Human liver transplantation as a model to study hepatitis C virus pathogenesis

Authors

  • Michael G. Hughes Jr.,

    1. Department of Surgery, Medical University of South Carolina, Charleston, SC
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  • Hugo R. Rosen

    Corresponding author
    1. Division of Gastroenterology and Hepatology, Department of Medicine, University of Colorado Health Sciences Center, Denver, CO
    2. Division of Liver Transplantation, Department of Medicine, University of Colorado Health Sciences Center, Denver, CO
    3. National Jewish Hospital, Denver, CO
    4. Denver VA, Denver, CO
    • Division of Gastroenterology and Hepatology, B-158, University of Colorado Health Sciences Center, Academic Office Building 1, Room 7614, 12631 East 17th Avenue, PO Box 6511, Aurora, CO 80045
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    • Telephone: 303-724-1858; FAX: 303-724-1891


Abstract

Hepatitis C is a leading etiology of liver cancer and a leading reason for liver transplantation. Although new therapies have improved the rates of sustained response, a large proportion of patients (∼50%) fail to respond to antiviral treatment, thus remaining at risk for disease progression. Although chimpanzees have been used to study hepatitis C virus biology and treatments, their cost is quite high, and their use is strictly regulated; indeed, the National Institutes of Health no longer supports the breeding of chimpanzees for study. The development of hepatitis C virus therapies has been hindered by the relative paucity of small animal models for studying hepatitis C virus pathogenesis. This review presents the strengths of human liver transplantation and highlights the advances derived from this model, including insights into viral kinetics and quasispecies, viral receptor binding and entry, and innate and adaptive immunity. Moreover, consideration is given to current and emerging antiviral therapeutic approaches based on translational research results. Liver Transpl 15:1395–1411, 2009. © 2009 AASLD.

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