Early HHV-6 replication is associated with morbidity non-related to CMV infection after kidney transplantation

Abstract

Herpesvirus 6, human DNA virus infections Clinical diagnosisPolymerase chain reaction A B S T R A C T Human herpesvirus type 6-(HHV-6) has been associated with morbidity after liver transplantation.Objective: The aim of this study was to determine the HHV-6 seroprevalence among donorrecipient pairs, analyze the incidence of early active infection, its clinical manifestation, interaction with CMV, and the related morbidity in the first year after kidney transplantation.Methods: 46 donor-recipient pairs had IgG evaluated by ELISA before transplantation: HHV-6-(Pambio -USA) and CMV-(Roche -USA). A frozen whole blood sample collected weekly (from the 1 st to the 6 th week) was retrospectively tested for HHV-6 viral load (VL) determination by real time quantitative PCR (qPCR, Nanogen -Italy). Patients were preemptively surveyed for CMV by pp65 antigenemia (Ag, APAAP, immunohistochemistry, Biotest -Germany) from the 4 th to the 12 th week after transplantation. Active infection was defined as qPCR-HHV6+ (viral-load/mL-VL) and Ag+ (+cells/100.000 granulocytes), for HHV-6 and CMV, respectively. DCMV was defined as simultaneous positive antigenemia and suggestive signs/symptoms. Concerning +qPCR-HHV6, associated factors, clinical manifestation, interaction with CMV and morbidity were searched. Conclusion: Latent HHV-6 infection is more common among recipients than donors before transplantation. Early active infection by this pathogen after transplantation does not increase DCMV incidence or severity during the first 3 months of follow-up. However, early HHV-6 replication is associated with other infections and hospitalizations in the first year.

Impact assessment and investigation of factors associated with herpesviruses viremia in the first year of renal transplantation

“…It has been demonstrated that ganciclovir or valganciclovir prophylaxis decreases HHV‐6 viremia incidence in SOT recipients, which could explain the low prevalence of HHV‐6 in our study, when compared to others . The low frequency of HHV‐6 detection in this cohort made it difficult to observe its influence on acute rejection, although such association is not a consensus among different authors …”

“…One of the limitations of the study could be the short follow‐up period for long‐term outcomes, such as PTLD. The modest sample size (82 patients, 409 samples) of the study may have limited further analysis, even though it is similar or even larger than other publications on the subject . Furthermore, information on EBV and HCMV serological status of donors were not available making it impossible to classify risk groups as D+/R‐.…”

“…This study demonstrates that immunosuppressive induction and maintenance therapies have a significant effect on EBV and HCMV viremia. Moreover, EBV, HCMV, and HHV‐6 viremia were detected in the first 3 months of transplantation, when immunosuppressive therapy is more intense …”

Association of HHV-6 With Outcomes in CMV-seronegative Liver Transplant Recipients With CMV-seropositive Donors Receiving Preemptive Antiviral Therapy

“…6 Some but not all studies have shown that HHV-6 is associated with outcomes including rejection, opportunistic infections, and mortality after transplantation. [6][7][8][9][10][11] However, these data are mainly based on studies that were conducted several decades ago, included small number of high-risk mostly D+R-patients (the subgroup at highest risk for poor outcomes), assessed short-term outcomes, and composed of patients who were receiving antiviral prophylaxis. 7,[12][13][14] The most important limitations of the previous studies pertain to methodologic issues, including use of suboptimal assays for the detection of viremia such as antibody responses and semi rather than sensitive quantitative molecular assays, and failure to distinguish high-grade HHV-6 replication from chromosomal integration.…”