Contributed by Guest Blogger: S. Bhutani ’14
Chronic Hepatitis B virus (HBV) is a common infectious disease. HBV infects hepatocytes, which are liver cells, thereby impairing liver function and leading to disease such as liver cancer. In chronic HBV the responses from the CD8 cytotoxic T-cell and CD4 helper T-cell are not substantial enough because high amounts of HBV impair T-cell immunity. Thus, ideal anti-viral treatments would need to reduce the amount of virus. In the past decade, the introduction of nucleoside and nucleotide analogs, compounds that look similar to nucleotides and deceive the virus into thinking it is being replicated, has improved treatment for HBV. However, the prominent nucleoside analog, lamivudine, that inhibits HBV replication, is no longer as effective because the virus has developed mutations that resist the drug. One new nucleotide analog, called adefovir dipivoxil, has been tested on chronic HBV patients in China.
In China 22 patients were tested along with 20 healthy controls. The patients were treated with adefovir dipivoxil once daily for 10 weeks. The presence of cytokines producing certain T-helper cells was measured, as was the amount of HBV DNA using biochemical markers. Before adefovir dipivoxil, the cytokines producing helper and killer T-cells were lower in the patients than the healthy individuals. There were two patients with HBV mutations, one which was lamivudine resistant and one which was adefovir dipivoxil resistant. Adefovir dipivoxil treatment resulted in an increase of Th1 and Th2 cytokines that produce CD4 T-cells in all patients except for the one with the adefovir dipivoxil resistant mutation, proving that this new drug can combat lamivudine resistant HBV mutations. The treated patients’ levels of cytokines peaked and then dropped and stayed at the cytokine levels of the healthy individuals. There was an inverse correlation between the amount of HBV DNA and cytokine levels; after treatment as cytokine levels increased, HBV DNA decreased.
Thus, this study suggests that adefovir dipivoxil inhibits HBV DNA polymerase thereby reducing the amount HBV and restoring T-cell immunity. However, it should be noted that even after the recent development of the drug, HBV mutations were still found. Thus will there ever be development of a treatment for which there no resistant mutations have already evolved?