Non-invasive biomarkers for monitoring the fibrogenic process in liver: A short survey

Table 1 Class I biomarkers of liver fibrogenesis

	Specimen			Method
	Serum	Urine	Liver biopsy
Extracellular matrix-related enzymes
Enzyme
Prolyl hydroxylase	+	-	+	Radioenzymatic, RIA
Monoamine-oxidase	+	-	(+)	Enzymatic
Lysyl oxidase	+	-	+	RIA
Lysyl hydroxylase	+	-	-	RIA
Galactosylhydroxylysyl-glucosyltransferase	+	-	+	RIA
Collagen peptidase	+	-	+	Enzymatic
N-Acetyl-β-D-glucosaminidase	+	+	+	Enzymatic
Collagen fragments and split products
Type of collagen
Type I-procollagen
N-terminal propeptide (PINP)	+	-	+	ELISA
C-terminal propeptide (PICP)	+	-	+	RIA
Type III-Procollagen
Intact Procollagen	+	-	-	RIA
N-terminal propeptide (PIIINP)
Complete propeptide (Col 1-3)	+	-	-	RIA
Globular domain of Propeptide (Col-1)	+	-	-	RIA
Type IV-Collagen
NC1-fragment (C-terminal) crosslinking domain (PIVP)	+	+	-	ELISA, RIA
7S domain ("7S Collagen")	+	+	-	RIA
Type VI-Collagen	+	+	+	RIA
Glycoproteins and matrix-metalloproteinase (inhibitors)
Marker
Laminin, P1-fragment	+	-	-	RIA, EIA
Undulin	+	-	-	EIA
Vitronectin	+	-	-	EIA
Tenascin	+	-	-	ELISA
YKL-40	+	-	+	RIA/ELISA
(pro)matrix metalloproteinase (MMP-2)	+	-	-	ELISA
Tissue inhibitor of metalloproteinases (TIMP-1, TIMP-2)	+	-	-	ELISA
sICAM-1 (soluble intercellular adhesion molecule, sCD54)
sVCAM-1 (soluble vascular cell adhesion molecule, sCD106)	+	-	-	ELISA
Glycosaminoglycans
Marker
Hyaluronic acid (Hyaluronan)	+	-	-	Radioligand assay ELISA
Molecular mediators
Marker
Transforming growth factor β (TGF-β)	+	-	+	ELISA
Connective tissue growth factor (CTGF/CCN2)	+	?	+	ELISA