title: Impact of circulating miR-122 for histological features and hepatocellular carcinoma of nonalcoholic fatty liver disease in Japan.
abstract: OBJECTIVE
  Relationships between circulating microRNA-122 (miR-122) and histological features of nonalcoholic fatty liver disease (NAFLD) are unclear.
  
  
  METHODS
  The impact of serum miR-122 levels for histological features and hepatocellular carcinoma (HCC) was investigated in 305 Japanese patients with histological proven NAFLD. Twenty-three patients were with HCC at the time of diagnosis of NAFLD, and four patients developed HCC during the follow-up. The cross-sectional or longitudinal evaluations were performed to investigate the impact for HCC.
  
  
  RESULTS
  Serum miR-122 levels (calibrated relative to the median levels of patients) partly affected severity of steatosis, ballooning, lobular inflammation, and stage. Multivariate analysis identified HCC and/or histological components of NASH as morphological factors that independently influenced serum miR-122 levels at the diagnosis of NAFLD. There was a strong correlation between serum miR-122 levels and AST, ALT levels. In cross-sectional evaluation, serum miR-122 levels of patients without HCC were significantly higher than those with HCC in patients of stage 3 but not stage 4. In longitudinal evaluation of one patient with follow-up time of 25 years, from the diagnosis of NAFLD until HCC, serum miR-122 levels had already tended to decrease before the progression of fibrosis stage.
  
  
  CONCLUSIONS
  HCC and/or histological components of NASH affected serum miR-122 levels, independently. In longitudinal evaluation of HCC patients, serum miR-122 levels had already tended to decrease before the progression of fibrosis stage. Further prospective studies are needed to investigate the impact of serum miR-122 for histological features and hepatocarcinogenesis of NAFLD.
authors.affiliation: Department of Hepatology, Toranomon Hospital, and Okinaka Memorial Institute for Medical Research, 2-2-2 Toranomon, Minato-ku, Tokyo, 105-0001, Japan. norioakuta@toranomon.gr.jp.
authors.forename: Norio
authors.initials: N
authors.lastname: Akuta
authors.affiliation: Department of Hepatology, Toranomon Hospital, and Okinaka Memorial Institute for Medical Research, 2-2-2 Toranomon, Minato-ku, Tokyo, 105-0001, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Kawamura
authors.affiliation: Department of Hepatology, Toranomon Hospital, and Okinaka Memorial Institute for Medical Research, 2-2-2 Toranomon, Minato-ku, Tokyo, 105-0001, Japan.
authors.forename: Fumitaka
authors.initials: F
authors.lastname: Suzuki
authors.affiliation: Department of Hepatology, Toranomon Hospital, and Okinaka Memorial Institute for Medical Research, 2-2-2 Toranomon, Minato-ku, Tokyo, 105-0001, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Saitoh
authors.affiliation: Department of Hepatology, Toranomon Hospital, and Okinaka Memorial Institute for Medical Research, 2-2-2 Toranomon, Minato-ku, Tokyo, 105-0001, Japan.
authors.forename: Yasuji
authors.initials: Y
authors.lastname: Arase
authors.affiliation: Department of Hepatology, Toranomon Hospital, and Okinaka Memorial Institute for Medical Research, 2-2-2 Toranomon, Minato-ku, Tokyo, 105-0001, Japan.
authors.forename: Hideo
authors.initials: H
authors.lastname: Kunimoto
authors.affiliation: Department of Hepatology, Toranomon Hospital, and Okinaka Memorial Institute for Medical Research, 2-2-2 Toranomon, Minato-ku, Tokyo, 105-0001, Japan.
authors.forename: Yushi
authors.initials: Y
authors.lastname: Sorin
authors.affiliation: Department of Hepatology, Toranomon Hospital, and Okinaka Memorial Institute for Medical Research, 2-2-2 Toranomon, Minato-ku, Tokyo, 105-0001, Japan.
authors.forename: Shunichiro
authors.initials: S
authors.lastname: Fujiyama
authors.affiliation: Department of Hepatology, Toranomon Hospital, and Okinaka Memorial Institute for Medical Research, 2-2-2 Toranomon, Minato-ku, Tokyo, 105-0001, Japan.
authors.forename: Hitomi
authors.initials: H
authors.lastname: Sezaki
authors.affiliation: Department of Hepatology, Toranomon Hospital, and Okinaka Memorial Institute for Medical Research, 2-2-2 Toranomon, Minato-ku, Tokyo, 105-0001, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Hosaka
authors.affiliation: Department of Hepatology, Toranomon Hospital, and Okinaka Memorial Institute for Medical Research, 2-2-2 Toranomon, Minato-ku, Tokyo, 105-0001, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Kobayashi
authors.affiliation: Department of Hepatology, Toranomon Hospital, and Okinaka Memorial Institute for Medical Research, 2-2-2 Toranomon, Minato-ku, Tokyo, 105-0001, Japan.
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Suzuki
authors.affiliation: Liver Research Laboratory, Toranomon Hospital, Tokyo, Japan.
authors.forename: Mariko
authors.initials: M
authors.lastname: Kobayashi
authors.affiliation: Department of Hepatology, Toranomon Hospital, and Okinaka Memorial Institute for Medical Research, 2-2-2 Toranomon, Minato-ku, Tokyo, 105-0001, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Ikeda
authors.affiliation: Department of Hepatology, Toranomon Hospital, and Okinaka Memorial Institute for Medical Research, 2-2-2 Toranomon, Minato-ku, Tokyo, 105-0001, Japan.
authors.forename: Hiromitsu
authors.initials: H
authors.lastname: Kumada
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D006528:Carcinoma, Hepatocellular / Q000097:blood / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D007564:Japan / Q000453:epidemiology; D008113:Liver Neoplasms / Q000097:blood / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D008137:Longitudinal Studies; D008297:Male; D035683:MicroRNAs / Q000097:blood*; D008875:Middle Aged; D009367:Neoplasm Staging; D065626:Non-alcoholic Fatty Liver Disease / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D011446:Prospective Studies; D055815:Young Adult
chemical_list: C531907:MIRN122 microRNA, human; D035683:MicroRNAs
keywords: Burned-out NASH; Fibrosis stage; Hepatocellular carcinoma; Longitudinal observation; MicroRNA-122; Nonalcoholic fatty liver disease; Nonalcoholic steatohepatitis; Relative expression