Use of N-acetyl-cysteine in the Perioperative Period of Liver Transplantation: A Scoping Review

Authors

  • Felipe Asafe Melo dos Santos Universidade de Pernambuco – Faculdade de Ciências Médicas – Departamento de Iniciação à Metodologia de Pesquisa – Recife (PE), Brazil. https://orcid.org/0009-0001-3633-8164
  • Guilherme Victor Costa Muniz Universidade de Pernambuco – Faculdade de Ciências Médicas – Departamento de Iniciação à Metodologia de Pesquisa – Recife (PE), Brazil. https://orcid.org/0009-0009-4034-9526
  • Maria Eloysa Reino Teixeira da Rocha Universidade de Pernambuco – Faculdade de Ciências Médicas – Departamento de Iniciação à Metodologia de Pesquisa – Recife (PE), Brazil. https://orcid.org/0009-0004-0932-3719
  • Samuel Fama Guimarães Diógenes Universidade de Pernambuco – Faculdade de Ciências Médicas – Departamento de Iniciação à Metodologia de Pesquisa – Recife (PE), Brazil. https://orcid.org/0009-0000-5313-174X
  • Davi Gueiros Behar Tôrres Universidade de Pernambuco – Faculdade de Ciências Médicas – Departamento de Iniciação à Metodologia de Pesquisa – Recife (PE), Brazil. https://orcid.org/0009-0009-5345-4165
  • Clara Medeiros de Lima Universidade de Pernambuco – Faculdade de Ciências Médicas – Departamento de Iniciação à Metodologia de Pesquisa – Recife (PE), Brazil. https://orcid.org/0009-0006-5543-4131
  • Breno Cipriano Bermond Universidade de Pernambuco – Faculdade de Ciências Médicas – Departamento de Iniciação à Metodologia de Pesquisa – Recife (PE), Brazil. https://orcid.org/0009-0005-1296-9091
  • Hugo Rafael de Souza e Silva Universidade de Pernambuco – Faculdade de Ciências Médicas – Departamento de Iniciação à Metodologia de Pesquisa – Recife (PE), Brazil. https://orcid.org/0000-0002-1476-797X
  • Manuela Izidio de Lima Universidade de Pernambuco – Faculdade de Ciências Médicas – Departamento de Iniciação à Metodologia de Pesquisa – Recife (PE), Brazil. https://orcid.org/0000-0003-4642-5584
  • Olival Cirilo Lucena da Fonseca Neto Universidade de Pernambuco – Hospital Universitário Oswaldo Cruz – Serviço de Cirurgia Geral e Transplante de Fígado – Recife (PE), Brazil. https://orcid.org/0000-0002-2383-8610

Keywords:

N-acetyl-cysteine, Liver Transplant, Reperfusion Ischemia

Abstract

Objective: To find evidence on the use of N-acetyl-cysteine (NAC) in the perioperative period of liver transplantation, since NAC, as it is the acetylated precursor of L-cysteine and reduced glutathione, contributes to the hepatic supply of glutathione, helping the liver to recover from ischemia and reperfusion injury. Methodology: This is a scoping review of the PubMed, VHL and Web of Science databases. The descriptors “Liver transplantation”, “N-acetyl-cysteine” and “Reperfusion Ischemia” were used, with the Boolean operator “AND”, and articles relevant to the topic were selected. Initially, 60 articles were selected, all published in the last 24 years, in Portuguese and/or English. After analysis, eight articles corresponded to the proposed objective. Results: The groups that received NAC during TxF showed post-reperfusion hypotension, lower intraoperative pH values, higher plasma concentrations of IL-4 and a significant increase in IL-10 levels five minutes before reperfusion. Inhibition of α-glutathione S-transferase (α-GST) was also observed after reperfusion, unlike the control group, which showed a significant increase in this enzyme. Furthermore, sVCAM-1 and sICAM-1 levels were significantly lower in the NAC group 24 hours after reperfusion compared with the placebo group. The maximum AST value during the first 72 postoperative hours was similar in both groups, although the peak ALT was lower in the NAC group than in the placebo group. In grafts that received NAC in the perfusion solution, survival rates at 3 and 12 months were 93% and 90%, respectively, and in the control group were 82% and 70%, respectively. The incidence of postoperative complications was 23% in the NAC group and 51% in the control group. The incidence of EPD was lower for the NAC group, which was 15% versus 32% in the control group. Regarding the administration of NAC during the intraoperative TxF, the one-year patient survival rate was 78.4% in the NAC group compared to 80.9% in the placebo group. Conclusion: Intraoperative administration of NAC during the anhepatic phase was associated with a protective effect against reperfusion injury, however in other studies limitations were observed in protection against liver injury, in biomarkers of oxidative stress, in inflammation and in the functioning of liver enzymes.

