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Published in: Langenbeck's Archives of Surgery 7/2019

01-11-2019 | Thrombosis | Original Article

Exploring pre-surgery donor-specific antibodies in the context of organ shortage in liver transplant

Authors: Savio G. Barreto, Mark E. Brooke-Smith, Eu Ling Neo, Paul Dolan, Richard Leibbrandt, Tim Emery, Robert Carroll, Alan Wigg, John W. Chen

Published in: Langenbeck's Archives of Surgery | Issue 7/2019

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Abstract

Background

There is a growing disparity between the number of liver transplant (LT) candidates and availability of suitable liver allografts. Antibody-mediated rejection (AMR), secondary to positive donor-specific antibodies (DSA), remains a concern in liver transplantation. This study aimed to correlate expression of DSA on pre-transplant screening and outcomes of LT, specifically development of AMR in liver allografts and liver function profile in the post-operative period.

Methods

Data of consecutive patients undergoing orthotopic LT (OLT) at the South Australian Liver Transplant Unit was analysed. All patients underwent DSA testing pre-transplant.

Results

Within a cohort of 96 patients, over a post-OLT median follow-up of 849 days, only 2 patients (2%) developed AMR. While both patients had a positive DSA test preoperatively, overall DSA positivity was noted in 31% patients, with a specificity for prediction of AMR of 0.708. No significant association was noted between AMR (p = 0.092), T cell–mediated rejection/TCMR (p = 0.797) or late hepatic artery thrombosis/LHAT (p = 0.521). There was no significant interaction effect between DSA positivity and serum bilirubin or transaminases over a period of 100 days.

