatory cell therapy in kidney transplantation (the ONE Study): a harmonised design and analysis of seven non-randomised, single-arm, phase 1/2A trials. Lancet 2020;395(10237):1627‒39. 链接1

[129] Jhun J, Lee SH, Lee SK, Kim HY, Jung ES, Kim DG, et al. Serial monitoring of immune markers being represented regulatory T cell/T helper 17 cell ratio: indicating tolerance for tapering immunosuppression after liver transplantation. Front Immunol 2018;9:352. 链接1

[130] Ronca V, Wootton G, Milani C, Cain O. The immunological basis of liver allograft rejection. Front Immunol 2020;11:2155. 链接1

[131] Chruscinski A, Rojas-Luengas V, Moshkelgosha S, Issachar A, Luo J, Yowanto H, et al. Evaluation of a gene expression biomarker to identify operationally tolerant liver transplant recipients: the LITMUS trial. Clin Exp Immunol 2022;207(1):123‒39. 链接1

[132] Lerut J, Van Thuyne V, Mathijs J, Lemaire J, Talpe S, Roggen F, et al. Anti-CD2 monoclonal antibody and tacrolimus in adult liver transplantation. Transplantation 2005;80(9):1186‒93. 链接1

[133] Langley RG, Papp K, Bissonnette R, Toth D, Matheson R, Hultquist M, et al. Safety profile of intravenous and subcutaneous siplizumab, an anti-CD2 monoclonal antibody, for the treatment of plaque psoriasis: results of two randomized, double-blind, placebo-controlled studies. Int J Dermatol 2010;49(7):818‒28. 链接1

[134] Thomson AW, Vionnet J, Sanchez-Fueyo A. Understanding, predicting and achieving liver transplant tolerance: from bench to bedside. Nat Rev Gastroenterol Hepatol 2020;17(12):719‒39. 链接1

[135] Charlton M, Levitsky J, Aqel B, O’Grady J, Hemibach J, Rinella M, et al. International liver transplantation society consensus statement on immunosuppression in liver transplant recipients. Transplantation 2018;102(5):727‒43. 链接1

[136] O’Connell PJ, Kuypers DR, Mannon RB, Abecassis M, Chadban SJ, Gill JS, et al. Clinical trials for immunosuppression in transplantation: the case for reform and change in direction. Transplantation 2017;101(7):1527‒34. 链接1

[137] Fairfield CJ, Harrison EM, Wigmore SJ. Duplicate publication bias weakens the validity of meta-analysis of immunosuppression after transplantation. World J Gastroenterol 2017;23(39):7198‒200. 链接1

[138] Schafer DF, Sorrell MF. Optimising immunosuppression. Lancet 2002;360(9340):1114‒5. 链接1

[139] Moher D. CONSORT: an evolving tool to help improve the quality of reports of randomized controlled trials. Consolidated standards of reporting trials. JAMA 1998;279(18):1489‒91. 链接1

[140] Smedman TM, Guren TK, Line PD, Dueland S. Transplant oncology: assessment of response and tolerance to systemic chemotherapy for metastatic colorectal cancer after liver transplantation—a retrospective study. Transpl Int 2019;32(11):1144‒50. 链接1

相关研究