Mutation preventing formation of hepatitis B e antigen in patients with chronic hepatitis B infection

Lancet. 1989 Sep 9;2(8663):588-91. doi: 10.1016/s0140-6736(89)90713-7.


Some patients with chronic hepatitis B virus (HBV) infection are HB e antigen (HBeAg) negative, have circulating HBV particles, and often have especially severe chronic hepatitis. To test the hypothesis that the absence of HBeAg production may be due to a change in the nucleotide sequence of the pre-core region of the genome, 18 Greek and 3 non-Greek patients positive for HB surface antigen underwent direct sequencing of HBV-DNA amplified from sera. In 7 out of 8 HBeAg negative patients, two mutations (guanosine to adenosine) were found in the terminal two codons of the pre-core region, giving the sequence TAGGACATG. The remaining patient had the first mutation only. The sequence TGGGGCATG was found in 4 of 5 of the HBeAg positive patients. The first mutation results in a translational stop codon that is predicted to result in failure to produce HBeAg. The rest of the pre-core region in the HBeAg negative patients was otherwise homologous to that of the HBeAg positive patients and to known sequences.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Base Sequence
  • Codon / genetics
  • DNA, Viral / analysis
  • DNA, Viral / genetics*
  • Gene Amplification
  • Greece
  • Hepatitis B / epidemiology
  • Hepatitis B / genetics*
  • Hepatitis B / immunology
  • Hepatitis B Antibodies / analysis
  • Hepatitis B Surface Antigens / immunology
  • Hepatitis B e Antigens / analysis
  • Hepatitis B e Antigens / genetics*
  • Hepatitis B e Antigens / immunology
  • Hepatitis B virus / genetics
  • Hepatitis B virus / physiology*
  • Hepatitis, Chronic / epidemiology
  • Hepatitis, Chronic / genetics*
  • Hepatitis, Chronic / immunology
  • Humans
  • Molecular Sequence Data
  • Mutation*
  • Protein Biosynthesis


  • Codon
  • DNA, Viral
  • Hepatitis B Antibodies
  • Hepatitis B Surface Antigens
  • Hepatitis B e Antigens