Double point mutation in the core promoter region of hepatitis B virus (HBV) genotype C may be related to liver deterioration in patients with chronic HBV infection.
OBJECTIVE
Hepatitis B virus (HBV) genotype C has a more severe pathogenesis than genotype B in Japan. We retrospectively investigated the relationship between HBV genotype and the core promoter (CP) (nt 1762 and 1764) and precore (PreC) (nt 1896) mutations of the HBV genome.


METHODS
A total of 129 Japanese patients (42 genotype B and 87 genotype C) with chronic HBV infection, living in two different geographical areas in Japan, were evaluated (mean follow-up period 10.1 +/- 3.8 years). In 2000, CP and PreC HBV mutations were analyzed by direct sequencing from sera. Hepatitis B e antigen (HBeAg), HBV DNA and serial alanine aminotransferase (ALT) changes were followed and determined using serological methods.


RESULTS
Genotype C patients had significantly higher rates of HBeAg (40.2%vs 2.4%), HBV DNA positivity (75.9%vs 7.1%) and ALT abnormality (71.3%vs 11.9%) than genotype B patients (all P < 0.05). Among genotype B patients, CP wild type (92.9%) was predominant and PreC mutation (88.1%) was predominant. However, among genotype C patients, CP mutation (75.9%) was predominant and PreC mutation (66.7%) was predominant. The CP mutation was found significantly more in genotype C than in genotype B (P < 0.05). Of the 67 patients with ALT abnormality, five (7.5%) genotype B and 62 (92.5%) genotype C patients (31 HBeAg positive and 31 negative) were found. Among the 31 genotype C patients who were HBeAg positive, the combination of CP mutation and PreC wild (54.8%) was predominant, while among the remaining 31 genotype C patients who were HBeAg negative, the combination of CP mutation and PreC mutant (71.0%) was predominant.


CONCLUSIONS
Genotype C might be one of the worse prognostic markers in patients with chronic HBV infection, possibly because of mutation in the CP region.
Nakashima
Hisashi
H
Departments of Environmental Medicine and Infectious Disease, Faculty of Medical Sciences, Kyushu University Hospital, Higashi-ku, Fukuoka 812-8582, Japan.
Furusyo
Norihiro
N
Kubo
Norihiko
N
Kashiwagi
Kenichiro
K
Etoh
Yoshitaka
Y
Kashiwagi
Seizaburou
S
Hayashi
Jun
J
D000328:Adult; D000410:Alanine Transaminase / Q000097:blood; D004279:DNA, Viral / Q000032:analysis; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D016679:Genome, Viral; D005838:Genotype; D006515:Hepatitis B virus / Q000235:genetics*; D019694:Hepatitis B, Chronic / Q000235:genetics* / Q000821:virology*; D006801:Humans; D007564:Japan; D008111:Liver Function Tests; D008297:Male; D008875:Middle Aged; D017354:Point Mutation; D011401:Promoter Regions, Genetic; D012189:Retrospective Studies
D004279:DNA, Viral; D000410:Alanine Transaminase