Novel Agents Inhibiting Hepatitis C Virus; Application to Prevention of Re-infection after Liver Transplantation

  • Author / Creator
    O'Shea, Daire T
  • Recurrent Hepatitis C virus infection drives inferior outcomes experienced by patients undergoing liver transplantation due to HCV-associated liver disease. Existing therapies exhibit increased toxicity, poor efficacy, and profound patient intolerability in the immediate transplantation period. Liver transplantation provides a window of opportunity to prevent re-infection of the allograft and drastically improve patients’ post-transplant outcomes. The anti-HCV activity of novel monoclonal antibodies(AR4a) and herbal extracts (Epigallocatechin-gallate, Silibinin) were studied in-vitro using HCV cell culture system and in-vivo using a humanized liver mouse model capable of supporting HCV replication. Alone these agents exhibit reliable cross-genotype HCV inhibition in-vitro. Combination therapy can completely prevent HCV infection. In-vivo EGCG alone fails to reliably protect against HCV-genotype1a challenge. AR4a alone and combined with EGCG robustly protects against the establishment of HCV infection. In common these agents have low toxicity potential and are thus applicable for use in complex transplant cohorts to prophylax against HCV re-infection.

  • Subjects / Keywords
  • Graduation date
  • Type of Item
  • Degree
    Master of Science
  • DOI
  • License
    This thesis is made available by the University of Alberta Libraries with permission of the copyright owner solely for non-commercial purposes. This thesis, or any portion thereof, may not otherwise be copied or reproduced without the written consent of the copyright owner, except to the extent permitted by Canadian copyright law.
  • Language
  • Institution
    University of Alberta
  • Degree level
  • Department
    • Department of Medicine
  • Specialization
    • Experimental Medicine
  • Supervisor / co-supervisor and their department(s)
    • Humar, Atul (Medicine)
    • Kneteman, Norm (Surgery)
  • Examining committee members and their departments
    • Tyrrell, Lorne (Medicine, Medical Microbiology and Immunology)
    • Houghton, Michael (Medical Microbiology and Immunology)