Liver Inclusion Appears to Be Protective Against Graft Loss-Due-to Chronic But Not Acute Rejection Following Intestinal Transplantation

Overview

Journal Transpl Int

Specialty General Surgery

Date 2023 Oct 2

PMID 37779512

Authors

Rodrigo Vianna

Jeffrey J Gaynor

Gennaro Selvaggi

Ahmed Farag

Jennifer Garcia

Akin Tekin

Marina M Tabbara

Gaetano Ciancio

Affiliations

Soon will be listed here.

Abstract

In intestinal transplantation, while other centers have shown that liver-including allografts have significantly more favorable graft survival and graft loss-due-to chronic rejection (CHR) rates, our center has consistently shown that modified multivisceral (MMV) and full multivisceral (MV) allografts have significantly more favorable acute cellular rejection (ACR) and severe ACR rates compared with isolated intestine (I) and liver-intestine (LI) allografts. In the attempt to resolve this apparent discrepancy, we performed stepwise Cox multivariable analyses of the hazard rates of developing graft loss-due-to acute rejection (AR) vs. CHR among 350 consecutive intestinal transplants at our center with long-term follow-up (median: 13.5 years post-transplant). Observed percentages developing graft loss-due-to AR and CHR were 14.3% (50/350) and 6.6% (23/350), respectively. Only one baseline variable was selected into the Cox model indicating a significantly lower hazard rate of developing graft loss-due-to AR: Transplant Type MMV or MV ( < 0.000001). Conversely, two baseline variables were selected into the Cox model indicating a significantly lower hazard rate of developing graft loss-due-to CHR: Received Donor Liver (LI or MV) ( = 0.002) and Received Induction ( = 0.007). In summary, while MMV/MV transplants (who receive extensive native lymphoid tissue removal) offered protection against graft loss-due-to AR, liver-containing grafts appeared to offer protection against graft loss-due-to CHR, supporting the results of other studies.

References

Abu-Elmagd K, Wu G, Costa G, Lunz J, Martin L, Koritsky D . Preformed and de novo donor specific antibodies in visceral transplantation: long-term outcome with special reference to the liver. Am J Transplant. 2012; 12(11):3047-60. DOI: 10.1111/j.1600-6143.2012.04237.x. View

Demetris A, Murase N, Ye Q, Galvao F, Richert C, Saad R . Analysis of chronic rejection and obliterative arteriopathy. Possible contributions of donor antigen-presenting cells and lymphatic disruption. Am J Pathol. 1997; 150(2):563-78. PMC: 1858300. View

Zhang R . Donor-Specific Antibodies in Kidney Transplant Recipients. Clin J Am Soc Nephrol. 2017; 13(1):182-192. PMC: 5753302. DOI: 10.2215/CJN.00700117. View

Selvaggi G, Gaynor J, Moon J, Kato T, Thompson J, Nishida S . Analysis of acute cellular rejection episodes in recipients of primary intestinal transplantation: a single center, 11-year experience. Am J Transplant. 2007; 7(5):1249-57. DOI: 10.1111/j.1600-6143.2007.01755.x. View

Taner T, Stegall M, Heimbach J . Antibody-mediated rejection in liver transplantation: current controversies and future directions. Liver Transpl. 2014; 20(5):514-27. DOI: 10.1002/lt.23826. View

Cheng E, Everly M, Kaneku H, Banuelos N, Wozniak L, Venick R . Prevalence and Clinical Impact of Donor-Specific Alloantibody Among Intestinal Transplant Recipients. Transplantation. 2016; 101(4):873-882. PMC: 7228620. DOI: 10.1097/TP.0000000000001391. View

Abu-Elmagd K, Kosmach-Park B, Costa G, Zenati M, Martin L, Koritsky D . Long-term survival, nutritional autonomy, and quality of life after intestinal and multivisceral transplantation. Ann Surg. 2012; 256(3):494-508. DOI: 10.1097/SLA.0b013e318265f310. View

