Hepatitis B and C
Dr Lee Markwick and Dr Antonio Riva at work in the Viral Hepatitis Research Laboratory. To hear Dr Shilpa Chokshi, Head of Group, taking about their work, please view our short film at: http://youtu.be/WArsDxiH1gk
Immune Mechanims of Viral Hepatitis
The outcome of Hepatitis B virus (HBV) or Hepatitis C virus (HCV) infection is determined primarily by the immune response of the infected individual's body (the host). The Foundation is supporting research to investigate the reason why in some people the body's immune response can effectively control viral replication spontaneously while in others it does not and leads to a long term chronic infection.
Chronic viral hepatitis is primarily the result of a complex interaction between a replicating non-cytopathic virus (Hepatitis B or C virus) and an impaired antiviral host immune response. Despite having distinct replication mechanisms and kinetics, Hepatitis B and C viral infections share several aspects of pathogenesis, natural history, and induced host immune responses. Both viruses are preferentially hepatotrophic and are capable of provoking acute and chronic necroinflammatory liver injury. Critically, current treatment regimens directed at these infections have limited efficacy.
The overall research programme of the group aims to investigate the mechanisms responsible for the pathogenesis of disease and control of viral replication in patients with chronic Hepatitis B and C virus infections, in order to aid the development of novel therapeutic interventions allowing the acquisition of an appropriate state of antiviral immunity and control/clearance of infection.
1. Characterisation of the antiviral activities of Cyclophillin Inhibitors DEB025 (Alisporivir) and NIM811, alone or in combination with the direct antiviral Telbivudine, on Hepatitis B virus replication and HBsAg secretion in vitro.
2. Analysis of innate and adaptive immune responses during Alisporivir treatment in Chronic Hepatitis C virus patients.
3. Characterisation of the relationship between the host immune responses and the durability of treatment-induced viral control in chronic HBV patients treated with oral antiviral therapy in the Gambia.
4. Identification of immunodominant and/or immunoprevalent T cell epitopes to aid the design of a therapeutic vaccine for chronic Hepatitis B virus infection.
5. To investigate relationship between IL-17 and the PD-1/PDL-1 pathway and the impact on virus-specific CD8+ T cell function during hepatitis B virus infection.
6. Analysis and correlation of serum lipid profiles with outcome of acute HCV infection