title: Hepatic and serum levels of miR-122 after chronic HCV-induced fibrosis.
abstract: OBJECTIVE
  The progression of liver fibrosis in patients with chronic hepatitis C (CHC) is important to decide on the treatment of the virus. As liver biopsy and liver stiffness measurement for staging of fibrosis present limitations, circulating levels of miR-122 have been suggested as a novel biomarker to predict the extent of liver injury. We evaluated the potential of miR-122 as an indicator of fibrosis progression in CHC infection and performed, for the first time, a comprehensive analysis of hepatic and circulating miR-122 levels in patients with CHC.
  
  
  METHODS
  Patients with well-documented CHC infection were selected from the database of HepNet, the German-Competence-Network on Viral Hepatitis. All patients underwent blood sampling and liver biopsy with grading of inflammation and staging of fibrosis. RNA was extracted from 84 liver biopsies and 164 serum samples of CHC patients. miR-122 levels in liver and serum samples were quantified by real-time PCR normalized to RNU6 or spiked-in RNA, respectively.
  
  
  RESULTS
  Hepatic levels of miR-122 decreased significantly with the severity of fibrosis (p = 0.001). In addition, circulating miR-122 levels correlated negatively with increasing stages of fibrosis, although the inverse correlation was moderate due to a two-phase miR-122 pattern during fibrosis progression. Thus, circulating miR-122 levels decreased in patients with severe fibrosis (F3, F4), while at early stages with distinct fibrotic structures (F2) and high inflammatory activity, miR-122 serum levels were elevated.
  
  
  CONCLUSIONS
  We conclude that during progression of fibrosis less miR-122 is released into the blood stream due to the loss of liver cells and the decrease of hepatic miR-122 levels. Although the release of circulating miR-122 possibly mirrors acute liver injury, in chronic liver disease and fibrosis, the loss of liver cells and the decreased hepatocellular miR-122 expression render miR-122 an inappropriate marker, when exclusively used for interpretation of fibrosis progression.
authors.affiliation: Department of Internal Medicine I, University of Bonn, Germany. jonel.trebicka@ukb.uni-bonn.de
authors.forename: Jonel
authors.initials: J
authors.lastname: Trebicka
authors.forename: Evrim
authors.initials: E
authors.lastname: Anadol
authors.forename: Natalia
authors.initials: N
authors.lastname: Elfimova
authors.forename: Ingo
authors.initials: I
authors.lastname: Strack
authors.forename: Michael
authors.initials: M
authors.lastname: Roggendorf
authors.forename: Sergei
authors.initials: S
authors.lastname: Viazov
authors.forename: Inga
authors.initials: I
authors.lastname: Wedemeyer
authors.forename: Uta
authors.initials: U
authors.lastname: Drebber
authors.forename: Jürgen
authors.initials: J
authors.lastname: Rockstroh
authors.forename: Tilman
authors.initials: T
authors.lastname: Sauerbruch
authors.forename: Hans-Peter
authors.initials: HP
authors.lastname: Dienes
authors.forename: Margarete
authors.initials: M
authors.lastname: Odenthal
mesh_terms: D015415:Biomarkers / Q000378:metabolism; D001706:Biopsy; D018450:Disease Progression; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000150:complications* / Q000378:metabolism*; D006801:Humans; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D008103:Liver Cirrhosis / Q000209:etiology* / Q000378:metabolism*; D008297:Male; D035683:MicroRNAs / Q000378:metabolism*; D012720:Severity of Illness Index
chemical_list: D015415:Biomarkers; C531907:MIRN122 microRNA, human; D035683:MicroRNAs