HBeAg
Clearance Linked to HBV Pre-core and Core Mutations
Interaction
between hepatitis B virus (HBV) and the host immune system is critical to the
outcome of HBV infection, as the balance between HBV-specific immune response
and viral replication influence the course of disease. Selective immune pressure
may be associated with the emergence of mutations within pre-core and core regions
of HBV that affect successful control of viral replication.
As reported
at the recent annual meeting of the American Association for the Study of Liver
Diseases (AASLD), researchers from King's College London School of Medicine conducted
a study to investigate the presence of HBV pre-core and core mutations in children
with hepatitis B, and their relation to viral replication and HBV "e"
antigen (HBeAg) clearance.
The study included 69 children (median age 13.25
years) divided into 5 groups according to the presence or absence of HBeAg, HBV
surface antigen (HBsAg), and alanine aminotransferase (ALT) levels:
Group
A (immunotolerant):HBsAg+, HBeAg+, normal ALT (n = 33); Group B
(immunoactive): HBsAg+, HBeAg+, elevated ALT (n = 17); Group C (low
HBV replication):- HBsAg+, HBeAg-, normal ALT (n = 13); Group D (HBeAg
negative chronic hepatitis B): HBsAg+, HBeAg-, elevated ALT (n = 2); Group
E (self-limited hepatitis B): HBsAg-, HBeAg-, normal ALT (n = 4).
HBV
DNA was isolated from patients' serum samples. The presence of point mutations
within HBV pre-core and core promoter regions and amino acid substitutions within
immunodominant epitopes of HBV core gene were analyzed by direct sequencing. HBV
DNA viral load was quantified using real-time PCR.
Results
HBV DNA viral
load was significantly higher in groups A, B, and D when compared with groups
C and E (P = 0.001).
The total number of point mutations within HBV pre-core and core promoter regions
and the number of amino acid substitutions within the immunodominant epitopes
of HBV core gene were higher in HBeAg negative patients compared with HBeAg positive
children (P = 0.001 and 0.055, respectively).
There was a strong inverse correlation between the number of pre-core and core
regions mutations and the presence of HBeAg (r = -0.628, P = 0.001 and r = -0.341,
P = 0.005, respectively).
Results as mean ± SEM are presented in the table below.
Group
HBV DNA
Pre-core region
Core region
A
7.89 ± 0.22
2.17 ± 0.23
4.82 ± 0.38
B
6.81 ± 0.52
2.27 ± 0.40
5.88 ± 0.75
C
3.94 ± 0.26
5.42 ± 0.33
6.54 ± 0.48
D
7.45 ± 1.23
6.5 ± 0.50
8.00 ± 0.00
E
0
ND
ND
Conclusion
In
conclusion, the researchers wrote, "Clearance of HBeAg is associated with
a high number of mutations within pre-core and core regions of HBV, suggesting
that the selective pressure of the immune system on hepatitis B virus is responsible
for the emergence of mutations within HBV pre-core and core regions."
Institute
of Liver Studies, King's College London School of Medicine, London, England, UK.
11/17/06
Reference I
Carey, A Giannattasio, S Bansal, and others. Clearance of HBeAg is linked with
emergence of mutations within pre-core and core regions of hepatitis B virus in
paediatric patients. 57th AASLD. Boston, MA. October 27-31, 2006. Abstract 671.
HBV DNA viral
load was significantly higher in groups A, B, and D when compared with groups
C and E (P = 0.001). 
