Protocolo de inmunosupresión en trasplante hepático: revisión de la literatura

Autores/as

DOI:

https://doi.org/10.52784/27112330.147

Palabras clave:

trasplante de hígado, inmunosupresión, inmunoterapia, rechazo de injerto, inhibidores, calcineurina, rapamicina, esteroides.

Resumen

El trasplante de hígado es el último recurso para el tratamiento de hepatopatías. Para evitar el rechazo del injerto se requieren esquemas de inmunosupresión que han ido evolucionando a lo largo de los años. Se realizó una revisión bibliográfica en la base de datos PubMed sobre las terapias inmunosupresoras disponibles para evitar el rechazo del injerto en el trasplante hepático, los esquemas utilizados, efectos adversos, interacciones y sus modificaciones desde la fase de inducción hasta el seguimiento posterior. Se encontró que la inducción habitual es con esteroides o terapia inmunológica clonal. En el mantenimiento, los inhibidores de la calcineurina son los más utilizados, las dosis se deben ajustar según sus niveles séricos y la presencia de efectos adversos como nefrotoxicidad o diabetes. Por otra parte, los inhibidores del mTOR han sido considerados como agentes reductores del riesgo de recidiva de cáncer hepatocelular. Las características del paciente y sus comorbilidades (embarazo, insuficiencia renal, diabetes, sepsis, carcinoma hepatocelular) requieren modificar el tratamiento e individualizarlo.

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Biografía del autor/a

Esteban González-Domínguez, Hospital Santa Inés, Universidad de Cuenca

Médico, Especialista en Gastroenterología, Hepatología y Trasplante Hepático, PhD en Gastroenterología. Hospital Santa Inés. Profesor, Facultad de Medicina, Universidad de Cuenca. Cuenca, Ecuador.

Diego Córdova, Universidad de Cuenca

Médico General, Universidad de Cuenca. Cuenca, Ecuador.

Paula Abad, Universidad de Cuenca

Médica General, Universidad de Cuenca. Cuenca, Ecuador.

Eduardo González, Hospital São Francisco de Assis

Médico, Especialista en Cirugía General, Hospital São Francisco de Assis. Belo Horizonte, Brasil.

Camila González, Universidad de Cuenca

Médica General, Universidad de Cuenca. Cuenca, Ecuador.

Juan José Cordero, Universidad de Cuenca

Estudiante de Medicina, Universidad de Cuenca. Cuenca, Ecuador.

Luis Flores, Hospital Santa Inés

Médico, Especialista en Cirugía General y del Aparato Digestivo, MSc en Trasplantes. Hospital Santa Inés. Cuenca, Ecuador.

Hernán Aguirre-Bermeo, Universidad de Cuenca

Médico, Especialista en Medicina Intensiva, PhD en Medicina Interna y Ventilación Mecánica. Hospital Santa Inés. Profesor, Facultad de Medicina, Universidad de Cuenca. Cuenca, Ecuador.

Referencias bibliográficas

Adam R, Hoti E. Liver transplantation: the current situation. Semin Liver Dis 2009;29:3-18. https://doi.org/10.1055/s-0029-1192052.

Azzam AZ. Liver transplantation as a management of hepatocellular carcinoma. World J Hepatol 2015;7:1347-1354. https://doi.org/10.4254/wjh.v7.i10.1347.

Geissler EK, Schlitt HJ. Immunosuppression for liver transplantation. Gut 2009;58:452-463. https://doi.org/10.1136/gut.2008.163527.

Moini M, Schilsky ML, Tichy EM. Review on immunosuppression in liver transplantation. World J Hepatol 2015;7:1355-1368. https://doi.org/10.4254/wjh.v7.i10.1355.

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. https://doi.org/10.1016/j.critrevonc.2005.03.012.

Thomson AW, Bonham CA, Zeevi A. Mode of action of tacrolimus (FK506): molecular and cellular mechanisms. Ther Drug Monit 1995;17:584-591. https://doi.org/10.1097/00007691-199512000-00007.

Starzl TE, Todo S, Fung J, Demetris AJ, Venkataramman R, Jain A. FK 506 for liver, kidney, and pancreas transplantation. Lancet 1989;2:1000-1004. https://doi.org/10.1016/s0140-6736(89)91014-3.

Armstrong VW, Oellerich M. New developments in the immunosuppressive drug monitoring of cyclosporine, tacrolimus, and azathioprine. Clin Biochem 2001;34:9-16. https://doi.org/10.1016/s0009-9120(00)00175-2.

