title: Crossmatch-positive liver transplantation in patients receiving thymoglobulin-rituximab induction.
abstract: 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.
authors.affiliation: 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.
authors.forename: Chandrashekhar A
authors.initials: CA
authors.lastname: Kubal
authors.forename: Richard S
authors.initials: RS
authors.lastname: Mangus
authors.forename: Romil
authors.initials: R
authors.lastname: Saxena
authors.forename: Andrew
authors.initials: A
authors.lastname: Lobashevsky
authors.forename: Nancy
authors.initials: N
authors.lastname: Higgins
authors.forename: Avinash
authors.initials: A
authors.lastname: Agarwal
authors.forename: Jonathan A
authors.initials: JA
authors.lastname: Fridell
authors.forename: A Joseph
authors.initials: AJ
authors.lastname: Tector
mesh_terms: D000208:Acute Disease; D058846:Antibodies, Monoclonal, Murine-Derived / Q000627:therapeutic use*; D000961:Antilymphocyte Serum / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D001706:Biopsy; D016009:Chi-Square Distribution; D002908:Chronic Disease; D015922:Complement C1q / Q000276:immunology; D015935:Complement C4b / Q000378:metabolism; D005260:Female; D006084:Graft Rejection / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D006085:Graft Survival / Q000187:drug effects; D006648:Histocompatibility / Q000187:drug effects*; D006650:Histocompatibility Testing; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007518:Isoantibodies / Q000097:blood; D016031:Liver Transplantation / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D010446:Peptide Fragments / Q000378:metabolism; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D012307:Risk Factors; D000069283:Rituximab; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D000961:Antilymphocyte Serum; D015415:Biomarkers; D007166:Immunosuppressive Agents; D007518:Isoantibodies; D010446:Peptide Fragments; D000069283:Rituximab; D015922:Complement C1q; D015935:Complement C4b; C032261:complement C4d; C512542:thymoglobulin