Table of Contents Author Guidelines Submit a Manuscript
Canadian Journal of Gastroenterology and Hepatology
Volume 2016 (2016), Article ID 5743521, 11 pages
http://dx.doi.org/10.1155/2016/5743521
Commentary

Highlights of the Fourth Canadian Symposium on Hepatitis C: Moving towards a National Action Plan

1Department of Microbiology & Immunology, McGill University, Montréal, QC, Canada H3A 2B4
2Liver Unit, Department of Medicine, Université de Montréal, Montréal, QC, Canada H3T 1J4
3The Kirby Institute, UNSW Australia, Sydney, NSW 2052, Australia
4British Columbia Centre for Disease Control, Vancouver, BC, Canada V5Z 4R4
5University of British Columbia, Vancouver, BC, Canada V6T 1Z4
6Toronto General Research Institute, University Health Network, Toronto, ON, Canada M5G 1L7
7Canadian Institutes of Health Research-Institute of Infection and Immunity, Ottawa, ON, Canada K1A 0W9
8Department of Epidemiology, McGill University, Montréal, QC, Canada H3A 1A2
9Toronto Western Hospital Liver Center, University Health Network, Toronto, ON, Canada M5T 2S8
10Li Ka Shing Institute of Virology, Department of Medical Microbiology & Immunology, University of Alberta, Edmonton, AB, Canada T6G 2E1
11Department of Microbiology & Immunology, University of Saskatchewan, Saskatoon, SK, Canada S7N 5E5

