Comparison of three pediatric studies investigating acute hepatitis of unknown etiology

doi:10.5501/wjv.v14.i4.110435

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World Journal of Virology

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2220-3249

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Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA

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World J Virol. Dec 25, 2025; 14(4): 110435
Published online Dec 25, 2025. doi: 10.5501/wjv.v14.i4.110435

Table 4 Detected viruses via metagenomic sequencing in the United Kingdom and United States studies, n (%)

England, agnostic (untargeted) metagenomic sequencing (n = 10)			Scotland, target enrichment metagenomic sequencing (n = 9)			United States, agnostic (untargeted) and target enrichment metagenomic sequencing (n = 16)
Whole- blood			Serum or plasma			Whole-blood or plasma
AAV-2 positive	DNA: 4/5 cases (80), RNA: 2/3 cases (66.7) (Two cases were positive for DNA and RNA)	DNA: 1.9-42.1 reads/million, RNA: 3.1-7.8 reads/million	AAV-2 positive	DNA: 9/9 cases (100), RNA: 6/6 cases (100)	DNA: 152.06-24967.81 reads/million, RNA: 113.25-12119.78 reads/million	Agnostic metagenomic sequencing (n = 14)
HAdV positive	DNA: 1/5 cases (20), RNA: 0/3 cases (0)	DNA: 0.1 reads/million	HAdV positive	DNA: 3/9 cases (33.3), RNA: cases1/9 (11.1)	DNA: 0.16-1.66 reads/million, RNA: 577.57 reads/million	AAV-2 positive	8/14 cases (57.1)	0.033-3.87 reads/million
HHV-6B positive	DNA: 0/5 cases (0), RNA: 0/3 cases (0)		HHV-6B positive	DNA: 3/4 cases (75), RNA: 0/4 cases (0)	DNA: 0.41-3.89 reads/million median	HAdV-41 positive	0/14 cases (0)
EBV positive	DNA: 1/5 cases (20), RNA: 0/3 cases (0)	Read count, no data	VZV positive	DNA: 1/4 cases (25), RNA: 0/4 cases (0)	DNA: 2.14 reads/million	EBV positive	2/14 cases (14.3)	0.00057-0.0056 reads/million
TTV positive	DNA: 1/5 cases (20), RNA: 0/3 cases (0)	Read count, no data	EBV positive	DNA: 1/4 cases (25), RNA: 0/4 cases (0)	DNA: 0.53 reads/million	CMV positive	1/14 cases (7.1)	0.0068 reads/million
			CMV positive	DNA: 1/4 cases (25), RNA: 1/4 cases (25)	DNA: 9.85 reads/million, RNA: 0.21 reads/million	HAdV-2 positive	1/14 cases (7.1)	0.74 reads/million
			HHV-7 positive	DNA: 0/4 cases (0), RNA: 1/4 cases (25)	RNA: 0.31 reads/million	EV-A71 positive	1/14 cases (7.1)	4.10 reads/million
						Tilling multiplex PCR amplicon for
						AAV-1- AAV-8 and HAdV-41 (n = 10)
						AAV-2 positive	9/10 cases (90)	0.513-388.147 reads/million
						HAdV-41 positive	7/10 cases (70)	0.012-0.97 reads/million
						Probe capture viral enrichment (n = 4)
						AAV-2 positive	4/4 cases (100)	0.054-183.976 reads/million
