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Órgano Oficial de la Asociación Mexicana de Hepatología

2005, Number 2

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Ann Hepatol 2005; 4 (2)

A prospective randomized trial of N-acetyl cysteine administration during cold preservation of the donor liver for transplantation

Khan AW, Fuller BJ, Shah SR, Davidson BR, Rolles K

Language: English
References: 38
Page: 121-126
PDF size: 60.08 Kb.


Text Extraction

Aims: N-acetyl cysteine (NAC), an anti oxidant and a glutathione precursor, is effective in ameliorating liver injury of Tylenol overdose. There is experimental evidence that it also reduces ischemia reperfusion (I/R) injury. This clinical study was undertaken to study the effect of NAC administered in the donor operation.
Methods: 22 patients were randomized to receive NAC (IV & Portal flush) or no NAC (Control Group) during donor operation. Peak AST levels and 1-hour post-reperfusion biopsies were used to assess I/R injury. Episodes of acute rejection were recorded together with immunosuppressive drug levels.
Results: There were 4 exclusions (re-exploration for post-operative hemorrhage x3, OLT for acute liver failure x1). The two groups (n = 9 each) were matched for recipient and donor ages and sex. Viral hepatitis accounted for cirrhosis in 3 patients in NAC Group and 6 patients in Control Group. Statistically, Cold and warm ischemia times were not significantly different as was the use of blood and blood products in both groups. Serum peak AST levels were similar and post- reperfusion biopsy showed moderate to severe reperfusion injury in 3 recipients in the NAC Group and 4 in the Control Group. Excluding ones associated with low Tacrolimus levels (n = 4), there were 6 episodes of acute rejection (2- mild, 4- moderate) in the NAC Group and 5 in the Control Group (3- mild,1- moderate, 1- severe).
Conclusion: In this pilot study, NAC administered during donor operation did not show a protective effect on I/R injury or on acute cellular rejection.


REFERENCES

  1. Jaeschke H. Preservation injury: mechanisms, prevention and consequences. J Hepatol 1996; 25: 774-780.

  2. Adam R, Bismuth H, Diamond T, Ducot B, Morino M, Astarcioglu I, et al. Effect of extended cold ischemia with UW solution on graft function after liver transplantation. Lancet 1992; 340: 1373-1376.

  3. Bzeizi KL, Jalan R, Plevris JN, Hayes PC. Primary graft dysfunction after liver transplantation: from pathogenesis to prevention. Liver Transpl Surg 1997; 3: 137-148.

  4. Fukuzawa K, Emre S, Senyuz O, Acarli K, Schwartz ME, Miller CM. N-acetylcysteine ameliorates reperfusion injury after warm hepatic ischemia. Transplantation 1995; 59: 6-9.

  5. Dunne JB, Davenport M, Williams R, Tredger JM. Evidence that S-adenosylmethionine and N-acetylcysteine reduce injury from sequential cold and warm ischemia in the isolated perfused rat liver. Transplantation 1994; 57: 1161-1168.

  6. Bilzer M, Gerbes AL. Preservation injury of the liver: Mechanisms and novel therapeutic strategies. J Hepatol 2000; 32: 508-515.

  7. Prescott LF, Illingworth RN, Critchley JA, Stewert MJ, Adam RD, Proudfppt AT. Intravenous N-acetylcysteine: the treatment of choice for paracetamol poisoning. Br Med J 1979; 2: 1097-1100.

  8. Smithson JE, Neuberger JM. Acute liver failure. Overview. Eur J Gastroenterol Hepatol 1999; 11: 943-947.

  9. Fernandez-Checa J, Kaplovitz N, Garcia-Ruiz C, Colell A. Mitochondrial glutathione: importance and transport. Seminars in Liver Disease 1998; 18: 389-401.

  10. Grattagliano I, Vendemiale G, Lauterburg B. Reperfusion injury of the liver: role of mitochondria and protection by glutathione ester. J Surg Res 1999; 86: 2-8.

  11. Vivot C, Stump DD, Schwartz ME, Thiese ND, Miller CM. N-acetylcysteine attenuates cold ischemia/reperfusion injury in the isolated perfused rat liver. Transplant Proc 1993; 25: 1983-1984.

  12. Thies JC, Stump DD, Schwartz ME, Thiese ND, Miller CM. N-acetylcysteine as a hepatoprotective agent in liver transplantation. Transpl Int 1998; 11 Suppl 1: S390-S392.

  13. Rodriguez J, Mamprin M, Mediavilla M, Guibert E. Glutathione movements during cold preservation of rat hepatocytes. Cryobiology 1998; 36: 236-244.

  14. Kurwazinski TR, Appleby JA, Hardy SC, Fuller B, Davidson B, Rolles K, et al. A prospective randomized clinical trial of liver preservation using high-sodium versus high-potassium lactobionate/raffinose solution. Transpl Int 1994; 7Suppl 1: S489-S492.

  15. Datta GS, Hudson M, Burroughs AK, Rolles K, Scheuer PJ, Dhillon AP, et al. Grading of cellular rejection after orthotopic liver transplantation. Hepatol 1995; 21: 47-57.

  16. Banff schema for grading liver allograft rejection: an international consensus document. Hepatology 1997; 25: 658-663.

