Comparison of two immunosuppressive regimens for liver transplant patients in a university hospital in Medellín, Colombia
DOI:
https://doi.org/10.52784/27112330.122Keywords:
liver transplantation, immunosuppression, graft rejection, cyclosporine, tacrolimus, azathioprine, mycophenolic acid.Abstract
Introduction. The development of immunosuppressive therapies in liver transplantation has been one of the major contributing factors that have reduced the presence of rejections and improved graft and patient survival. The present study was conducted to determine the effectiveness of two immunosuppressive schemes in a cohort of liver transplant patients, between 2006 and 2017, at a university hospital in Medellin, Colombia. Methodology. A retrospective observational study was performed to compare two immunosuppressive treatment schemes with cyclosporine (CsA) and azathioprine (AZA) versus tacrolimus (TAC) and mycophenolate (MMF). Results. A total of 147 patients were included in the study, 79 women and 68 men, with a median age of 55 years. The incidence rate of acute rejection in the CsA/AZA group was 7.3 while in the TAC/MMF group was 13.8, with a rate ratio of 0.53 (95%CI=0.31-0.89) for every 100 person-year, this difference being statistically significant (p=0.02). There were no significant differences between the groups regarding the presence of chronic rejection, graft or patient survival. With respect to adverse effects associated with the treatment, there was only a significant difference in the presence of diarrhea in the TAC/MMF group. Conclusion. A significant difference was only found in terms of a higher number of acute rejections in the group treated with TAC/MMF. These findings are in agreement with local experience, in which this scheme can be used in selected patients, with good clinical results and lower costs for the health system. So far, this is the first retrospective study in Colombia and Latin America to make a comparison such as the one presented.
Downloads
References
Peery AF, Crockett SD, Barritt AS, Dellon ES, Eluri S, Gangarosa LM, et al. Burden of gastrointestinal, liver, and pancreatic diseases in the United States. Gastroenterology 2015;149:1731-1741. https://doi.org/10.1053/j.gastro.2015.08.045.
Flemming J, Dewit Y, Mah J, Saperia J, Groome P, Booth C. Incidence of cirrhosis in young birth cohorts in Canada from 1997 to 2016: a retrospective population-based study. Lancet Gastroenterol Hepatol 2018;4:217-226. https://doi.org/10.1016/S2468-1253(18)30339-X.
Li B, Zhang C, Zhan YT. Nonalcoholic fatty liver disease cirrhosis: A review of its epidemiology, risk factors, clinical presentation, diagnosis, management, and prognosis. Can J Gastroenterol Hepatol 2018;2018:2784537. https://doi.org/10.1155/2018/2784537.
National Institute of Health Consensus Statement. Liver Transplantation 1983;4:1-5. Acceso 15 de febrero de 2020. Disponible en https://consensus.nih.gov/1983/1983livertransplantation036html.htm.
Alqahtani SA. Update in liver transplantation. Curr Opin Gastroenterol 2012;28:230-238. https://doi.org/10.1097/MOG.0b013e3283527f16.
Vernon G, Baranova A, Younossi ZM. Systematic review: the epidemiology and natural history of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis in adults. Aliment Pharmacol Ther 2011;34:274-285. https://doi.org/10.1111/j.1365-2036.2011.04724.x.
European Association for the Study of the Liver (EASL). Clinical Practice Guidelines for the management of patients with decompensated cirrhosis. J Hepatol 2018;69:406-460. https://doi.org/10.1016/j.jhep.2018.03.024.
U.S. Department of Health and Human Services, Health Resources and Services Administration, Healthcare Systems Bureau, Division of Transplantation. Annual report of the U.S. Organ Procurement and Transplantation Network and the Scientific Registry of Transplant Recipients: Transplant data 1999-2008. Rockville M: U.S. Department of Health and Human Services; 2009. Acceso 23 de febrero de 2020. Disponible en https://srtr.transplant.hrsa.gov/annual_reports/2018_ADR_Preview.aspx.
European Association for the Study of the Liver (EASL). Clinical Practice Guidelines: Liver transplantation. J Hepatol 2016;64:433-485. https://doi.org/10.1016/j.jhep.2015.10.006.
U.S. Multicenter FK506 Liver Study Group. A comparison of tacrolimus (FK 506) and cyclosporine for immunosuppression in liver transplantation. N Engl J Med 1994;331:1110-1115. https://doi.org/10.1056/nejm199410273311702.
