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Hepadna
Updates
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UPDATE
#1:
Are
Boosters for the Hepatitis B Vaccine Necessary?
Zanetti,
Alessandro, et al. “Long term immunogenicity of hepatitis
B vaccination and policy for booster: an Italian multicentre study.”
Lancet. 15 October 2005; 366: 1379-84.
A
study published in the Lancet in October 2005 concluded that immunological
memory after immunization for Hepatitis B persists for more than
10 years, and furthermore, that booster doses for the Hepatitis
B vaccine are not necessary to ensure long-term protection. These
conclusions were based on data from studies on infants and adolescents
in Italy, where universal anti-hepatitis-B vaccination of infants
and adolescents was implemented in 1991. This study involved a total
of 1212 children and 446 Air Force recruits, who were vaccinated
during infancy and adolescence. They found that sufficient levels
of protective antibodies were retained in 64% of children and 89%
of adolescents.
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UPDATE
#2:
A New Treatment for Chronic Hepatitis B
U.S.
Food and Drug Administration. “Updates: New Treatment for
Chroni Hepatitis B.” July-August 2005. <http://www.fda.gov/fdac/departs/2005/405_upd.html>
The
FDA has approved Baraclude (entecavir), a new drug to treat chronic
hepatitis B in adults. Baraclude works by interfering with the reproduction
of the virus, thus slowing the progression of chronic hepatitis
B. Three studies comparing Baraclude with Lamivudine has shown that
Baraclude treatment results in significant improvement in liver
inflammation, scarring, and overall well-being. Some major side
effects include headache, abdominal pain, diarrhea, fatigue, dizziness,
and a severe, but brief, worsening of hepatitis B after discontinuation
of the treatment. Bristol-Myers Squibb Co. will be conducting a
large post-marketing study of the drug to investigate cancer risk
and liver complications.
***
UPDATE
#3:
Peginterferon alfa-2a is superior to Lamivudine.
Lau,
George, et al. “Peginteferon Alfa-2a, Lamivudine, and the
Combination for HBeAg-Positive Chronic Hepatitis B.” The New
England Journal of Medicine. 30 June, 2005. 352: 2682-95. <http://content.nejm.org/cgi/content/full/352/26/2682>
This
study published in the New England Journal of Medicine compared
the efficacy and safety of pegylated interferon alfa plus lamivudine,
pegylated interferon alfa without lamivudine, and lamivudine alone
for the treatment of Hepatitis B e antigen (HBeAg)—positive
chronic hepatitis B. After 24 weeks of treatment, a significantly
larger proportion of those who received peginterferon alfa-2a alone,
or peginterferon alfa-2a plus lamivudine had HBeAg seroconversion.
Furthermore, a significant proportion of this same group had lower
HBV DNA levels (below 100,000 copies per mL). Lastly, while 0 patients
receiving only lamivudine had hepatitis B surface antigen seroconversion,
a total of 16 patients receiving peginterferon alfa-2a experienced
seroconversion. This study concludes that in patients with chronic
hepatitis B, peginterferon alfa-2a is superior over lamivudine.
***
UPDATE
#4:
Foscarnet as a potential antiviral treatment for hepatitis B virus
Han,
Yan-Xing, et al. “Antiviral therapeutic efficacy of foscarnet
in hepatitis B virus infection.” Antiviral research. October
2005; 68(3): 147-53.
Foscarnet
is a DNA polymerase inhibitor for herpes viruses. This study evaluated
the therapeutic efficacy of foscarnet in hepatitis B virus (HBV)
infection. Foscarnet was administered intravenously for 4 weeks
to HBV-positive patients, and was found to significantly reduce
HBeAg and HBV DNA copies. Furthermore, kidney function remained
the same, and 21 patienets who had exhibited resistance to lamivudine,
showed a response to positive response to foscarnet. In addition,
foscarnet was also examined in vitro and in vivo, and was found
to significantly inhibit HBV DNA replication. This study proposes
that foscarnet could be a new therapeutic drug for patients with
chronic liver disease, whether or not they are resistant to lamivudine.
Since its structure and action of mechanism differes from that of
lamivudine, foscarnet could possibly be used in combination with
lamivudine and other antivirals.
***
UPDATE
#5:
Reverse Transcription-associated dephosphorylation of hepadnavirus
nucleocapsids
Perlman,
David. Berg, Eric. O’Connor, Peter. Costello, Catherine. Hu,
Jianming. “Reverse Transcription-associated Dephosphorylation
of Hepadnavirus Nucleocapsids.” PNAS. 10 June, 2005, 102(25):
9020-25.
Because
of their partially double-stranded genome, hepatitis B viruses replicate
their DNA through an RNA intermediate by reverse transcription.
This process begins with the packaging of the pre-genomic RNA into
nucleocapsids, with reverse transcription taking place within the
nucleocapsids. Only these “mature” nucleocapsids (those
containing dsDNA) are secreted as virions. Mass spectrometric analysis
revealed that the core proteins from these “mature”
nucleocapsids are completely dephosphorylated. This study concludes
that hepadnavirus nucleocapsids undergo a change in phosphorylation
state in order to fulfill its multiple roles at different stages
in viral replication. Furthermore, while phosphorylation is required
for efficient RNA packaging and DNA synthesis, dephosphorylation
of the nucleocapsids probably serves as a trigger for virion envelopment
and secretion.
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