Chronic hepatitis C virus (HCV) infection is established in 80% of infected individuals and leads to cirrhosis, hepatocellular carcinoma (HCC) and end-stage liver disease. Despite new direct-acting antivirals (DAA), treatment failures, reinfection rates after clearance or treatment, viral resistance, treatment costs and the lack of a vaccine challenge over 170 million infected people infected worldwide and about 1% of the Canadian population.
It is imperative that our limited understanding of HCV immunopathogenesis and the long term immunological effects of chronic infection and potent DAAs be improved. An effective immune responses to HCV includes anti-viral cytotoxic CD8+ T-cell (CTL) activity, which is impaired in chronic infection. We identified generalized blood/liver CTL impairment in chronic HCV mono-infection and HCV-HIV co-infection (the #1 co-morbidity in 25% of HIV+ individuals). Co-infection with HCV and HIV is of particular concern as individuals experience faster liver disease progression and dual causes of CD8+ T-cell deficiency from both viruses.
Our research suggests that chronic HCV infection is damaging host immune systems and the consequences of this have not been investigated in depth. We will focus on identifying potential associations of this immunodeficiency with HCV infection, treatments, level of liver fibrosis and the development of HCC. Our research aims to ultimately improve chronic HCV infection care in Canada and beyond, and may provide insight into other immunity-damaging chronic diseases (e.g. HIV, malaria, helminthes, autoimmunity).
