Evaluation of liver failure in a pediatric transplant recipient of a liver allograft with inherited chromosomally integrated HHV-6B.
BACKGROUND
Active infections of human herpesvirus 6B (HHV-6B) are frequent in immunocompromised recipients after transplantation. Nevertheless, they need to be distinguished from latent inherited chromosomally integrated genomes (iciHHV-6) present in about 1% of the population to avoid unnecessary administration of toxic antivirals.


METHODS
A 5-year-old child presented with acute liver allograft rejection associated with HHV-6 DNA in plasma, which led to an unfavorable outcome. We investigated the possibility of HHV-6 infection derived from an iciHHV-6 present in the donor's liver using molecular and histopathology studies in various tissues, including quantification of HHV-6 DNA, genotyping, sequencing for antiviral resistance genes, relative quantification of viral transcripts, and detection of gB and gH viral proteins.


RESULTS
The presence of iciHHV-6B was evidenced in the donor with signs of reactivation in the gallbladder and transplanted liver (detection of HHV-6B mRNA and late proteins). This localized expression could have played a role in liver rejection. Low viral loads in the recipient's plasma, with identical partial U39 sequences, were in favor of viral DNA released from the transplanted liver rather than a systemic infection.


CONCLUSIONS
Determination of iciHHV-6 status before transplantation should be considered to guide clinical decisions, such as antiviral prophylaxis, viral load monitoring, and antiviral therapy.
['Bonnafous|Pascale|P|0000-0001-5528-9356', 'Phan|Tuan L|TL|', 'Himes|Ryan|R|', 'Eldin|Karen|K|', 'Gautheret-Dejean|Agnès|A|', 'Prusty|Bhupesh K|BK|', 'Agut|Henri|H|', 'Munoz|Flor M|FM|']
D064591:Allografts D002675:Child, Preschool D002877:Chromosomes, Human D004279:DNA, Viral D017809:Fatal Outcome D006084:Graft Rejection D015654:Herpesvirus 6, Human D006801:Humans D040582:Inheritance Patterns D017093:Liver Failure D016031:Liver Transplantation D019349:Roseolovirus Infections D016662:Virus Integration
iciHHV-6 horizontal transmission liver transplantation