Evaluation of liver failure in a pediatric transplant recipient of a liver allograft with inherited chromosomally integrated HHV-6B

J Med Virol. 2020 Feb;92(2):241-250. doi: 10.1002/jmv.25600. Epub 2019 Oct 20.

Abstract

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.

Keywords: horizontal transmission; iciHHV-6; liver transplantation.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Allografts / virology
  • Child, Preschool
  • Chromosomes, Human / genetics
  • Chromosomes, Human / virology
  • DNA, Viral / blood
  • Fatal Outcome
  • Graft Rejection / diagnosis
  • Graft Rejection / virology*
  • Herpesvirus 6, Human / genetics
  • Herpesvirus 6, Human / isolation & purification
  • Humans
  • Inheritance Patterns
  • Liver Failure / diagnosis
  • Liver Failure / virology*
  • Liver Transplantation
  • Roseolovirus Infections / diagnosis*
  • Roseolovirus Infections / virology
  • Virus Integration

Substances

  • DNA, Viral