Journal of Viral Hepatitis
Early View (Articles online in advance of print)
Summary. MicroRNAs (miRNAs) are stably present in human serum. The
relationship between circulating miRNAs and hepatitis B virus (HBV) infected
liver disease has not been previously reported. Applied Biosystems array-based
miRNA expression profiling was performed on pooled sera obtained from identified
groups of chronic asymptomatic carriers (ASC), patients with chronic hepatitis B
(CHB) and HBV-associated acute-on-chronic liver failure (ACLF), as well as
healthy controls (HC). Nine miRNAs were verified in more clinical samples by
RT-PCR. The correlation between miRNAs expression and the relationship between
miRNA levels and clinical characteristics was analysed. Results showed that
circulating miRNAs were detected in all disease and control samples, and their
numbers increased with symptom severity, from 37 in HC, 77 in ASC, 101 in CHB,
to 135 in ACLF. The expression levels of most miRNAs were also up-regulated in
HBV-infected patients when compared to HC. Expression of the liver-specific
miR-122 was significantly up-regulated in HBV-infected patients. Concomitant
regulation of miRNAs not in clusters was disrupted by HBV infection. However,
such disruption was not observed for miRNAs in paralogous clusters. Furthermore,
the level of miRNAs in the CHB serum was up-regulated most in hepatitis B e
antigen–positive patients. The expression levels of miR-122 and miR-194
correlated negatively with the age of patients with CHB or ACLF. Functional
analysis showed that miR-122 could inhibit HBV replication in Huh7 and HepG2
cells. In all, our study revealed that a number of miRNAs were differentially
expressed during HBV infection and underscored the potential importance of
miR-122 in the infection process.