Ryo Fukuda, Rumi Mohammad, Sachiko Hamamoto, Norihisa Ishimura, Shunnji Ishihara, Shuji Akagi, Makoto Watanabe, Yoshikazu Kinoshita

Clinical Relevance of Precore and Basal Core Promoter Variants of Hepatitis B Virus During Natural Hepatitis B e Antigen Seroconversion May Be Overstated

  • Gastroenterology
  • Pediatrics, Perinatology and Child Health
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ABSTRACTBackgroundClinical relevance of nucleotide changes in precore and basal core promoters in the hepatitis B virus genome during hepatitis B e antigen seroconversion may be overstated. The authors investigated the existence and changes in the relative proportion of variants to wild virus that occur with seroconversion.MethodsSera from 30 school‐aged long‐term hepatitis B virus carriers, including 11 tested before and after seroconversion during 1 to 8 years of follow‐up, were evaluated for variations in nucleotide sequences of the basal core promoter (T1762 and A1764), precore region (A1869), and carboxyl‐terminus of the X region of the hepatitis B virus genome using an amplification refractory mutation detection system with mutant‐specific primers.ResultsAll variants were found to already exist before seroconversion at various wild‐type/mutant ratios. The positive rates of these variants were not changed with loss of hepatitis B e antigen. Although there was a relative increase in the concentration of these mutants in wild‐type/mutant mixed populations, most patients with only a wild‐type population maintained the same pattern after loss of hepatitis B e antigen.ConclusionsOur results indicate that hepatitis B virus exists as a quasi species, and correlations of nucleotide sequences with clinical and serologic findings must be done with caution.

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