Graft-Versus-Host Disease after Liver Transplantation

  • Kim, Hye-young (Department of Surgery, Seoul National University College of Medicine) ;
  • Yi, Nam-Joon (Department of Surgery, Seoul National University College of Medicine) ;
  • Suh, Kyung-Suk (Department of Surgery, Seoul National University College of Medicine) ;
  • Hong, Geon (Department of Surgery, Seoul National University College of Medicine) ;
  • Jeon, Young-Min (Department of Surgery, Seoul National University College of Medicine) ;
  • Lee, Kwang-Woong (Department of Surgery, Seoul National University College of Medicine) ;
  • Park, Myung-Hee (Department of Clinical Pathology, Seoul National University College of Medicine) ;
  • Cho, Eung-Ho (Department of Surgery, Korea Cancer Center Hospital) ;
  • Lee, Kuhn-Uk (Department of Surgery, Seoul National University College of Medicine)
  • Published : 2010.12.31

Abstract

Purpose: Graft-Versus-Host Disease (GVHD) is a rare (0.1~2%) but severe complication after liver transplantation (LT). It is the most lethal complication after LT and there are currently no effective preventive or therapeutic measures available. Approximately 90 such cases have been reported in the literature, but only one case has been reported in Korea. Methods: We performed a retrospective analysis of 767 patients who underwent LT (living donor : deceased donor=554 : 213) at Seoul National University Hospital, Korea from 1998 to 2009. Four patients (4/767, 0.52%) with histologically proven GVHD were found. The diagnosis of GVHD was made according to observing macrochimerism in the peripheral blood and the affected tissue biopsy. Results: Four patients underwent LT due to Hepatitis B virus-related liver cirrhosis and two of these patients had coexisting hepatocellular carcinoma. Three patients received livers from deceased donors and one received a liver from a live donor. All their blood matching were identical. The first diagnosed case underwent human leukocyte antigen (HLA) typing only after LT and it showed complete one-way donor-recipient HLA matching. The onset of GVHD occurred between 10 days and 55 days after LT. All the patients developed high-grade fever, skin rash, neutropenia, diarrhea and the main signs and symptoms related to GVHD. All the patients died because of sepsis despite intensive treatment. Conclusion: GVHD after LT is an extremely rare and fatal complication and it is difficult to diagnose. Therefore, we should perform pre-transplant HLA matching and try to establish an early diagnosis for patients who are clinical suspicious of having GVHD. Further study in this area is needed and physicians need to be alert to detect this malady.

Keywords

References

  1. Mawad R, Hsieh A, Damon L. Graft-versus-host disease presenting with pancytopenia after en bloc multiorgan transplantation: case report and literature review. Transplant Proc 2009;41:4431-4433. https://doi.org/10.1016/j.transproceed.2009.06.229
  2. Taylor AL, Gibbs P, Sudhindran S, et al. Monitoring systemic donor lymphocyte macrochimerism to aid the diagnosis of graft-versus-host disease after liver transplantation. Transplantation 2004;77:441-446. https://doi.org/10.1097/01.TP.0000103721.29729.FE
  3. Cho EH, Suh KS, Yang SH, et al. Acute graft versus host disease following living donor liver transplantation: first Korean report. Hepatogastroenterology 2007;54:2120-2122.
  4. Whalen JG, Jukic DM, English JC 3rd. Rash and pancytopenia as initial manifestations of acute graft-versus-host disease after liver transplantation. J Am Acad Dermatol 2005;52: 908-912. https://doi.org/10.1016/j.jaad.2005.01.126
  5. Taylor AL, Gibbs P, Bradley JA. Acute graft versus host disease following liver transplantation: the enemy within. Am J Transplant 2004;4:466-474. https://doi.org/10.1111/j.1600-6143.2004.00406.x
  6. Kanehira K, Riegert-Johnson DL, Chen D, Gibson LE, Grinnell SD, Velgaleti GV. FISH diagnosis of acute graft-versus-host disease following living-related liver transplant. J Mol Diagn 2009;11:355-358. https://doi.org/10.2353/jmoldx.2009.080172
  7. Kohler S, Pascher A, Junge G, et al. Graft versus host disease after liver transplantation - a single center experience and review of literature. Transpl Int 2008;21:441-451. https://doi.org/10.1111/j.1432-2277.2007.00625.x
  8. Arrieta A, Maruri N, Rinon M, Fernandez JR, Ortiz de Urbina J, Garcia Masdevall MD. Confirmation of graft-versus-host disease by HLA typing after liver transplantation. Transplant Proc 2002;34:278-279. https://doi.org/10.1016/S0041-1345(01)02833-0
  9. Perri R, Assi M, Talwalkar J, et al. Graft vs. host disease after liver transplantation: a new approach is needed. Liver Transpl 2007;13:1092-1099. https://doi.org/10.1002/lt.21203
  10. Lu Y, Wu LQ, Zhang BY, Cao JY. Graft-versus-host disease after liver transplantation: successful treatment of a case. Transplant Proc 2008;40:3784-3786. https://doi.org/10.1016/j.transproceed.2008.03.164
  11. Smith DM, Agura E, Netto G, et al. Liver transplant-associated graft-versus-host disease. Transplantation 2003;75:118-126. https://doi.org/10.1097/00007890-200301150-00022
  12. Kuball J, Theobald M, Ferreira EA, et al. Control of organ transplant-associated graft-versus-host disease by activated host lymphocyte infusions. Transplantation 2004;78:1774-1779. https://doi.org/10.1097/01.TP.0000144183.77279.EC
  13. Schrager JJ, Vnencak-Jones CL, Graber SE, et al. Use of short tandem repeats for DNA fingerprinting to rapidly diagnose graft-versus-host disease in solid organ transplant patients. Transplantation 2006;81:21-25. https://doi.org/10.1097/01.tp.0000190431.94252.3f
  14. Lehner F, Becker T, Sybrecht L, et al. Successful outcome of acute graft-versus-host disease in a liver allograft recipient by withdrawal of immunosuppression. Transplantation 2002; 73:307-310. https://doi.org/10.1097/00007890-200201270-00030
  15. Kamei H, Oike F, Fujimoto Y, Yamamoto H, Tanaka K, Kiuchi T. Fatal graft-versus-host disease after living donor liver transplantation: differential impact of donor-dominant one-way HLA matching. Liver Transpl 2006;12:140-145. https://doi.org/10.1002/lt.20573
  16. Soejima Y, Shimada M, Suehiro T, et al. Graft-versus-host disease following living donor liver transplantation. Liver Transpl 2004;10:460-464. https://doi.org/10.1002/lt.20101
  17. Chan EY, Larson AM, Gernsheimer TB, et al. Recipient and donor factors influence the incidence of graft-vs.-host disease in liver transplant patients. Liver Transpl 2007;13:516-522. https://doi.org/10.1002/lt.21082
  18. Pollack MS, Speeg KV, Callander NS, et al. Severe, late-onset graft-versus-host disease in a liver transplant recipient documented by chimerism analysis. Hum Immunol 2005;66: 28-31.
  19. Jacobsohn DA, Hallick J, Anders V, McMillan S, Morris L, Vogelsang GB. Infliximab for steroid-refractory acute GVHD: a case series. Am J Hematol 2003;74:119-124. https://doi.org/10.1002/ajh.10392
  20. Ringden O, Uzunel M, Rasmusson I, et al. Mesenchymal stem cells for treatment of therapy-resistant graft-versus-host disease. Transplantation 2006;81:1390-1397. https://doi.org/10.1097/01.tp.0000214462.63943.14