title: Serum microRNA-125b correlates with hepatitis B viral replication and liver necroinflammation.
abstract: MicroRNAs (miRNAs) were recently reported to play an important role in hepatitis B virus (HBV) infection and related diseases. We evaluated the correlation between serum miRNA-125b, viral replication and liver necroinflammation in Chinese patients with chronic hepatitis B (CHB) infection. Serum miRNA-125b levels in samples from 211 CHB patients were determined by RT-PCR. Liver biopsies were collected from 138 patients. Serum miRNA-125b, miRNA-122 and miRNA-124 levels were determined. Correlations between serum miRNA-125b, viral replication and liver necroinflammation were analysed. The receiver operating characteristic (ROC) curve was used to assess the discriminating power of serum miRNA-125b to grade liver necroinflammation (G). HepG2.2.15 cells were transfected with miRNA-125b mimics. Intracellular viral core DNA was extracted and analysed by Southern blot. We found that serum miRNA-125b was positively correlated with the serum HBV DNA level. HBV replication capacity increased after transfection with miRNA-125b mimics. Patients with CHB with moderate-to-severe liver necroinflammation (G ≥2) showed significantly higher (p <0.001) serum miRNA-125b levels than those with G <2. In patients with alanine transaminase levels less than twice the upper limit of normal, serum miRNA-125b combined with miRNA-124 yielded an area under the ROC curve of 0.816, with 70.4% sensitivity and 84.9% specificity to discriminate the grade of liver necroinflammation (G ≥2). Hence, we concluded that miRNA-125b may enhance HBV replication. Serum miRNA-125b correlates with viral load. Serum miRNA-125b alone or combined with miRNA-124 has the potential to discriminate grades of liver necroinflammation, particularly in Chinese patients with CHB who have normal or mildly increased alanine transaminase levels.
authors.affiliation: Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China.
authors.forename: F
authors.initials: F
authors.lastname: Li
authors.affiliation: Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China.
authors.forename: P
authors.initials: P
authors.lastname: Zhou
authors.affiliation: Institute of Virology, University Hospital of Essen, University of Duisburg-Essen, Essen, Germany.
authors.forename: W
authors.initials: W
authors.lastname: Deng
authors.affiliation: Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China.
authors.forename: J
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China.
authors.forename: R
authors.initials: R
authors.lastname: Mao
authors.affiliation: Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China.
authors.forename: J
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China.
authors.forename: J
authors.initials: J
authors.lastname: Yu
authors.affiliation: Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China.
authors.forename: F
authors.initials: F
authors.lastname: Yang
authors.affiliation: Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Institute of Virology, University Hospital of Essen, University of Duisburg-Essen, Essen, Germany. Electronic address: mengji.lu@uni-due.de.
authors.forename: M
authors.initials: M
authors.lastname: Lu
authors.affiliation: Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China; Key Laboratory of Medical Molecular Virology of the Ministry of Education and Ministry of Health, Fudan University, Shanghai, China. Electronic address: jmzhang@fudan.edu.cn.
authors.forename: J
authors.initials: J
authors.lastname: Zhang
mesh_terms: D000293:Adolescent; D000328:Adult; D015415:Biomarkers / Q000097:blood; D001706:Biopsy; D002460:Cell Line; D002681:China; D004279:DNA, Viral / Q000097:blood*; D005260:Female; D006515:Hepatitis B virus / Q000502:physiology*; D019694:Hepatitis B, Chronic / Q000473:pathology* / Q000821:virology*; D022781:Hepatocytes / Q000821:virology; D006801:Humans; D008099:Liver / Q000473:pathology*; D008297:Male; D035683:MicroRNAs / Q000097:blood*; D008875:Middle Aged; D009336:Necrosis / Q000473:pathology; D012372:ROC Curve; D060888:Real-Time Polymerase Chain Reaction; D012680:Sensitivity and Specificity; D044967:Serum / Q000737:chemistry; D012720:Severity of Illness Index; D014779:Virus Replication; D055815:Young Adult
chemical_list: D015415:Biomarkers; D004279:DNA, Viral; C509207:MIRN124 microRNA, human; C531888:MIRN125 microRNA, human; D035683:MicroRNAs
keywords: Chronic hepatitis B; hepatitis B virus; liver necroinflammation prediction; microRNA-125b; viral replication