Evolution of the hepatitis B virus gene during chronic infection in seven patients

J Med Virol. 1994 Jun;43(2):148-54. doi: 10.1002/jmv.1890430209.


We analyzed the evolution of the precore/core gene of hepatitis B virus (HBV) over a period of 6 to 11 years in seven patients with chronic HBV infection, who exhibited a variety of clinical features. Sequence analysis revealed the following results: (1) HBeAg to anti-HBe seroconversion was correlated roughly with the occurrence of precore-defective mutants, and several years appeared to be required for complete replacement of wild types by mutants; (2) core gene mutations preceded precore-defective mutations and tended to increase with time, although not cumulatively. They occurred not only during serum alanine aminotransferase (ALT) elevations but also after ALT returned to normal; (3) ALT fluctuations appeared to subside with complete replacement of the wild type by the mutant type and/or substantial accumulation of core gene mutations; (4) unexpectedly, the anti-HBe-positive "healthy" carrier was found to harbor the wild type precore gene, as did the HBeAg-positive "healthy" carrier; however, the core gene of the former evolved at a rapid rate; and (5) a partial deletion was recognized in the core gene at the onset of fatal hepatic failure in one patient. Thus, the precore/core mutation was closely related with the clinical features in the patients.

MeSH terms

  • Adolescent
  • Adult
  • Amino Acid Sequence
  • Base Sequence
  • Chronic Disease
  • Female
  • Genes, Viral / genetics*
  • Hepatitis B / microbiology*
  • Hepatitis B virus / genetics*
  • Humans
  • Male
  • Middle Aged
  • Molecular Sequence Data
  • Mutation / genetics
  • Polymerase Chain Reaction
  • Sequence Analysis, DNA
  • Time Factors