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

Schroeder, Regina Barbosa; Michelon, Tatiana Ferreira; Garbin, Gabriela; Garcia, Valter; da Silveira, Janaina Gomes; Santos, Luciano; Neumann, Jorge; Keitel, Elizete

doi:10.1016/S1413-8670(12)70296-9

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Abstract

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 1st to the 6th 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 4th to the 12th 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.

Results

Pre-transplant HHV-6 seroprevalence was significantly higher among kidney recipients compared to their donors (82.6×54.8%; p=0.005 [3.9 (1.4–10.4)]). Active infection by this virus occurred in 26.1% (12/46), with no association with previous IgG (p=0.412). Median VL was 125 copies/mL (53–11.264), and the median Ag was 21 +cells (2–740). There was no association between HHV-6 and CMV activation after transplantation (p=0.441), neither concerning DCMV (p=0.596). Median highest Ag+ and days of ganciclovir treatment were similar between qPCR-HHV6 + or − (p=0.206 and p=0.124, respectively). qPCR-HHV6+ was associated with higher incidence of bacterial (p=0.009) and fungal (p = 0.001) infections, and higher number (p=0.001) of hospital admission and longer duration of hospitalization over the first 6 and 12 months post-transplantation (p=0.033 and p=0.001).

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.

Keywords:

Cytomegalovirus infections

Herpesvirus 6, human

DNA virus infections

Clinical diagnosis

Polymerase chain reaction

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