Epstein Barr Virus (EBV) Dnaemia Is An Early Surrogate Marker for Later Development of Immunosuppression-Related Adverse Events in Solid Organ Transplant (SOT) Recipients

Abstract

Background: EBV DNAemia (EBVd) has been suggested as a surrogate marker of immunosuppression following SOT. Monitoring EBVd might help to identify patients at highest risk for late immunosuppression-related adverse events. Methods: We analyzed a cohort of SOT recipients at our institution (2003-2005) who survived more than 180 days after transplant. Patients were followed until March, 2010. EBVd determined in whole blood by real-time PCR assay Abbott EBV PCR KIT (Abbott Diagnostics, Chicago, Ill, USA) was monitored during the first six months. We evaluated the duration and intensity of EBVd, according to: (1) high grade viraemia (higher than 1000 copies/mL); (2) persistent viremia (longer than 30 days);. These parameters were evaluated as potential predictors of late adverse events (occurring after the sixth month): graft dysfunction (GD), graft loss (GL), death, opportunistic infection (OI), severe infection (SI) and organic neoplasia (ON). A Cox proportional hazard model was used to estimate the effect of early EBV replication on these late events along the study period. Results: The cohort consisted of 81 patients: 53 renal, 21 liver, and 7 cardiac transplants. A median of 10 samples were screened per patient (range 1-15). EBVd was detected in 71/81 patients (87.7%) and within the first week after transplant in 42.9%. Persistent EBV viraemia was found in 39 patients (48%) and high EBV viraemia in 43 (53%). Multivariate Cox proportional hazard model demonstrated that early persistent VEB viremia a clear trend for an increased risk for developing either ON or SI (Hazard Ratio [HR]: 2.78, Confidence Interval 95% [CI]: 1.07-7.23; P=0.04). High early EBV viraemia increased the risk for either late SI (HR 13.14; CI: 1.72-100.56;P= 0.01) or OI(HR: 11.88; CI: 1.54-91;P=0.02). We did not found a higher incidence of GD nor GL neither in patients with persistent or high EBV infection. Conclusions: EBVd is detectable in the majority of SOT along the first six moths after Tx. High and persistent EBV viraemia during the first six months are surrogate markers of increased risk of immunosuppression-related late adverse events.