Abstract
Chronic hepatitis B virus (HBV) infections significantly increase the risk of developing liver cirrhosis and hepatocellular carcinoma (HCC). Despite the availability of an effective vaccine, more than 250 million people remain chronically infected worldwide. Although antiviral therapy effectively suppresses viral replication, it does not offer a cure or eliminate the risk of HCC development, underscoring the need for novel treatment strategies. For decades, immunological studies on chronic HBV infection have predominantly focused on T cells, while B cells have largely been understudied. However, achieving long-term HBV suppression and a functional cure for chronic hepatitis B cannot be accomplished without concomitant functional restoration of anti-HBV humoral immunity.
Emerging evidence has highlighted the role of B cells in the pathogenesis of chronic HBV infection. In recent years, clinical practice has underscored the importance of B cells in chronic hepatitis B. Notably, B cell depletion therapy with rituximab has been shown to significantly increase the risk of HBV reactivation, prompting adjustments to clinical treatment guidelines. It is now recognized that various B cell (dys)functions contribute to chronic HBV infection and that B cells play a critical role in maintaining continuous viral control. Nevertheless, the exact role of B cells in chronic hepatitis B remains unclear. In this thesis, I explored the role of B cells in chronic hepatitis B using advanced single-cell technologies to uncover new insights and enhance our understanding of their role in disease.
Overall, the work described in this thesis contributes to a better understanding of the role of B cells in chronic HBV infection, highlighting their responsiveness to the virus and their potential as targets for novel immunomodulatory therapies. Current treatment options for chronic HBV infection are limited and insufficient, as they do not lead to a cure. Achieving a cure will likely require a coordinated approach that combines antiviral therapies with immunomodulatory strategies to restore functional anti-HBV humoral immunity. Our findings may help to guide such efforts aimed at rejuvenating immunity against HBV.
Emerging evidence has highlighted the role of B cells in the pathogenesis of chronic HBV infection. In recent years, clinical practice has underscored the importance of B cells in chronic hepatitis B. Notably, B cell depletion therapy with rituximab has been shown to significantly increase the risk of HBV reactivation, prompting adjustments to clinical treatment guidelines. It is now recognized that various B cell (dys)functions contribute to chronic HBV infection and that B cells play a critical role in maintaining continuous viral control. Nevertheless, the exact role of B cells in chronic hepatitis B remains unclear. In this thesis, I explored the role of B cells in chronic hepatitis B using advanced single-cell technologies to uncover new insights and enhance our understanding of their role in disease.
Overall, the work described in this thesis contributes to a better understanding of the role of B cells in chronic HBV infection, highlighting their responsiveness to the virus and their potential as targets for novel immunomodulatory therapies. Current treatment options for chronic HBV infection are limited and insufficient, as they do not lead to a cure. Achieving a cure will likely require a coordinated approach that combines antiviral therapies with immunomodulatory strategies to restore functional anti-HBV humoral immunity. Our findings may help to guide such efforts aimed at rejuvenating immunity against HBV.
| Original language | English |
|---|---|
| Awarding Institution |
|
| Supervisors/Advisors |
|
| Award date | 11 Feb 2025 |
| Place of Publication | Rotterdam |
| Print ISBNs | 978-94-6510-359-4 |
| Publication status | Published - 11 Feb 2025 |