Neuhaus P, Pichlmayr R. Randomised trial comparing tacrolimus (FK506) and cyclosporin in prevention of liver allograft rejection. European FK506 Multicentre Liver Study Group. Lancet 1994;344:423-428.
Woodruff M. Immunosuppression and its complications. Proc R Soc Med 1969;62:411-416.
Sterneck M, Wiesner R, Ascher N, Roberts J, Ferrell L, Ludwig J, et al. Azathioprine hepatotoxicity after liver transplantation. Hepatology 1991;14:806-810. https://doi.org/10.1002/hep.1840140511.
Choudhary NS, Saigal S, Shukla R, Kotecha H, Saraf N, Soin AS. Current status of immunosuppression in liver transplantation. J Clin Exp Hepatol 2013;3:150-158. https://doi.org/10.1016/j.jceh.2013.04.005.
Santos O, Londoño M, Marín J, Muñoz O, Mena Á, Guzmán C, et al. An experience of liver transplantation in Latin America: a medical center in Colombia. Colomb Med (Cali) 2015;46:8-13.
Santos-Sánchez OM, Muñoz OG, Marín-Zuluaga JI, Restrepo-Gutiérrez JC. Trasplante hepático en un centro de Colombia: comparación de dos periodos. Rev Colomb Gastroenterol 2019;34:117-124. https://doi.org/10.22516/25007440.391.
Vera A, Contreras F, Guevara F. Incidence and risk factors for infections after liver transplant: single-center experience at the University Hospital Fundación Santa Fe de Bogotá, Colombia. Transplant Infectious Disease 2011;13:608-615. https://doi.org/10.1111/j.1399-3062.2011.00640.x.
Wiesner RH, Fung JJ. Present state of immunosuppressive therapy in liver transplant recipients. Liver Transpl 2011;17 (Suppl 3):S1-9. https://doi.org/10.1002/lt.22410.
Fung J, Kelly D, Kadry Z, Patel-Tom K, Eghtesad B. Immunosuppression in liver transplantation: beyond calcineurin inhibitors. Liver Transpl 2005;11:267-280. https://doi.org/10.1002/lt.20373.
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;7:442-450. https://doi.org/10.1053/jlts.2001.23356.
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.
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;16:2816-2835. https://doi.org/10.1111/ajt.13909.
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;6:1578-1585. https://doi.org/10.1111/j.1600-6143.2006.01360.x.
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.
Glanemann M, Klupp J, Langrehr JM, Schröer G, Platz KP, Stange B, et al. Higher immunosuppressive efficacy of mycophenolate mofetil in combination with FK 506 than in combination with cyclosporine A. Transplant Proc 2000;32:522-523. https://doi.org/10.1016/s0041-1345(00)00872-1.
Ziolkowski J, Paczek L, Niewczas M, Senatorski G, Oldakowska-Jedynak U, Wyzgal J, et al. Effect of immunosuppressive regimen on acute rejection and liver graft function. Transplant Proc 2003;35:2281-2283. https://doi.org/10.1016/s0041-1345(03)00794-2.
Remuzzi G, Bertani T. Renal vascular and thrombotic effects of cyclosporine. Am J Kidney Dis 1989;13:261-272. https://doi.org/10.1016/s0272-6386(89)80032-0.
Nieto-Ríos JF, Serna-Higuita LM, Vélez-Rivera JD, Giraldo-Salazar HA, Vélez-Morales JF, Pérez-Guerra V, et al. Enfermedad renal crónica en pacientes trasplantados de hígado en el Hospital Pablo Tobón Uribe 2005-2013. Rev Colomb Gastroenterol 2015;30:399-406.
Muduma G, Saunders R, Odeyemi I, Pollock RF. Systematic review and meta-analysis of tacrolimus versus ciclosporin as primary immunosuppression after liver transplant. PLOS ONE 2016;11:e0160421. https://doi.org/10.1371/journal.pone.0160421.
Downloads
Published
How to Cite
Issue
Section
License
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
La política de reconocimiento de autoría de Hepatología se basa en los criterios indicados por el ICMJE para conferir crédito de un trabajo a una persona, a la vez que se le atribuye responsabilidad por la publicación del mismo.
