Crossmatch-positive liver transplantation in patients receiving thymoglobulin-rituximab induction

Transplantation. 2014 Jan 15;97(1):56-63. doi: 10.1097/TP.0b013e3182a688c0.

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.

MeSH terms

  • Acute Disease
  • Antibodies, Monoclonal, Murine-Derived / therapeutic use*
  • Antilymphocyte Serum / therapeutic use*
  • Biomarkers / blood
  • Biopsy
  • Chi-Square Distribution
  • Chronic Disease
  • Complement C1q / immunology
  • Complement C4b / metabolism
  • Female
  • Graft Rejection / immunology
  • Graft Rejection / pathology
  • Graft Rejection / prevention & control*
  • Graft Survival / drug effects
  • Histocompatibility / drug effects*
  • Histocompatibility Testing
  • Humans
  • Immunosuppressive Agents / therapeutic use*
  • Isoantibodies / blood
  • Liver Transplantation* / adverse effects
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Peptide Fragments / metabolism
  • Proportional Hazards Models
  • Retrospective Studies
  • Risk Factors
  • Rituximab
  • Time Factors
  • Treatment Outcome

Substances

  • Antibodies, Monoclonal, Murine-Derived
  • Antilymphocyte Serum
  • Biomarkers
  • Immunosuppressive Agents
  • Isoantibodies
  • Peptide Fragments
  • Rituximab
  • Complement C1q
  • Complement C4b
  • complement C4d
  • thymoglobulin