Circulating microRNAs in hepatitis B virus–infected patients

Abstract

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.

MicroRNAs in Liver Disease: Bench to Bedside

“…66 However, a relationship between HB surface antigen (HBsAg) positivity and miRs was not found. 65 There was also no significant correlation observed between miR expression and ALT or HBV DNA levels. Patient age negatively correlated with miR levels, with lower levels of miR-122 and miR-194 in older population.…”

“…65 The level of serum miRs in HBV patients was significantly higher in hepatitis B 'e' antigen (HBeAg) positive patients compared to HBeAg negative patients, with miR-122 and miR-194 being the highest differentially expressed. 65 This suggests that miR expression may be associated with HBeAg production in CHB patients. As HBeAg seroconversion is considered to be an important end point in CHB treatment, miR expression may aid the development of anti-HBV therapeutics.…”

“…The occurrence of miRs has been shown in sera of HBV infected patients and these circulating miRs correlate positively with the severity of HBV-induced liver disease. 65 Around 100 miRs including miR-122, miR-16, miR-223, miR-19b, miR-20a, miR-92a, miR-106a, let-7b and miR-194, were amplified from HBV patients using TaqMan qRT-PCR assays. 65 The level of serum miRs in HBV patients was significantly higher in hepatitis B 'e' antigen (HBeAg) positive patients compared to HBeAg negative patients, with miR-122 and miR-194 being the highest differentially expressed.…”

“…65 Around 100 miRs including miR-122, miR-16, miR-223, miR-19b, miR-20a, miR-92a, miR-106a, let-7b and miR-194, were amplified from HBV patients using TaqMan qRT-PCR assays. 65 The level of serum miRs in HBV patients was significantly higher in hepatitis B 'e' antigen (HBeAg) positive patients compared to HBeAg negative patients, with miR-122 and miR-194 being the highest differentially expressed. 65 This suggests that miR expression may be associated with HBeAg production in CHB patients.…”

Function and clinical potential of microRNAs in hepatocellular carcinoma

“…Increasing evidence suggests that unique miRNA signatures may serve as valuable diagnostic and prognostic biomarkers in HCC (79). miRNAs are present in various body fluids, including serum and plasma (80,81). Furthermore, miRNAs exhibit significant stability under extreme conditions, such as low pH (acidic environment) and resistance to RNAase, and are considered as alternative non-invasive biomarkers (80,82).…”