Frequent Detection of the Human Herpesvirus 6-Specific Genomes in the Livers of Children with Various Liver Diseases

Abstract

This study was performed to investigate the frequency of human herpesvirus 6 (HHV-6) infection of the liver in children with a variety of liver diseases and to evaluate the role of HHV-6 infection in pediatric patients with prolonged non-B non-C hepatitis. Detection of the HHV-6 genomes in liver, in peripheral blood mononuclear cells (PBMC), and in plasma was performed by PCR or by in situ hybridization. Liver biopsy materials from 48 patients, in whom HHV-6 infection was serologically confirmed, were available for PCR analysis. Sequences of the HHV-6B genome were detectable in the livers of 36 of 48 patients (75%). The presence of the genome was not associated with serum transaminase activities. The genome was detectable in PBMC of 22 of 31 (71%) patients tested. In these 31 patients HHV-6 was detected in both the livers and PBMC of 20, was detected in PBMC but not in the livers of 2, was detected in the livers but not in PBMC of 3, and was detected in neither of samples of 6. In situ hybridization of the livers of six patients showed the presence of the HHV-6B genome in the nuclei of hepatocytes. The anti-HHV-6 immunoglobulin M antibody was detectable in 2 of 9 of the non-B non-C hepatitis patients, whereas none of the 22 patients with etiology-defined liver diseases tested positive. Cell-free viral DNA was not detectable in either group of patients. Our results showed that HHV-6B is frequently present in the livers of children with a variety of liver diseases but do not support the assumption that HHV-6B infection of the liver is associated with prolonged non-B non-C hepatitis.

High intrahepatic HHV-6 virus loads but neither CMV nor EBV are associated with decreased graft survival after diagnosis of graft hepatitis

“…However, HHV-6 DNA has also been amplified from liver tissue [8,9,23,24] and HHV-6 antigen was detected in hepatocytes [9]. Of note, replication of HHV-6 in a hepatoma cell line suggested that HHV-6 may indeed replicate in hepatocytes also in vivo [25].…”

“…Recently, several studies suggested a role for HHV-6 in the pathogenesis of hepatitis, in particular graft hepatitis [5][6][7]. HHV-6 was detected both in lymphocytes and hepatocytes [8,9] but the clinical relevance of HHV-6 in graft hepatitis, for example an association of HHV-6 infection and graft survival, has not been proven so far [10].…”

Human herpesvirus 6 (HHV‐6) is transmitted from parent to child in an integrated form and characterization of cases with chromosomally integrated HHV‐6 DNA

“…These individuals included transplant recipients with their donors, and patients suspected of having an acute-or convalescent-phase herpesvirus infection. DNA was extracted from the samples and HHV-6 DNA was detected by PCR as previously described TanakaTaya et al, 1996;Fujisaki et al, 1998;Miyoshi et al, 2001;Ozaki et al, 2001;Sugimoto et al, 2002]. At least two additional PBMC samples were obtained examined from individuals whose PCR was positive for HHV-6.…”

Update on Human Herpesvirus 6 Biology, Clinical Features, and Therapy

“…The host tissue range of HHV-6 in vivo is even broader. It includes brain tissue (60,110,248), liver tissue (155,186,319), tonsillar tissue (347), salivary glands (130), and endothelium (55). Bone marrow progenitors were found to harbor latent HHV-6, which may be transmitted longitudinally to differentiated blood cells of different lineages (251).…”