Different precore/core mutations of hepatitis B interact with, limit, or favor liver fibrosis severity.

Abstract

BACKGROUND AND AIM:

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: Alexandra Ducancelle, Adeline Pivert, Sandrine Bertrais, Jérôme Boursier, Viorica Balan, Pascal Veillon, Hélène le Guillou-Guillemette, Vincent Thibault, Sandrine Castelain, Bénédicte Roquebert, Marianne Coste-Burel, Vincent Mackiewicz, Evelyne Schvoerer, Sylvie Larrat, Sarah Maylin, Sophie Alain, Véronique Loustaud-Ratti, Emmanuel Gordien, Joël Gozlan, Véronique Brodard, Stéphane Chevaliez, Paul Calès, Françoise Lunel-Fabiani
• Journal: Journal of gastroenterology and hepatology (J Gastroenterol Hepatol) Vol. 31 Issue 10 Pg. 1750-1756 (Oct 2016) ISSN: 1440-1746 [Electronic] Australia
• PMID: 26992056 (Publication Type: Journal Article, Multicenter Study)
• Copyright: © 2016 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

Chemical References

• DNA, Viral
• Hepatitis B Surface Antigens

Topics

• Adult
• Age Factors
• Aged
• DNA, Viral (analysis, genetics)
• Female
• Hepatitis B Surface Antigens (genetics)
• Hepatitis B virus (genetics, pathogenicity)
• Hepatitis B, Chronic (complications, virology)
• Humans
• Liver Cirrhosis (virology)
• Male
• Middle Aged
• Mutation
• Promoter Regions, Genetic (genetics)
• Risk Factors
• Severity of Illness Index
• Sex Factors
• Virulence (genetics)