Approximately 400 million people worldwide are chronically infected with the hepatitis B virus (HBV) and it is estimated that between 500,000 and 1 million people die annually from cirrhosis and hepatocellular carcinoma due to HBV infection.1-3 Despite the availability of safe and effective vaccines for more than two decades, HBV infection still is one of the major global health problems. Patients with chronic hepatitis B can present in one of four phases of infection.4 In the immunotolerant phase, hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) are detectable, HBV DNA levels are high and there is minimal hepatic inflammation. When infected at childhood, this immunotolerant phase may last 10 to 30 years with a low rate of spontaneous HBeAg clearance.5 In the immuno-active phase, HBsAg, HBeAg and high HBV DNA are still present, while an active immune response results in hepatic inflammation with elevation of serum alanine aminotransferase (ALT) levels. Spontaneous loss of HBeAg and seroconversion to anti-HBe can occur. The immune-control phase follows HBeAg-seroconversion, with minimal hepatic inflammation and low HBV DNA levels due to a continuous host immune response. There is however a subgroup of HBeAg-negative chronic hepatitis B patients where biochemical and histological activity recurs with higher HBV DNA levels compared to patients in the immune-control phase. These patients have HBV variants that hamper the production of the HBeAg. The most commonly described mutation is a G to A switch at position 1896 of the pre-core region of the hepatitis B genome. This mutation leads to a translational stop codon in the leader sequence of the HBeAg protein, resulting in the inhibition of the protein synthesis.

Financial support for this theses was kindly given by: AstraZeneca B.V., Boehringer Ingelheim B.V., Janssen-Cilag B.V., Roche Nederland B.V., Schering-Plough B.V., Zambon Nederland B.V. and the Erasmus University Rotterdam.
H.L.A. Janssen (Harry)
Erasmus University Rotterdam
Erasmus MC: University Medical Center Rotterdam

ter Borg, M. (2008, December 3). Immune Modulating Therapy and its Viral Kinetics in Chronic Hepatitis B. Retrieved from