Association of core promoter/precore mutations and viral load in e antigen-negative chronic hepatitis B patients

J Viral Hepat. 2006 May;13(5):336-42. doi: 10.1111/j.1365-2893.2005.00688.x.

Abstract

Apart from core promoter A1762T/G1764A and precore G1896A mutations, other hepatitis B virus (HBV) mutants are detected in hepatitis B e antigen (HBeAg)-negative chronic hepatitis B (CHB). The aim of this study was to determine the effects of those mutants on clinical manifestation and viral loads of genotypes B and C HBV. Seventy-nine HBeAg-negative CHB patients with hepatitis flare were enrolled in this study and their HBV precore/core region were sequenced. Serial biochemical profiles and viral loads were assessed and compared. Fifty-three patients (67%) were infected by genotype B HBV and 26 (33%) were infected by genotype C HBV. The clinical manifestation and HBV viral loads were comparable between the two groups. However, genotype B was significantly associated with precore G1896A mutation (92.5%), and more mutations within nucleotide 1809-1817 were detected in patients infected by genotype B as compared with those infected by genotype C (18.9%vs 3.8%). Most of the cases had mutations at the -2, -3 or -5 position from the precore AUG initiation codon. Triple core promoter mutations T1753C/A1762T/G1764A [corrected] appeared to be linked to genotype C rather than genotype B HBV (19.2%vs 1.9%; P = 0.013). In multivariate analysis, the presence of either triple core promoter 1753/1762/1764 mutation or nucleotide 1809-1817 mutation was the only factor associated with lower HBV viral load (<70 Meq/mL) (odds ratio = 9.01; 95% CI 1.11-71.43; P = 0.04). In conclusion, minor HBV variants with mutations in the core promoter and precore region were detectable in genotypes B and C. Such HBV variants are genotype specific and related to viraemia levels.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Alanine Transaminase / blood
  • DNA, Viral / chemistry
  • DNA, Viral / genetics
  • Female
  • Genotype
  • Hepatitis B / blood
  • Hepatitis B / immunology
  • Hepatitis B / virology*
  • Hepatitis B e Antigens / genetics
  • Hepatitis B e Antigens / immunology*
  • Hepatitis B virus / genetics*
  • Hepatitis B virus / immunology
  • Humans
  • Male
  • Middle Aged
  • Polymerase Chain Reaction
  • Polymorphism, Single Nucleotide
  • Promoter Regions, Genetic
  • RNA, Viral / blood
  • Sequence Analysis, DNA
  • Statistics, Nonparametric
  • Viral Load

Substances

  • DNA, Viral
  • Hepatitis B e Antigens
  • RNA, Viral
  • Alanine Transaminase