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References

Liu J, Man K. Mechanistic insight and clinical implications of ischemia/reperfusion injury post liver transplantation. Cell Mol Gastroenterol Hepatol. 2023 Jan 1;15(6):1463-74. https://doi.org/10.1016/j.jcmgh.2023.03.003

Aliakbarian M, Nikeghbalian S, Ghaffaripour S, Bahreini A, Shafiee M, Rashidi M, et al. Effects of N-Acetylcysteine Addition to University of Wisconsin Solution on the Rate of Ischemia-Reperfusion Injury in Adult Orthotopic Liver Transplant. Exp Clin Transplant Off J Middle East Soc Organ Transplant. 2017 Aug; 15(4): 432-6. https://doi.org/10.6002/ect.2014.0263

Fonseca-Neto OCL da, Miranda LEC, Sabat BD, Amorim AG, Adeodato L, Melo PSV de, et al. O doador marginal: experiência de um centro de transplante de fígado. ABCD Arq Bras Cir Dig São Paulo. 2008 Mar; 21:1-5. https://doi.org/10.1590/S0102-67202008000100001

D’Amico F, Vitale A, Piovan D, Bertacco A, Ramirez Morales R, Chiara Frigo A, et al. Use of N-acetylcysteine during liver procurement: a prospective randomized controlled study. Liver Transpl. 2013;19(2):135-44. https://doi.org/10.1002/lt.23527

Weigand MA, Plachky J, Thies JC, Spies-Martin D, Otto G, Martin E, et al. N-cetylcysteine attenuates the increase in α-glutathione s-transferase and circulating icam-1 and vcam-1 after reperfusion in humans undergoing liver transplantation1. Transplantation. 2001 Aug 27; 72(4): 694. https://doi.org/10.1097/00007890-200108270-00023

Gómez-Gavara C, Moya-Herraiz Á, Hervás D, Pérez-Rojas J, LaHoz A, López-Andújar R. The potential role of efficacy and safety evaluation of N-Acetylcysteine administration during liver procurement. The NAC-400 Single Center Randomized Controlled Trial. Transplantation. 2021 Oct 105 (10): 2245. https://doi.org/10.1097/TP.0000000000003487

Kakaei F, Fasihi M, Hashemzadeh S, Zarrintan S, Beheshtirouy S, Asvadi-Kermani T, et al. Effect of N-acetylcysteine on liver and kidney function tests after surgical bypass in obstructive jaundice: a randomized controlled trial. Asian J Surg. 2020 Jan 1; 43(1): 322-9. https://doi.org/10.1016/j.asjsur.2019.05.009

Santiago FM, Bueno P, Olmedo C, Muffak-Granero K, Comino A, Serradilla M, et al. Effect of N-acetylcysteine administration on intraoperative plasma levels of Interleukin-4 and Interleukin-10 in liver transplant recipients. Transplant Proc. 2008 Nov 1; 40(9): 2978-80. https://doi.org/10.1016/j.transproceed.2008.08.103

Khan AW, Fuller BJ, Shah SR, Davidson BR, Rolles K. A prospective randomized trial of N-acetyl cysteine administration during cold preservation of the donor liver for transplantation: Original Article. Ann Hepatol. 2005 Apr 1; 4(2): 121-6. https://doi.org/10.1016/S1665-2681(19)32075-7

JBI Manual for Evidence Synthesis - JBI Global Wiki. [cited Apr. 2, 2024]. Available in: https://jbi-global-wiki.refined.site/space/MANUAL.

