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Virus–drug interactions—molecular insight into immunosuppression and HCV

Nature Reviews Gastroenterology & Hepatology volume 9, pages 355362 (2012) | Download Citation

Abstract

Liver transplantation is an effective treatment for end-stage liver disease that is attributable to chronic HCV infection. However, long-term outcomes are compromised by universal virological recurrence in the graft. Reinfection that occurs after transplantation has increased resistance to current interferon-based antiviral therapy and often leads to accelerated development of cirrhosis. Important risk factors for severe HCV recurrence are linked to immunosuppression. Owing to the lack of good randomized, controlled trials, the optimal choice of immunosuppressants is still debated. By contrast, much progress has been made in the understanding of HCV biology and the antiviral action of interferons. These new insights have greatly expanded our knowledge of the molecular interplay between HCV and immunosuppressive drugs. In this article, we explore the effect of different immunosuppressants on the complex cellular events involved in HCV infection and interferon signalling. Potential implications for clinical practice and future drug development are discussed.

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Acknowledgements

The authors would like to thank Petra de Ruiter for critically reading the manuscript and sharing unpublished data. The authors received financial support from the Erasmus MC Translational Research Fund and the Liver Research Foundation Rotterdam (SLO).

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Affiliations

  1. Department of Gastroenterology and Hepatology, Erasmus MC-University Medical Center, sGravendijkwal 230, Room L458, 3015 CE Rotterdam, The Netherlands

    • Qiuwei Pan
    • , Herold J. Metselaar
    •  & Harry L. A. Janssen
  2.  Department of Surgery and Laboratory of Experimental Transplantation and Intestinal Surgery, Erasmus MC-University Medical Center, sGravendijkwal 230, Room L458, 3015 CE Rotterdam, The Netherlands

    • Hugo W. Tilanus
    •  & Luc J. W. van der Laan

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Contributions

Q. Pan and L. J. W. van der Laan contributed equally to all aspects of the article. H. W. Tilanus, H. J. Metselaar and H. L. A. Janssen contributed equally to discussion of the content and review/editing of the manuscript before submission.

Competing interests

H. J. Metselaar has been a consultant and speaker for Astrellas and Novarits. He has also received grant/research support from Astrellas. The other authors declare no competing interests.

Corresponding authors

Correspondence to Harry L. A. Janssen or Luc J. W. van der Laan.

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https://doi.org/10.1038/nrgastro.2012.67

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