Epidemiology and Clinical Impact of HHV-6 DNAemia after pediatric liver transplantation
Kei Sakamoto1, Masaki Yamada1, Ayaka Shiraga1, Yusuke Tokuda1, Akinari Fukuda2, Seisuke Sakamoto2, Akira Ishiguro3, Ken-Ichi Imadome1, Mureo Kasahara2.
1Division of Advanced Medicine for Virus Infections, National Center for Child Health and Development, Tokyo, Japan; 2Center for Organ Transplantation, National Center for Child Health and Development, Tokyo, Japan; 3Center for Postgraduate Education and Training, National Center for Child Health and Development, Tokyo, Japan
Background: HHV-6 is a ubiquitous β-herpesvirus that infects most infants and establishes latency without sequelae. However, as seen in other herpesviruses, HHV-6 may cause severe disease in immunocompromised children (1).
It is also known that pediatric liver transplant (LT) recipients with primary viral infection are at higher risk of developing clinically significant diseases, and HHV-6 infection occurs in approximately one-third of LT recipients (2), (3). Hence, HHV-6 infections may result in severe infections. However, there is scant evidence investigating the role and clinical impact of HHV-6 infection after LT. Therefore, this study aimed to describe the epidemiology of HHV-6 infection and its clinical impact following pediatric LT.
Methods: Clinical and virological data of 285 LT recipients from July 1, 2014 to June 30, 2019 were retrospectively reviewed. HHV-6 DNA was measured by real-time PCR using leftover DNA extracted from whole blood for clinical use. HHV-6 loads exceeding > 1,000 copies/µg DNA were defined as high. Chi-square test, Mann-Whitney U test, and cumulative incidence functions were used, and a p-value < 0.05 was considered significant. The study protocol was reviewed and approved by the Ethics Committee.
Results: 1664 samples from 182 LT recipients were identified for analysis. HHV-6 was detected in 734/1664 (44%) samples. HHV-6 DNAemia was developed in 69% of LT recipients within the first three months post-LT and in 75% within one year. There were 104/1664 (6.3%) samples exceeding in > 1,000 copies/µg DNA seen in 54/182 (30%) LT recipients. There was only one patient who developed HHV-6 disease with febrile syndrome. Recipients < 2 years of age developed HHV-6 DNAemia more frequently.
When compared between high load and non-high load groups, LT recipients who developed high HHV-6 load were younger (HHV-6 high vs. non-high: median 0.7 years vs. 1.3 years, p = 0.0002) and experienced more rejection (54% vs. 40%) though not reaching to the statistical significance.
Conclusion: HHV-6 DNAemia frequently occurs, especially in young pediatric LT recipients, but the overall risk for HHV-6 disease was low.
Child Health and Development Grants 2022C-7.
[1] Griffiths PD, Clark DA, Emery VC. Betaherpesviruses in transplant recipients. J Antimicrob Chemother. 2000;45 Suppl T3:29–34.
[2] Al Fawaz T, Ng V, Richardson SE, Barton M, Allen U. Clinical consequences of human herpesvirus-6 DNAemia in peripheral blood in pediatric liver transplant recipients. Pediatr Transplantation. 2014;18(1):47–51.
[3] Yasui T, Suzuki T, Yoshikawa T, Yatsuya H, Kawamura Y, Miura H, et al. Clinical course of human herpesvirus 6 infection in pediatric living donor liver transplantation. Pediatr Transplant. 2018;22(7):e13239.
