title: Serum connective tissue markers as predictors of advanced fibrosis in patients with chronic hepatitis B and D.
abstract: OBJECTIVE
  Liver biopsy to assess fibrosis is invasive and prone to sampling error. While algorithms of serum markers to predict fibrosis stage have been described for chronic hepatitis C, these cannot be applied equally well to hepatitis B.
  
  
  METHODS
  We therefore determined 9 serum fibrosis markers, liver biochemical tests and ultrasound parameters in 109 consecutive adult patients with chronic hepatitis B and D. All patients had compensated liver disease. Using the METAVIR score, advanced disease was defined as fibrosis stage ≥F2, and active inflammation as grade ≥A2. A gold standard was created considering splenomegaly and/or platelets <150,000 as indicators of advanced fibrosis irrespective of histology. Area under receiver operating characteristics curves was used for assessment of single markers and odds ratio for their combinations.
  
  
  RESULTS
  Patients with advanced disease were older, had lower albumin, higher gamma glutamyl transferase and lower platelet. Levels of 6 of the 9 fibrosis markers, tissue inhibitor of metalloproteinases-1, procollagen type III aminoterminal propeptide, matrix metalloproteinase-2, laminin, hyaluronan and collagen IV correlated with advanced fibrosis. Markers useful for fibrosis prediction also predicted marked inflammation. Using the gold standard, age, prothrombin time, gamma glutamyl transferase and albumin were independent predictors of fibrosis with odds ratio's of 3.11, 4.18, 3.35 and 5.25, respectively. Their combined use predicted fibrosis with an odds ratio of 228.8. Tissue inhibitor of metalloproteinases-1 and hyaluronan were powerful predictors of fibrosis (Odds ratio's of 8.65 and 8.38). Their combined use revealed an odds ratio of 28.6, when compared with the gold standard.
  
  
  CONCLUSIONS
  In conclusion, advanced liver fibrosis in chronic hepatitis B and D may be predicted with use of these two fibrosis markers.
authors.affiliation: Department of Gastroenterology, University of Ankara School of Medicine, Ankara, Turkey. gulserenseven@yahoo.com
authors.forename: Gülseren
authors.initials: G
authors.lastname: Seven
authors.forename: Senem Ceren
authors.initials: SC
authors.lastname: Karatayli
authors.forename: S Kenan
authors.initials: SK
authors.lastname: Köse
authors.forename: Mustafa
authors.initials: M
authors.lastname: Yakut
authors.forename: Gökhan
authors.initials: G
authors.lastname: Kabaçam
authors.forename: Murat
authors.initials: M
authors.lastname: Törüner
authors.forename: Aylin Okçu
authors.initials: AO
authors.lastname: Heper
authors.forename: Michael
authors.initials: M
authors.lastname: Voelker
authors.forename: Esra
authors.initials: E
authors.lastname: Erden
authors.forename: A Mithat
authors.initials: AM
authors.lastname: Bozdayi
authors.forename: Ozden
authors.initials: O
authors.lastname: Uzunalımoğlu
authors.forename: Hakan
authors.initials: H
authors.lastname: Bozkaya
authors.forename: Cihan
authors.initials: C
authors.lastname: Yurdaydin
authors.forename: Detlef
authors.initials: D
authors.lastname: Schuppan
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D015415:Biomarkers / Q000097:blood; D001706:Biopsy; D005260:Female; D019694:Hepatitis B, Chronic / Q000097:blood* / Q000000981:diagnostic imaging; D019701:Hepatitis D, Chronic / Q000097:blood* / Q000000981:diagnostic imaging; D006801:Humans; D006820:Hyaluronic Acid / Q000097:blood*; D008103:Liver Cirrhosis / Q000097:blood* / Q000000981:diagnostic imaging; D008111:Liver Function Tests; D016015:Logistic Models; D008297:Male; D011237:Predictive Value of Tests; D012372:ROC Curve; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000097:blood*; D014463:Ultrasonography
chemical_list: D015415:Biomarkers; D019715:Tissue Inhibitor of Metalloproteinase-1; D006820:Hyaluronic Acid