title: High association of T1858-G1896 precore mutations with impaired base pairing and high hepatitis B virus DNA levels in HBeAg-negative chronically infected patients.
abstract: The progression of liver disease in hepatitis B virus (HBV) infection is fostered by active virus replication. Mutations in the basal core promoter (BCP) and precore (PC) regions of the HBV genome are known to have an impact on viral replication. The aim of the present study was to assess the correlation of mutation profiles in the BCP and PC regions with the viral load in HBeAg-negative chronically infected patients. The HBV genotype, BCP/PC mutations, serum HBV DNA levels, and associated serological markers were analyzed in 92 HBeAg-negative chronically infected patients. Sequence analysis of the BCP and PC regions revealed variability of 19% and 24.1%, respectively. This variability was primarily associated with five critical positions (1753, 1762, 1764, 1896 and 1899). An elevated HBV viral load (>20,000 IU/ml) was classically correlated with F2-F4 liver fibrosis, elevated serum alanine aminotransferase levels, 1762/1764 and 1753 combination mutations, and surprisingly, with an 1858T-1896G double mutation that impairs base pairing at the base of the bulge in the ε encapsidation signal. An analysis of covariance confirmed the independent nature of the relationship between the 1858T-1896G double mutation and the HBV viral load. In conclusion, independently of conventional parameters, this study demonstrates that a high serum HBV DNA level was also associated with PC 1858-1896 mutations. These BCP/PC mutations may have important clinical implications as predictive factors for HBV DNA increase.
authors.affiliation: Virology Department, Centre de Biologie Humaine, Centre Hospitalo-Universitaire Amiens Picardie, 80054, Amiens Cedex, France. sandrine.castelain@u-picardie.fr.|EA4294, Université de Picardie Jules Verne, Amiens, France. sandrine.castelain@u-picardie.fr.
authors.forename: Sandrine
authors.initials: S
authors.lastname: Castelain
authors.affiliation: Virology Department, Centre de Biologie Humaine, Centre Hospitalo-Universitaire Amiens Picardie, 80054, Amiens Cedex, France.|EA4294, Université de Picardie Jules Verne, Amiens, France.
authors.forename: Véronique
authors.initials: V
authors.lastname: Descamps
authors.affiliation: Virology Department, Centre de Biologie Humaine, Centre Hospitalo-Universitaire Amiens Picardie, 80054, Amiens Cedex, France.|EA4294, Université de Picardie Jules Verne, Amiens, France.
authors.forename: Etienne
authors.initials: E
authors.lastname: Brochot
authors.affiliation: EA4294, Université de Picardie Jules Verne, Amiens, France.
authors.forename: François
authors.initials: F
authors.lastname: Helle
authors.affiliation: Virology Department, Centre de Biologie Humaine, Centre Hospitalo-Universitaire Amiens Picardie, 80054, Amiens Cedex, France.|EA4294, Université de Picardie Jules Verne, Amiens, France.
authors.forename: Gilles
authors.initials: G
authors.lastname: Duverlie
authors.affiliation: Hepatology Department, Centre Hospitalo-Universitaire Amiens Picardie, Amiens, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Nguyen-Khac
authors.affiliation: Virology Department, Centre de Biologie Humaine, Centre Hospitalo-Universitaire Amiens Picardie, 80054, Amiens Cedex, France.|EA4294, Université de Picardie Jules Verne, Amiens, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: François
mesh_terms: D000914:Antibodies, Viral / Q000097:blood; D020029:Base Pairing; D015415:Biomarkers; D004279:DNA, Viral / Q000097:blood*; D015967:Gene Expression Regulation, Viral; D005838:Genotype; D006513:Hepatitis B e Antigens / Q000097:blood*; D006515:Hepatitis B virus / Q000235:genetics*; D019694:Hepatitis B, Chronic / Q000097:blood* / Q000821:virology*; D006801:Humans; D009154:Mutation
chemical_list: D000914:Antibodies, Viral; D015415:Biomarkers; D004279:DNA, Viral; D006513:Hepatitis B e Antigens