Conclusion

AMR following LT is uncommon. A positive DSA pre-transplant does not imply a definite risk of AMR. Also, there does not exist a significant interaction in time between DSA expression and serum bilirubin or transaminase levels. Until there emerges evidence to the contrary, it appears reasonable to consider DSA-positive donors within the broad context of marginal donors in the context of a worldwide shortage of LT donor allografts.
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Literature
1.
go back to reference Jadlowiec CC, Taner T (2016) Liver transplantation: current status and challenges. World J Gastroenterol 22:4438–4445CrossRef Jadlowiec CC, Taner T (2016) Liver transplantation: current status and challenges. World J Gastroenterol 22:4438–4445CrossRef
2.
go back to reference Casavilla A, Ramirez C, Shapiro R et al (1995) Experience with liver and kidney allografts from non-heart-beating donors. Transplantation 59:197–203CrossRef Casavilla A, Ramirez C, Shapiro R et al (1995) Experience with liver and kidney allografts from non-heart-beating donors. Transplantation 59:197–203CrossRef
3.
go back to reference Dasari BVM, Schlegel A, Mergental H et al (2017) The use of old donors in liver transplantation. Best Pract Res Clin Gastroenterol 31:211–217CrossRef Dasari BVM, Schlegel A, Mergental H et al (2017) The use of old donors in liver transplantation. Best Pract Res Clin Gastroenterol 31:211–217CrossRef
4.
go back to reference Busuttil RW, Tanaka K (2003) The utility of marginal donors in liver transplantation. Liver Transpl 9:651–663CrossRef Busuttil RW, Tanaka K (2003) The utility of marginal donors in liver transplantation. Liver Transpl 9:651–663CrossRef
5.
go back to reference Beal EW, Black SM, Mumtaz K et al (2017) High center volume does not mitigate risk associated with using high donor risk organs in liver transplantation. Dig Dis Sci 62(9):2578-2585 Beal EW, Black SM, Mumtaz K et al (2017) High center volume does not mitigate risk associated with using high donor risk organs in liver transplantation. Dig Dis Sci 62(9):2578-2585
6.
go back to reference Ozhathil DK, Li YF, Smith JK et al (2011) Impact of center volume on outcomes of increased-risk liver transplants. Liver Transpl 17:1191–1199CrossRef Ozhathil DK, Li YF, Smith JK et al (2011) Impact of center volume on outcomes of increased-risk liver transplants. Liver Transpl 17:1191–1199CrossRef
7.
go back to reference Patel R, Terasaki PI (1969) Significance of the positive crossmatch test in kidney transplantation. N Engl J Med 280:735–739CrossRef Patel R, Terasaki PI (1969) Significance of the positive crossmatch test in kidney transplantation. N Engl J Med 280:735–739CrossRef
8.
go back to reference Terasaki PI (2003) Humoral theory of transplantation. Am J Transplant 3:665–673CrossRef Terasaki PI (2003) Humoral theory of transplantation. Am J Transplant 3:665–673CrossRef
9.
go back to reference Demetris AJ, Bellamy C, Hubscher SG et al (2016) Comprehensive update of the Banff Working Group on liver allograft pathology: introduction of antibody-mediated rejection. Am J Transplant 2016(16):2816–2835CrossRef Demetris AJ, Bellamy C, Hubscher SG et al (2016) Comprehensive update of the Banff Working Group on liver allograft pathology: introduction of antibody-mediated rejection. Am J Transplant 2016(16):2816–2835CrossRef
10.
go back to reference Kulkarni HS, Bemiss BC, Hachem RR (2015) Antibody-mediated rejection in lung transplantation. Curr Transplant Rep 2:316–323CrossRef Kulkarni HS, Bemiss BC, Hachem RR (2015) Antibody-mediated rejection in lung transplantation. Curr Transplant Rep 2:316–323CrossRef
11.
go back to reference Demetris AJ, Bellamy CO, Gandhi CR et al (2016) Functional immune anatomy of the liver-as an allograft. Am J Transplant 16:1653–1680CrossRef Demetris AJ, Bellamy CO, Gandhi CR et al (2016) Functional immune anatomy of the liver-as an allograft. Am J Transplant 16:1653–1680CrossRef
12.
go back to reference O'Leary JG, Michelle Shiller S, Bellamy C et al (2014) Acute liver allograft antibody-mediated rejection: an inter-institutional study of significant histopathological features. Liver Transpl 20:1244–1255CrossRef O'Leary JG, Michelle Shiller S, Bellamy C et al (2014) Acute liver allograft antibody-mediated rejection: an inter-institutional study of significant histopathological features. Liver Transpl 20:1244–1255CrossRef
13.
go back to reference Taner T, Gandhi MJ, Sanderson SO et al (2012) Prevalence, course and impact of HLA donor-specific antibodies in liver transplantation in the first year. Am J Transplant 12:1504–1510CrossRef Taner T, Gandhi MJ, Sanderson SO et al (2012) Prevalence, course and impact of HLA donor-specific antibodies in liver transplantation in the first year. Am J Transplant 12:1504–1510CrossRef
14.
go back to reference EASL (2016) EASL Clinical practice guidelines: liver transplantation. J Hepatol 64:433–485CrossRef EASL (2016) EASL Clinical practice guidelines: liver transplantation. J Hepatol 64:433–485CrossRef
15.
go back to reference Bekker J, Ploem S, de Jong KP (2009) Early hepatic artery thrombosis after liver transplantation: a systematic review of the incidence, outcome and risk factors. Am J Transplant 9:746–757CrossRef Bekker J, Ploem S, de Jong KP (2009) Early hepatic artery thrombosis after liver transplantation: a systematic review of the incidence, outcome and risk factors. Am J Transplant 9:746–757CrossRef
16.
go back to reference Lefaucheur C, Loupy A, Vernerey D et al (2013) Antibody-mediated vascular rejection of kidney allografts: a population-based study. Lancet 381:313–319CrossRef Lefaucheur C, Loupy A, Vernerey D et al (2013) Antibody-mediated vascular rejection of kidney allografts: a population-based study. Lancet 381:313–319CrossRef
17.
