Association of hepatitis B viral precore mutations with fulminant hepatitis B in Japan

Virology. 1991 Nov;185(1):460-3. doi: 10.1016/0042-6822(91)90799-h.


We studied the precore DNA sequences of hepatitis B viral genomes in five patients with fulminant hepatitis B and in five with acute self-limited hepatitis B from Japan. Using the polymerase chain reaction, three to four independent HBV DNA clones from each patient were obtained and analyzed. We demonstrated that patients with fulminant hepatitis B carried HBV genomes with a G to A mutation at nucleotide positions 1898 (five of five patients; 18 of 18 clones, 100%) and 1901 (five of five patients; 12 of 18 clones, 66%) in the precore region. The first mutation results in an in-phase stop codon (TAG) in the precore open reading frame and the absence of HBeAg production. In contrast, a G to A mutation was found in 6 of 16 clones (37%) in position 1898 and in 0 of 16 clones (0%) in position 1901 from patients with acute self-limited hepatitis. We concluded that both of the precore mutations are commonly associated with fulminant hepatitis B and may contribute to the pathogenesis of fulminant hepatitis. A hypothetical model for the biological significance of these two mutations is proposed.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Base Sequence
  • Cloning, Molecular
  • Female
  • Genome, Viral*
  • Hepatitis B / microbiology*
  • Hepatitis B / physiopathology
  • Hepatitis B Surface Antigens / analysis
  • Hepatitis B e Antigens / analysis
  • Hepatitis B virus / genetics*
  • Hepatitis B virus / isolation & purification
  • Humans
  • Immunoglobulin M / analysis
  • Male
  • Middle Aged
  • Molecular Sequence Data
  • Mutation*
  • Oligodeoxyribonucleotides
  • Polymerase Chain Reaction / methods
  • Restriction Mapping


  • Hepatitis B Surface Antigens
  • Hepatitis B e Antigens
  • Immunoglobulin M
  • Oligodeoxyribonucleotides