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  • Review Article
  • Published:

Recurrent HCV after liver transplantation—mechanisms, assessment and therapy

Nature Reviews Gastroenterology & Hepatology volume 11, pages 710–721 (2014)Cite this article

Subjects

Key Points

  • HCV recurrence occurs in all patients with a detectable HCV viral load at the time of liver transplantation and results in increased morbidity and decreased graft survival compared with other patient groups

  • Fibrosis progression is accelerated after a liver transplant, which results in graft cirrhosis in up to 30% of patients within 5 years

  • Fibrosis should be assessed at 12 months after transplantation to identify patients with rapid fibrosis progression; transient elastography is a sensitive noninvasive tool to assess fibrosis in these patients

  • Current antiviral therapy utilizes a PEG-IFN component, which limits the number of patients who can be treated and decreases tolerability, with disappointing sustained virologic response rates

  • New combinations of different classes of direct-acting antiviral agents (DAAs) will obviate the requirement for PEG-IFN and will probably have a considerable effect on therapy before and after liver transplantation

  • Preliminary data suggest that DAAs will decrease the recurrence of HCV infection and provide notable improvements in patient and graft outcomes

Abstract

Chronic HCV infection is the leading indication for liver transplantation. However, as a result of HCV recurrence, patient and graft survival after liver transplantation are inferior compared with other indications for transplantation. HCV recurrence after liver transplantation is associated with considerable mortality and morbidity. The development of HCV-related fibrosis is accelerated after liver transplantation, which is influenced by a combination of factors related to the virus, donor, recipient, surgery and immunosuppression. Successful antiviral therapy is the only treatment that can attenuate fibrosis. The advent of direct-acting antiviral agents (DAAs) has changed the therapeutic landscape for the treatment of patients with HCV. DAAs have improved tolerability, and can potentially be used without PEG-IFN for a shorter time than previous therapies, which should result in better outcomes. In this Review, we describe the important risk factors that influence HCV recurrence after liver transplantation, highlighting the mechanisms of fibrosis and the integral role of hepatic stellate cells. Indirect and direct assessment of fibrosis, in addition to new antiviral therapies, are also discussed.

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Figure 1: Natural history of recurrent HCV after liver transplantation.
Figure 2: Pathways and mechanisms of hepatic stellate cell activation.

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Acknowledgements

D.J. would like to acknowledge the support of a grant from King's College Hospital Charity (grant number 96080).

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Authors and Affiliations

  1. Institute of Liver Studies, King's College Hospital, Denmark Hill, SE5 9RS, London, UK

    Deepak Joshi, Ivana Carey & Kosh Agarwal

  2. UCL Institute for Liver and Digestive Health, University College London, Royal Free Hospital Campus U3, Rowland Hill Street, NW3 2PF, London, UK

    Massimo Pinzani

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D.J. and M.P. researched data for the article, contributed to discussion of the content, wrote the article and reviewed/edited the manuscript before submission. I.C. researched data for the article, contributed to discussion of the content and reviewed/edited the manuscript before submission. K.A. contributed to discussion of the content, wrote the article and reviewed/edited the manuscript before submission.

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Joshi, D., Pinzani, M., Carey, I. et al. Recurrent HCV after liver transplantation—mechanisms, assessment and therapy. Nat Rev Gastroenterol Hepatol 11, 710–721 (2014). https://doi.org/10.1038/nrgastro.2014.114

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