New options in the treatment of chronic hepatitis

Abstract

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.