Host genomics and HCV treatment response

Authors

  • Paul J Clark,

    1. Duke Clinical Research Institute, Duke University Medical Center, Durham, North Carolina, USA
    2. The Kirby Institute for Infection, Immunity and Society, University of New South Wales, Sydney, New South Wales, Australia
    Search for more papers by this author
  • Alexander J Thompson

    Corresponding author
    1. Duke Clinical Research Institute, Duke University Medical Center, Durham, North Carolina, USA
    2. Department of Gastroenterology, St Vincent's Hospital (Melbourne), The University of Melbourne, Victoria, Australia
    3. Victorian Infectious Diseases Reference Laboratory, Melbourne, Victoria, Australia
      Dr Alexander J Thompson, St Vincent's Hospital (Melbourne), Gastroenterology Department, Level 4 Daly Wing, 35 Victoria Parade, Fitzroy, Vic. 3068, Australia. Email: alexander.thompson@svhm.org.au
    Search for more papers by this author

Dr Alexander J Thompson, St Vincent's Hospital (Melbourne), Gastroenterology Department, Level 4 Daly Wing, 35 Victoria Parade, Fitzroy, Vic. 3068, Australia. Email: alexander.thompson@svhm.org.au

Abstract

In 2009, an association between the interleukin-28B (IL28B) polymorphism and treatment outcome for genotype 1 (G1) hepatitis C virus (HCV) infection, as well as spontaneous clearance of HCV, was reported. Since the initial publications, over 100 articles have appeared in the peer-reviewed literature, with many more manuscripts in press and abstracts presented at scientific meetings. Despite the proliferation of data concerning the IL28B polymorphism and HCV infection, there remain many critical unanswered questions about clinical implications and the underlying biological mechanisms. In this review, we discuss the basic principles of genome-wide association study methodologies that are important for interpreting the results of genetic association studies. We then review the current literature concerning the association between IL28B variants and interferon (IFN) treatment response in patients with chronic HCV infection, as well as spontaneous HCV clearance. We consider the relevance of the IL28B polymorphism to non-G1 HCV, as well as the special treatment populations of HIV/HCV co-infection and recurrent HCV post-liver transplantation. We review current knowledge of the biological mechanisms underlying this genetic association, including the link to liver IFN-stimulated gene expression, and identify continuing gaps in our knowledge and key research priorities. Finally, pegylated-IFN and ribavirin is no longer the standard of care for the treatment of G1 HCV, and we conclude by considering the relevance of IL28B polymorphisms in the era of direct-acting antivirals.

Ancillary