Expression profile and clinical significance of miRNAs at different stages of chronic hepatitis B virus infection.

OBJECTIVE To study the expression profile and clinical significance of microRNAs (miRNAs) at different stages of chronic hepatitis B virus (HBV) infection. METHODS The miRNA expression profiles of peripheral blood mononuclear cells (PBMCs) at different stages of chronic HBV infection were screened using miRNA microarray and validated using real-time quantitative polymerase chain reaction (qPCR). RESULTS Significant differences in miRNA expression profiles of PBMCs were observed between patients in IA and IT phases of CHB. Expression was significantly down-regulated in the former but up-regulated in the latter group. No significant differences in inactive hepatitis B surface antigen carriers were observed. Changes in expression of six miRNAs determined by real-time qPCR were consistent with those determined by microarray. Areas under the receiver operation characteristic curve of the six miRNAs distinguishing immune tolerance and clearance of chronic HBV infection were 99.4%, 98.4%, 96.7%, 100%, 100%, and 99.6%. Positive correlation was found between the levels of hsa- miR-146a and ALT (r = 0.56, P < 0.01) while negative correlation was found between the levels of hsa-miR-548ah-5p and HBV DNA (r = -0.73, P < 0.01). CONCLUSIONS Abnormal expression of miRNAs and the resulting gradual decline in the various immune states of patients with chronic HBV infection may play important roles in maintenance of the immune homeostatic mechanisms of chronic HBV infection. Hsa-miR-548ah-5p, hsa-miR-3191-5p and hsa-miR-4711-3p can be used as potential molecular markers to distinguish among different stages of chronic HBV infection.