Given that a positive CDC-XM was not contraindication to ITx, similar immunosuppression was used while B-cell-targeted therapies were not used, this observation can better explain the unique immunoprotective effect of liver allografts on ABMR. (27.2)39 (51.3)0.0001?Crohns disease38 (17.9)29 (21.4)9 (11.9)NS?Motility disorders24 (11.3)17 (12.5)7 (9.2)NS?Gardners syndrome14 (6.7)12 (8.8)2 (2.6)NS?Radiation enteritis8 (3.8)7 (5.1)1 (1.3)NS?Gastric bypass10 (4.7)8 (5.9)2 CP 945598 HCl (Otenabant HCl) (2.6)NS?Others42 (19.8)26 (19.1)16 (21.1)NSCold-ischemic times, hours7.8 1.57.4 1.48.6 1.5<0.0001Positive CMV donor, (%)107 (50.5)60 (44.1)47 (61.8)0.01Splenectomy, (%)58 (27.4)8 (5.9)50 (65.8)<0.0001Donor BMTx, (%)32 (15.1)22 (16.2)10 (13.2)NSDonor bowel irradiation, (%)21 (9.9)17 (12.5)4 (5.3)NS(%)55 (25.9)34 (25.0)21 (27.6)NSPreformed DSA, (%)44/154 (28.6)30/99 (30.3)14/55 (25.5)NSDSA, (%)35/154 (22.7)28/99 (28.3)7/55 (12.9)0.03Acute rejection ( 360 days), (%)133 (62.7)92 (67.6)41 (53.9)0.05Acute ABMR, (%)17/154 (11.0)15/99 (15.2)2/55 (3.6)0.03ACR, (%)116 (54.7)77 (56.6)39 (51.3)NS?Mild91 (42.9)58 (42.6)33 (43.4)0.91?Moderate54 (25.5)42 (30.9)12 (15.8)0.02?Severe35 (16.5)29 (21.3)6 (7.9)0.01Median first acute rejection, months1.0 (0.1C35.4)0.8 (0.5C35.4)1.6 (0.1C31.3)NSChronic rejection, (%)36 (17.0)33 (24.3)3 (3.9)0.0002Causes of graft failure, (%)89 (42.0)56 (41.2)33 (43.4)NS?Rejection47 (22.2)42 (30.9)5 (6.6)<0.0001?Infection26 (12.3)7 (5.1)19 (25.0)<0.0001?Technical4 (1.9)1 (0.7)3 (3.9)NS?Primary-non-function1 (0.5)01 F3 (1.3)NS?Graft-versus-host disease1 (0.5)01 (1.3)NS?Neoplasm1 (0.5)01 (1.3)NS?Others4 (1.9)3 (2.2)0NS?Unknown6 (2.8)3 (2.2)3 (3.9)NSRetransplantation, (%)24 (11.3)22 (16.2)2 (2.6)0.003Mortality 360 days22 (10.4)8 (5.9)14 (18.4)0.004 Open in a separate window PRA, panel reactive antibody; HLA, human leukocyte antigen; DSA, donor-specific antibody; ACR, acute cellular rejection; ABMR, antibody-mediated rejection; NS, not significant. Table 3. Type and timeline of post-transplant fatal infections in the liver-exclusive versus the liver-inclusive allograft DSAs were predominantly against class II HLA both in 6/7 (85.7%) for LITx and in 25/28 (89.3%) for LETx. The average time to detect a DSA was 16.7 15.1 months for LITx versus 18.9 15.3 month for LETx. Chronic rejection With a mean follow-up of 44.9 months, a total of 36 (16.9%) allografts developed pathology-confirmed chronic rejection. Of these, only 3/76 (3.9%) of LITx had chronic rejection (simultaneous liver and intestinal allograft chronic rejection in 2 and solitary intestinal chronic rejection in 1), which was significantly less frequent compared to 33 of 136 (24.3%) LETx (DSA (OR 25.42, 95% CI: 7.72C89.73; DSA76.49 (8.83C97.55)0.000125.42 (7.72C89.73)<0.0001?Duration of TPN (mos)1.01 (0.99C1.02)0.22?Number of surgery1.21 (0.71C1.98)0.75?Rejection number 360 days3.21 (1.05C5.73)0.031.93 (1.46C2.57)0.04reported 209 ITx recipients and found an increased incidence of overall rejection and severity in recipients of the isolated intestinal and combined liver-intestinal allograft compared to the multivisceral allograft with a liver or without a liver [25]. The discrepancy between two observations may be related to the differences in the patient population and in the time span to study the frequency of rejection. In their study, pediatric patients accounted for 61%, which may contribute less frequency and severity of acute rejection after transplantation of a larger amount of lymphoid tissue. The relative immatured immune system in pediatric patients may be more immunologically educable at a central or peripheral level than the matured immune system in adults [25,26]. In addition, our study focused on ACR within the first year after ITx to make our two study groups more comparable. Several potential mechanisms have been proposed to explain the reduced cellular immune response in transplant recipients. It has been noted that the liver allograft harbors donor-derived hematopoietic cells, which migrate out CP 945598 HCl (Otenabant HCl) of the liver graft at the time of graft implantation to establish a state of chimerism [27]. Persistent chimerism can lead to CP 945598 HCl (Otenabant HCl) clonal depletion of host alloreactive T cells, which has been speculated as one of the major factors that help promote long-term graft survival or tolerance induction after transplantation [28,29]. Recent data indicate that chimerism is associated with a lower incidence of rejection after intestinal and multivisceral transplantation [30]. Our earlier study examined the risk factors for acute ABMR and showed that the presence of a liver component was associated with a lower risk of developing acute ABMR after ITx [21]. In this observation, we further compared the recipients between LITx and LETx to confirm a protective effect of liver allografts against humoral rejection. There were no significant differences between LETx and LITx in terms CP 945598 HCl (Otenabant HCl) of the proportions of a positive CDC-XM, pre-existing DSA and the levels of PRA, indicating that these two groups might face a similar immunologic challenge pre transplantation. Given that a positive CDC-XM was not contraindication to ITx, similar immunosuppression was.