Subject: 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

Journal of Gastroenterology and Hepatology
Volume 19 Issue 5 Page 541 - May 2004
doi:10.1111/j.1440-1746.2003.03318.x


HEPATOLOGY
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
HISASHI NAKASHIMA*, NORIHIRO FURUSYO*,, NORIHIKO KUBO*, KENICHIRO
KASHIWAGI*, YOSHITAKA ETOH*, SEIZABUROU KASHIWAGI and JUN HAYASHI*,

Abstract

Background and Aim: 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.

Conclusion: Genotype C might be one of the worse prognostic markers
in
patients with chronic HBV infection, possibly because of mutation in
the CP
region.