{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T13:59:58Z","timestamp":1780322398390,"version":"3.54.1"},"reference-count":12,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,4,26]],"date-time":"2023-04-26T00:00:00Z","timestamp":1682467200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pediatr."],"abstract":"<jats:p>The 2022 worldwide epidemic of acute hepatitis and liver failure in young children has led to a focus on unusual causes for childhood acute hepatitis. In the UK epidemic, human herpes virus subtype 6B (HHV-6B) was detected along with adenovirus subtype-41F in severely affected children, especially in those requiring liver transplantation (LT). The lifting of COVID lock-down measures has coincided with the rise in these common childhood infections with a higher than expected rate of systemic complications. The sudden exposure of young children to common childhood infections from which they were protected during the pandemic may have induced an abnormal immune mediated response potentiated by multiple pathogen exposure. Primary HHV-6 infection is one such common childhood infection. Classically known as Roseola infantum due to the appearance of a widespread erythematous rash on fever subsidence (exanthema subitem), it has a peak incidence of 6\u201312 months of age and almost all children will have been infected by age 2. It is the virus most frequently associated with febrile convulsions but the more serious complications of hepatitis and liver failure are rare. We report on the historic cases of three female infants who had suspected primary HHV-6B infection, acute hepatitis and rapid progression to acute liver failure (ALF) requiring LT. Appearances of their native liver were identical to those described in children in the recent hepatitis epidemic. Deteriorating clinical trajectories of recurrent graft hepatitis and rejection-like episodes followed and all three succumbed to graft failure with HHV-6B detected posthumously in their liver allografts. Our case series and the serious complications observed with the recent rise in common childhood infections is a reminder that these routinely encountered pathogens can be deadly especially in the young immunologically untrained. We advocate for HHV-6 to be screened for routinely in children with acute hepatitis and the use of effective HHV-6 anti-viral prophylaxis to prevent recurrence post-transplant.<\/jats:p>","DOI":"10.3389\/fped.2023.1143051","type":"journal-article","created":{"date-parts":[[2023,4,26]],"date-time":"2023-04-26T06:11:17Z","timestamp":1682489477000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":6,"title":["Case report: Acute liver failure in children and the human herpes virus 6-? A factor in the recent epidemic"],"prefix":"10.3389","volume":"11","author":[{"given":"Suz","family":"Warner","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel M.","family":"Brown","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gary M.","family":"Reynolds","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zania","family":"Stamataki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deirdre A.","family":"Kelly","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,4,26]]},"reference":[{"key":"B1","year":"2022"},{"key":"B2","year":"2022"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1007\/s00134-022-06765-3","article-title":"Outbreak of hepatitis in children: clinical course of children with acute liver failure admitted to the intensive care unit","author":"Deep","year":"2022","journal-title":"Intensive Care Med"},{"key":"B4","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1016\/j.cppeds.2008.10.003","article-title":"Persistent and recurring viral infections: the human herpesviruse","volume":"39","author":"Schleiss","year":"2009","journal-title":"Curr Probl Pediatr Adoesc Health Care"},{"key":"B5","doi-asserted-by":"publisher","first-page":"210","DOI":"10.1111\/liv.13506","article-title":"HHV-6 in liver transplantation: a literature review","volume":"38","author":"Phan","year":"2018","journal-title":"Liver Int"},{"key":"B6","doi-asserted-by":"publisher","first-page":"361","DOI":"10.1093\/infdis\/jiy644","article-title":"Evaluating for human herpesvirus 6 in the liver explants of children with liver failure of unknown etiology","volume":"220","author":"Yang","year":"2019","journal-title":"J Infect Dis"},{"key":"B7","doi-asserted-by":"publisher","first-page":"536","DOI":"10.1097\/01.TP.0000069233.13409.DF","article-title":"Human herpesvirus-6 and acute liver failure","volume":"76","author":"Harma","year":"2003","journal-title":"Transplantation"},{"key":"B8","doi-asserted-by":"publisher","first-page":"1063","DOI":"10.1016\/j.jhep.2011.12.017","article-title":"High intrahepatic HHV-6 virus loads but neither CMV nor EBV are associated with decreased graft survival after diagnosis of graft hepatitis","volume":"56","author":"Pischke","year":"2012","journal-title":"J Hepatol"},{"key":"B9","doi-asserted-by":"publisher","first-page":"e13014","DOI":"10.1111\/tid.13014","article-title":"Primary infection with human herpes virus type 6, post-pediatric liver transplantation-A pathogen to remember","volume":"21","author":"Pappo-Toledano","year":"2019","journal-title":"Transpl Infect Dis"},{"key":"B10","doi-asserted-by":"publisher","first-page":"599","DOI":"10.1093\/jpids\/piaa166","article-title":"Human herpesvirus 6 infection in pediatric\u00a0liver transplantation: single-center study of incidence, outcomes and management","volume":"10","author":"Mysore","year":"2021","journal-title":"J Pediatric Infect Dis Soc"},{"key":"B11","doi-asserted-by":"publisher","first-page":"367","DOI":"10.1097\/01.tp.0000195771.83614.0b","article-title":"Pre-transplant human herpesvirus 6 infection of patients with acute liver failure is a risk factor for post- transplant human herpesvirus 6 infection of the liver","volume":"81","author":"Harma","year":"2006","journal-title":"Transplantation"},{"key":"B12","doi-asserted-by":"publisher","first-page":"403","DOI":"10.1309\/AJCP0FWI2XAHECBJ","article-title":"Acute hepatitis with periportal confluent necrosis associated with human herpesvirus 6 infection in liver transplant patients","volume":"140","author":"Buyse","year":"2013","journal-title":"Am J Clin Pathol"}],"container-title":["Frontiers in Pediatrics"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fped.2023.1143051\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,4,26]],"date-time":"2023-04-26T06:11:21Z","timestamp":1682489481000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fped.2023.1143051\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,4,26]]},"references-count":12,"alternative-id":["10.3389\/fped.2023.1143051"],"URL":"https:\/\/doi.org\/10.3389\/fped.2023.1143051","relation":{},"ISSN":["2296-2360"],"issn-type":[{"value":"2296-2360","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,4,26]]},"article-number":"1143051"}}