title: Staging chronic hepatitis C in seven categories using fibrosis biomarker (FibroTest™) and transient elastography (FibroScan®).
abstract: OBJECTIVE
  FibroTest™ (FT) and Transient Elastography (TE) have been validated as non-invasive markers of METAVIR fibrosis stages from F0 to F4 using biopsy, and as prognostic markers of liver related mortality in patients with chronic hepatitis C. The aim was to extend the validation of FT and TE as markers of critical steps defined by occurrence of cirrhosis without complications (F4.1), esophageal varices (F4.2), and severe complications (F4.3): primary liver cancer, variceal bleeding, or decompensation (ascites, encephalopathy, or jaundice).
  
  
  METHODS
  The updated individual data of 3927 patients (1046 cirrhotics) without complications at baseline were pooled from three prospective cohorts called "EPIC", "Paris", and "Bordeaux" cohorts.
  
  
  RESULTS
  At 5 years, among 501 patients without varices at baseline (F4.1) varices occurred in 19 patients [F4.2 incidence of 4.0% (95% CI 2.2-5.8)]. The predictive performance (AUROC) of FT was 0.77 (0.66-0.84; p<0.001). At 10 years severe complications occurred in 203 patients, [F4.3 incidence of 13.4% (9.6-17.1)], including primary liver cancer in 84 patients [6.4% (3.5-9.3)]. FT was predictive (Cox adjusted on treatment) of severe complications [AUROC 0.79 (76-82); p<0.0001], including primary liver cancer [AUROC 0.84 (80-87); p<0.0001]. Similarly TE was predictive of severe complications [AUROC 0.77 (72-81); p<0.0001], including primary liver cancer [AUROC 0.86 (81-90); p<0.0001].
  
  
  CONCLUSIONS
  FibroTest™ and TE increase were associated with the occurrence of all severe complications including hepatocellular carcinoma, hepatic insufficiency, and variceal bleeding. FibroTest™ increase was also associated with the occurrence of esophageal varices.
authors.affiliation: Assistance Publique Hôpitaux de Paris (AP-HP), University Pierre Marie Curie (UPMC), INSERM, UMR_S 938, Liver Center, Paris, France. Electronic address: tpoynard@teaser.fr.
authors.forename: Thierry
authors.initials: T
authors.lastname: Poynard
authors.affiliation: University of Bordeaux, Bordeaux, France; Service de Biochimie Métabolique, Groupe Hospitalier Pitié-Salpêtrière (GHPS), AP-HP, Paris, France.
authors.forename: Julien
authors.initials: J
authors.lastname: Vergniol
authors.affiliation: BioPredictive, Paris, France.
authors.forename: Yen
authors.initials: Y
authors.lastname: Ngo
authors.affiliation: University of Bordeaux, Bordeaux, France; Service de Biochimie Métabolique, Groupe Hospitalier Pitié-Salpêtrière (GHPS), AP-HP, Paris, France.
authors.forename: Juliette
authors.initials: J
authors.lastname: Foucher
authors.affiliation: BioPredictive, Paris, France.
authors.forename: Mona
authors.initials: M
authors.lastname: Munteanu
authors.affiliation: University of Bordeaux, Bordeaux, France; Service de Biochimie Métabolique, Groupe Hospitalier Pitié-Salpêtrière (GHPS), AP-HP, Paris, France.
authors.forename: Wassil
authors.initials: W
authors.lastname: Merrouche
authors.affiliation: University of Milano, 1st Division of Gastroenterology, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Colombo
authors.affiliation: Infectious Disease Unit, GHPS, AP-HP, Paris, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Thibault
authors.affiliation: University of Miami Center for Liver Diseases, University of Miami School of Medicine, Miami, FL, USA.
authors.forename: Eugene
authors.initials: E
authors.lastname: Schiff
authors.affiliation: Former employees Merck Sharp & Dohme Corp, Whitehouse Station, NJ, USA.
authors.forename: Clifford A
authors.initials: CA
authors.lastname: Brass
authors.affiliation: Former employees Merck Sharp & Dohme Corp, Whitehouse Station, NJ, USA.
authors.forename: Janice K
authors.initials: JK
authors.lastname: Albrecht
authors.affiliation: Assistance Publique Hôpitaux de Paris (AP-HP), University Pierre Marie Curie (UPMC), INSERM, UMR_S 938, Liver Center, Paris, France.
authors.forename: Marika
authors.initials: M
authors.lastname: Rudler
authors.affiliation: BioPredictive, Paris, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Deckmyn
authors.affiliation: Assistance Publique Hôpitaux de Paris (AP-HP), University Pierre Marie Curie (UPMC), INSERM, UMR_S 938, Liver Center, Paris, France.
authors.forename: Pascal
authors.initials: P
authors.lastname: Lebray
authors.affiliation: Assistance Publique Hôpitaux de Paris (AP-HP), University Pierre Marie Curie (UPMC), INSERM, UMR_S 938, Liver Center, Paris, France.
authors.forename: Dominique
authors.initials: D
authors.lastname: Thabut
authors.affiliation: Assistance Publique Hôpitaux de Paris (AP-HP), University Pierre Marie Curie (UPMC), INSERM, UMR_S 938, Liver Center, Paris, France.
authors.forename: Vlad
authors.initials: V
authors.lastname: Ratziu
authors.affiliation: University of Bordeaux, Bordeaux, France; Service de Biochimie Métabolique, Groupe Hospitalier Pitié-Salpêtrière (GHPS), AP-HP, Paris, France.
authors.forename: Victor
authors.initials: V
authors.lastname: de Ledinghen
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000209:etiology; D015331:Cohort Studies; D018450:Disease Progression; D054459:Elasticity Imaging Techniques / Q000379:methods*; D004932:Esophageal and Gastric Varices / Q000175:diagnosis / Q000209:etiology; D005260:Female; D048550:Hepatic Insufficiency / Q000209:etiology; D019698:Hepatitis C, Chronic / Q000145:classification / Q000150:complications / Q000473:pathology*; D006801:Humans; D008103:Liver Cirrhosis / Q000145:classification / Q000150:complications / Q000473:pathology*; D008113:Liver Neoplasms / Q000209:etiology; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011446:Prospective Studies
keywords: Cirrhosis complications; Elastography; FibroTest™; Fibrosis stages; Hepatocellular carcinoma; Prognostic factors; Surrogate markers