title: Validation of liver fibrosis biomarker (FibroTest) for assessing liver fibrosis progression: proof of concept and first application in a large population.
abstract: OBJECTIVE
  Time-dependent statistics have been used to assess liver fibrosis progression (LFP) in liver diseases from birth to first biopsy, in a limited number of patients. Non-invasive biomarkers such as FibroTest (FT) should allow the estimation of LFP on larger populations. We aimed at validating this concept by comparing LFP using FT vs. biopsy (P1) and then at applying the non-invasive method to a large population (P2).
  
  
  METHODS
  In P1, LFP was assessed using biopsy and FT in 2472 untreated patients: 770 with chronic hepatitis C, 723 with hepatitis B, 761 with non-alcoholic fatty liver disease (NAFLD), and 218 with alcoholic fatty liver disease (ALD). In P2, 342,346 interpretable FT prospectively measured were used. LFP was estimated using transition rates (cumulative hazard rate) to cirrhosis (F4) or to minimal fibrosis (>F0).
  
  
  RESULTS
  In P1, there was a significant concordance between FT and biopsy estimates of hazards with intraclass correlation (ICC)=0.961 (95% CI 0.948-0.970) and 0.899 (95% CI 0.135-0.969) for F4 and >F0, respectively. This concordance persisted according to the disease and the gender. The more rapid LFP to F4 (biopsy/FT) was observed for men with ALD (1.44/1.62), and the slower for women with NAFLD (0.09/0.02). In P2, the LFP started to increase for men at the age of 30 years. The cumulative fibrosis progression rate to minimal fibrosis in women crossed the "man curve" around the age of 80 years. The following factors were associated with LFP to F4 (all p<0.0001): male gender (Relative Risk=3.29), HIV co-infection (2.33), and residency in Middle East (2.67) or Eastern Europe (2.15).
  
  
  CONCLUSIONS
  Validated biomarkers such as FibroTest should allow powerful analysis of fibrosis progression in chronic liver diseases and better identification of risk factors.
authors.affiliation: APHP UPMC Paris Liver Center, Paris, France. tpoynard@teaser.fr
authors.forename: Thierry
authors.initials: T
authors.lastname: Poynard
authors.forename: Mona
authors.initials: M
authors.lastname: Munteanu
authors.forename: Olivier
authors.initials: O
authors.lastname: Deckmyn
authors.forename: Yen
authors.initials: Y
authors.lastname: Ngo
authors.forename: Fabienne
authors.initials: F
authors.lastname: Drane
authors.forename: Jean Marie
authors.initials: JM
authors.lastname: Castille
authors.forename: Chantal
authors.initials: C
authors.lastname: Housset
authors.forename: Vlad
authors.initials: V
authors.lastname: Ratziu
authors.forename: Françoise
authors.initials: F
authors.lastname: Imbert-Bismut
mesh_terms: D000328:Adult; D000367:Age Factors; D016632:Apolipoprotein A-I / Q000097:blood; D001663:Bilirubin / Q000097:blood; D015415:Biomarkers / Q000097:blood*; D001706:Biopsy; D018450:Disease Progression; D005061:Europe, Eastern / Q000208:ethnology; D005235:Fatty Liver, Alcoholic / Q000150:complications; D005260:Female; D006242:Haptoglobins / Q000378:metabolism; D019694:Hepatitis B, Chronic / Q000150:complications; D019698:Hepatitis C, Chronic / Q000150:complications; D006801:Humans; D008103:Liver Cirrhosis / Q000097:blood* / Q000209:etiology / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D008877:Middle East / Q000208:ethnology; D000511:alpha-Macroglobulins / Q000378:metabolism; D005723:gamma-Glutamyltransferase / Q000097:blood
chemical_list: D016632:Apolipoprotein A-I; D015415:Biomarkers; D006242:Haptoglobins; D000511:alpha-Macroglobulins; D005723:gamma-Glutamyltransferase; D001663:Bilirubin