Hepatitis B Virus
Today, about 2 billion people carry serological markers of HBV. About 400 million of them are chronically infected with HBV. According to the center of disease control (CDC) about 15% of chronically HBV infected people are prone to develop hepatocellular carcinoma (HCC) within a decade if they do not receive appropriate treatment.
HBV-related HCC has a poor prognosis and HBV has therefore been classified by the world health organization (WHO) as the most important naturally occurring human carcinogen. Despite the existence of a prophylactic vaccine, the number of infections will rise in the upcoming decades due to the increasing world population and the limitation of prophylaxis in the poor countries.
In industrial countries HBV is primarily transmitted via the parenteral route. 90-95% of the acutely infected, immuno competent individuals clear the virus, thereby gaining life long immune protection. About 5-10% of them develop chronic Hepatitis B (300.000-500.000 persons in Germany). In contrast, in high endemic areas, particularly Central Africa and Eastern Asia (see the Figure above: "Geographic Pattern of HBV Prevalence"), the main mode of transmission is vertically from mother to child. Unfortunately, infection of not fully immuno-competent children results in a 90-98% chronic course of the disease. Hepatitis B-related HCC is therefore the most common malignancy in many of these countries.
Currently approved therapeutic regiments for the treatment of chronic hepatitis B virus (HBV) infections either address replication steps of the viral genome after an already established infection (Lamivudine, Adefovir, Entecavir) or act as modulators of the immune system (Interferon alpha). Unfortunately, only 10-25% of the patients preserve a sustained virological response upon such therapies, reflecting -inter alia- the fast selection of nucleo(s)tide resistant mutants. Despite the availability of a preventative vaccine, it is therefore of utmost importance to develop novel therapeutics that target so far unaffected replication steps e.g. virus entry.