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

Ai-Sheng Ho,Chia-Chi Wang,Wen-Ming Wang,Jing-Ying Lee,Chun-Chia Cheng,Meng-Lun Liu,Shui-Cheng Lee

doi:10.1186/1423-0127-17-58

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.

Highlights

In hepatitis C virus (HCV)-infected patients, liver fibrosis is a noticeable disease and could progress to liver cirrhosis or hepatocellular carcinoma gradually
Liver biopsy followed by histological examination is still the gold standard for the assessment of liver fibrosis [2]
Two-dimension difference gel electrophoresis (2DDIGE), first proposed by Unlu et al [6], allow different samples to be labeled with cy3 or cy5 flour in one gel

Summary

Introduction

In hepatitis C virus (HCV)-infected patients, liver fibrosis is a noticeable disease and could progress to liver cirrhosis or hepatocellular carcinoma gradually. Liver biopsy followed by histological examination is still the gold standard for the assessment of liver fibrosis [2]. It has several limits and disadvantages such as invasive character and. Two-dimension difference gel electrophoresis (2DDIGE), first proposed by Unlu et al [6], allow different samples to be labeled with cy or cy flour in one gel It used cy2-labeled internal standard to tell the differences and found out the reliable biomarkers among different gels. Multi-analyte profiling (xMAP) technique was used to quantify the concentration of putative biomarkers By using these methods, we could identify and quantify the candidate biomarkers, which could be a serologic predictor for the severity of liver fibrosis. Searching for noninvasive serologic biomarkers for liver fibrosis is an importantly clinical issue

Methods

Results

Conclusion