Late Persistent Positive EBV Viral Load and Risk of Solid Cancer in Kidney Transplant Patients

Transplantation. 2017 Jun;101(6):1473-1478. doi: 10.1097/TP.0000000000001280.

Abstract

Background: Recent studies reported that posttransplant Epstein-Barr virus (EBV) replication is frequent and indicates overimmunosuppression. We hypothesized that long-term EBV replication may identify overimmunosuppressed patients at higher risk of cancer.

Methods: We analyzed a prospective cohort of renal transplant recipients having routine EBV PCR surveillance. All cancers (except EBV-related neoplasia) were recorded.

Results: Mean follow up was 94 + 23 months. Samples (8412) were available in 669 patients. Three hundred eighty-eight of the 669 patients (58%) had at least 1 positive viremia during follow-up.Epstein-Barr virus D+/R- patients (P = 0.046) as well as those having received antithymocyte globulin (P < 0.001) were more likely to develop persistent EBV viremia. Eighty-six patients (12.9%) developed a cancer during follow-up. The cumulated incidence of cancer was higher in patients with persistent high EBV replication (22.4% vs 10.2%, P = 0.005). The effect of persistent EBV infection remained significant even after adjustment for all confounding factors (hazard ratio, 1.69; 95% confidence interval, 1.10-2.61; P = 0.018). Age, history of antithymocyte globulin use, smoking, and history of cancer were also associated with cancer occurrence.

Conclusions: Persistent high EBV viral load is associated with the occurrence of solid cancer. In this setting, more intensive screening and/or minimization of immunosuppressive treatment are probably required.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Age Factors
  • Antilymphocyte Serum / adverse effects
  • Epstein-Barr Virus Infections / diagnosis
  • Epstein-Barr Virus Infections / epidemiology
  • Epstein-Barr Virus Infections / immunology
  • Epstein-Barr Virus Infections / virology*
  • Female
  • France / epidemiology
  • Herpesvirus 4, Human / growth & development*
  • Herpesvirus 4, Human / immunology
  • Humans
  • Immunocompromised Host
  • Immunosuppressive Agents / adverse effects
  • Incidence
  • Kaplan-Meier Estimate
  • Kidney Transplantation / adverse effects*
  • Logistic Models
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Neoplasms / diagnosis
  • Neoplasms / epidemiology
  • Neoplasms / immunology
  • Neoplasms / virology*
  • Opportunistic Infections / diagnosis
  • Opportunistic Infections / epidemiology
  • Opportunistic Infections / immunology
  • Opportunistic Infections / virology*
  • Proportional Hazards Models
  • Risk Factors
  • Smoking / adverse effects
  • Time Factors
  • Treatment Outcome
  • Viral Load*
  • Virus Replication

Substances

  • Antilymphocyte Serum
  • Immunosuppressive Agents