title: Serum microRNA-124 is a novel biomarker for liver necroinflammation in patients with chronic hepatitis B virus infection.
abstract: Patients with chronic hepatitis B virus (HBV) infection and normal or mildly increased transaminases may have sustained significant liver damage, as verified by liver biopsy. However, no suitable noninvasive method exists for identifying liver necroinflammation in such patients. We aimed to investigate the power of microRNA-124 as a novel biomarker for liver necroinflammation. A total of 131 recruited patients with chronic HBV infection underwent liver biopsy for grading of necroinflammation (G) and staging of fibrosis (S). Thirty healthy individuals were included as controls (HCs). Serum microRNA-124 and microRNA-122 levels were measured using qRT-PCR. Forty-five patients from the study population receiving entecavir therapy were monitored for changes in serum microRNA-124 levels in association with improved liver histology. The capacity of serum microRNA-124 levels in discriminating the grade of liver necroinflammation was compared with alanine aminotransferase (ALT) with liver biopsy validation. Serum microRNA-124 levels were significantly higher in patients with chronic HBV infection than in HCs (P < 0.0001). Patients with considerable liver necroinflammation (G ≥ 2) had significantly higher serum miRNA-124 levels than those without or with mild necroinflammation (P < 0.0001). After 48 weeks of antiviral therapy, serum microRNA-124 levels considerably declined in 45 patients (P < 0.0001), which were associated with histological improvement. In patients with normal ALT and a serum HBV DNA load >10(4) copies/mL, receiver operating characteristic (ROC) curve of serum microRNA-124 levels yielded an area under ROC curve (AUC) of 0.840, with 58.3% sensitivity and 91.7% specificity in discriminating between moderate-to-severe liver necroinflammation (G ≥ 2).
authors.affiliation: Department of Infectious Diseases, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China.
authors.forename: J-Y
authors.initials: JY
authors.lastname: Wang
authors.forename: R-C
authors.initials: RC
authors.lastname: Mao
authors.forename: Y-M
authors.initials: YM
authors.lastname: Zhang
authors.forename: Y-J
authors.initials: YJ
authors.lastname: Zhang
authors.forename: H-Y
authors.initials: HY
authors.lastname: Liu
authors.forename: Y-L
authors.initials: YL
authors.lastname: Qin
authors.forename: M-J
authors.initials: MJ
authors.lastname: Lu
authors.forename: J-M
authors.initials: JM
authors.lastname: Zhang
mesh_terms: D000328:Adult; D000368:Aged; D000410:Alanine Transaminase / Q000097:blood; D000998:Antiviral Agents / Q000627:therapeutic use; D015415:Biomarkers / Q000097:blood*; D001706:Biopsy; D003955:Diagnostic Tests, Routine / Q000379:methods*; D005260:Female; D019694:Hepatitis B, Chronic / Q000175:diagnosis* / Q000188:drug therapy; D006801:Humans; D008099:Liver / Q000473:pathology*; D008103:Liver Cirrhosis / Q000473:pathology; D008297:Male; D035683:MicroRNAs / Q000097:blood*; D008875:Middle Aged; D012372:ROC Curve; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index
chemical_list: D000998:Antiviral Agents; D015415:Biomarkers; C509207:MIRN124 microRNA, human; D035683:MicroRNAs; D000410:Alanine Transaminase
keywords: biomarker; chronic HBV infection; diagnosis; liver necroinflammation; microRNA-124