Chronic infections with the hepatitis B virus or the hepatitis C virus affect over 500 million people worldwide. Patients acutely infected with hepatitis B virus or the hepatitis C virus develop a strong immune response to the virus shortly after infection. However, in the majority of hepatitis C virus patients and in a subset of hepatitis B virus patients, the virus-specific immune response diminishes due to a spectrum of immune evasion strategies of the virus. As a consequence a life-long infection is established in the liver of the patients.
At present, it is unclear why the immune system fails in a large number of patients, whereas in other patients the immune system is able to actively resolve the infection. Once a chronic hepatitis B virus or the hepatitis C virus infection is established, it is well known that viral, host and environmental factors all influence disease progression. Host-related factors that appear to have an impact on the progression of viral hepatitis to cirrhosis and liver cancer include: age, gender and family history, but also genetic factors: MHC class I and II genes and polymorphisms of immunity-related genes.
Currently, a good understanding of these factors is lacking, and molecular markers that promote the development of cirrhosis and liver cancer upon infection with viral hepatitis should be identified. The host response to these viruses is also linked to outcome of antiviral therapy. Given the highly variable outcome of antiviral treatment in chronic viral hepatitis patients, markers predictive for response to antiviral treatment are highly useful in clinical decision making, and systems biology approaches to identify predictive biomarkers are performed in this project.
A second objective within this area of research is to identify antibodies as a novel intervention tor treatment and prevention of chronic hepatitis C. These antibodies are isolated from B-cells from patients who after clearance of a primary infection did not become re-infected, despite continuation of intravenously injecting drugs. Given the huge genetic diversity of hepatitis C virus, these antibodies should be able to neutralize all major circulating different genotypes. Identification and characterization of such antibodies, including the epitopes they target, will ultimately contribute to the development of a vaccine against hepatitis C.