Crossmatch-Positive Liver Transplantation in Patients Receiving Thymoglobulin-Rituximab Induction

Background Positive crossmatch (CM) in liver transplantation (LT) is associated with worse outcomes. Role of induction immunosuppression in this setting remains to be studied. Methods One thousand consecutive LT patients receiving rabbit antithymocyte globulinrituximab induction were studied. Pretransplantation sera of 55 CM-positive (CM+) patients were tested for C1q-fixing donor-specific antibodies (DSA). Diagnosis of antibody-mediated rejection required presence of diffuse vascular C4d expression on liver biopsies. Results CM was positive in 112 (11%) recipients. Antibody-mediated rejection was observed in 3 (0.03%) patients, whereas acute cellular rejection (ACR) occurred in 31 (3%) patients. CM+ status was associated with a higher incidence of ACR (9% in CM+ vs. 2% in CM-negative [CM-]; P<0.01) and chronic rejection (4% in CM+ vs. 1% in CM-; P<0.01). Graft survival was slightly lower in CM+ patients (at 1 year; 85% in CM+ vs. 89% in CM-; P=0.26). Patients with autoimmune hepatitis, primary sclerosing cholangitis, and primary biliary cirrhosis as a group had a tendency toward CM+ status as well as developing ACR. Upon multivariate analysis, CM status was the strongest predictor of ACR (B=1.14; P=0.02). Only half of CM+ patients harbored C1q-fixing DSA. Presence of C1q-fixing DSA was not associated with increased incidence of ACR. Conclusions In LT, CM+ status is associated with an increased incidence of acute rejection, chronic rejection, and slightly worse graft survival. With the use of rabbit antithymocyte globulin +/- rituximab induction, overall low rejection rates can be achieved in CM+ LT.