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Permanent link (DOI): https://doi.org/10.7939/R30D68

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

Descriptions

Other title
Subject/Keyword
Hepatitis C virus
Immunotherapy
Liver transplantation
Epigallocatechin gallate
Type of item
Thesis
Degree grantor
University of Alberta
Author or creator
O'Shea, Daire T
Supervisor and department
Kneteman, Norm (Surgery)
Humar, Atul (Medicine)
Examining committee member and department
Houghton, Michael (Medical Microbiology and Immunology)
Tyrrell, Lorne (Medicine, Medical Microbiology and Immunology)
Department
Department of Medicine
Specialization
Experimental Medicine
Date accepted
2013-05-09T15:57:46Z
Graduation date
2013-11
Degree
Master of Science
Degree level
Master's
Abstract
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.
Language
English
DOI
doi:10.7939/R30D68
Rights
Permission is hereby granted to the University of Alberta Libraries to reproduce single copies of this thesis and to lend or sell such copies for private, scholarly or scientific research purposes only. Where the thesis is converted to, or otherwise made available in digital form, the University of Alberta will advise potential users of the thesis of these terms. The author reserves all other publication and other rights in association with the copyright in the thesis and, except as herein before provided, neither the thesis nor any substantial portion thereof may be printed or otherwise reproduced in any material form whatsoever without the author's prior written permission.
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File title: Critical care clinics
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