Towards a functional cure for chronic hepatitis B

Chronic hepatitis B (CHB) is an infectious disease caused by the bloodborne hepatitis B virus in patients that do not spontaneously clear the virus after infection. The virus affects the liver and can lead to hepatitis, liver cirrhosis and livercancer. For patients living with CHB, viral suppressive medication is available but no effective curative treatment has yet been found. The major goal in current research is to find an treatment option that leads to a ‘functional cure’ which means that the virus is inactively present in the liver. This state of infection/cure drastically reduces the risk of CHB related complications. In this thesis, attention is paid to several aspects that contribute to the development of a functional cure in patients with CHB. First, we looked at the immunological response of patients during an acute infection in order to gain more insight into the process of viral clearance or lack thereof. We furthermore evaluate the utility of several novel markers for CHB including the hepatitis B core related antigen (HBcrAg) and the viral RNA. We also show that the extent to which the virus integrates into the human genome differs between patients in different phases of their infection. In the last part, we describe the effect of different treatments against CHB on safety and efficacy. This includes the long-term effect of a combination treatment with PEG-interferon and adefovir/tenofovir, and data on the safety and tolerability of using an FXR agonist for the treatment of CHB.