A Pilot Study Of Serum MicroRNA Signature As A Novel Biomarker For Occult Hepatitis B Virus Infection

Objective The implementation of hepatitis B surface antigen (HBsAg) screening tests has significantly enhanced blood transfusion safety. However, the transmission of HBsAg-negative blood components can still occur in the acute phase of infection during the seronegative window period or during chronic stages of infection such as occult hepatitis virus B infection (OBI). OBI, characterized by the presence of HBV infection without detectable HBsAg, is capable to elude the routine detection with HBV serologic markers and harbor a potential risk of HBV transmission through blood transfusion or organ transplantation. Here, we test the hypothesis that OBI patients have a differentially expressed profile of microRNA (miRNA) in serum, and this unique serum miRNA signature can serve as a biomarker to detect OBI.Methods Since OBI patients were difficult to obtain, we first studied the serum miRNA profile in Chronic HBV instead. Employing a strategy of initial screening by Solexa sequencing followed by validation with qRT-PCR, we identified13HBV-specific serum miRNAs. We then studied the expression level of these13miRNAs in serum of OBI patients by Taqman Probe-based qRT-PCR.Results After screening these13miRNAs in the serum of30healthy controls,29HBV patients and11OBI patients, we obtained four miRNAs, let-7c, miR-23b, miR-122, and miR-150, which are differentially expressed in OBI sera compared to healthy control sera. This4-serum miRNA signature shows a high level of accuracy in discriminating both OBI (AUC=0.999) and HBV (AUC=0.989) cases from the non-infected controls. Cluster analysis also demonstrates that this4-miRNA signature can clearly separate OBI patients from the control group.Conclusions Our results demonstrate for the first time that a profile of serum miRNAs can serve as a sensitive and accurate biomarker for OBI detection.