O'Grady JG, Burroughs A, Hardy P, Elbourne D, Truesdale A. Tacrolimus versus microemulsified ciclosporin in liver transplantation: the TMC randomised controlled trial. Lancet 2002;360:1119-1125. https://doi.org/10.1016/s0140-6736(02)11196-2.

Burghuber CK, Roberts TK, Knechtle SJ. The clinical relevance of alloantibody in liver transplantation. Transplant Rev (Orlando) 2015;29:16-22. https://doi.org/10.1016/j.trre.2014.06.001.

Kitchens WH, Yeh H, Markmann JF. Hepatic retransplant: what have we learned? Clin Liver Dis 2014;18:731-751. https://doi.org/10.1016/j.cld.2014.05.010.

Augustine JJ, Bodziak KA, Hricik DE. Use of sirolimus in solid organ transplantation. Drugs 2007;67:369-391. https://doi.org/10.2165/00003495-200767030-00004.

Schuler W, Sedrani R, Cottens S, Häberlin B, Schulz M, Schuurman HJ, et al. SDZ RAD, a new rapamycin derivative: pharmacological properties in vitro and in vivo. Transplantation 1997;64:36-42. https://doi.org/10.1097/00007890-199707150-00008.

Kovarik JM, Sabia HD, Figueiredo J, Zimmermann H, Reynolds C, Dilzer SC, et al. Influence of hepatic impairment on everolimus pharmacokinetics: implications for dose adjustment. Clin Pharmacol Ther 2001;70:425-430.

De Simone P, Fagiuoli S, Cescon M, De Carlis L, Tisone G, Volpes R, et al. Use of everolimus in liver transplantation: Recommendations from a working group. Transplantation 2017;101:239-251. https://doi.org/10.1097/tp.0000000000001438.

Bianco R, Garofalo S, Rosa R, Damiano V, Gelardi T, Daniele G, et al. Inhibition of mTOR pathway by everolimus cooperates with EGFR inhibitors in human tumours sensitive and resistant to anti-EGFR drugs. Br J Cancer 2008;98:923-930. https://doi.org/10.1038/sj.bjc.6604269.

Finn RS. Current and future treatment strategies for patients with advanced hepatocellular carcinoma: Role of mTOR inhibition. Liver Cancer 2012;1:247-256. https://doi.org/10.1159/000343839.

Zimmerman MA, Trotter JF, Wachs M, Bak T, Campsen J, Skibba A, et al. Sirolimus-based immunosuppression following liver transplantation for hepatocellular carcinoma. Liver Transpl 2008;14:633-638. https://doi.org/10.1002/lt.21420.

Toso C, Merani S, Bigam DL, Shapiro AM, Kneteman NM. Sirolimus-based immunosuppression is associated with increased survival after liver transplantation for hepatocellular carcinoma. Hepatology 2010;51:1237-1243. https://doi.org/10.1002/hep.23437.

Gomez-Camarero J, Salcedo M, Rincon D, Lo Iacono O, Ripoll C, Hernando A, et al. Use of everolimus as a rescue immunosuppressive therapy in liver transplant patients with neoplasms. Transplantation 2007;84:786-791. https://doi.org/10.1097/01.tp.0000280549.93403.dd.

Bilbao I, Sapisochin G, Dopazo C, Lazaro JL, Pou L, Castells L, et al. Indications and management of everolimus after liver transplantation. Transplant Proc 2009;41:2172-2176. https://doi.org/10.1016/j.transproceed.2009.06.087.

Zhu AX, Kudo M, Assenat E, Cattan S, Kang YK, Lim HY, et al. Effect of everolimus on survival in advanced hepatocellular carcinoma after failure of sorafenib: the EVOLVE-1 randomized clinical trial. JAMA 2014;312:57-67. https://doi.org/10.1001/jama.2014.7189.

Kirchner GI, Meier-Wiedenbach I, Manns MP. Clinical pharmacokinetics of everolimus. Clin Pharmacokinet 2004;43:83-95. https://doi.org/10.2165/00003088-200443020-00002.

Rubín-Suárez A, Bilbao-Aguirre I, Fernández-Castroagudin J, Pons-Miñano JA, Salcedo-Plaza M, Varo-Pérez E, et al. Recommendations of everolimus use in liver transplant. Gastroenterol Hepatol 2017;40:629-640. https://doi.org/10.1016/j.gastrohep.2017.05.008.

