Liver-inclusive intestinal transplantation results in decreased alloimmune-mediated rejection but increased infection

Abstract

Background and aimsA co-transplanted liver allograft has been thought to protect other organs from rejection-mediated injury; however, detailed analyses of co-transplanted liver on intestinal allograft outcomes have not been conducted to date. The aim of the study was to compare immune-mediated injury, causes of graft failure and clinical outcomes between recipients who underwent either a liver-inclusive intestinal transplant (LITx) or liver-exclusive intestinal transplant (LETx).MethodsBetween May 2000 and May 2010, 212 adult patients undergoing LITx (n =76) and LETx (n =136) were included. LITx underwent either liver combined intestinal or full multivisceral transplantation. LETx underwent either isolated intestinal or modified multivisceral transplantation.ResultsDuring 44.9 ± 31.4 months of follow-up, death-censored intestinal graft survival was significantly higher for LITx than LETx (96.9%, 93.2% and 89.9% vs 91.4%, 69.3% and 60.0% at 1, 3 and 5 years; p =0.0001). Incidence of graft loss due to rejection was higher in LETx than in LITx (30.9% vs 6.6%; p <0.0001), while infection was the leading cause of graft loss due to patient death in LITx (25.0% vs 5.1%; p <0.0001). Despite similar immunosuppression, the average number (0.87 vs 1.42, p =0.02) and severity of acute cellular rejection episode (severe grade: 7.9% vs 21.3%; p =0.01) were lower in LITx than in LETx. Incidence of acute antibody-mediated rejection was also significantly lower in LITx than in LETx (3.6% vs 15.2%; p =0.03). Incidence of chronic rejection was reduced in LITx (3.9% vs 24.3%; p =0.0002).ConclusionsIntestinal allografts with a liver component appear to decrease risk of rejection but increase risk of infection. Our findings emphasize that LITx has characteristic immunologic and clinical features. Lower immunosuppression may need to be considered for patients who undergo LITx to attenuate increased risk of infection.

Current outcomes after pediatric and adult intestinal transplantation

“…Abu-Elmagd et al [4] reported 38 technical complications in 500 ITx cases (7.6%). Most common technical complications were vascular thrombosis (14), gastrointestinal / biliary leaks (11), arterial pseudo-aneurysms (7), and technically flawed donor/recipient operations (6). Graft loss and patient death occurred in 22 cases (58%).…”

“…Abu-Elmagd et al [4] reported infection as cause of graft loss in 11% of ITx recipients whereas Silva et al reported infection as cause of patient death in 17% of ITx recipients [7]. Wu et al [11] reported that lethal infection accounted for 57% of graft loss in liver-inclusive ITx grafts while accounting only for 12.5% of graft loss in nonliver inclusive ITx grafts. ITR data show that sepsis remains the leading cause of early graft loss and early patient mortality after ITx in 50% of cases [2].…”

“…Abu Elmagd et al [4] noted that recipients of nonliver inclusive ITx grafts suffered a significantly higher long-term risk of graft loss due to rejection compared to recipients of liver inclusive allografts. Wu et al [11] noted that ACR leading to graft loss occurred in 5% of nonliver inclusive grafts versus 2.5% of liver-inclusive ITx grafts. The average number of ACR episodes per patient within first year after ITx was significantly lower in liver inclusive ITx group (0.87, range 0-5) compared to the nonliver inclusive ITx group (1.42, range 0-9; P ¼ 0.02) [11].…”

“…Wu et al [11] noted that ACR leading to graft loss occurred in 5% of nonliver inclusive grafts versus 2.5% of liver-inclusive ITx grafts. The average number of ACR episodes per patient within first year after ITx was significantly lower in liver inclusive ITx group (0.87, range 0-5) compared to the nonliver inclusive ITx group (1.42, range 0-9; P ¼ 0.02) [11]. Together, these findings suggest that inclusion of liver with intestine graft provides immunologic protection against rejection for the intestinal allograft.…”

Benefits of Combined Liver Transplant: Protection or Tolerance?

“…Indeed, a decrease in the induction of NF-kB during the early phase of transplantation, therefore, plays a protective role against the allo-immune response [77]. Another more recent study highlighted the protective effect of liver on the severity of the acute episode of cell rejection, on the incidence of chronic rejection, as well as on the acute rejection induced by antibodies, while the infection was the leading cause of graft loss, suggesting that the reduction in IS may be considered for reducing the increased risk of infection [78].…”