Occurrence of post-transplant lymphoproliferative disorders among over thousand adult recipients: any role for hepatitis C infection?

Background: Post-transplant lymphoproliferative disorders represent an increasingly important complication of organ transplantation. Although the majority of the post-transplant lymphoproliferative disorder are etiologically related to Epstein-Barr virus infection other factors may play a role. Hepatitis C virus may induce clonal expansion of B-lymphocytes and has been associated with extrahepatic lymphoproliferative disorders. Objectives In this study, we have evaluated: (i) the prevalence of post-transplant lymphoproliferative disorder; (ii) presence of Epstein-Barr virus in post-transplant lymphoproliferative disorder tissue; and (iii) the potential association between post-transplant lymphoproliferative disorder development and hepatitis C virus infection in a large cohort of adult solid organ transplant recipients. Methods: The study involved 1011 liver, heart and kidney-transplanted patients. Different immunosuppression therapy was recorded from all patients, all were screened for hepatitis C virus infection. When post-transplant lymphoproliferative disorder developed, Epstein-Barr virus encoded RNA by in-situ hybridization and EBNA-1 and gp220 by polymerase chain reaction was assessed in tissue samples. Results: The overall prevalence of post-transplant lymphoproliferative disorder was 1.4% (2.5% in heart, 0.9% in liver and 0.8% in kidney-transplanted patients) and significantly higher in hepatitis C virus positive than in hepatitis C virus negative patients (3.6 % vs 1.2 %; P=0.04). Epstein-Barr virus was present in 10 (77%) out of 13 tumors tested. Two out of three Epstein-Barr virus-negative post-transplant lymphoproliferative disorder developed. in hepatitis C virus-positive patients. Thirteen out of 15 (86%) post-transplant lymphoproliferative disorder patients had undergone antithymocyte globulin/ OKT3 induction therapy. Conclusions: Epstein-Barr virus, induction immunosuppression, rejection therapy and also hepatitis C virus infection may play a role in the multifactorial pathogenesis of post-transplant lymphoproliferative disorder.