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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™
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Timely Information for Practicing Physicians
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FEBRUARY 2005
HEPATITIS B VIRUS (HBV) VACCINATION
Need for boosters and significance of HBsAg escape mutants. HBV vaccine is recommended by the WHO
for all newborn infants, as well as for adolescents, health care workers, and
other groups at risk. Two issues regarding HBV vaccine remain uncertain: (1)
how long will protection last, and (2) will mutant viruses that are not
protected by the current vaccines arise. Two recent studies address these
issues. Chung-Yi Lu and others at National Taiwan University measured anti-HBs titers
in 2 cohorts of children 15 years after neonatal immunization with
plasma-derived HBV vaccines. Group A comprised 78 children who were born to
HBeAg+, HBsAg carrier mothers and developed protective levels of anti-HBs.
Group B comprised 113 apparently healthy children whose anti-HBs titers after
vaccination were unknown. The authors
found that anti-HBs antibodies were undetectable
in 29.9% of children in Group A and 62.4% of children in Group B. Anti-HBc was
detected in 33.3% of children in Group A and 4.4% of children in Group B. One
HBsAg carrier was detected in Group A and 4 in Group B. After a single booster
dose of HBV vaccination, only 2.7% and 3.3% of children remained anti-HBs– in Groups A and B,
respectively. This investigation demonstrated a waning immunity in a large
proportion of children 15 years after neonatal immunization and suggested that
booster vaccinations may be needed in seronegative subjects. However, it must
be emphasized that initial immune response was not documented in Group B
children, and it is possible that some children had inadequate rather than
waning anti-HBs titer. More
long-term and larger studies are needed to better delineate how long protection
lasts. H-Y Hsu et al. conducted 3 nationwide serosurveys in Taiwan to determine the prevalence of HBV S
mutants in the population. Mutations that occur in the “a” determinant of the
gene that codes for HBsAg, the region where the immunogenic epitopes that are
neutralized by anti-HBs are located, may render the virus undetectable by
commercial assays and could allow the virus to escape neutralization by
anti-HBs induced by conventional vaccines. Two types of mutations may occur:
one that alters the antigenicity of one of the amino acids in HBsAg (most
commonly involving a glycin- to-arginine change occurring at AA position 145),
or a mutation that decreases expression of HBsAg. The first of these mutations
results in a mutant HBV strain that may escape detection by monoclonal enzyme
immunoassays but can often be detected by polyclonal assays. The second
mutation can result in circulating levels of HBsAg below the threshold of
detection of commercial assays. These HBV variants have been reported to occur infrequently
in immunized groups and among infants who received HBV vaccine and hepatitis B
immune globulin. The study by Hsu et al. tested persons who were HBsAg+ or had
anti-HBc for the presence of HBV DNA. In those who were HBV DNA+, the
prevalence of variants ranged from 8% at baseline to 20% to 28% at 5 to 15
years after the initiation of a universal infant HBV vaccine program. However,
the prevalence of these variants in the entire population tested was <1% and
did not increase with time. When these variants
are found in individuals, the levels of HBV DNA are very low (2 to 3 logs),
making it unlikely that HBV infection will be passed to others. Further
studies are needed to determine if S variant infections can be transmitted and
whether current vaccines provide cross-protection against mutants. (Lu C-Y Hepatology
2004;40:1415-1420; Hsu H-Y, et al. Gut
2004;53:1499-1503)
HEPATOCELLULAR
CARCINOMA (HCC)
Effectiveness
of prophylactic lamivudine administration. Previous
studies have shown that HBeAg positivity was associated with exacerbation of
liver damage in patients with HBV-related HCC who were treated with
transhepatic arterial infusion chemotherapy (THAIC). In the current study,
Hiroaki Nagamatsu et al. retrospectively investigated the effect of prophylactic
lamivudine therapy in 8 patients with HBV-related HCC who were treated at the Kurume
University
Hospital
in Japan
with THAIC from 2000 to 2002. Lamivudine 100 mg daily was administered for an
average of 28 days prior to chemotherapy and throughout chemotherapy. All 8
patients were HBsAg+ and HBeAg+. Nine HBeAg+ patients with HBV-related HCC who
received THAIC from 1993 to 1999 without lamivudine prophylaxis served as
historical controls. Lamivudine therapy resulted in significant reductions of HBV
DNA levels. Increases in ALT, AST, and total bilirubin levels and prolongation
of prothrombin times occurred in control patients; 6 had exacerbation of liver
damage, and 3 died of liver disease due to HBV reactivation. None of the
patients given lamivudine prophylaxis developed exacerbation of liver damage.
Results in this small study suggest that prophylactic lamivudine therapy may
prevent exacerbation of liver damage due to chemotherapy-induced HBV
reactivation in HBeAg+ patients. (Nagamatsu H, et al. Am J Gastroenterol 2004;99:2369-2375)
LAMIVUDINE-RESISTANT
HBV
Comparison
of adefovir and tenofovir. Florian van Bommel et
al. analyzed treatment of 53 consecutive patients with lamivudine-resistant HBV
infection with either adefovir (n=18) for 60 to 80 weeks
or tenofovir (n=35) for 72 to 130 weeks.
Of the tenofovir-treated patients, 21 were coinfected with HIV. Tenofovir
therapy was associated with an early suppression of HBV DNA, resulting in a
reduction of HBV DNA levels at week
48 to <105 copies/mL in 100% of tenofovir-treated patients, vs.
44% of adefovir-treated patients. Both agents were well tolerated, with no
evidence of phenotypic resistance. These data suggest that tenofovir may be a
potentially effective alternative treatment for patients with lamivudine-resistant
HBV infection. Controlled trials with larger numbers of patients are warranted.
(van Bommel F, et al. Hepatology
2004;40:1421-1425)
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