Novel biomarkers predict liver fibrosis in hepatitis C patients: alpha 2 macroglobulin, vitamin D binding protein and apolipoprotein AI

Abstract

BackgroundThe gold standard of assessing liver fibrosis is liver biopsy, which is invasive and not without risk. Therefore, searching for noninvasive serologic biomarkers for liver fibrosis is an importantly clinical issue.MethodsA total of 16 healthy volunteers and 45 patients with chronic hepatitis C virus (HCV) were enrolled (F0: n = 16, F1: n = 7, F2: n = 17, F3: n = 8 and F4: n = 13, according to the METAVIR classification). Three serum samples of each fibrotic stage were analyzed by two-dimension difference gel electrophoresis (2D-DIGE). The differential proteins were identified by the cooperation of MALDI-TOF/TOF and MASCOT; then western blotting and Bio-Plex Suspension Array were used to quantify the protein levels.ResultsThree prominent candidate biomarkers were identified: alpha 2 macroglobulin (A2M) is up regulated; vitamin D binding protein (VDBP) and apolipoprotein AI (ApoAI) are down regulated. The serum concentration of A2M was significantly different among normal, mild (F1/F2) and advanced fibrosis (F3/F4) (p < 0.01). The protein levels of VDBP and ApoAI were significantly higher in normal/mild fibrosis, when compared to those in advanced fibrosis (both p < 0.01).ConclusionsThis study not only reveals three putative biomarkers of liver fibrosis (A2M, VDBP and ApoAI) but also proves the differential expressions of those markers in different stages of fibrosis. We expect that combination of these novel biomarkers could be applied clinically to predict the stage of liver fibrosis without the need of liver biopsy.

Antimicrobial implications of vitamin D

“…Thus, vitamin D-binding protein level is potentially a way to predict the stage of liver fibrosis without biopsy. 77 Vitamin D is linked not only to liver fibrosis but also of respiratory infections. Vitamin D also reduces the production of proinflammatory cytokines, which may reduce the risk of cytokine storm in H1N1 infection.…”

Rat liver sinusoidal endothelial cells (LSECs) express functional low density lipoprotein receptor-related protein-1 (LRP-1)

“…The  2 M-proteinase complex, the "activated"  2 M ( 2 M*), becomes a specific ligand for the LRP-1, and is eliminated from the circulation by LRP-mediated endocytosis and subsequently degraded [41].  2 M was recently found to be a noninvasive serological biomarker that could predict the stage of liver fibrosis [20] The expression and function of the LRP-1 in liver was so far studied in PCs or PC-like cell lines [2,6,7,42,43]. Using RAP and  2 M* as potent ligands for LRP-1, we investigated whether this receptor is also expressed in LSECs .…”

New Methodologies for Assessing the Presence and Ecological Effects of Pesticides in Doñana National Park (SW Spain)

“…CHI3l3 (chitinase 3-like 3 protein), produced by macrophages upon inflammation (Welch et al, 2002), mediates asthma inflammatory response (Shuhui et al, 2009). A2M (α2-macroglobulin), a plasma proteinase inhibitor, binds many biologically important molecules (LaMarre et al, 1991), inhibits the degradation of matrix proteins and reduce inflammation in liver (Ho et al, 2010). Thus, A2M overexpression in DRS mice might help to the resolution of the inflammatory response and to recover homeostasis.…”