title: Staging chronic hepatitis B into seven categories, defining inactive carriers and assessing treatment impact using a fibrosis biomarker (FibroTest®) and elastography (FibroScan®).
abstract: OBJECTIVE
  The first aim was to extend the validation of FibroTest® (FT) and transient elastography (TE) as markers of occurrence of cirrhosis without complications (F4.1), oesophageal varices (F4.2), and severe complications (F4.3) in patients with chronic hepatitis B (CHB). The second aim was to validate a previous definition of an inactive carrier based on normal FT and ActiTest® (normal-FT-AT). The third aim was to assess the long-term dynamics of fibrosis in patients with sustained virological response.
  
  
  METHODS
  The 10-year updated individual data of 1434 patients were pooled from two prospective cohorts.
  
  
  RESULTS
  Of the 1312 patients without a history of complications, varices had occurred after 10 years in 14 patients (F4.2, incidence of 1.7%, 95% CI [0.6-2.8]), and severe complications in 25 (F4.3 3.7% [1.8-5.7]), including hepatocellular carcinoma (HCC) in 21 (3.7% [1.5-5.8]). Using Cox-multivariate analysis adjusted for treatment, viral load, HBeAg status and ALT, FT, and TE were predictive of liver complications (n=37; AUROC=0.83 [0.71-0.90]; p<0.0001) and (n=8/844; AUROC=0.82 [0.72-0.89]; p<0.0001) respectively. Normal FT-AT better identified patients with lower fibrosis progression than the ALT-based standard: 3/163 (1.8%) vs. 16/181 (8.8%; p=0.004) in the Paris cohort, and 5/195 (2.6%) vs. 15/228 (6.6%; p=0.05) in the Bordeaux cohort. Of the 582 responders, 23 had complications (incidence 6.2% [3.2-9.1]) including 19 HCC (5.8% [2.6-9.0]) and 10 with varices (2.6% [0.8-4.4]). Of the 138 responders with advanced fibrosis, only 31% (15-47%) had fibrosis regression.
  
  
  CONCLUSIONS
  FibroTest® and TE identified three categories of cirrhosis with increasing morbidity. Normal FibroTest® and ActiTest® were better able to identify inactive hepatitis B carriers than the standard definition. Despite virological response, the overall incidence of cirrhosis increased, with a remaining 5.8% risk of HCC.
authors.affiliation: Assistance Publique Hôpitaux de Paris (AP-HP), Groupe Hospitalier Pitié-Salpêtrière, Paris, France; University Pierre et Marie Curie (UPMC) University of Paris VI, Paris, France; INSERM, UMRS 938, Paris, France. Electronic address: tpoynard@teaser.fr.
authors.forename: Thierry
authors.initials: T
authors.lastname: Poynard
authors.affiliation: University of Bordeaux, Bordeaux, 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.
authors.forename: Juliette
authors.initials: J
authors.lastname: Foucher
authors.affiliation: Assistance Publique Hôpitaux de Paris (AP-HP), Groupe Hospitalier Pitié-Salpêtrière, Paris, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Thibault
authors.affiliation: BioPredictive, Paris, France.
authors.forename: Mona
authors.initials: M
authors.lastname: Munteanu
authors.affiliation: University of Bordeaux, Bordeaux, France.
authors.forename: Wassil
authors.initials: W
authors.lastname: Merrouche
authors.affiliation: Assistance Publique Hôpitaux de Paris (AP-HP), Groupe Hospitalier Pitié-Salpêtrière, Paris, France.
authors.forename: Pascal
authors.initials: P
authors.lastname: Lebray
authors.affiliation: Assistance Publique Hôpitaux de Paris (AP-HP), Groupe Hospitalier Pitié-Salpêtrière, 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), Groupe Hospitalier Pitié-Salpêtrière, Paris, France.
authors.forename: Hugo
authors.initials: H
authors.lastname: Perazzo
authors.affiliation: Assistance Publique Hôpitaux de Paris (AP-HP), Groupe Hospitalier Pitié-Salpêtrière, Paris, France.
authors.forename: Dominique
authors.initials: D
authors.lastname: Thabut
authors.affiliation: Assistance Publique Hôpitaux de Paris (AP-HP), Groupe Hospitalier Pitié-Salpêtrière, Paris, France.
authors.forename: Vlad
authors.initials: V
authors.lastname: Ratziu
authors.affiliation: University of Bordeaux, Bordeaux, France.
authors.forename: Victor
authors.initials: V
authors.lastname: de Ledinghen
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D006528:Carcinoma, Hepatocellular / Q000209:etiology; D002353:Carrier State / Q000097:blood / Q000175:diagnosis; D015331:Cohort Studies; D018450:Disease Progression; D054459:Elasticity Imaging Techniques; D004932:Esophageal and Gastric Varices / Q000209:etiology; D005260:Female; D019694:Hepatitis B, Chronic / Q000145:classification* / Q000150:complications / Q000175:diagnosis; D006801:Humans; D008103:Liver Cirrhosis / Q000097:blood / Q000175:diagnosis; D008113:Liver Neoplasms / Q000209:etiology; D008297:Male; D011446:Prospective Studies; D019562:Viral Load
chemical_list: D015415:Biomarkers
keywords: Chronic hepatitis B; Cirrhosis complications; Elastography; FibroSure; FibroTest®; Fibrosis stages; Hepatocellular carcinoma; Prognostic factors; Progression of fibrosis in virological responders; Regression fibrosis; Surrogate markers