Immunosuppression in Donation After Circulatory Death Liver Transplantation: Can Induction Modify Graft Survival?

Abstract

Recipients of donation after circulatory death (DCD) LTs historically have an increased risk of graft failure. Antibody induction (AI) with antithymocyte globulin (ATG) or anti‐interleukin 2 receptor (anti‐IL2R) immunotherapy may decrease the incidence of graft failure by mitigating ischemia/reperfusion injury. A retrospective review of the United Network for Organ Sharing (UNOS) database for LTs between 2002 and 2015 was conducted to determine whether ATG or anti‐IL2R AI was associated with graft survival in DCD. A secondary endpoint was postoperative renal function as measured by estimated glomerular filtration rate at 6 and 12 months. Among DCD recipients, ATG (hazard ratio [HR] = 0.71; P = 0.03), but not anti‐IL2R (HR = 0.82; P = 0.10), was associated with a decrease in graft failure at 3 years when compared with recipients without AI. ATG (HR = 0.90; P = 0.02) and anti‐IL2R (HR = 0.94; P = 0.03) were associated with a decreased risk of graft failure in donation after brain death (DBD) liver recipients at 3 years compared with no AI. When induction regimens were compared between DCD and DBD, only ATG (HR = 1.19; P = 0.19), and not anti‐IL2R (HR = 1.49; P < 0.01) or no AI (HR = 1.77; P < 0.01), was associated with similar survival between DCD and DBD. In conclusion, AI therapy with ATG was associated with improved longterm liver allograft survival in DCD compared with no AI. ATG was associated with equivalent graft survival between DCD and DBD, suggesting a beneficial role of immune cell depletion in DCD outcomes.

Detrimental impact of early biopsy‐proven rejection in liver transplantation

“…The 90‐day interval was selected for this study because of an absence of data on the consequences of rejection in this window and to provide more clarity on the importance of immunosuppressive titration in the peri‐operative period. Third, there have been subtle changes in the center's immunosuppression protocol over the period of the study, including the implementation of an invasive fungal infection prophylaxis regimen that involves limited early antimetabolite use in some patients and growing use of thymoglobulin induction in DCD recipients 7,8 . Although neither thymoglobulin or antimetabolite administration differed between patients with EBPR and those without in our cohort, these protocol changes may have impacted the results of the study.…”

“…22 The role of induction therapy in liver transplantation remains a topic of debate with some studies demonstrating benefit in select populations (particularly DCD recipients) and others showing no benefit. 7,[23][24][25][26] EBPR may assume more importance in the coming years as more centers consider transplanting patients with HCC who have received immunotherapy for their malignancies. 27 No such patients were included in this study, and rejection following immunotherapy may have different biologic behavior.…”

“…A recent multi‐center study concluded that low‐dose aspirin provided significant protection against rejection 22 . The role of induction therapy in liver transplantation remains a topic of debate with some studies demonstrating benefit in select populations (particularly DCD recipients) and others showing no benefit 7,23–26 . EBPR may assume more importance in the coming years as more centers consider transplanting patients with HCC who have received immunotherapy for their malignancies 27 .…”

“…Tacrolimus trough goals are 5–9 ng/mL for the first 90 days. Antibody‐based induction therapy is generally omitted in transplants from donors after brain death (DBD), and anti‐thymocyte globulin (ATG) is typically administered to recipients of donation after circulatory death (DCD) allografts 7 . The final determination on induction therapy is at the discretion of the transplanting surgeon.…”

Strategies to Improve the Utilization and Function of DCD Livers

“…Furthermore, data show that using thymoglobulin as an induction agent for DCD liver transplants has reduced both ischemic reperfusion injury and biliary complications. [82][83][84] Its use has been shown to be safe, with no major sequelae in platelet or white blood cell counts. 85 Furthermore, some studies have even noted that the use of thymoglobulin induction with DCD liver transplantation is independently associated with increased graft survival free from DCD-associated cholangiopathy on multivariable analysis.…”