Tedesco-Silva H, Saliba F, Barten MJ, De Simone P, Potena L, Gottlieb J, et al. An overview of the efficacy and safety of everolimus in adult solid organ transplant recipients. Transplant Rev 2021:100655. https://doi.org/https://doi.org/10.1016/j.trre.2021.100655.

Di Maira T, Little EC, Berenguer M. Immunosuppression in liver transplant. Best Pract Res Clin Gastroenterol 2020;46-47:101681. https://doi.org/10.1016/j.bpg.2020.101681.

Adams DH, Sanchez-Fueyo A, Samuel D. From immunosuppression to tolerance. J Hepatol 2015;62:S170-185. https://doi.org/10.1016/j.jhep.2015.02.042.

Lennard L. The clinical pharmacology of 6-mercaptopurine. Eur J Clin Pharmacol 1992;43:329-339. https://doi.org/10.1007/bf02220605.

Maltzman JS, Koretzky GA. Azathioprine: old drug, new actions. J Clin Invest 2003;111:1122-1124. https://doi.org/10.1172/JCI18384.

Parhar KS, Gibson PS, Coffin CS. Pregnancy following liver transplantation: review of outcomes and recommendations for management. Can J Gastroenterol 2012;26:621-626. https://doi.org/10.1155/2012/137129.

Genestier L, Fournel S, Flacher M, Assossou O, Revillard JP, Bonnefoy-Berard N. Induction of Fas (Apo-1, CD95)-mediated apoptosis of activated lymphocytes by polyclonal antithymocyte globulins. Blood 1998;91:2360-2368.

Goralczyk AD, Bari N, Abu-Ajaj W, Lorf T, Ramadori G, Friede T, et al. Calcineurin inhibitor sparing with mycophenolate mofetil in liver transplantion: a systematic review of randomized controlled trials. Am J Transplant 2012;12:2601-2607. https://doi.org/10.1111/j.1600-6143.2012.04157.x.

Calmus Y, Scheele JR, Gonzalez-Pinto I, Jaurrieta EJ, Klar E, Pageaux GP, et al. Immunoprophylaxis with basiliximab, a chimeric anti-interleukin-2 receptor monoclonal antibody, in combination with azathioprine-containing triple therapy in liver transplant recipients. Liver Transpl 2002;8:123-131. https://doi.org/10.1053/jlts.2002.30882.

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;8:132-142. https://doi.org/10.1053/jlts.2002.30302.

Kirkman RL, Barrett LV, Gaulton GN, Kelley VE, Ythier A, Strom TB. Administration of an anti-interleukin 2 receptor monoclonal antibody prolongs cardiac allograft survival in mice. J Exp Med 1985;162:358-362. https://doi.org/10.1084/jem.162.1.358.

Takeishi K, Ikegami T, Yoshizumi T, Itoh S, Harimoto N, Harada N, et al. Thymoglobulin for steroid-resistant immune-mediated graft dysfunction during simeprevir-based antiviral treatment for post-transplantation hepatitis C: case report. Transplant Proc 2015;47:794-795. https://doi.org/10.1016/j.transproceed.2014.11.056.

Schumann A, Fiedler M, Beckebaum S, Cicinnati VR, Herzer K, Lenz V, et al. Donor- and recipient-derived immunity in ABO incompatible living-related liver transplantation. Hum Immunol 2015;76:631-635. https://doi.org/10.1016/j.humimm.2015.09.008.

Tydén G, Donauer J, Wadström J, Kumlien G, Wilpert J, Nilsson T, et al. Implementation of a protocol for ABO-incompatible kidney transplantation--a three-center experience with 60 consecutive transplantations. Transplantation 2007;83:1153-1155. https://doi.org/10.1097/01.tp.0000262570.18117.55.

Boillot O, Baulieux J, Wolf P, Messner M, Cherqui D, Gugenheim J, et al. Low rejection rates with tacrolimus-based dual and triple regimens following liver transplantation. Clin Transplant 2001;15:159-166. https://doi.org/10.1034/j.1399-0012.2001.150303.x.

González MG, Madrazo CP, Rodríguez AB, Gutiérrez MG, Herrero JI, Pallardó JM, et al. An open, randomized, multicenter clinical trial of oral tacrolimus in liver allograft transplantation: a comparison of dual vs. triple drug therapy. Liver Transpl 2005;11:515-524. https://doi.org/10.1002/lt.20382.

Penninga L, Wettergren A, Wilson CH, Chan AW, Steinbrüchel DA, Gluud C. Antibody induction versus corticosteroid induction for liver transplant recipients. Cochrane Database Syst Rev 2014:Cd010252. https://doi.org/10.1002/14651858.CD010252.pub2.