						HAdV-41 positive	3/4 cases (75)	0.126-0.803 reads/million
						Total (target enhancement)
						AAV-2 positive	13/14 cases (92.9)
						HAdV-41 positive	10/14 cases (71.4)
Liver			Liver			Liver
AAV-2 positive	DNA: 5/5 cases (100), RNA: 4/4 cases (100)	DNA: 7.3-42 reads/million, RNA: 0.6-9.9 reads/million	AAV-2 positive	DNA: 4/4 cases (100), RNA: 1/1 case (100)	DNA: 637.16-39653.48 reads/million, RNA: 3089.09 reads/million	Agnostic metagenomic sequencing (n = 1)
HAdV positive	DNA: 0/5 cases (0), RNA: 0/4 cases (0)		HAdV positive	DNA: 3/4 cases (75), RNA: 0/4 cases (0)	DNA: 419.33-1349.78 reads/million	AAV-2 positive	1/1 case (100)	1.42 reads/million
HHV-6B positive	DNA: 5/5 cases (100), RNA: 0/4 cases (0)	DNA: 0.09-4.1 reads/million	Feces
TTV positive	DNA: 2/5 cases (40), RNA: 0/4 cases (0)	Read count, no data	AAV2 positive	DNA: 1/7 cases (14.2), RNA: 1/7 cases (14.2)	DNA: 3156.64 reads/million, RNA: 554.03 reads/million	Tilling multiplex PCR amplicon for AAV1-AAV8 and HAdV-41 (n = 1)
Astrovirus VA3 positive	DNA: 1/5 cases (20), RNA: 0/4 cases (0)	Read count, no data	HAdV positive	DNA: 4/7 cases (57.1), RNA: 0/7 cases (0)	DNA: 0.72-10512 reads/million	AAV-2 positive	1/1 case (100)	9210.435 reads/million
			Rectal swab			HAdV-41 positive	1/1 case (100)	0.012 reads/million
			AAV2 positive	DNA: 1/1 case (100), RNA: 0/1 case (0)	DNA: 108.68 reads/million	Nasopharyngeal swab
			HAdV positive	DNA: 1/1 case (100), RNA: 0/1 case (0)	DNA: 2.93 reads/million	Agnostic metagenomic sequencing (n = 1)
			Throat swab			HAdV-1 positive	1/1 case (100)	23.58 reads/million
			AAV2 positive	DNA: 1/6 cases (16.7), RNA: 0/6 case (0)	DNA: 670.26 reads/million	Feces
			HAdV positive	DNA: 2/6 cases (33.3), RNA: 0/6 case (0)	DNA: 152.96-14453.17 reads/million	Agnostic metagenomic sequencing (n = 2)
						Picobirnavirus positive	1/2 cases (50)	0.32 reads/million
Total			Total			Total
AAV-2 positive	9/10 cases (90)		AAV-2 positive	9/9 cases (100)		AAV-2 positive	13/16 cases (81.3)
HAdV positive	1/10 cases (10)		HAdV positive	6/9 cases (66.7)		HAdV (serotypes 1, 2 and 41) positive	12/16 cases (75)
HHV-6B positive	5/10 cases (50)		HHV-6B positive	3/4 cases (75)		EBV positive	2/16 cases (12.5)
EBV positive	1/10 cases (10)		VZV positive	1/4 cases (25)		CMV positive	1/16 cases (6.3)
TTV positive	3/10 cases (30)		EBV positive	1/4 cases (25)		EV-A71 positive	1/16 cases (6.3)
Astrovirus VA3 positive	1/10 cases (20)		CMV positive	2/4 cases (50)		Picobirnavirus positive	1/16 cases (6.3)
			HHV-7 positive	1/4 cases (25)
Control			Control			Control
No data			Plasma or serum			Whole blood or plasma
			AAV2 positive			Agnostic metagenomic sequencing (n = 113)
			G1	DNA: 0/13 (0), RNA: 0/13 (0)		AAV-2 positive	1/113 (0.9)	97.65 reads/million
