The short-term aim of
chronic hepatitis B treatment is the suppression of Hepatitis B Virus (HBV) replication, as shown by the loss of HBV
DNA by
DNA hybridization and the loss of
Hepatitis B e Antigen (
HBeAg). Loss of
Hepatitis B s
Antigen (
HBsAg) and HBV
DNA as assayed by Polymerase Chain Reaction (PCR) is very difficult to achieve. There are two important treatment approaches. The first is
immunomodulation, comprising
Interferon (IFN) and other
cytokine treatment and therapeutic vaccination. The second is
antiviral treatment, which mainly includes treatment with
nucleoside analogs. There are many limitations to IFN treatment, because it has succeeded only in a small number of patients with a high level of
transaminase and a low level of HBV
DNA. The theoretical basis of therapeutic vaccination is the use of a
vaccine that contains
epitopes known to stimulate Human Leucocyte
Antigen (HLA)-restricted cytotoxic T cell activity in order to lyse the HBV-infected hepatocytes. Several strategies of
hepatitis vaccination are the incorporation of both pre-S and S
antigen, the incorporation of a Cytotoxic T Lymphocyte (CTL)-specific
antigen, the use of an HBV
vaccine complexed to
Hepatitis B Immune Globulin (
HBIG), and
DNA vaccination. One of the limitations of therapeutic vaccination is the short duration of immunity to the CTL
antigen.
Lamivudine is an oral
nucleoside analog with potent
antiviral action. It rapidly reduces the HBV
DNA level, a level that soon returns to pretreatment level after
drug administration is terminated. This
drug does not affect the covalently bond closed circular (ccc)
DNA of infected hepatocytes; it only inhibits the formation of new viruses. One-year of
Lamivudine treatment significantly improved necroinflammation and reduced the progression of
fibrosis and the histologic activity index.
HBeAg seroconversion occurred after prolonged treatment. The emergence of a
tyrosine-
methionine asparagine aspargine YMDD mutant is one of the drawbacks of
lamivudine treatment. Therefore a combination with other
antiviral agents or immune modulators, such as therapeutic vaccination, is likely to be more effective.