No abstract

Based on investigations of liver biopsy material, certain cellular genes have been implicated as correlates of success or failure to interferon alpha-ribavirin (IFN/RBV) therapy against hepatitis C. The current study aimed at determining whether expression of host genes thought to be relevant to HCV replication in the liver would be correlated with HCV infection status in peripheral blood mononuclear cells (PBMCs) and also with patient responsiveness to IFN/RBV treatment. Therefore, PBMCs from patients with chronic hepatitis C responding (n = 35) or not (n = 49) to IFN/RBV and from healthy controls (n = 15) were evaluated for HCV RNA load and cellular gene expression. Non-responders had 3- to 10-fold higher basal levels of interleukin (IL)-8, IFN-stimulated gene 15 (ISG15), 2',5'-oligoadenylate synthetase (OAS), and Toll-like receptors (TLR)-4, -5, and -7 compared to responders. Non-responders with similar post-treatment follow-ups as responders persistently expressed 6- to 20-fold greater levels of IL-8, ISG15, and OAS after therapy. Higher expression of IFN-α, IFN-γ, and IFN-λ was found in PBMCs of individuals achieving sustained virological response, either before or after therapy. Pre-treatment HCV RNA loads in PBMCs of non-responders were significantly higher (P = 0.016) than those of responders. In conclusion, the data indicate that immune cells of responders and non-responders to IFN/RBV therapy exhibited significantly different virological and host gene expression profiles. Elevated baseline HCV loads and TLR-4, -5, and -7 levels, and persistently high levels of IL-8, ISG15, and OAS were correlated with IFN non-responsiveness. The results warrant further investigations on the utilization of PBMCs for predicting success or failure to IFN-based therapies.

BACKGROUND: Despite growing awareness of the significant burden of disease caused by hepatitis C virus (HCV) infection worldwide, understanding of the epidemiology and demographic distribution of HCV infection in Canada, specifically in Atlantic Canada, is limited. Currently, data on the demographic and clinical profile of HCV-infected individuals in Newfoundland and Labrador is limited. The aim of this study is to address this knowledge gap. Methods: A retrospective cohort study of HCV-positive individuals referred for specialized care in St. John’s, Newfoundland, between 1996 and 2014, was conducted. Descriptive data were obtained through chart review and access to a database consisting of individuals referred for specialized HCV care in St. John’s. Results: During the study period, 767 individuals were referred for specialized HCV care, of whom 714 were included in our analysis. These individuals represent 57.5% of HCV-positive cases identified by the province’s public health department during the same time frame. HCV infection was more common among men (68.2%) and urban dwellers (74.8%). The majority of cases were HCV genotype 1 (52.1%). Intravenous and intranasal drug use were the most common self-reported risk factors for HCV transmission. High loss-to-follow-up rates were found among those referred from the province’s correctional system. Conclusions: This study provides important insights into the demographic and clinical profile of individuals referred for HCV-related care in Newfoundland and Labrador and fills a gap in the current understanding of HCV-positive individuals in this Atlantic province. These findings can help inform future directions for HCV-related health policy, resource allocation, and clinical care initiatives in Newfoundland and Labrador and across Canada.