Publication Name	World Journal of Virology
Manuscript ID	110435
Country	Japan

Category	Virology
Manuscript Type	Minireviews
Article Title	Comparison of three pediatric studies investigating acute hepatitis of unknown etiology
Manuscript Source	Invited Manuscript
All Author List	Haruki Komatsu
Funding Agency and Grant Number
Corresponding Author	Haruki Komatsu, MD, PhD, Department of Pediatrics, Komatsu Children’s Clinic, 4-2-1 Midorigaoka-nishi, Yachiyo 276-0040, Chiba, Japan. haruki-komatsu@chive.ocn.ne.jp
Key Words	Adeno-associated virus; Cidofovir; Coinfection; Helper virus; Herpes virus; Human adenovirus; Human leukocyte antigen; Metagenomic sequencing; Phylogenetic tree analysis; Real-time PCR
Core Tip	The rate of positivity for adeno-associated virus serotype 2 (AAV-2) was 80% or greater in cases of acute hepatitis of unknown etiology (AHUE) according to metagenomic sequencing and real-time polymerase chain reaction. AAV-2 RNA was detected in the nuclei and cytoplasm of ballooned hepatocytes through in situ hybridization. No distinct clade was observed in the phylogenetic tree analysis of whole genomes of AAV-2 isolated from cases. Coinfection of AAV-2 with one or more helper viruses (HAdV, HHV-6B, EBV, etc.), a high viral load of AAV-2 in blood, anti-AAV-2 IgM and human leukocyte antigen (HLA) typing (HLA-DRB1*04: 01, HLA-DQA1*03: 03 and HLA-DRB4*01: 03) could be candidate diagnostic criteria for AHUE.
Citation	Komatsu H. Comparison of three pediatric studies investigating acute hepatitis of unknown etiology. World J Virol 2025; In press

Received	2025-06-06 16:54
Peer-Review Started	2025-06-06 16:55
To Make the First Decision
Return for Revision	2025-06-25 09:27
Revised	2025-08-12 21:51
Second Decision	2025-09-19 02:44
Accepted by Journal Editor-in-Chief
Accepted by Executive Editor-in-Chief	2025-09-19 06:34
Articles in Press	2025-09-19 06:34
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ISSN	2220-3249 (online)
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