Tricco AC, Lillie E, Zarin W, O’Brien KK, Colquhoun H, Levac D, et al. PRISMA Extension for Scoping Reviews (PRISMA- ScR): checklist and explanation. Ann Intern Med. 2018 Oct 2; 169(7): 467-73. https://doi.org/10.7326/M18-0850

Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ. 2021 Mar 29; 372 :n71. https://doi.org/10.1136/bmj.n71

Santiago FM, Olmedo C, Muffak-Granero K, Comino A, Villar JM, Garrote D, et al. Intraoperative pH values after N-acetylcysteine administration during liver transplantation. Transplant Proc. 2010 Oct 1; 42(8): 3164-6. https://doi.org/10.1016/j.transproceed.2010.05.130

Hilmi IA, Peng Z, Planinsic RM, Damian D, Dai F, Tyurina YY, et al. N-acetylcysteine does not prevent hepatorenal ischaemia–reperfusion injury in patients undergoing orthotopic liver transplantation. Nephrol Dial Transplant. 2010 Jul 1; 25(7): 2328-33. https://doi.org/10.1093/ndt/gfq077

Olthoff KM, Kulik L, Samstein B, Kaminski M, Abecassis M, Emond J, et al. Validation of a current definition of early allograft dysfunction in liver transplant recipients and analysis of risk factors. Liver Transpl. 2010 Jul; 16(8): 943–9. https://doi.org/10.1002/lt.22091

Liu ZX, Kaplowitz N. Immune-mediated drug-induced liver disease. Clin Liver Dis. 2002 Aug; 6(3): 755-74. https://doi.org/10.1016/S1089-3261(02)00025-9

Ntamo Y, Ziqubu K, Chellan N, Nkambule BB, Nyambuya TM, Mazibuko-Mbeje SE, et al. Clinical use of N-acetyl cysteine during liver transplantation: implications of oxidative stress and inflammation as therapeutic targets. Biomed Pharmacother. 2022 Mar 1;147: 112638. https://doi.org/10.1016/j.biopha.2022.112638

Soares ROS, Losada DM, Jordani MC, Évora P, Castro-e-Silva O. Ischemia/reperfusion injury revisited: an overview of the latest pharmacological strategies. Int J Mol Sci. 2019 Jan; 20(20): 5034. https://doi.org/10.3390/ijms20205034

Ntamo Y, Ziqubu K, Chellan N, Nkambule BB, Nyambuya TM, Mazibuko-Mbeje SE, et al. Drug-induced liver injury: clinical evidence of N-acetyl cysteine protective effects. Oxid Med Cell Longev. 2021 Dec 6; 2021: e3320325. https://doi.org/10.1155/2021/3320325

Hoffmann K, Büchler MW, Schemmer P. Supplementation of amino acids to prevent reperfusion injury after liver surgery and transplantation – Where do we stand today? Clin Nutr. 2011 Apr 1; 30(2): 143-7. https://doi.org/10.1016/j.clnu.2010.09.006

Taut FJH, Breitkreutz R, Zapletal CM, Thies JC, Babylon A, Martin E, et al. Influence of N-acetylcysteine on hepatic amino acid metabolism in patients undergoing orthotopic liver transplantation. Transpl Int. 2001 Sep 1; 14(5): 329-33. Available in: https://pubmed.ncbi.nlm.nih.gov/11692217/

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Published

2024-09-16

How to Cite

Santos, F. A. M. dos, Muniz, G. V. C., Rocha, M. E. R. T. da, Diógenes, S. F. G., Tôrres, D. G. B., Lima, C. M. de, Bermond, B. C., Silva, H. R. de S. e, Lima, M. I. de, & Fonseca Neto , O. C. L. da. (2024). Use of N-acetyl-cysteine in the Perioperative Period of Liver Transplantation: A Scoping Review. Brazilian Journal of Transplantation, 27. Retrieved from https://bjt.emnuvens.com.br/revista/article/view/587

Issue

Vol. 27 (2024)

Section

Review Article

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Copyright (c) 2024 Felipe Asafe Melo dos Santos, Guilherme Victor Costa Muniz, Maria Eloysa Reino Teixeira da Rocha, Samuel Fama Guimarães Diógenes, Davi Gueiros Behar Tôrres, Clara Medeiros de Lima, Breno Cipriano Bermond, Hugo Rafael de Souza e Silva, Manuela Izidio de Lima, Olival Cirilo Lucena da Fonseca Neto

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This work is licensed under a Creative Commons Attribution 4.0 International License.