go back to reference Cuadrado A, San Segundo D, Lopez-Hoyos M et al (2015) Clinical significance of donor-specific human leukocyte antigen antibodies in liver transplantation. World J Gastroenterol 21:11016–11026CrossRef Cuadrado A, San Segundo D, Lopez-Hoyos M et al (2015) Clinical significance of donor-specific human leukocyte antigen antibodies in liver transplantation. World J Gastroenterol 21:11016–11026CrossRef
18.
go back to reference Loupy A, Vernerey D, Tinel C et al (2015) Subclinical rejection phenotypes at 1 year post-transplant and outcome of kidney allografts. J Am Soc Nephrol. 26:1721–1731CrossRef Loupy A, Vernerey D, Tinel C et al (2015) Subclinical rejection phenotypes at 1 year post-transplant and outcome of kidney allografts. J Am Soc Nephrol. 26:1721–1731CrossRef
19.
go back to reference Orandi B, Chow E, Hsu A et al (2015) Quantifying renal allograft loss following early antibody-mediated rejection. Am J Transplant 15:489–498CrossRef Orandi B, Chow E, Hsu A et al (2015) Quantifying renal allograft loss following early antibody-mediated rejection. Am J Transplant 15:489–498CrossRef
20.
go back to reference O'Leary JG, Kaneku H, Demetris AJ et al (2014) Antibody-mediated rejection as a contributor to previously unexplained early liver allograft loss. Liver Transpl 20:218–227CrossRef O'Leary JG, Kaneku H, Demetris AJ et al (2014) Antibody-mediated rejection as a contributor to previously unexplained early liver allograft loss. Liver Transpl 20:218–227CrossRef
21.
go back to reference Castillo-Rama M, Castro MJ, Bernardo I et al (2008) Preformed antibodies detected by cytotoxic assay or multibead array decrease liver allograft survival: role of human leukocyte antigen compatibility. Liver Transpl 14:554–562CrossRef Castillo-Rama M, Castro MJ, Bernardo I et al (2008) Preformed antibodies detected by cytotoxic assay or multibead array decrease liver allograft survival: role of human leukocyte antigen compatibility. Liver Transpl 14:554–562CrossRef
22.
go back to reference O'Leary JG, Demetris AJ, Friedman LS et al (2014) The role of donor-specific HLA alloantibodies in liver transplantation. Am J Transplant 14:779–787CrossRef O'Leary JG, Demetris AJ, Friedman LS et al (2014) The role of donor-specific HLA alloantibodies in liver transplantation. Am J Transplant 14:779–787CrossRef
23.
go back to reference Hogen R, DiNorcia J, Dhanireddy K (2017) Antibody-mediated rejection: what is the clinical relevance? Curr Opin Organ Transplant 22:97–104CrossRef Hogen R, DiNorcia J, Dhanireddy K (2017) Antibody-mediated rejection: what is the clinical relevance? Curr Opin Organ Transplant 22:97–104CrossRef
24.
go back to reference Cheng EY (2017) The role of humoral alloreactivity in liver transplantation: lessons learned and new perspectives. J Immunol Res 2017:3234906PubMedPubMedCentral Cheng EY (2017) The role of humoral alloreactivity in liver transplantation: lessons learned and new perspectives. J Immunol Res 2017:3234906PubMedPubMedCentral
25.
go back to reference Del Bello A, Congy-Jolivet N, Muscari F et al (2014) Prevalence, incidence and risk factors for donor-specific anti-HLA antibodies in maintenance liver transplant patients. Am J Transplant 14:867–875CrossRef Del Bello A, Congy-Jolivet N, Muscari F et al (2014) Prevalence, incidence and risk factors for donor-specific anti-HLA antibodies in maintenance liver transplant patients. Am J Transplant 14:867–875CrossRef
26.
go back to reference Kaneku H, O'Leary JG, Banuelos N et al (2013) De novo donor-specific HLA antibodies decrease patient and graft survival in liver transplant recipients. Am J Transplant 13:1541–1548CrossRef Kaneku H, O'Leary JG, Banuelos N et al (2013) De novo donor-specific HLA antibodies decrease patient and graft survival in liver transplant recipients. Am J Transplant 13:1541–1548CrossRef
27.
go back to reference Demetris AJ, Nakamura K, Yagihashi A et al (1992) A clinicopathological study of human liver allograft recipients harboring preformed IgG lymphocytotoxic antibodies. Hepatology 16:671–681CrossRef Demetris AJ, Nakamura K, Yagihashi A et al (1992) A clinicopathological study of human liver allograft recipients harboring preformed IgG lymphocytotoxic antibodies. Hepatology 16:671–681CrossRef
28.
go back to reference Levitsky J, Goldberg D, Smith AR et al (2017) Acute rejection increases risk of graft failure and death in recent liver transplant recipients. Clin Gastroenterol Hepatol 15:584–593 e582CrossRef Levitsky J, Goldberg D, Smith AR et al (2017) Acute rejection increases risk of graft failure and death in recent liver transplant recipients. Clin Gastroenterol Hepatol 15:584–593 e582CrossRef
29.
go back to reference Levitsky J, Kaneku H, Jie C et al (2016) Donor-specific hla antibodies in living versus deceased donor liver transplant recipients. Am J Transplant 16:2437–2444CrossRef Levitsky J, Kaneku H, Jie C et al (2016) Donor-specific hla antibodies in living versus deceased donor liver transplant recipients. Am J Transplant 16:2437–2444CrossRef
30.
go back to reference Sis B, Jhangri GS, Bunnag S et al (2009) Endothelial gene expression in kidney transplants with alloantibody indicates antibody-mediated damage despite lack of C4d staining. Am J Transplant 9:2312–2323CrossRef Sis B, Jhangri GS, Bunnag S et al (2009) Endothelial gene expression in kidney transplants with alloantibody indicates antibody-mediated damage despite lack of C4d staining. Am J Transplant 9:2312–2323CrossRef
Metadata
Title
Exploring pre-surgery donor-specific antibodies in the context of organ shortage in liver transplant
Authors
Savio G. Barreto
Mark E. Brooke-Smith
Eu Ling Neo
Paul Dolan
Richard Leibbrandt
Tim Emery
Robert Carroll
Alan Wigg
John W. Chen
Publication date
01-11-2019
Publisher
Springer Berlin Heidelberg
Keyword
Thrombosis
Published in
Langenbeck's Archives of Surgery / Issue 7/2019
Print ISSN: 1435-2443
Electronic ISSN: 1435-2451
DOI
https://doi.org/10.1007/s00423-019-01831-9

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