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:Cd010253. https://doi.org/10.1002/14651858.CD010253.pub2.

Ojo AO, Held PJ, Port FK, Wolfe RA, Leichtman AB, Young EW, et al. Chronic renal failure after transplantation of a nonrenal organ. N Engl J Med 2003;349:931-940. https://doi.org/10.1056/NEJMoa021744.

O'Riordan A, Wong V, McCormick PA, Hegarty JE, Watson AJ. Chronic kidney disease post-liver transplantation. Nephrol Dial Transplant 2006;21:2630-2636. https://doi.org/10.1093/ndt/gfl247.

Karie-Guigues S, Janus N, Saliba F, Dumortier J, Duvoux C, Calmus Y, et al. Long-term renal function in liver transplant recipients and impact of immunosuppressive regimens (calcineurin inhibitors alone or in combination with mycophenolate mofetil): the TRY study. Liver Transpl 2009;15:1083-1091. https://doi.org/10.1002/lt.21803.

Haddad EM, McAlister VC, Renouf E, Malthaner R, Kjaer MS, Gluud LL. Cyclosporin versus tacrolimus for liver transplanted patients. Cochrane Database Syst Rev 2006:Cd005161. https://doi.org/10.1002/14651858.CD005161.pub2.

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;248:956-967. https://doi.org/10.1097/SLA.0b013e31819009c9.

Sgourakis G, Dedemadi G. Corticosteroid-free immunosuppression in liver transplantation: an evidence-based review. World J Gastroenterol 2014;20:10703-10714. https://doi.org/10.3748/wjg.v20.i31.10703.

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;12:3008-3020. https://doi.org/10.1111/j.1600-6143.2012.04212.x.

Saliba F, De Simone P, Nevens F, De Carlis L, Metselaar HJ, Beckebaum S, et al. Renal function at two years in liver transplant patients receiving everolimus: results of a randomized, multicenter study. Am J Transplant 2013;13:1734-1745. https://doi.org/10.1111/ajt.12280.

Fischer L, Saliba F, Kaiser GM, De Carlis L, Metselaar HJ, De Simone P, et al. Three-year outcomes in de novo liver transplant patients receiving everolimus with reduced tacrolimus: Follow-up results from a randomized, multicenter study. Transplantation 2015;99:1455-1462. https://doi.org/10.1097/tp.0000000000000555.

Hojo M, Morimoto T, Maluccio M, Asano T, Morimoto K, Lagman M, et al. Cyclosporine induces cancer progression by a cell-autonomous mechanism. Nature 1999;397:530-534. https://doi.org/10.1038/17401.

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;59:1193-1199. https://doi.org/10.1016/j.jhep.2013.07.012.

Duvoux C, Toso C. mTOR inhibitor therapy: Does it prevent HCC recurrence after liver transplantation? Transplant Rev (Orlando) 2015;29:168-174. https://doi.org/10.1016/j.trre.2015.02.003.

Cholongitas E, Mamou C, Rodríguez-Castro KI, Burra P. Mammalian target of rapamycin inhibitors are associated with lower rates of hepatocellular carcinoma recurrence after liver transplantation: a systematic review. Transpl Int 2014;27:1039-1049. https://doi.org/10.1111/tri.12372.

Starzl TE, Iwatsuki S, Van Thiel DH, Gartner JC, Zitelli BJ, Malatack JJ, et al. Evolution of liver transplantation. Hepatology (Baltimore, Md) 1982;2:614-636. https://doi.org/10.1002/hep.1840020516.

Jain A, Nalesnik M, Reyes J, Pokharna R, Mazariegos G, Green M, et al. Posttransplant lymphoproliferative disorders in liver transplantation: a 20-year experience. Ann Surg 2002;236:429-436. https://doi.org/10.1097/00000658-200210000-00005.

Marino D, Burra P, Boccagni P, Calabrese F, Canova F, Trentin C, et al. Post-transplant lymphoproliferative disorders in liver transplanted patients: a single-centre experience. Anticancer Res 2010;30:2383-2391.

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Publicado

2022-01-20

Cómo citar

González-Domínguez, E., Córdova, D., Abad, P., González, E., González, C., Cordero, J. J., … Aguirre-Bermeo, H. (2022). Protocolo de inmunosupresión en trasplante hepático: revisión de la literatura. Hepatología, 3(1), 40–56. https://doi.org/10.52784/27112330.147

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