title: Clinical significance and evolution of core promoter and precore mutations in HBeAg-positive patients with HBV genotype B and C: a longitudinal study.
abstract: OBJECTIVE
  The aims of this longitudinal study were to investigate whether the clinical outcome and evolution of core promoter and precore mutations were different during hepatitis B e antigen (HBeAg) seroconversion between hepatitis B virus (HBV) genotypes B and C in HBeAg-positive patients with chronic hepatitis B.
  
  
  METHODS
  The core promoter and precore sequences were determined from serial sera of 156 HBeAg-positive patients with chronic HBV infection.
  
  
  RESULTS
  In HBV genotype C, the T1762/A1764 mutant was detected earlier than the A1896 mutant, and the frequency was significantly higher than in HBV genotype Ba over the entire follow-up period. In HBV genotype Ba, A1896 was found earlier than the T1762/A1764 mutant, and the frequency was significantly higher than in genotype C only before HBeAg seroconversion, and the A1896 mutant played an important role in HBeAg seroconversion in HBV genotype Ba. In addition, the T1846 variant was an independent factor associated with HBeAg seroconversion. Furthermore, HBV genotype C was associated with the development of G or C1753 and T1766/A1768 mutations, and the reactivation of hepatitis after HBeAg seroconversion. Based on Cox's regression analysis, the significant risk factors of liver cirrhosis were older age at entry [hazard ratio (HR)=1.085, 95% confidence interval (CI)=1.036-1.136, P=0.001], alanine transaminase (ALT) >80 U/l (HR=3.48, 95% CI=1.37-8.86, P=0.009), and the T1762/A1764 mutant (HR=5.54, 95% CI=2.18-14.08, P<0.001).
  
  
  CONCLUSIONS
  Our study showed that different HBV genotypes were associated with various mutations in the core promoter and precore regions during HBeAg seroconversion. T1762/A1764 mutation could be useful in predicting clinical outcomes in HBeAg-positive patients with HBV infection.
authors.affiliation: Division of Hepatogastroenterology, Chang Gung University College of Medicine, Kaohsiung, Taiwan.
authors.forename: Chien-Hung
authors.initials: CH
authors.lastname: Chen
authors.forename: Chuan-Mo
authors.initials: CM
authors.lastname: Lee
authors.forename: Chao-Hung
authors.initials: CH
authors.lastname: Hung
authors.forename: Tsung-Hui
authors.initials: TH
authors.lastname: Hu
authors.forename: Jing-Houng
authors.initials: JH
authors.lastname: Wang
authors.forename: Jyh-Chwan
authors.initials: JC
authors.lastname: Wang
authors.forename: Sheng-Nan
authors.initials: SN
authors.lastname: Lu
authors.forename: Chi-Sin
authors.initials: CS
authors.lastname: Changchien
mesh_terms: D000328:Adult; D000367:Age Factors; D000410:Alanine Transaminase / Q000097:blood; D004279:DNA, Viral / Q000097:blood*; D005260:Female; D005500:Follow-Up Studies; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006512:Hepatitis B Core Antigens / Q000235:genetics*; D006513:Hepatitis B e Antigens / Q000235:genetics*; D006515:Hepatitis B virus / Q000235:genetics*; D019694:Hepatitis B, Chronic / Q000150:complications / Q000175:diagnosis* / Q000201:enzymology / Q000235:genetics / Q000276:immunology; D006801:Humans; D053208:Kaplan-Meier Estimate; D008103:Liver Cirrhosis / Q000201:enzymology / Q000235:genetics / Q000276:immunology / Q000821:virology*; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011379:Prognosis; D011401:Promoter Regions, Genetic; D016016:Proportional Hazards Models; D018570:Risk Assessment; D012307:Risk Factors; D012720:Severity of Illness Index; D013997:Time Factors
chemical_list: D004279:DNA, Viral; D006512:Hepatitis B Core Antigens; D006513:Hepatitis B e Antigens; D000410:Alanine Transaminase