title: Different precore/core mutations of hepatitis B interact with, limit, or favor liver fibrosis severity.
abstract: OBJECTIVE
  The impact of basal core promoter (BCP) and precore (PC) mutants of the hepatitis B virus (HBV) on liver disease severity remains controversial. The aim of the present study was to screen BCP and PC mutations in 252 HBV surface antigen (HBsAg) positive carriers in France and to assess relationships between these mutations and severe fibrosis.
  
  
  METHODS
  Direct sequencing of the precore/core gene was used to detect A1762T/G1764A and G1757A mutations in the BCP and G1896A and G1899A mutations in the PC region.
  
  
  RESULTS
  The prevalences of A1762T/G1764A, G1757A, G1896A, and G1899A mutations were 34.1%, 38.7%, 54.9%, and 29.3% (P < 0.001), respectively. The independent predictors of severe fibrosis (≥F3 Metavir) were older age (P < 0.001), male gender (P = 0.012), elevated alanine aminotransferase (P < 0.001), and the double A1762T/G1764A mutant with no other mutations (P = 0.011). Interestingly, the association of the G1899A mutation with the double A1762T/G1764A mutant significantly counteracted the deleterious effect of the sole double A1762T/G1764A mutant (odds ratio [OR] = 0.28 vs. OR = 3.55, respectively, P = 0.028).
  
  
  CONCLUSIONS
  Patients with the A1762T/G1764A mutation have a higher risk of severe fibrosis. The G1899A mutation is a protective factor against severe fibrosis that counteracted the deleterious effect of the A1762T/G1764A mutation. Finally, host phenotypic and HBV genotypic markers independently predict fibrosis severity.
authors.affiliation: Laboratory of Virology, University Hospital & LUNAM University and HIFIH laboratory, UPRES EA 3859, SFR 4208, Angers, France. alducancelle@chu-angers.fr.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Ducancelle
authors.affiliation: Laboratory of Virology, University Hospital & LUNAM University and HIFIH laboratory, UPRES EA 3859, SFR 4208, Angers, France.
authors.forename: Adeline
authors.initials: A
authors.lastname: Pivert
authors.affiliation: Liver-Gastroenterology Department, University Hospital & LUNAM University and HIFIH laboratory, UPRES EA 3859, SFR 4208, Angers, France.
authors.forename: Sandrine
authors.initials: S
authors.lastname: Bertrais
authors.affiliation: Liver-Gastroenterology Department, University Hospital & LUNAM University and HIFIH laboratory, UPRES EA 3859, SFR 4208, Angers, France.
authors.forename: Jérôme
authors.initials: J
authors.lastname: Boursier
authors.affiliation: Laboratory of Virology, University Hospital & LUNAM University and HIFIH laboratory, UPRES EA 3859, SFR 4208, Angers, France.
authors.forename: Viorica
authors.initials: V
authors.lastname: Balan
authors.affiliation: Laboratory of Virology, University Hospital & LUNAM University and HIFIH laboratory, UPRES EA 3859, SFR 4208, Angers, France.
authors.forename: Pascal
authors.initials: P
authors.lastname: Veillon
authors.affiliation: Laboratory of Virology, University Hospital & LUNAM University and HIFIH laboratory, UPRES EA 3859, SFR 4208, Angers, France.
authors.forename: Hélène
authors.initials: H
authors.lastname: le Guillou-Guillemette
authors.affiliation: Laboratory of Virology, Pontchaillou Hospital, Rennes University Hospital, Rennes, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Thibault
authors.affiliation: Laboratory of Virology, Amiens University Hospital, and EA 4294, Amiens, France.
authors.forename: Sandrine
authors.initials: S
authors.lastname: Castelain
authors.affiliation: Laboratory of Virology, Bichat Claude Bernard Hospital, Paris-Diderot University, Paris, France.
authors.forename: Bénédicte
authors.initials: B
authors.lastname: Roquebert
authors.affiliation: Laboratory of Virology, Hôtel Dieu Hospital & LUNAM University, and EA4271, Nantes, France.
authors.forename: Marianne
authors.initials: M
authors.lastname: Coste-Burel
authors.affiliation: Laboratory of Virology, Beaujon Hospital & University (HUPNVS), Paris, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Mackiewicz
authors.affiliation: Laboratory of Virology, Nancy Hospital & University, Vandoeuvre-les-Nancy, France.
authors.forename: Evelyne
authors.initials: E
authors.lastname: Schvoerer
authors.affiliation: Virology Department, Reference Center of Neuromuscular Disease, Grenoble University Hospital, La Tronche, France.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Larrat
authors.affiliation: Laboratory of Virology, Saint Louis Hospital & University, Paris, France.
authors.forename: Sarah
authors.initials: S
authors.lastname: Maylin
authors.affiliation: Laboratory of Virology, UMR Inserm 1092, Dupuytren Hospital & University, Limoges, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Alain
authors.affiliation: Liver-Gastroenterology Department, Dupuytren Hospital & University, Limoges, France.
authors.forename: Véronique
authors.initials: V
authors.lastname: Loustaud-Ratti
authors.affiliation: Laboratory of Virology, University Hospital of Paris Seine-Saint-Denis, Avicenne, Associated with the National Reference Center for Viral Hepatitis B, C and Delta in France, Bobigny, France.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Gordien
authors.affiliation: Laboratory of Virology, Saint Antoine University Hospital, Paris, France.
authors.forename: Joël
authors.initials: J
authors.lastname: Gozlan
authors.affiliation: Laboratory of Virology, Robert Debré Hospital, Reims, France.
authors.forename: Véronique
authors.initials: V
authors.lastname: Brodard
authors.affiliation: Laboratory of Virology, Henri Mondor Hospital, National Reference Centre for Viral Hepatitis B, C and Delta, and Inserm U955, Créteil, France.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Chevaliez
authors.affiliation: Liver-Gastroenterology Department, University Hospital & LUNAM University and HIFIH laboratory, UPRES EA 3859, SFR 4208, Angers, France.
authors.forename: Paul
authors.initials: P
authors.lastname: Calès
authors.affiliation: Laboratory of Virology, University Hospital & LUNAM University and HIFIH laboratory, UPRES EA 3859, SFR 4208, Angers, France.
authors.forename: Françoise
authors.initials: F
authors.lastname: Lunel-Fabiani
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D004279:DNA, Viral / Q000032:analysis / Q000235:genetics; D005260:Female; D006514:Hepatitis B Surface Antigens / Q000235:genetics; D006515:Hepatitis B virus / Q000235:genetics* / Q000472:pathogenicity; D019694:Hepatitis B, Chronic / Q000150:complications / Q000821:virology*; D006801:Humans; D008103:Liver Cirrhosis / Q000821:virology*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011401:Promoter Regions, Genetic / Q000235:genetics; D012307:Risk Factors; D012720:Severity of Illness Index; D012737:Sex Factors; D014774:Virulence / Q000235:genetics
chemical_list: D004279:DNA, Viral; D006514:Hepatitis B Surface Antigens
keywords: A1762T/G1764A; BCP mutation; G1896A; G1899A; HBV genotype; Hepatitis B; PC mutation; fibrosis