Editorial
Copyright ©2009 The WJG Press and Baishideng.
World J Gastroenterol. May 28, 2009; 15(20): 2433-2440
Published online May 28, 2009. doi: 10.3748/wjg.15.2433
Table 1 Class I biomarkers of liver fibrogenesis
Specimen
Method
SerumUrineLiver 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
Table 2 Class II biomarkers of liver fibrogenesis
IndexParametersChronic liver diseaseSensitivity (%)Specificity (%)
PGAA-IndexProthrombin time, γGT, apolipoprotein A1, α2-macroglobulinAlcohol7989
Bonacini-IndexALT/AST-ratio, INR, platelet countHCV4698
Sheth-IndexAST/ALT (De Ritis)HCV53100
Park-IndexHCV4796
PGA-IndexProthrombin time, γGT, apolipoprotein A1Mixed9181
Fortunato-ScoreFibronectin, prothrombin time, PCHE, ALT, Mn-SOD, β-NAGHCV94
Fibrotest (Fibro-Score)Haptoglobin, α2-macroglobulin, apolipoprotein A1, γGT, bilirubinHCV7585
HBV
Pohl-ScoreAST/ALT-ratio, platelet countHCV4199
ActitestFibrotest + ALTHCV
Forns-IndexAge, platelet count, γGT, cholesterolHCV9451
Wai-Index (APRI)AST, platelet countHCV8975
Rosenberg-Score (ELF-Score)PIIINP, hyaluronan, TIMP-1Mixed9041
Patel-Index (FibroSpect)Hyaluronan, TIMP-1, α2-macroglobulinHCV7773
Sud-Index (fibrosis probability-index, FPI)Age, AST, cholesterol, insulin resistance (HOMA), past alcohol intakeHCV9644
Leroy-ScorePIIINP, MMP-1HCV6092
Fibrometer testPlatelet count, prothrombin index, AST, α2-macro-globulin, hyaluronan, urea, ageMixed8184
HepascoreBilirubin, γGT, hyaluronan, α2-macroglobulin, age, genderHCV6389
Testa-IndexPlatelet count/spleen diameter-ratioHCV7879
FIB-4Platelet count, AST, ALT, ageHCV/HIV7074
FibroIndexPlatelet count, AST, γ-globulinHCV3897
Table 3 Future candidate biomarkers of non-invasive diagnosis and follow-up of liver fibrogenesis
BiomarkerSpecimenAssay technologyPathobiochemical basis
CTGFSerumImmunoassayTGF-β induced expression in and secretion by hepatocytes and hepatic stellate cells
FibrocytesBlood, buffy coatFlow cytometry of CD34+, CD45+, Coll I+ cells qPCRSupplementation of local fibroblasts at site of liver injury by bone-marrow derived fibrocytes
BMP-7SerumImmunoassayAntagonist of TGF-β, inhibitor of EMT
G-CSFBloodImmunoassaysMobilization of bone-marrow derived fibrocytes
GM-CSF
M-CSF
ProteomicsSerumMass spectrometry (MS)Fibrosis-specific serum protein profiles
GlycomicsSerumAdaptation of DNA-sequencer/fragment analyzer technology to profiling of desialylated N-linked oligo-saccharidesFibrosis-specific profiles of desialylated serum protein linked oligosaccharides (N-glycans)
Xylosyl-transferase (EC 2.4.2.26)SerumLC-MS/MSKey enzyme in the biosynthesis of glycosaminoglycan chains in proteoglycans, e.g. in hepatic stellate cells and hepatocytes