Hepatitis B virus core protein mutations are concentrated in B cell epitopes in progressive disease and in T helper cell epitopes during clinical remission

J Infect Dis. 1997 May;175(5):1093-100. doi: 10.1086/516447.


The distribution and temporal and clinical features of amino acid substitutions of the core protein of hepatitis B (HB) virus were analyzed, using at least 2 sequential samples from 27 patients. Six patients seroconverted from HBe antigen (HBeAg)-positive to anti-HBe-positive (3 went into remission), and 21 were continuously anti-HBe positive with progressive hepatitis. Precore mutations, which terminate HBeAg translation, all appeared by the second sample. Most core mutations occurred between the first and second samples; significantly fewer occurred after the second. In seroconverters who went into remission, mutations occurred in the T helper epitope from aa 50 to 69 (P = .00045); for anti-HBe-positive patients with ongoing disease, mutations occurred in B cell epitopes (P = .0007 for aa 74-83). An ineffective anti-HBc B cell response accounts for ongoing disease and selection of mutations after seroconversion. In those who remit, mutations in the major T helper epitope allow immune escape, thus minimizing immune-mediated hepatitis.

MeSH terms

  • Adult
  • Aged
  • Amino Acid Sequence
  • DNA, Viral / blood
  • Epitopes / analysis
  • Female
  • Greece
  • Hepatitis B / blood
  • Hepatitis B / immunology*
  • Hepatitis B Core Antigens / genetics*
  • Hepatitis B Core Antigens / immunology
  • Hepatitis B e Antigens / genetics*
  • Hepatitis B e Antigens / immunology
  • Hepatitis B virus / genetics*
  • Humans
  • Male
  • Middle Aged
  • Point Mutation*
  • T-Lymphocytes, Helper-Inducer / immunology*


  • DNA, Viral
  • Epitopes
  • Hepatitis B Core Antigens
  • Hepatitis B e Antigens