title: Circulating microRNA-22 correlates with microRNA-122 and represents viral replication and liver injury in patients with chronic hepatitis B.
abstract: Hepatitis B virus (HBV) infection is associated with increased expression of microRNA-122. Serum microRNA-122 and microRNA-22 levels were analyzed in 198 patients with chronic HBV who underwent liver biopsy and were compared with quantitative measurements of HBsAg, HBeAg, HBV DNA, and other clinical and histological findings. Levels of serum microRNA-122 and microRNA-22 were determined by reverse transcription-TaqMan PCR. Serum levels of microRNA-122 and microRNA-22 were correlated (R(2)  = 0.576; P < 0.001), and both were elevated in chronic HBV patients. Significant linear correlations were found between microRNA-122 or microRNA-22 and HBsAg levels (R(2)  = 0.824, P < 0.001 and R(2)  = 0.394, P < 0.001, respectively) and ALT levels (R(2)  = 0.498, P < 0.001 and R(2)  = 0.528, P < 0.001, respectively). MicroRNA-122 levels were also correlated with HBV DNA titers (R(2)  = 0.694, P < 0.001 and R(2)  = 0.421, P < 0.001). Levels of these microRNAs were significantly higher in HBeAg-positive patients compared to HBeAg-negative patients (P < 0.001 and P < 0.001). MicroRNA-122 levels were also lower in patients with advanced liver fibrosis (P < 0.001) and lower inflammatory activity (P < 0.025). These results suggest that serum micro-RNA levels are significantly associated with multiple aspects of HBV infection. The biological meaning of the correlation between microRNA-122 and HBsAg and should be investigated further.
authors.affiliation: Department of Gastroenterology and Metabolism, Applied Life Sciences, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
authors.forename: Keiko
authors.initials: K
authors.lastname: Arataki
authors.forename: C Nelson
authors.initials: CN
authors.lastname: Hayes
authors.forename: Sakura
authors.initials: S
authors.lastname: Akamatsu
authors.forename: Rie
authors.initials: R
authors.lastname: Akiyama
authors.forename: Hiromi
authors.initials: H
authors.lastname: Abe
authors.forename: Masataka
authors.initials: M
authors.lastname: Tsuge
authors.forename: Daiki
authors.initials: D
authors.lastname: Miki
authors.forename: Hidenori
authors.initials: H
authors.lastname: Ochi
authors.forename: Nobuhiko
authors.initials: N
authors.lastname: Hiraga
authors.forename: Michio
authors.initials: M
authors.lastname: Imamura
authors.forename: Shoichi
authors.initials: S
authors.lastname: Takahashi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Aikata
authors.forename: Tomokazu
authors.initials: T
authors.lastname: Kawaoka
authors.forename: Yoshiiku
authors.initials: Y
authors.lastname: Kawakami
authors.forename: Waka
authors.initials: W
authors.lastname: Ohishi
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Chayama
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000410:Alanine Transaminase / Q000097:blood; D015415:Biomarkers / Q000097:blood*; D001706:Biopsy; D004279:DNA, Viral / Q000097:blood; D005260:Female; D006514:Hepatitis B Surface Antigens / Q000097:blood; D006515:Hepatitis B virus / Q000472:pathogenicity*; D019694:Hepatitis B, Chronic / Q000175:diagnosis / Q000473:pathology*; D006651:Histocytochemistry; D006801:Humans; D008099:Liver / Q000473:pathology* / Q000821:virology*; D008297:Male; D035683:MicroRNAs / Q000097:blood*; D008875:Middle Aged; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019562:Viral Load; D014779:Virus Replication; D055815:Young Adult
chemical_list: D015415:Biomarkers; D004279:DNA, Viral; D006514:Hepatitis B Surface Antigens; C531907:MIRN122 microRNA, human; C548375:MIRN22 microRNA, human; D035683:MicroRNAs; D000410:Alanine Transaminase