Metagenomic and transcriptomic investigation of pediatric acute liver failure cases reveals a common pathway predominated by monocytes
Since the appearance of the cluster of pediatric hepatitis of unknown origin in 2022, several groups have reported an association of adenoviruses and AAV2 in a high number of cases in contrast to controls. The adenoviruses detected were heterogeneous in both species-adenovirus C and F-and sequences. The mechanisms of disease that accounts for fulminant liver failure, occurring in 5% of pediatric hepatitis cases, remain incompletely described. The current study adds to previous data by including pediatric acute liver failure cases during the upsurge, enabling the analyses of inflammation expression profiles in cases with different viruses in relation to pediatric controls. This led to the discovery of transcriptome upregulation of monocyte pathways in liver explants from the cases. This inflammatory transcriptomic signature was comparable for AAV2, adenoviruses, and/or herpesviruses-positive transplant cases.
Authors
- Aloys C.M. Kroes (ORCID: https://orcid.org/0000-0002-9866-2461)
- Jutte J.C. de Vries (ORCID: https://orcid.org/0000-0003-2530-6260)
- Marius C. van den Heuvel (ORCID: https://orcid.org/0000-0001-6985-7107)
- Lilli Gard (ORCID: https://orcid.org/0000-0001-9182-8986)
- Stefan A. Boers (ORCID: https://orcid.org/0000-0002-1560-6799)
- Sander T. H. Bontemps
- Emilie P. Buddingh (ORCID: https://orcid.org/0000-0002-2755-9408)
- Ellen C. Carbo (ORCID: https://orcid.org/0000-0002-6801-616X)
- Hailiang Mei (ORCID: https://orcid.org/0000-0003-1781-5508)
- Simon P. Jochems (ORCID: https://orcid.org/0000-0002-4835-1032)
- Igor A. Sidorov (ORCID: https://orcid.org/0000-0001-6519-4983)
- Karin J. von Eije (ORCID: https://orcid.org/0000-0003-0627-5673)
- Willem S. Lexmond
- Ruben H J de Kleine (ORCID: https://orcid.org/0000-0003-3975-3184)
- A Kroon
- Rick Hennevelt
- Xuewei Zhou (ORCID: https://orcid.org/0000-0002-9436-0175)
- Vincent E. de Meijer
- Elisabeth H. Schölvinck
Institutions
- University Medical Center Groningen (NL)
- University of Groningen (NL)
- Leiden University Medical Center (NL)
- GenomeScan (Netherlands) (NL)
Publication Details
- Journal
- mBio
- Published
- 2025-03-18
- DOI
- https://doi.org/10.1128/mbio.03913-24
- Citations
- 2
- Primary Topic
- Virus-based gene therapy research
- Type
- article
- Field-Weighted Citation Impact
- 3.63