title: Circulating microRNAs in patients with chronic hepatitis C and non-alcoholic fatty liver disease.
abstract: MicroRNAs miR-122, miR-34a, miR-16 and miR-21 are commonly deregulated in liver fibrosis and hepatocellular carcinoma. This study examined whether circulating levels of these miRNAs correlate with hepatic histological disease severity in patients with chronic hepatitis C infection (CHC) or non-alcoholic fatty-liver disease (NAFLD) and can potentially serve as circulating markers for disease stage assessment. We first used an in vitro model of hepatitis C virus (HCV) infection to measure the extracellular levels of these four miRNAs. Whereas miR-21 extracellular levels were unchanged, extracellular levels of miR-122, miR-34a and to a lesser extent miR-16, steadily increased during the course of HCV infection, independently of viral replication and production. Similarly, in CHC patients, serum levels of miR-122, miR-34a and miR-16 were significantly higher than in control individuals, while miR-21 levels were unchanged. There was no correlation between the serum levels of any of these microRNAs and HCV viral loads. In contrast, miR-122 and miR-34a levels positively correlated with disease severity. Identical results were obtained in an independent cohort of CHC patients. We extended the study to patients with NAFLD. As observed in CHC patients, serum levels of miR-122, miR-34a and miR-16 were significantly higher in NAFLD patients than in controls, while miR-21 levels were unchanged. Again, miR-122 and miR-34a levels positively correlated with disease severity from simple steatosis to steatohepatitis. In both CHC and NAFLD patient groups, serum levels of miR-122 and miR-34a correlated with liver enzymes levels, fibrosis stage and inflammation activity. miR-122 levels also correlated with serum lipids in NAFLD patients.
  
  
  CONCLUSIONS
  Serum levels of miR-34a and miR-122 may represent novel, noninvasive biomarkers of diagnosis and histological disease severity in patients with CHC or NAFLD.
authors: Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.
authors: Silvia
authors: S
authors: Cermelli
authors: Anna
authors: A
authors: Ruggieri
authors: Jorge A
authors: JA
authors: Marrero
authors: George N
authors: GN
authors: Ioannou
authors: Laura
authors: L
authors: Beretta
mesh_terms: D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D005234:Fatty Liver / Q000097:blood* / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000097:blood* / Q000235:genetics; D006801:Humans; D035683:MicroRNAs / Q000097:blood*; D065626:Non-alcoholic Fatty Liver Disease; D012720:Severity of Illness Index
chemical_list: D015415:Biomarkers; C531907:MIRN122 microRNA, human; C505362:MIRN16 microRNA, human; C524940:MIRN21 microRNA, human; C522425:MIRN34 microRNA, human; D035683:MicroRNAs