title: Cytokeratin-18 and hyaluronic acid levels predict liver fibrosis in children with non-alcoholic fatty liver disease.
abstract: OBJECTIVE
  There is a need to replace liver biopsy with non-invasive markers that predict the degree of liver fibrosis in fatty liver disease related to obesity. Therefore, we studied four potential serum markers of liver fibrosis and compared them with histopathological findings in liver biopsy in children with non-alcoholic fatty liver disease (NAFLD).
  
  
  METHODS
  We determined fasting serum level of hyaluronic acid (HA), laminin, YKL-40 and cytokeratin-18 M30 in 52 children (age range 4-19, mean 12 years, 80 % of them were overweight or obese) with biopsy-verified NAFLD. Viral hepatitis, autoimmune and metabolic liver diseases (Wilson's disease, alpha-1-antitrypsin deficiency, cystic fibrosis) were excluded. Fibrosis stage was assessed in a blinded fashion by one pathologist according to Kleiner. Receiver operating characteristics (ROC) analysis was used to calculate the power of the assays to detect liver fibrosis (AccuROC, Canada).
  
  
  RESULTS
  Liver fibrosis was diagnosed in 19 children (37 %). The levels of HA and CK18M30 were significantly higher in children with fibrosis compared to children without fibrosis (p=0.04 and 0.05 respectively). The ability of serum HA (cut-off 19.1 ng/ml, Se=84 %, Sp=55 %, PPV=52 %, NPV=86 %) and CK18M30 (cut-off 210 u/l, Se=79 %, Sp=60 %, PPV=56 %, NPV=82 %) to differentiate children with fibrosis from those without fibrosis was significant (AUC=0.672 and 0.666, respectively). The combination of both markers was superior (AUC=0.73, p=0.002). Laminin and YKL-40 levels did not allow a useful prediction.
  
  
  CONCLUSIONS
  Cytokeratin-18 and hyaluronic acid are suitable serum markers predicting liver fibrosis in children with NAFLD. Studying these markers may identify patients at risk of disease progression.
authors.affiliation: Department of Pediatrics, Gastroenterology and Allergology, Medical University of Bialystok, Bialystok, Poland. lebensztejn@hoga.pl
authors.forename: Dariusz M
authors.initials: DM
authors.lastname: Lebensztejn
authors.forename: Aldona
authors.initials: A
authors.lastname: Wierzbicka
authors.forename: Piotr
authors.initials: P
authors.lastname: Socha
authors.forename: Maciej
authors.initials: M
authors.lastname: Pronicki
authors.forename: Elżbieta
authors.initials: E
authors.lastname: Skiba
authors.forename: Irena
authors.initials: I
authors.lastname: Werpachowska
authors.forename: Maciej
authors.initials: M
authors.lastname: Kaczmarski
mesh_terms: D000293:Adolescent; D015415:Biomarkers / Q000097:blood; D001706:Biopsy; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D005234:Fatty Liver / Q000097:blood / Q000473:pathology*; D005260:Female; D006801:Humans; D006820:Hyaluronic Acid / Q000097:blood*; D053538:Keratin-18 / Q000097:blood*; D007797:Laminin / Q000097:blood; D008099:Liver / Q000473:pathology; D008103:Liver Cirrhosis / Q000097:blood / Q000175:diagnosis* / Q000473:pathology; D008297:Male; D065626:Non-alcoholic Fatty Liver Disease; D009765:Obesity / Q000097:blood / Q000473:pathology; D010446:Peptide Fragments / Q000097:blood*; D012372:ROC Curve; D055815:Young Adult
chemical_list: D015415:Biomarkers; D053538:Keratin-18; D007797:Laminin; C561463:M30 cytokeratin-18 peptide, human; D010446:Peptide Fragments; D006820:Hyaluronic Acid