title: The Enhanced Liver Fibrosis (ELF) score: normal values, influence factors and proposed cut-off values.
abstract: OBJECTIVE
  Progressive fibrosis is a major cause of morbidity and mortality in chronic liver disease. To replace liver biopsy for disease staging, multiple serum markers are under evaluation with multiparametric panels yielding the most promising results. The Enhanced Liver Fibrosis (ELF) score is an ECM marker set consisting of tissue inhibitor of metalloproteinases 1 (TIMP-1), amino-terminal propeptide of type III procollagen (PIIINP) and hyaluronic acid (HA) showing good correlations with fibrosis stages in chronic liver disease.
  
  
  METHODS
  The ELF score was measured in 400 healthy controls and 79 chronic hepatitis C patients using an ADVIA Centaur automated system. The ELF score was calculated using the published algorithm combining TIMP-1, PIIINP and HA values. Patients' fibrosis stage was defined histologically. ROC analyses were performed to study marker validity. Reference values and influence factors for the ELF score were validated.
  
  
  RESULTS
  ELF score reference values ranged from 6.7 to 9.8 and were significantly higher for men vs. women (7.0-9.9 vs. 6.6-9.3, respectively). Afternoon values were slightly higher than morning values (6.7-9.9 vs. 6.6-9.5, respectively). Age was a notable influence factor. We identified three cut-off values: 7.7 for a high sensitivity exclusion of fibrosis, 9.8 for a high specificity identification of fibrosis (sensitivity 69%, specificity 98% for moderate fibrosis), and 11.3 to discriminate cirrhosis (sensitivity 83%, specificity 97%). ELF score validity was superior to the results of the single tests.
  
  
  CONCLUSIONS
  The ELF score can predict moderate fibrosis and cirrhosis. However, influence factors such as gender and age need to be taken into account.
authors.affiliation: Institute of Clinical Chemistry, Hannover Medical School, Hannover, Germany. lichtinghagen.ralf@mh-hannover.de
authors.forename: Ralf
authors.initials: R
authors.lastname: Lichtinghagen
authors.forename: Daniel
authors.initials: D
authors.lastname: Pietsch
authors.forename: Heike
authors.initials: H
authors.lastname: Bantel
authors.forename: Michael P
authors.initials: MP
authors.lastname: Manns
authors.forename: Korbinian
authors.initials: K
authors.lastname: Brand
authors.forename: Matthias J
authors.initials: MJ
authors.lastname: Bahr
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000465:Algorithms; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D018450:Disease Progression; D005260:Female; D019698:Hepatitis C, Chronic / Q000097:blood* / Q000473:pathology*; D006801:Humans; D006820:Hyaluronic Acid / Q000097:blood; D008103:Liver Cirrhosis / Q000097:blood* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000097:blood; D011347:Procollagen / Q000097:blood; D012372:ROC Curve; D012016:Reference Values; D012720:Severity of Illness Index; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000097:blood; D055815:Young Adult
chemical_list: D015415:Biomarkers; D010446:Peptide Fragments; D011347:Procollagen; C560822:TIMP1 protein, human; D019715:Tissue Inhibitor of Metalloproteinase-1; C041876:procollagen Type III-N-terminal peptide; D006820:Hyaluronic Acid
keywords: ALT; AP; AST; AUC; CHC; CI; Cirrhosis; ECM; ELF; ELF score; HA; HCV; HSC; Hyaluronate; Hyaluronic acid; Kcal; Liver fibrosis; PIIINP; ROC; TIMP; TIMP-1; alanine aminotransferase; alkaline phosphatase; amino-terminal propeptide of type III procollagen; area under the curve.; aspartate aminotransferase; chronic hepatitis C; confidence interval; enhanced liver fibrosis; extracellular matrix; gamma-glutamyltransferase; hepatic stellate cells; hepatitis C virus; hyaluronic acid; kilocalories; receiver operating characteristics; tissue inhibitor of metalloproteinases 1; γGT