Grant: Travel Awards - Institute Community Support

Background: Chronic hepatitis C virus (HCV) infection affects about 170 million people worldwide and can result in fibrosis, hepatocellular carcinoma (HCC), and end stage liver disease (ESLD). Although effective HCV treatments exist, liver fibrosis does not always reverse after cure. Current treatment rates remain too low to reduce ESLD or HCV transmission, due to high drug costs and strict patient qualifications. HCV-specific CD8+ T cells, eradicate infected cells, exhibit impaired cytotoxic potential, survival, and proliferation during chronic infection. CD8+ T cells from HCV-infected individuals, regardless of their specificity, have decreased cytokine signalling and their survival is inversely correlated with liver fibrosis. Objective: Delineate the function of circulating CD8+ T cells in HCV-infected individuals with either minimal or advanced fibrosis by measuring indicators of effector function. Methods: Thawed CD8+ T cells are isolated from untreated, HCV-infected samples and assessed for subset distribution, cytokine expression, and cytolytic activity while correlating with fibrotic scores. A longitudinal study of 24 patients receiving HCV therapy will determine the reversibility of the observed CD8+ T cell impairment and fibrosis. Results: Preliminary data suggests that the proportion of naive CD8+ T cells in patients with high fibrosis is lower than in uninfected individuals. HCV+ individuals with high fibrosis have more naive and effector memory CD8+ T cells expressing IFN-y and CD107a following in vitro stimulation, and fewer central memory CD8+ T cells expressing perforin compared to controls. Conclusion: Our data suggests a functional alteration of immune cells is associated with advancing liver fibrosis in HCV infection. It is not known whether generalized immune impairment persists following successful treatment. Identification of the relationship between immune impairment and liver fibrosis would provide prognostic indicators of liver disease.