Editorial Board:
Emmet B. Keeffe, MD (Chair);
Anna Lok,
MD; Brian McMahon, MD; Albert Min, MD; Myron
Tong, MD; Naoky Tsai, MD; Bruce Tung, MD
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HBV Watch™
Timely Information for Practicing Physicians
TOPIC REVIEW: HBV
GENOTYPE TESTING
Research tool or ready
for “prime time.”
Seven genotypes of HBV (A to G) have been identified, and several small studies
of the influence of genotype on clinical outcomes have been reported. Genotype
A is mainly found in the USA, Northern Europe, India, and Africa. Genotypes B and C are
predominantly found in Asia. Two subtypes of genotype B, Bj
found in Japan and Ba
found elsewhere in Asia,
are being characterized. Genotype D is mainly found in Southern Europe, the Middle East, and India. Genotype E is found in parts of Africa, G in the USA and Europe, and F appears to be a “New World” HBV found in indigenous Native
Americans of Central and South America. Last year a purported genotype H was identified in
persons from Central
America
and California, but this finding has not been verified. All HBV genotypes
have been found in the USA, with genotypes A and C being most
common, followed by genotypes B and D. Preliminary data suggests that HBV
genotype may be related to clinical outcomes. The HBV genome transcribes only
four polypeptides: core, surface, polymerase and X protein (a transactivating
protein that may be involved in pathogenesis of HCC). HBV consists of a
circular, partially double-stranded DNA containing overlapping genes where
sections of the genome are involved in the transcription of more than one
protein product. In addition, certain mutations in the HBV genome, which
determine viral and host outcomes, may be in part genotype-related and directly
contribute to disease outcome. The pre-core mutation, which blocks production
of HBeAg, occurs frequently in genotypes B, C and D around the time of HBeAg
seroconversion, but is less common in genotype A. Studies from Italy and Greece
have suggested that genotype D is associated with anti-HBe negative chronic
hepatitis, which is more severe and occurs later in life, with the pre-core
mutant emerging as the predominant viral population. In one study, a mutation
in the core promoter/HBX region of the HBV genome was associated with an
increased risk of developing HCC. Some studies from Asia have suggested genotype C is more
frequently associated with severe liver disease and HCC than is genotype B, and
genotype B is associated with seroconversion from HBeAg to anti-HBe at a
younger age than genotype C. However, a few studies have contradicted the
former finding. Recent studies have also suggested that response to interferon
is better in genotype B, and lamivudine resistance emerges more frequently in
genotype Ba. While the role of HBV genotypes in liver
disease outcomes deserves further study and may lead to the identification of
patient subgroups that warrant closer follow-up for the development of chronic
hepatitis or HCC, testing for HBV genotypes is not yet clinically applicable.
We will periodically update the readers of HBV Watch on research findings
regarding HBV genotypes and their clinical relevance.
ANTIVIRAL THERAPY
Treatment of hepatitis B and C dual infection. Chun-Jen Liu and colleagues report the treatment of 24 patients with
chronic hepatitis seropositive for both HBsAg and anti-HCV with IFN-a2a (6
MU thrice weekly for 12 weeks and then 3 MU thrice weekly for another 12 weeks)
plus ribavirin 1200 mg daily. Twenty-one patients were serum HCV RNA-positive
and 3 HCV RNA-negative. Among the 21 coinfected HCV RNA-positive patients, the
HCV clearance rate 24 weeks post-treatment was similar to that observed in 30
patients with chronic HCV alone treated with the same therapeutic regimen (43%
and 60%, respectively; p = 0.63). The serum ALT normalization rate for the
dually infected patients at 24 weeks post-treatment was 43% in patients who
were HCV RNA-positive and 0% in patients who were HCV RNA-negative.
Interestingly, there was a change in the dominant virus in a few of the
patients. These results suggest that combination IFN-a2a plus
ribavirin therapy can achieve sustained HCV RNA clearance in dually infected
patients comparable to that attained in patients with chronic HCV alone
infection. (Liu C-J, et al. Hepatology 2003;37:568-576)
Lamivudine treatment of children. Corina Hartman et al conducted a study in
which 20 children (ages 8.5 to 19 years) with chronic HBV infection
unresponsive to prior interferon therapy were treated with lamivudine 3
mg/kg/day (maximum, 100 mg/day). After 1 year of treatment, the median serum
ALT level had decreased from 1.5 to 0.9 times the upper limit of normal, and
HBV DNA levels had declined in 95% of patients. Eight (44%) of 18 evaluable
patients achieved sustained undetectable HBV DNA levels. YMDD mutants were
detected in 11 (65%) of 17 evaluable children, and only one child became
HBeAg-negative. These data show that
lamivudine treatment suppressed HBV replication and improved serum ALT values
in children with chronic HBV who had failed to respond to interferon. However,
lamivudine therapy was associated with a high rate of YMDD mutant formation and
a low rate of HBeAg seroconversion. (Hartman C, et al. Pediatr Infect Dis J 2003;22:224-229)
HBV VACCINATION
Newborn vaccination
program in Taiwan.
A universal HBV vaccination program for newborns was initiated in Taiwan in 1985. Hans Hsienhong Lin and others reviewed a series of annual surveys for
HBsAg performed in high school freshman (N = 10,194) in eastern Taiwan. They found that from 1991 to 2001
the HBsAg carrier rate had decreased from 20.3% to 4.4% in males and from 14.3%
to 2.4% in females. These findings demonstrate that the Taiwanese national
vaccination program is effective and that protection against HBV has persisted
for ³15 years. (Lin HH, et al. J Med Virol 2003;69:471-474)
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