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Hepadna Updates


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.


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.


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.


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.


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.