title: Occurrence of post-transplant lymphoproliferative disorders among over thousand adult recipients: any role for hepatitis C infection?
abstract: 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.
  
  
  OBJECTIVE
  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.
authors.affiliation: Department of Surgical and Gastroenterological Sciences, University of Padua, Padua Italy. burra@unipd.it
authors.forename: Patrizia
authors.initials: P
authors.lastname: Burra
authors.forename: Andrea
authors.initials: A
authors.lastname: Buda
authors.forename: Ugolino
authors.initials: U
authors.lastname: Livi
authors.forename: Paolo
authors.initials: P
authors.lastname: Rigotti
authors.forename: Giacomo
authors.initials: G
authors.lastname: Zanus
authors.forename: Fiorella
authors.initials: F
authors.lastname: Calabrese
authors.forename: Alida
authors.initials: A
authors.lastname: Caforio
authors.forename: Chiara
authors.initials: C
authors.lastname: Menin
authors.forename: Daniele
authors.initials: D
authors.lastname: Canova
authors.forename: Fabio
authors.initials: F
authors.lastname: Farinati
authors.forename: Savina Maria
authors.initials: SM
authors.lastname: Luciana Aversa
mesh_terms: D000328:Adult; D000368:Aged; D004812:Epidemiologic Methods; D020031:Epstein-Barr Virus Infections / Q000150:complications; D005260:Female; D006084:Graft Rejection / Q000188:drug therapy; D016027:Heart Transplantation; D006526:Hepatitis C / Q000150:complications*; D006689:Hodgkin Disease / Q000821:virology; D006801:Humans; D007165:Immunosuppression Therapy / Q000379:methods; D016030:Kidney Transplantation; D016031:Liver Transplantation; D008223:Lymphoma / Q000821:virology*; D008297:Male; D008875:Middle Aged; D016377:Organ Transplantation; D011183:Postoperative Complications / Q000821:virology*