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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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EPIDEMIOLOGY
Genotype and precore/core variants.
Chi-Jen Chu and colleagues of the U.S. HBV Epidemiology Study
Group conducted a nationwide study that enrolled 694 consecutive patients with
chronic HBV infection seen in 17 U.S. liver centers during a 1-year
period to investigate the associations of HBV genotype and HBV precore/core
variants with patient demographics, serum HBV DNA levels, and severity of liver
disease. All seven HBV genotypes were found
to be present in the U.S., and a strong association between
ethnicity and HBV genotype was observed (P
< 0.001). The most common genotypes
were A (34.7%) and C (30.8%). Patients with genotype A were most likely to
have wild-type sequences in both the precore and core promoter regions, while
patients with genotype D were most likely to have mutations in both
regions. Precore and core promoter
variants were detected in 27% and 44% of patients, respectively, and were more
often found in HBeAg-negative than in HBeAg-positive patients (P < 0.001). These variants were also associated with
higher serum HBV DNA levels in HBeAg-negative patients. In addition, patients with core promoter
variants were more likely to have hepatic decompensation. These results suggest that HBV genotype
differences and precore/core promoter variants may account for heterogeneity of
disease severity and response to antiviral treatment among U.S. patients with HBV infection. Physicians also need to be aware of the
common occurrence of HBV precore and core promoter variants and their
association with HBeAg-negative chronic hepatitis B. (Chu C-J et al. Gastroenterology
2003;125:444-451. Chu C-J et al. Hepatology 2003;38:619-628.)
LAMIVUDINE THERAPY
Long-term treatment enhances durability of HBeAg
loss. Soo Hyung Ryu and coworkers at the Asian Medical Center at the University of Ulsan College of Medicine (Seoul, South Korea) administered lamivudine (100 mg/d)
to 85 patients with chronic HBV infection for at least an additional 24 months
after they had achieved HBeAg seroconversion.
Serum HBeAg and/or HBV DNA reappeared in 15 patients (18%) during the
period of additional lamivudine therapy.
The median time to viral breakthrough was 15 months (range, 5-32 mo) after viral response.
Sixty-one patients were evaluable for analysis following the cessation
of lamivudine therapy. Among these
patients, serum HBV DNA and HBeAg were detected in 16 patients (26%) and 8
patients (13%), respectively, at the end of follow-up. The cumulative reappearance rates of serum
HBV DNA at 6 months, 1 year, and 2 years were 15%, 21%, and 31%,
respectively. The cumulative
reappearance rates of serum HBeAg at 6 months, 1 year, and 2 years were 11%,
13%, and 16%, respectively. Most
relapses (81%) occurred within 12 months after the cessation of lamivudine therapy
and were associated with an elevation of serum ALT (94%). Multivariate analysis identified older age (P = 0.03) and the presence of precore
mutation before the initiation of therapy (P
= 0.04) to be independent predictors for post-treatment viral relapse. This investigation was a single-arm study that
did not include a control treatment arm.
However, the breakthrough rates observed in this study were lower than
those reported in previous Asian trials, suggesting that additional lamivudine
treatment may increase the durability of lamivudine-induced HBeAg
seroconversion. Further randomized,
controlled trials are needed to confirm these results. (Ryu SH et al. J Hepatol 2003;39:614-619.)
Transient restoration of antiviral
T-cell responses. Previous studies have shown that
lamivudine therapy can induce the recovery of antiviral T-cell responses in
patients with chronic HBV infection. Carolina Boni
and others conducted a long-term analysis of the immune response in 12
lamivudine-treated patients with HBeAg-positive chronic hepatitis B to
determine the durability of the recovery of T-cell responsiveness associated
with lamivudine treatment. They found
that the restoration of CD4- and CD8-mediated reactivity against HBV induced by
lamivudine occurred early. However, this
period of immune restoration was soon followed by a persistent decline in T-cell
responsiveness that began within 5-6 months of the start of treatment. The transient nature of the immune
reconstitution induced by lamivudine indicates that therapeutic stimulation of
HBV-specific T-cell responses to complement lamivudine treatment needs to be
done soon after initiation of lamivudine therapy. The short duration of the recovery of T-cell
responsiveness may also give the hepatitis B virus a better chance to
reactivate after lamivudine is withdrawn. (Boni C et al. J Hepatol 2003;39:595-605.)
HBV VACCINATION
Lack of association with multiple
sclerosis. An association between the
administration of HBV vaccine and the onset or relapse of multiple sclerosis
and other demyelinating diseases has been suggested by previous studies. Thus Vittorio Demicheli et al performed a literature review that included
9 published and 2 unpublished comparative studies (5 case-control studies, 1
case crossover study, 1 cohort study, and 4 ecological studies). Noncomparative
studies and those not testing for an association between HBV vaccination and
multiple sclerosis were not included. Although point estimates showed variable values, no analysis of
either a single study or pooled studies demonstrated a statistically
significant association.
Therefore, this review failed to find conclusive evidence of an
association between the administration of HBV vaccination and multiple
sclerosis. (Demicheli
V et al. J Viral Hepat
2003;10:343-344.)
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