title: Precore/Core promoter variants to predict significant fibrosis in both HBeAg positive and negative chronic hepatitis B.
abstract: OBJECTIVE
  Assessing fibrosis is essential in patients with chronic hepatitis B (CHB). The objective was to investigate the relationship between fibrosis, host and viral factors to identify non-invasive markers of significant fibrosis in a large cohort of unselected, well-characterized, treatment-naïve CHB patients.
  
  
  METHODS
  Three hundred and seventy-seven HBsAg-positive patients (97 HBeAg-positive and 280 HBeAg-negative, genotypes A to E) who had liver biopsy were consecutively included. Host and viral factors (ALT, HBsAg and HBV-DNA levels, HBV genotype and precore (PC)/basal core promoter (BCP) variants) were determined on the day of the biopsy. Fibrosis stage was assessed using METAVIR score.
  
  
  RESULTS
  Thirty-nine percent of the patients had significant fibrosis (METAVIR F ≥ 2). On univariate analysis, the stages of fibrosis F ≥ 2 were associated with older age (P < 0.0001), male gender (P = 0.01), higher ALT and HBV-DNA levels (P < 0.0001 and P = 0.0003, respectively), the presence of BCP (P < 0.0001) and BCP/PC variants (P < 0.0001). On multivariate analysis, age (P < 0.0001), the presence of HBV variants (P < 0.0001), HBV-DNA level (P = 0.0006) and ALT level (P = 0.02) were independently associated with significant fibrosis. The diagnostic accuracy of the combination (age, ALT, HBV-DNA, HBV variants) in predicting fibrosis F ≥ 2 was evidenced by a c-index of 0.76 (CI 95% 0.71-0.81).
  
  
  CONCLUSIONS
  We identified strong independent risk factors (age, ALT, HBV-DNA, HBV variants) predicting significant fibrosis (F ≥ 2) independently of HBeAg status in patients with CHB. Patients with BCP variants have a higher risk of severe liver disease. The detection of these mutants may help to predict significant fibrosis (F ≥ 2).
authors.affiliation: Team Physiopathology and Treatment of Viral Hepatitis, Centre de Recherche sur l'Inflammation, Laboratory of Excellence Labex INFLAMEX, INSERM, UMR-1149, University Denis Diderot Paris 7, PRES Sorbonne Paris Cité, Paris, France.
authors.forename: Martine
authors.initials: M
authors.lastname: Lapalus
authors.affiliation: IAME, Inserm UMR-1137, University Denis Diderot Paris 7, Sorbonne Paris Cité, Paris, France.|Department of Biostatistics, Bichat Hospital, AP-HP, Paris, France.
authors.forename: Cédric
authors.initials: C
authors.lastname: Laouenan
authors.affiliation: Team Physiopathology and Treatment of Viral Hepatitis, Centre de Recherche sur l'Inflammation, Laboratory of Excellence Labex INFLAMEX, INSERM, UMR-1149, University Denis Diderot Paris 7, PRES Sorbonne Paris Cité, Paris, France.
authors.forename: Ana-Carolina
authors.initials: AC
authors.lastname: Cardoso
authors.affiliation: Team Physiopathology and Treatment of Viral Hepatitis, Centre de Recherche sur l'Inflammation, Laboratory of Excellence Labex INFLAMEX, INSERM, UMR-1149, University Denis Diderot Paris 7, PRES Sorbonne Paris Cité, Paris, France.
authors.forename: Emilie
authors.initials: E
authors.lastname: Estrabaud
authors.affiliation: Team Physiopathology and Treatment of Viral Hepatitis, Centre de Recherche sur l'Inflammation, Laboratory of Excellence Labex INFLAMEX, INSERM, UMR-1149, University Denis Diderot Paris 7, PRES Sorbonne Paris Cité, Paris, France.
authors.forename: Roberto J
authors.initials: RJ
authors.lastname: Carvalho-Filho
authors.affiliation: Team Physiopathology and Treatment of Viral Hepatitis, Centre de Recherche sur l'Inflammation, Laboratory of Excellence Labex INFLAMEX, INSERM, UMR-1149, University Denis Diderot Paris 7, PRES Sorbonne Paris Cité, Paris, France.
authors.forename: Qian
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Team Physiopathology and Treatment of Viral Hepatitis, Centre de Recherche sur l'Inflammation, Laboratory of Excellence Labex INFLAMEX, INSERM, UMR-1149, University Denis Diderot Paris 7, PRES Sorbonne Paris Cité, Paris, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Lada
authors.affiliation: Team Physiopathology and Treatment of Viral Hepatitis, Centre de Recherche sur l'Inflammation, Laboratory of Excellence Labex INFLAMEX, INSERM, UMR-1149, University Denis Diderot Paris 7, PRES Sorbonne Paris Cité, Paris, France.
authors.forename: Kevin
authors.initials: K
authors.lastname: Appourchaux
authors.affiliation: Service d'Hépatologie, PMAD Hôpital Beaujon, AP-HP, Clichy, France.
authors.forename: Feryel
authors.initials: F
authors.lastname: Mouri
authors.affiliation: Service d'Hépatologie, PMAD Hôpital Beaujon, AP-HP, Clichy, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Boyer
authors.affiliation: Service d'Anatomie Pathologique, Hôpital Beaujon, Clichy, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Bedossa
authors.affiliation: Team Physiopathology and Treatment of Viral Hepatitis, Centre de Recherche sur l'Inflammation, Laboratory of Excellence Labex INFLAMEX, INSERM, UMR-1149, University Denis Diderot Paris 7, PRES Sorbonne Paris Cité, Paris, France.|Service d'Hépatologie, PMAD Hôpital Beaujon, AP-HP, Clichy, France.
authors.forename: Tarik
authors.initials: T
authors.lastname: Asselah
authors.affiliation: Team Physiopathology and Treatment of Viral Hepatitis, Centre de Recherche sur l'Inflammation, Laboratory of Excellence Labex INFLAMEX, INSERM, UMR-1149, University Denis Diderot Paris 7, PRES Sorbonne Paris Cité, Paris, France.
authors.forename: Michelle
authors.initials: M
authors.lastname: Martinot-Peignoux
authors.affiliation: Team Physiopathology and Treatment of Viral Hepatitis, Centre de Recherche sur l'Inflammation, Laboratory of Excellence Labex INFLAMEX, INSERM, UMR-1149, University Denis Diderot Paris 7, PRES Sorbonne Paris Cité, Paris, France.|Service d'Hépatologie, PMAD Hôpital Beaujon, AP-HP, Clichy, France.
authors.forename: Patrick
authors.initials: P
authors.lastname: Marcellin
mesh_terms: D000328:Adult; D015415:Biomarkers; D004279:DNA, Viral / Q000097:blood; D005260:Female; D005355:Fibrosis; D005838:Genotype; D006514:Hepatitis B Surface Antigens / Q000097:blood; D006513:Hepatitis B e Antigens / Q000097:blood*; D006515:Hepatitis B virus / Q000235:genetics*; D019694:Hepatitis B, Chronic / Q000150:complications*; D006801:Humans; D008099:Liver / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009154:Mutation; D011379:Prognosis; D011401:Promoter Regions, Genetic; D012307:Risk Factors; D055815:Young Adult
chemical_list: D015415:Biomarkers; D004279:DNA, Viral; D006514:Hepatitis B Surface Antigens; D006513:Hepatitis B e Antigens
keywords: basal core promoter variant; chronic hepatitis B; non-invasive marker; precore variant; significant fibrosis