Comparison of three pediatric studies investigating acute hepatitis of unknown etiology

Table 10 Histological analysis of liver from cases of acute hepatitis of unknown etiology

	England	Scotland	United States
Histology	Ballooning hepatocytes	Destruction of the sinus structures and irregularly arranged fibers were detected	Acute hepatitis with portal and lobular inflammation, ranging from mild to severe activity
	Disrupted liver architecture with varying degrees of perivenular, bridging or pan-acinar necrosis	Lobular hepatitis with periportal and interface inflammation	Increased sinusoidal macrophage with occasional forms demonstrating hemophagocytosis
	No evidence of fibrosis	Intracellular inclusions, bile duct proliferation and ballooning of hepatocyte of varying severity were observed	Marked fibrosis is rare
		Mild-to-moderate fibrotic changes were noted, but no evidence of confluent fibrosis
		Modified hepatic activity index for scoring of necroinflammatory ranged from 6 to 11 (maximum score, 18)
Immunohistochemistry	Infiltrating cells were predominantly stained with CD8+ T cells, but also included CD20+ B cells	Accumulation of MHC class II + cells was observed	Negative for adenovirus, HSV1, HSV2, CMV or VZV
	Widespread staining with the CD79a pan-B cell lineage, which identified plasma cells, was observed	Negative for complement
	Staining for Adenovirus and AAV-2 was negative
	MHC class I and II staining were increased but not specific
	C4d staining showed very weak
Macrophage-derived cells were positive for staining with HHV-6B antibody in all five explanted livers
In situ hybridization	No data	AAV-2 RNA was detected in the nuclei and cytoplasm of ballooned hepatocytes and arterial endothelial cells	No data
		AAV-2 RNA-positive cells were quantified at a high level
		HAdV RNA and HHV6 RNA were detectable, but at negligible levels
Co-detection by indexing analysis	No data	Prominent proliferation of epithelial cells was detected with increased CD68+ macrophages and activated CD4+ and CD8+ T cells and CD20+ B cells	No data
		High expression of the interferon-induced GTP-binding protein MX1 was observed

AAV: Adeno-associated virus; CMV: Cytomegalovirus; HAdV: Human adenovirus; HHV: Human herpes virus; MHC: Major histocompatibility complex; VZV: Varicella-zoster virus.