  17. Angelescu M, HoffmanW, Zapletal C Bredt M, Kraus T, Herfarth C, Klar E. Histomorphological analysis of preservation injury as determinant of graft quality in clinical liver transplantation. Transplant Proc 1999; 31: 1074-1076.

  18. Neil DA, Hubscher SG. Are parenchymal changes in early post-transplant biopsies related to preservation-reperfusion injury or rejection? Transplantation 2001; 71: 1566-1572.

  19. Kakizoe S, Yanaga K, Starzl TE, Demetris AJ. Evaluation of protocol before transplantation and after reperfusion biopsies from human orthotopic liver allografts: considerations of preservation and early immunological injury. Hepatology 1990; 11: 932-941.

  20. Clavien PA, Harvey PR, Strasberg SM. Preservation and reperfusion injures in liver allografts. An overview and synthesis of current studies. Transplantation 1992; 53: 957-978.

  21. D’Allessandro AM, Kalayoglu M, Sollinger HW, Pirsch JD, Southard JH, Belzer FO. The predictive value of donor liver biopsies on the development of primary nonfunction after orthotopic liver transplantation. Transplant Proc 1991; 23: 1536-1537.

  22. Bao YM, Adam R, Sebagh M, Reynes M, Bismuth H. Risk factors of preservation injury and prognostic value of reperfusion biopsy in outcome of liver transplantation. Transplant Proc 1996; 28: 123-124.

  23. Porte RJ, Ploeg RJ, Bockel JH, Thorogood J, Persijn GG, Hermans J, et al. Long-term graft survival after liver transplantation in the UW era: late effects of cold ischemia and primary dysfunction. European Multicentre Study Group. Transpl Int 1998; 11 Suppl: S164-S167.

  24. Nakano H, Boudjema K, Alexandre E, Imbs P, Chenard MP, Wolf P, et al. Protective effects of N-acetylcysteine on hypothermic ischemia-reperfusion injury of rat liver. Hepatology 1995; 22: 539-545.

  25. Southard JH, Marsh DC, McAnulty JF, Belzer FO. The importance of O2 derived free radical injury to organ preservation and transplantation. Transplant Proc 1987; 49: 1380-1381.

  26. Compagnon P, Wang H, Lindell S, Ametani M, Mangino M, D’Allessandro A, Southard J. Brain death does not affect hepatic allograft function and survival after orthotopic transplantation in a canine model. Transplantation 2002; 73: 1218-1227.

  27. Weigand M, Plachky J, Thies J, Spies-Martin D, Otto G, Martin E, Bardenheuer H. N-acetylcysteine attenuates the increase in a-glutathione S-transferase amd circulating ICAM-1 and VCAM-1 after reperfusion in humans undergoing liver transplantation. Transplantation 2001; 72: 694-698.

  28. Manika A, Trinh T, Lagace G, et al. N-acetylcysteine in pig liver transplantation from non-heart beating donors. Transplantation 1999; 68: 327-330.

  29. Steib A, Freys G, Collin F, Launoy A, Mark G, Boudjema K. Does N-acetyl cysteine improve hemodynamics and graft function in liver transplantation? Liver Transpl Surg 1998; 4: 152-157.

  30. So P-W, Butler P, Parkes H, Davidson B, Fuller B. 1H NMR studies on the effective delivery of N-acetylcysteine for transplantation by hypothermic flush. CryoLetters 2001; 22: 80-81.

  31. Olsson B, Johansson M, Gabrielsson J, Bolme P. Pharmacokinetics and bioavailability of reduced and oxidized N-acetylcysteine. Eur J Clin Pharmacol 1988; 34: 77-82.

  32. Jaeschke H, Smith CV, Mitchell JR. Hypoxic damage generates reactive oxygen species in isolated perfused rat liver. Biochem Biophys Res Commun 1988; 150: 568-574.

  33. Shoskes DA, Parfrey NA, Halloran PF. Increased major histocompatibility complex antigen expression in unilateral ischemic acute tubular necrosis in the mouse. Transplantation 1990; 49: 201-207.

  34. Howard TK, Klintmalm GB, Coffer JB, Husberg BS, Goldstein RM, Gonwa TA. The influence of preservation injury on rejection in the hepatic transplant recipient. Transplantation 1990; 49: 103-107.

  35. Piratvisuth T, Tredger JM, Hayllar KA, Williams R. Contribution of true cold and rewarming ischemia times to factors determining outcome after orthotopic liver transplantation. Liver Transpl Surg 1995; 1: 296-301.

  36. Pirenne J, Gunson B, Khaleef H, Hubscher S, Afford S, McMaster P, Adams D. Influence of ischemia-reperfusion injury on rejection after liver transplantation. Transplant Proc 1997; 29: 366-367.

  37. Shackleton CR, Martin P, Melinek J, Stothers L, Millis JM, Olthoff KM, et al. Lack of correlation between the magnitude of preservation injury and the incidence of acute rejection, need for OKT3, and conversion to FK506 in cyclosporine-treated primary liver allograft recipients. Transplantation 1995; 60: 554-558.

  38. Katz E, Mor E, Schwartz ME, Thiese N, Patel T, Miller CM. Preservation injury in clinical liver transplantation: incidence and effect on rejection and survival. Clin Transplant 1994; 8: 492-496.




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