title: High level of hepatitis B virus DNA after HBeAg-to-anti-HBe seroconversion is related to coexistence of mutations in its precore and basal core promoter.
abstract: OBJECTIVE
  G1896A mutation in precore or A1762T/G1764A mutations in basal core promoter are suspected to be responsible for patients with detectable level of HBV DNA in serum after seroconversion from HBeAg to anti-HBe. However, G1896A variant has impaired, while A1762T/G1764A variant may have intact replication ability. They themselves or their coexistence status may play different roles in such meaningless seroconversion. For these reasons, the significances of these two types of mutations were comparatively investigated in this study.
  
  
  METHODS
  One hundred and sixty-five sera with positive anti-HBe and HBV DNA were collected from different patients. Mutations of G1896A and A1762T/G1764A among these serum samples were detected using competitively differentiated PCR. HBV DNA was demonstrated using real-time quantitative PCR.
  
  
  RESULTS
  G1896A and/or A1762T/G1764A mutations were detected in 89.1% (147/165) out of patients with detectable HBV DNA in serum after HBeAg-to-anti-HBe seroconversion. The positive rate of G1896A variants was significantly higher than that of A1762T/G1764A mutations (77.6% vs 50.3%, chi2 = 26.61, P<0.01). The coexistence positive rate of these two types of mutations was 38.8% (64/165). Coexistence mutations were found in 77.1% (64/83) out of sera with A1762T/G1764A mutations, and in 50.0% (64/128) out of sera with G1896A mutation. Compared with variants with G1896A mutation only, the coexistence mutations were predominant in patients with high level of serum HBV DNA, and related to higher total bilirubin, lower serum albumin and progressive liver diseases.
  
  
  CONCLUSIONS
  The coexistence of G1896A mutation and A1762T/G1764A mutations is very common, and responsible for the major cases with high level of HBV DNA in serum and progressive liver diseases after HBeAg-to-anti-HBe seroconversion. This coexistence mutation variant may have higher pathogenicity and replication ability.
authors.affiliation: Department of Infectious Diseases, Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510630, Guangdong Province, China. xiaomoupeng@hotmail.com
authors.forename: Xiao-Mou
authors.initials: XM
authors.lastname: Peng
authors.forename: Gui-Mei
authors.initials: GM
authors.lastname: Huang
authors.forename: Jian-Guo
authors.initials: JG
authors.lastname: Li
authors.forename: Yang-Su
authors.initials: YS
authors.lastname: Huang
authors.forename: Yong-Yu
authors.initials: YY
authors.lastname: Mei
authors.forename: Zhi-Liang
authors.initials: ZL
authors.lastname: Gao
mesh_terms: D000328:Adult; D004279:DNA, Viral / Q000097:blood*; D005260:Female; D006510:Hepatitis B Antibodies / Q000097:blood*; D006513:Hepatitis B e Antigens / Q000276:immunology*; D006515:Hepatitis B virus / Q000235:genetics* / Q000276:immunology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics; D019562:Viral Load
chemical_list: D004279:DNA, Viral; D006510:Hepatitis B Antibodies; D006513:Hepatitis B e Antigens