title: Performance of Serum microRNAs -122, -192 and -21 as Biomarkers in Patients with Non-Alcoholic Steatohepatitis.
abstract: OBJECTIVE
  Liver biopsies are the current gold standard in non-alcoholic steatohepatitis (NASH) diagnosis. Their invasive nature, however, still carries an increased risk for patients' health. The development of non-invasive diagnostic tools to differentiate between bland steatosis (NAFL) and NASH remains crucial. The aim of this study is the evaluation of investigated circulating microRNAs in combination with new targets in order to optimize the discrimination of NASH patients by non-invasive serum biomarkers.
  
  
  METHODS
  Serum profiles of four microRNAs were evaluated in two cohorts consisting of 137 NAFLD patients and 61 healthy controls. In a binary logistic regression model microRNAs of relevance were detected. Correlation of microRNA appearance with known biomarkers like ALT and CK18-Asp396 was evaluated. A simplified scoring model was developed, combining the levels of microRNA in circulation and CK18-Asp396 fragments. Receiver operating characteristics were used to evaluate the potential of discriminating NASH.
  
  
  RESULTS
  The new finding of our study is the different profile of circulating miR-21 in NASH patients (p<0.0001). Also, it validates recently published results of miR-122 and miR-192 to be differentially regulated in NAFL and NASH. Combined microRNA expression profiles with CK18-Asp396 fragment level scoring model had a higher potential of NASH prediction compared to other risk biomarkers (AUROC = 0.83, 95% CI = 0.754-0.908; p<0.001). Evaluation of score model for NAFL (Score = 0) and NASH (Score = 4) had shown high rates of sensitivity (91%) and specificity (83%).
  
  
  CONCLUSIONS
  Our study defines candidates for a combined model of miRNAs and CK18-Asp396 levels relevant as a promising expansion for diagnosis and in turn treatment of NASH.
authors.affiliation: Department of Gastroenterology and Hepatology, University Hospital Zürich (USZ), Zürich, Switzerland.|Zürich Center for Integrative Human Physiology (ZIHP), University of Zürich (UZH), Zürich, Switzerland.
authors.forename: Philip P
authors.initials: PP
authors.lastname: Becker
authors.affiliation: Division of Hepatology, University Hospital Würzburg (UKW), Würzburg, Germany.
authors.forename: Monika
authors.initials: M
authors.lastname: Rau
authors.affiliation: Division of Hepatology, University Hospital Würzburg (UKW), Würzburg, Germany.
authors.forename: Johannes
authors.initials: J
authors.lastname: Schmitt
authors.affiliation: Institute of Clinical Epidemiology und Biometry University of Würzburg, Würzburg, Germany.
authors.forename: Carolin
authors.initials: C
authors.lastname: Malsch
authors.affiliation: School of Life Sciences, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
authors.forename: Christian
authors.initials: C
authors.lastname: Hammer
authors.affiliation: Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.
authors.forename: Heike
authors.initials: H
authors.lastname: Bantel
authors.affiliation: Department of Gastroenterology and Hepatology, University Hospital Zürich (USZ), Zürich, Switzerland.
authors.forename: Beat
authors.initials: B
authors.lastname: Müllhaupt
authors.affiliation: Department of Gastroenterology and Hepatology, University Hospital Zürich (USZ), Zürich, Switzerland.|Division of Hepatology, University Hospital Würzburg (UKW), Würzburg, Germany.|Zürich Center for Integrative Human Physiology (ZIHP), University of Zürich (UZH), Zürich, Switzerland.
authors.forename: Andreas
authors.initials: A
authors.lastname: Geier
mesh_terms: D000328:Adult; D017209:Apoptosis; D015415:Biomarkers / Q000097:blood*; D001706:Biopsy; D016022:Case-Control Studies; D015331:Cohort Studies; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D008099:Liver / Q000473:pathology*; D008297:Male; D035683:MicroRNAs / Q000097:blood*; D065626:Non-alcoholic Fatty Liver Disease / Q000097:blood* / Q000175:diagnosis; D009765:Obesity / Q000097:blood; D012372:ROC Curve; D012044:Regression Analysis; D012680:Sensitivity and Specificity; D055815:Young Adult
chemical_list: D015415:Biomarkers; C531907:MIRN122 microRNA, human; C546783:MIRN192 microRNA, human; C524940:MIRN21 microRNA, human; D035683:MicroRNAs