Mutations in the basic core promoter region of hepatitis B virus. Relationship with precore variants and HBV genotypes in a Spanish population of HBV carriers

J Hepatol. 2004 Mar;40(3):507-14. doi: 10.1016/j.jhep.2003.11.015.

Abstract

Background/aims: To determine the prevalence and significance of hepatitis B virus (HBV) basic core promoter (BCP) mutations and to establish their relationship with precore (preC) mutations, HBV genotypes and HBV-DNA levels.

Methods: BCP and preC mutations and genotypes were determined by sequencing.

Results: Genomic analysis was performed in 129 (71%) of 182 patients. BCP mutations were detected in 83% of 18 HBeAg-negative (e-) chronic hepatitis B (CHB) patients with fluctuating ALT levels, and in 76% of 58 e- CHB with elevated ALT. The prevalence was lower and similar, 55% in 30 HBeAg-positive CHB (e+ CHB) with elevated ALT and in 23 e- inactive carriers. Frequency of preC mutations was higher in e- CHB (80%) than in e- inactive carriers (65%). Among e- CHB, patients with elevated ALT and preC mutations at nt 1896 showed highest HBV-DNA, regardless of BCP mutations. BCP mutations were similar in genotypes A and D, while preC mutations were most common in genotype D (82 vs. 40%). Simultaneous presence of the main BCP (1762, 1764) and preC (1896, 1899) mutations was associated with the degree of histological injury.

Conclusions: Combined BCP and preC mutational and genotype analysis provides clinically relevant information in the study of HBV infection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Alanine Transaminase / blood
  • Base Sequence
  • DNA, Viral / analysis
  • Female
  • Gene Frequency*
  • Genetic Variation*
  • Genotype
  • Hepatitis B e Antigens / blood
  • Hepatitis B virus / genetics*
  • Hepatitis B virus / immunology
  • Hepatitis B virus / physiology
  • Heterozygote*
  • Humans
  • Male
  • Middle Aged
  • Mutation*
  • Promoter Regions, Genetic / genetics
  • Protein Structure, Tertiary / genetics
  • Spain
  • Viral Core Proteins / genetics*
  • Virus Replication

Substances

  • DNA, Viral
  • Hepatitis B e Antigens
  • Viral Core Proteins
  • Alanine Transaminase