Non invasive fibrosis biomarkers reduce but not substitute the need for liver biopsy

Table 4 Direct non invasive markers of liver fibrosis

Author	Liver disease	Marker	Characteristics	Pathophisiology
McHutchison[61] Murawaki[62] Halfon[63] Pares[64] Suzuki[65] Naveau[66] Santos[67] Montazeri[68]	HCV, AFLD, NAFLD, HBV	Hyaluronic acid	Component of the ECM in every tissue	Synthesized by HSCs and degraded by sinusoidal endothelial cells
Santos[67] Walsh[69]	HCV, NAFLD	Laminin	Co-expressed with type IV collagen in basement membranes	Increased deposition in viral disease
Tran[70] Saitou[71]	AFLD, HCV	YKL-40	Human cartilage glicoprotein	Involved in remodelling and degradation of ECM
Sakugawa[72] Murawaki[73] Walsh[69] Saitou[71] Santos[67]	HCV, NAFLD	Type IV collagen/ 7s domain	Main collagen component of the basement membrane	Increase with severity of liver fibrosis
Guechot[74] Pares[64]	HCV, AFLD	Procollagen III	Propeptide	Released during matrix deposition and remodelling
Boeker[75] Murawaki[62]	HCV	MMP-2	Collagenase	Correlates with fibrosis
Boeker[75]	HCV	TIMP-1	Metalloproteinase	Inhibitor of collagenase
Patel[76]	HCV	Three-marker panel	Combination of hyaluronic acid, TIMP-1, α2M	Better accuracy by combined markers

AFLD = alcoholic fatty liver disease; NAFLD = non alcoholic fatty liver disease; ECM = extracellular matrix; HSCs = hepatic stellate cells; YKL-40 = human cartilage glycoprotein-39; MMP-2 = metalloproteinase 2; TIMP-1 = tissue inhibitor metalloproteinase 1; α₂M = alfa-2-macroglobulin.