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.
Type de document :
Article dans une revue
Journal of Gastroenterology and Hepatology, Wiley, 2016, 31 (10), pp.1750 - 1756. 〈http://onlinelibrary.wiley.com/doi/10.1111/jgh.13338/abstract〉. 〈10.1111/jgh.13338〉
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https://hal.univ-lorraine.fr/hal-01482298
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Soumis le : vendredi 3 mars 2017 - 14:36:07
Dernière modification le : jeudi 5 avril 2018 - 10:36:59

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Alexandra Ducancelle, Adeline Pivert, Sandrine Bertrais, Jérôme Boursier, Viorica Balan, et al.. Different precore/core mutations of hepatitis B interact with, limit, or favor liver fibrosis severity. Journal of Gastroenterology and Hepatology, Wiley, 2016, 31 (10), pp.1750 - 1756. 〈http://onlinelibrary.wiley.com/doi/10.1111/jgh.13338/abstract〉. 〈10.1111/jgh.13338〉. 〈hal-01482298〉

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