Kubal C, Mangus R, Saxena R, Lobashevsky A, Higgins N, Fridell J . Prospective Monitoring of Donor-specific Anti-HLA Antibodies After Intestine/Multivisceral Transplantation: Significance of De Novo Antibodies. Transplantation. 2015; 99(8):e49-56. DOI: 10.1097/TP.0000000000000614. View

Abu-Elmagd K, Costa G, Bond G, Wu T, Murase N, Zeevi A . Evolution of the immunosuppressive strategies for the intestinal and multivisceral recipients with special reference to allograft immunity and achievement of partial tolerance. Transpl Int. 2008; 22(1):96-109. DOI: 10.1111/j.1432-2277.2008.00785.x. View

10.

Ruiz P, Bagni A, Brown R, Cortina G, Harpaz N, Magid M . Histological criteria for the identification of acute cellular rejection in human small bowel allografts: results of the pathology workshop at the VIII International Small Bowel Transplant Symposium. Transplant Proc. 2004; 36(2):335-7. DOI: 10.1016/j.transproceed.2004.01.079. View

11.

Kato T, Gaynor J, Selvaggi G, Mittal N, Thompson J, McLaughlin G . Intestinal transplantation in children: a summary of clinical outcomes and prognostic factors in 108 patients from a single center. J Gastrointest Surg. 2004; 9(1):75-89. DOI: 10.1016/j.gassur.2004.10.012. View

12.

Abu-Elmagd K, Costa G, Bond G, Soltys K, Sindhi R, Wu T . Five hundred intestinal and multivisceral transplantations at a single center: major advances with new challenges. Ann Surg. 2009; 250(4):567-81. DOI: 10.1097/SLA.0b013e3181b67725. View

13.

Farmer D, Venick R, Colangelo J, Esmailian Y, Yersiz H, Duffy J . Pretransplant predictors of survival after intestinal transplantation: analysis of a single-center experience of more than 100 transplants. Transplantation. 2010; 90(12):1574-80. DOI: 10.1097/TP.0b013e31820000a1. View

14.

Talayero P, Boluda E, Gomez Massa E, Castro Panete M, Prieto Bozano G, Hernandez Oliveros F . Donor-Specific Antibodies in Pediatric Intestinal and Multivisceral Transplantation: The Role of Liver and Human Leukocyte Antigen Mismatching. Liver Transpl. 2018; 24(12):1726-1735. DOI: 10.1002/lt.25323. View

15.

Petit L, Rabant M, Canioni D, Suberbielle-Boissel C, Goulet O, Chardot C . Impacts of donor-specific anti-HLA antibodies and antibody-mediated rejection on outcomes after intestinal transplantation in children. Pediatr Transplant. 2017; 21(2). DOI: 10.1111/petr.12847. View

16.

Lakkis F, Arakelov A, Konieczny B, Inoue Y . Immunologic 'ignorance' of vascularized organ transplants in the absence of secondary lymphoid tissue. Nat Med. 2000; 6(6):686-8. DOI: 10.1038/76267. View

17.

Gerlach U, Lachmann N, Sawitzki B, Arsenic R, Neuhaus P, Schoenemann C . Clinical relevance of the de novo production of anti-HLA antibodies following intestinal and multivisceral transplantation. Transpl Int. 2013; 27(3):280-9. DOI: 10.1111/tri.12250. View

18.

Willicombe M, Roufosse C, Brookes P, McLean A, Galliford J, Cairns T . Acute cellular rejection: impact of donor-specific antibodies and C4d. Transplantation. 2014; 97(4):433-9. DOI: 10.1097/01.TP.0000437431.97108.8f. View

19.

Starzl T, Zinkernagel R . Transplantation tolerance from a historical perspective. Nat Rev Immunol. 2002; 1(3):233-9. PMC: 3228352. DOI: 10.1038/35105088. View

20.

Patel R, Terasaki P . Significance of the positive crossmatch test in kidney transplantation. N Engl J Med. 1969; 280(14):735-9. DOI: 10.1056/NEJM196904032801401. View