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Description of current research

More than 400 million people worldwide are chronically infected with the hepatitis B virus (HBV) or the hepatitis C virus (HCV). Viral hepatitis is the major cause for liver failure and hepatocellular carcinoma, and the main indication for liver transplantation. The available anti-viral drugs are only partly effective, toxic and expensive, and more efficient therapies are urgently needed. Innate and adaptive immune responses play an important role in viral clearance and disease pathogenesis. However, adaptive immunity to both HBV and HCV are almost completely absent in chronically infected patients. In addition, detailed studies on patients co-infected with HIV are being performed.

The research lines of the laboratory of dr. André Boonstra focus on the immune response towards human chronic viruses, including HBV, HCV, HEV and HIV. The research has a strong translational character and aims to provide basic and applied knowledge to better understand the immune parameters determining viral persistence, improve current anti-viral therapies and develop novel therapeutic strategies to combat chronic viral infections.

In this, various longitudinal studies focused on improvement of therapy, and participation in a number of multi-center Phase I/II clinical trials are being performed in close collaboration with clinicians of the department of Hepatology (prof.dr. Rob de Man and dr. Rob de Knegt) and the department of Infectious Diseases (prof.dr. Annelies Verbon en dr. Bart Rijnders).

Specific projects include:

  • Determination of the effect of HBV, HCV and HIV on innate immune responses mediated by macrophages/monocytes, and NK cells
  • Immunomodulatory activities of IFN-alpha and IFN-lambda
  • Immunomonitoring of chronic HBV and HCV patients during standard-of-care and experimental antiviral therapy, including narlaprevir (MSD), TLR7 agonists (Anadys), peg-IFNα /ribavirin therapy (CIRES study), triple antiviral therapy using telaprevir (ETIM study), and various studies using novel direct acting antivirals (DAA).
  • Identification of novel molecular markers to predict disease progression and the response to antiviral therapy of individual patients chronically infected with HBV, HCV and HIV using SNP analysis, GWAS Affymetrix arrays, RNAseq, metabolomics, and multiplexing protein platforms
  • Mouse models to study intrahepatic immunology and viral hepatitis (HBV, HCV, HEV and LCMV)