Adeno-associated virus type 2 in US children with acute severe hepatitis

Servellita, Venice; Sotomayor-González, Alicia; Lamson, Daryl M.; Foresythe, Abiodun; Huh, Hee Jae; Bazinet, Adam L.; Bergman, Nicholas H.; Bull, Robert L.; Garcia, Karla Y; Goodrich, Jennifer S.; Lovett, Sean; Parker, Kisha; Radune, Diana; Hatada, April; Pan, Chao-Yang; Rizzo, Kyle; Bertumen, J Bradford; Morales, Christina; Oluniyi, Paul E.; Nguyen, Jenny; Tan, Jessica; Stryke, Doug; Jaber, Rayah; Leslie, Matthew T.; Lyons, Zin; Hedman, Hayden D.; Parashar, Umesh D.; Sullivan, Maureen; Wroblewski, Kelly; Oberste, M. Steven; Tate, Jacqueline E.; Baker, Julia M; Sugerman, David; Cubeñas-Potts, Caelin; Lu, Xiaoyan; Chhabra, Preeti; Ingram, L. Amanda; Shiau, Henry; Britt, William J.; Sanchez, Luz Helena Gutierrez; Ciric, Caroline; Rostad, Christina A.; Vinjé, Jan; Kirking, Hannah L.; Wadford, Debra A.; Raborn, R. Taylor; George, Kirsten St.; Chiu, Charles Y.

doi:10.1038/s41586-023-05949-1

Cited by 72 publications

(78 citation statements)

References 43 publications

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“…Thus, despite AdV being isolated from blood samples from many of these children, its role in the pathogenesis of their illness remains in question. Most recently, reports of broader viral testing of samples from children with unexplained hepatitis have found many to be positive for adeno-associated virus 2 (AAV2) DNA (13,14). Most of these children also had positive testing for AdV and HHV-6.…”

Section: Discussionmentioning

confidence: 99%

Adenovirus is Not Detected in Liver Tissue From a Historical Multicenter Cohort of Children With Acute Liver Failure

Chapin¹,

Diamond

Harris

et al. 2023

Journal of Pediatric Gastroenterology &Amp; Nutrition

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There has been a recent surge in cases of pediatric acute hepatitis and pediatric acute liver failure (PALF) of unknown cause. Several reports have described clusters of these children who were positive for adenovirus (AdV) DNA, primarily in peripheral blood but some in liver tissue. We tested archived liver tissue specimens from a historical cohort of 44 children with PALF who were enrolled in a multicenter biorepository between 2007 and 2014 for AdV 40/41 using quantitative polymerase chain reaction. Most children had final diagnosis indeterminate. All samples were negative. Our findings suggest that AdV was unlikely to be an unidentified cause of indeterminate PALF during this past era. The significance of AdV viremia in contemporary cohorts of children with PALF remains unknown and requires further study.

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Section: Discussionmentioning

confidence: 99%

Adenovirus is Not Detected in Liver Tissue From a Historical Multicenter Cohort of Children With Acute Liver Failure

Chapin¹,

Diamond

Harris

et al. 2023

Journal of Pediatric Gastroenterology &Amp; Nutrition

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“…However, the etiological link between the pediatric hepatitis and HAdV or coronavirus has not been established. Recently, three independent research groups [7][8][9] have found compelling evidence supporting the pathogenesis of an unexpected adeno-associated virus-2 (AAV-2) infection.…”

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confidence: 99%

“…It is noteworthy that either HAdV, human herpesvirus 6 (HHV-6), or Epstein−Barr virus was also tested positive in most cases, most probably as helper virus enabling AAV-2 replication. 8,9 Theoretically, assuming that helper viruses are absent, AAV-2 per se could hardly induce liver damage severe enough to require liver transplantation, as input virions could only infect a very small portion of hepatocytes and therefore elicited limited immune responses.…”

mentioning

confidence: 99%

“…Along with the observation of infiltrated activated T lymphocytes around AAV‐2 infected hepatocytes and the evidenced increase of T‐cell‐response‐associated cytokines, these data provisionally support a notion that immune‐mediated pathogenesis constitutes the primary cause of liver injury in children. It is noteworthy that either HAdV, human herpesvirus 6 (HHV‐6), or Epstein−Barr virus was also tested positive in most cases, most probably as helper virus enabling AAV‐2 replication 8,9 . Theoretically, assuming that helper viruses are absent, AAV‐2 per se could hardly induce liver damage severe enough to require liver transplantation, as input virions could only infect a very small portion of hepatocytes and therefore elicited limited immune responses.…”

mentioning

confidence: 99%

“…However, as earlier summarized by Tacke, 15 several limitations do exist in these three studies, including insufficient case numbers, lack of detailed clinical information of the subjects, and the retrospective nature rather than gold-standard prospective trials of these studies. [7][8][9] Additionally, the high prevalence of HLA-DRB1*04:01 in Anglo−Saxon might partially explain the preferential distribution of cases in the United Kingdom and the United States but might not persuasively answer the uneven prevalence of pediatric hepatitis in Asia, as several dozen cases have been reported in Japan 15 while no cases were found in China despite China's over 10fold population size, considering their close genetic background. As possibility of linkage disequilibrium could not be fully excluded, 7 lager studies are still needed to decipher the role that HLA-DRB1*04:01 the susceptible allele played in the pathogenesis of pediatric hepatitis, or if not, the real prime culprit.…”

mentioning

confidence: 99%

See 2 more Smart Citations

Looking back on the outbreak of acute severe hepatitis with unknown etiology in children in 2022: What do we know now and where do we go from here?

Zheng

Wang

2023

Journal of Medical Virology

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The influence of the COVID‐19 pandemic on the spectrum of neonatal disease in a tertiary hospital in China: A retrospective analysis

Wang,

Song,

et al. 2024

Health Science Reports

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Background and AimsNeonatal diseases are a significant threat to global public health, affecting the homeostasis and well‐being of patients and reflecting the status of, and challenges to, regional, national, and global healthcare systems. This study sought to investigate how the disease spectrum observed among neonatal inpatients changed after the onset of the coronavirus disease 2019 (COVID‐19) pandemic.MethodsThe present hospital‐based retrospective study analyzed the demographic and clinical characteristics of 19,943 hospitalized newborns from January 2018 to December 2022 using data derived from pediatric department registers.ResultsAccording to the International Classification of Diseases 11th Revision (ICD‐11) classification criteria, the two most common neonatal disorders during this study period were “Certain conditions originating in the perinatal period” and “Disease of the respiratory system.” Following the start of the COVID‐19 pandemic (2020 onwards), the number of neonatal patients declined markedly (5742 per year vs. 2820 per year), and the incidence of “Disease of the respiratory system” was significantly lower than in 2018–2019 (25.72% vs. 17.46%).ConclusionThe study offers detailed insights into the shifts in neonatal disease patterns at the Seventh Medical Center of the PLA General Hospital following the onset of the COVID‐19 pandemic, providing a foundation for future research and policymaking efforts.

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Adeno-associated virus type 2 in US children with acute severe hepatitis

Cited by 72 publications

References 43 publications

Adenovirus is Not Detected in Liver Tissue From a Historical Multicenter Cohort of Children With Acute Liver Failure

Adenovirus is Not Detected in Liver Tissue From a Historical Multicenter Cohort of Children With Acute Liver Failure

Looking back on the outbreak of acute severe hepatitis with unknown etiology in children in 2022: What do we know now and where do we go from here?

The influence of the COVID‐19 pandemic on the spectrum of neonatal disease in a tertiary hospital in China: A retrospective analysis

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