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

Kubal, Chandrashekhar A.1,5; Mangus, Richard S.1; Saxena, Romil2; Lobashevsky, Andrew3; Higgins, Nancy3; Agarwal, Avinash4; Fridell, Jonathan A.1; Tector, A. Joseph1

doi: 10.1097/TP.0b013e3182a688c0
Clinical and Translational Research

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 globulin±rituximab 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.

1 Transplant Division, Department of Surgery, Indiana University School of Medicine, Indianapolis, IN.

2 Department of Pathology, Indiana University School of Medicine, Indianapolis, IN.

3 Transplant Immunology Laboratory, Methodist Hospital, Indiana University School of Medicine, Indianapolis, IN.

4 Transplant Division, Department of Surgery, University of Virginia, Charlottesville, VA.

5 Address correspondence to: Chandrashekhar A. Kubal, M.D., Ph.D., Transplant Division, Department of Surgery, Indiana University School of Medicine, 550 North University Boulevard, Room 4601, Indianapolis, IN.

The authors declare no funding or conflicts of interest.

E-mail: sakubal@iupui.edu

C.A.K. participated in the research design, performance of the research, data analysis, and writing of the article. R.S.M. and A.J.T. participated in the research design, performance of the research, and writing of the article. R.S., A.L., and N.H. participated in the performance of the research and writing of the article. A.A. participated in the research design and performance of the research. J.A.F. participated in the writing of the article.

Received 26 February 2013. Revision requested 22 March 2013.

Accepted 22 July 2013.

Accepted September 12, 2013

© 2014 by Lippincott Williams & Wilkins