Impact of circulating miR-122 for histological features and hepatocellular carcinoma of nonalcoholic fatty liver disease in Japan

Hepatol Int. 2016 Jul;10(4):647-56. doi: 10.1007/s12072-016-9729-2. Epub 2016 Apr 13.

Abstract

Background and aim: 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.

Keywords: Burned-out NASH; Fibrosis stage; Hepatocellular carcinoma; Longitudinal observation; MicroRNA-122; Nonalcoholic fatty liver disease; Nonalcoholic steatohepatitis; Relative expression.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Carcinoma, Hepatocellular / blood
  • Carcinoma, Hepatocellular / epidemiology
  • Carcinoma, Hepatocellular / genetics*
  • Carcinoma, Hepatocellular / pathology
  • Cross-Sectional Studies
  • Female
  • Humans
  • Japan / epidemiology
  • Liver Neoplasms / blood
  • Liver Neoplasms / epidemiology
  • Liver Neoplasms / genetics*
  • Liver Neoplasms / pathology
  • Longitudinal Studies
  • Male
  • MicroRNAs / blood*
  • Middle Aged
  • Neoplasm Staging
  • Non-alcoholic Fatty Liver Disease / epidemiology
  • Non-alcoholic Fatty Liver Disease / genetics*
  • Non-alcoholic Fatty Liver Disease / pathology
  • Prospective Studies
  • Young Adult

Substances

  • MIRN122 microRNA, human
  • MicroRNAs