Abstract

Hepatitis B virus (HBV) constitutes an important risk factor for cirrhosis and hepatocellular carcinoma (HCC). The link between circulating microRNAs and HBV has been previously reported, although not as a marker of liver disease progression in chronic hepatitis B (CHB). The aim of this study was to characterize miRNA expression profiles between CHB with and without cirrhosis or HCC. A total of 12 subjects were recruited in this study. We employed an Affymetrix Gene Chip miRNA 3.0 Array to provide universal miRNA coverage. We compared microRNA expression profiles between CHB with and without cirrhosis/HCC to discover possible prognostic markers associated with the progression of CHB. Our results indicated 8 differently expressed microRNAs, of which miRNA-935, miRNA-342, miRNA-339, miRNA-4508, miRNA-3615, and miRNA-3200 were up-regulated, whereas miRNA-182 and miRNA-4485 were down-regulated in patients with CHB who progressed to cirrhosis/HCC as compared to those without progression. We demonstrated the differential expression of miRNA-935, miRNA-342, miRNA-339, miRNA-4508, miRNA-3615, miRNA-3200, miRNA-182, and miRNA-4485 between patients with HBV without cirrhosis/HCC and those who had progressed to these more severe conditions. These miRNAs may serve as novel and non-invasive prognostic markers for early detection of CHB-infected patients who are at risk of progression to cirrhosis and/or HCC.

Highlights

  • Hepatitis B virus (HBV) constitutes an important risk factor for cirrhosis and hepatocellular carcinoma (HCC)

  • To identify differentially expressed miRNAs between chronic hepatitis B (CHB) with and without cirrhosis/HCC, miRNA microarray was performed using 12 samples (n=4 for CHB without cirrhosis/HCC, n=4 for CHB with cirrhosis/HCC and n=4 for Healthy control) that were matched in terms of age, sex, and ethnicity

  • We identified 8 detectable microRNAs with p value 0.05 and fold expression change ≥ 2 or ≤ −2 between the CHB with cirrhosis/ HCC and CHB without cirrhosis/HCC groups

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Summary

Introduction

Hepatitis B virus (HBV) constitutes an important risk factor for cirrhosis and hepatocellular carcinoma (HCC). Conclusions: We demonstrated the differential expression of miRNA-935, miRNA-342, miRNA-339, miRNA-4508, miRNA-3615, miRNA-3200, miRNA-182, and miRNA-4485 between patients with HBV without cirrhosis/HCC and those who had progressed to these more severe conditions. These miRNAs may serve as novel and non-invasive prognostic markers for early detection of CHB-infected patients who are at risk of progression to cirrhosis and/or HCC. 240 million individuals are chronically infected with HBV worldwide with three quarters being within the Asia-Pacific region(1) Among those with chronic HBV infection (CHB), up to 40% develop serious liver complications such as liver cirrhosis and HCC. Emerging evidence has revealed the role of microRNAs (miRNAs) in various diseases including chronic inflammatory disease such

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