			G2	DNA: 0/12 (0), RNA: 0/12 (0)		HAdV-41 positive	4/113 (3.5)	0.07-6.14 reads/million
			HAdV positive			HAdV-2 positive	2/113 (1.8)	0.015-0.035 reads/million
			G1	DNA: 0/13 (0), RNA: 0/13 (0)
			G2	DNA: 6/12 (50), RNA: 2/12 (16.7)	DNA: 1.63-29950.78 reads/million, RNA: 2.36-13.74 reads/million	Tilling multiplex PCR amplicon for AAV-1-AAV-8 and HAdV-41 (n = 113)
			HSV1			AAV-2 positive	4/113 (3.5)	2.178-44265.146 reads/million
			G1	DNA: 0/13 (0), RNA: 0/13 (0)		G1	0/42
			G2	DNA: 1/12 (8.3), RNA: 1/12 (8.3)	DNA: 3.5 reads/million, RNA: 11.38 reads/million	G2	0/30
			HSV2			G3	3/23
			G1	DNA: 0/13 (0), RNA: 0/13 (0)		G4	1/18
			G2	DNA: 1/12 (8.3), RNA: 1/12 (8.3)	DNA: 10.37 reads/million, RNA: 22.92 reads/million	HAdV-41 positive	9/113 (8.0)	0.412-7857.512 reads/million
			VZV			G1	0/42
			G1	DNA: 0/13 (0), RNA: 0/13 (0)		G2	0/30
			G2	DNA: 1/12 (8.3), RNA: 1/12 (8.3)	DNA: 2.68 reads/million, RNA: 4.02 reads/million	G3	9/23 (Of HAdV positive 9 cases, 3 were positive for AAV-2)
			EBV			G4	0/18
			G1	DNA: 3/13 (23.1), RNA: 3/13 (23.1)	DNA: 1.23-114.38 reads/million, RNA: 0.1-1.0 reads/million
			G2	DNA: 3/12 (25), RNA: 3/12 (25)	DNA: 1.64-272.4 reads/million, RNA: 1.38-17.58 reads/million
			CMV
			G1	DNA: 1/13 (7.7), RNA: 0/13 (0)	DNA: 17.06 reads/million
			G2	DNA: 5/12 (41.7), RNA: 1/12 (8.3)	DNA: 8.26-3634.02 reads/million, RNA: 3185.33 reads/million
			HHV6A
			G1	DNA: 0/13 (0), RNA: 3/13 (23.1)	RNA: 0.08-5.1 reads/million
			G2	DNA: 1/12 (8.3), RNA: 1/12 (8.3)	DNA: 1.67 reads/million, RNA: 12.38 reads/million
			HHV6B
			G1	DNA: 0/13 (0), RNA: 0/13 (0)
			G2	DNA: 3/12 (25), RNA: 2/12 (16.7)	DNA: 0.18-5062.23 reads/million, RNA: 206.17-5819.09 reads/million
			HHV7
			G1	DNA: 0/13 (0), RNA: 1/13 (7.7)	RNA: 0.1 reads/million
			G2	DNA: 0/12 (0), RNA: 2/12 (16.7)	RNA: 2.0-10.54 reads/million
			HHV8
			G1	0/13 (0)
			G2	DNA: 2/12 (16.7), RNA: 1/12 (8.3)	DNA: 2.01-75.91 reads/million, RNA: 1.34 reads/million

AAV: Adeno-associated virus; CMV: Cytomegalovirus; EBV: Epstein-Barr virus; EV: Enterovirus; HAdV: Human adenovirus; HHV: Human herpes virus; TTV: Torque teno virus; VZV: Varicella-zoster virus; PCR: Polymerase chain reaction.

Full Size Table

Citation: Komatsu H. Comparison of three pediatric studies investigating acute hepatitis of unknown etiology. World J Virol 2025; 14(4): 110435
URL: https://www.wjgnet.com/2220-3249/full/v14/i4/110435.htm
DOI: https://dx.doi.org/10.5501/wjv.v14.i4.110435

Komatsu H. Comparison of three pediatric studies investigating acute hepatitis of unknown etiology. World J Virol 2025; 14(4): 110435 [PMID: 41479581 DOI: 10.5501/wjv.v14.i4.110435]

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