Received 5 August 2015; Accepted 1 October 2015

Copyright © 2016 Selena M. Sagan et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. J. Pawlotsky, J. J. Feld, S. Zeuzem, and J. H. Hoofnagle, “From non-A, non-B hepatitis to hepatitis C virus cure,” Journal of Hepatology, vol. 62, no. 1, pp. S87–S99, 2015. View at Publisher · View at Google Scholar
  2. J. Grebely, M. Bilodeau, J. J. Feld et al., “The Second Canadian Symposium on hepatitis C virus: a call to action,” Canadian Journal of Gastroenterology, vol. 27, pp. 627–632, 2013. View at Google Scholar
  3. S. A. MacParland, M. Bilodeau, J. Grebely et al., “The 3rd Canadian symposium on hepatitis C virus: expanding care in the interferon-free era,” Canadian Journal of Gastroenterology and Hepatology, vol. 28, no. 9, pp. 481–487, 2014. View at Publisher · View at Google Scholar
  4. M. Sulkowski, “Treatment for chronic hepatitis c virus infection: challenges and opportunities in the era of highly effective antiviral therapy,” in Proceedings of the 4th Canadian Symposium on Hepatitis C Virus, Banff, Canada, 2015.
  5. E. J. Gane, C. A. Stedman, R. H. Hyland et al., “Nucleotide polymerase inhibitor sofosbuvir plus ribavirin for hepatitis C,” New England Journal of Medicine, vol. 368, no. 1, pp. 34–44, 2013. View at Publisher · View at Google Scholar
  6. M. J. Sofia, D. Bao, W. Chang et al., “Discovery of a β-d-2′-deoxy-2′-α-fluoro-2′-β-C-methyluridine nucleotide prodrug (PSI-7977) for the treatment of hepatitis C virus,” Journal of Medicinal Chemistry, vol. 53, no. 19, pp. 7202–7218, 2010. View at Publisher · View at Google Scholar
  7. D. Lamarre, P. C. Anderson, M. Bailey et al., “An NS3 protease inhibitor with antiviral effects in humans infected with hepatitis C virus,” Nature, vol. 426, no. 6963, pp. 186–189, 2003. View at Publisher · View at Google Scholar
  8. T. L. Kieffer, C. Sarrazin, J. S. Miller et al., “Telaprevir and pegylated interferon-alpha-2a inhibit wild-type and resistant genotype 1 hepatitis C virus replication in patients,” Hepatology, vol. 46, no. 3, pp. 631–639, 2007. View at Publisher · View at Google Scholar · View at Scopus
  9. M. Gao, R. E. Nettles, M. Belema et al., “Chemical genetics strategy identifies an HCV NS5A inhibitor with a potent clinical effect,” Nature, vol. 465, no. 7294, pp. 96–100, 2010. View at Publisher · View at Google Scholar
  10. R. E. Nettles, M. Gao, M. Bifano et al., “Multiple ascending dose study of BMS-790052, a nonstructural protein 5A replication complex inhibitor, in patients infected with hepatitis C virus genotype 1,” Hepatology, vol. 54, no. 6, pp. 1956–1965, 2011. View at Publisher · View at Google Scholar
  11. A. S. Lok, D. F. Gardiner, E. Lawitz et al., “Preliminary study of two antiviral agents for hepatitis C genotype 1,” New England Journal of Medicine, vol. 366, no. 3, pp. 216–224, 2012. View at Publisher · View at Google Scholar
  12. M. S. Sulkowski, D. F. Gardiner, M. Rodriguez-Torres et al., “Daclatasvir plus sofosbuvir for previously treated or untreated chronic HCV infection,” The New England Journal of Medicine, vol. 370, pp. 211–221, 2014. View at Publisher · View at Google Scholar
  13. F. McPhee, D. Hernandez, F. Yu et al., “Resistance analysis of hepatitis C virus genotype 1 prior treatment null responders receiving daclatasvir and asunaprevir,” Hepatology, vol. 58, no. 3, pp. 902–911, 2013. View at Publisher · View at Google Scholar
  14. P. Ferenci, D. Bernstein, J. Lalezari et al., “ABT-450/r-Ombitasvir and Dasabuvir with or without Ribavirin for HCV,” The New England Journal of Medicine, vol. 370, no. 21, pp. 1983–1992, 2014. View at Publisher · View at Google Scholar
  15. F. Poordad, C. Hezode, R. Trinh et al., “ABT-450/r–ombitasvir and dasabuvir with ribavirin for hepatitis C with cirrhosis,” New England Journal of Medicine, vol. 370, no. 21, pp. 1973–1982, 2014. View at Publisher · View at Google Scholar
  16. F. Poordad, E. Lawitz, K. V. Kowdley et al., “Exploratory study of oral combination antiviral therapy for hepatitis C,” The New England Journal of Medicine, vol. 368, no. 1, pp. 45–53, 2013. View at Publisher · View at Google Scholar
  17. K. V. Kowdley, S. C. Gordon, K. R. Reddy et al., “Ledipasvir and sofosbuvir for 8 or 12 weeks for chronic HCV without cirrhosis,” The New England Journal of Medicine, vol. 370, no. 20, pp. 1879–1888, 2014. View at Publisher · View at Google Scholar · View at Scopus
  18. S. H. Al Marzooqi and J. J. Feld, “Sorting out cirrhosis: mechanisms of non-response to hepatitis C therapy,” Liver International, vol. 35, no. 8, pp. 1923–1933, 2015. View at Publisher · View at Google Scholar
  19. M. Sulkowski, C. Hezode, J. Gerstoft et al., “Efficacy and safety of 8 weeks versus 12 weeks of treatment with grazoprevir (MK-5172) and elbasvir (MK-8742) with or without ribavirin in patients with hepatitis C virus genotype 1 mono-infection and HIV/hepatitis C virus co-infection (C-WORTHY): a randomised, open-label phase 2 trial,” The Lancet, vol. 385, no. 9973, pp. 1087–1097, 2015. View at Publisher · View at Google Scholar
  20. M. S. Sulkowski, I. M. Jacobson, and D. R. Nelson, “Daclatasvir plus sofosbuvir for HCV infection,” The New England Journal of Medicine, vol. 370, pp. 1560–1561, 2014. View at Google Scholar
  21. E. Lawitz, M. S. Sulkowski, R. Ghalib et al., “Simeprevir plus sofosbuvir, with or without ribavirin, to treat chronic infection with hepatitis C virus genotype 1 in non-responders to pegylated interferon and ribavirin and treatment-naive patients: the COSMOS randomised study,” The Lancet, vol. 384, no. 9956, pp. 1756–1765, 2014. View at Publisher · View at Google Scholar
  22. N. Afdhal, S. Zeuzem, P. Kwo et al., “Ledipasvir and sofosbuvir for untreated HCV genotype 1 infection,” The New England Journal of Medicine, vol. 370, no. 20, pp. 1889–1898, 2014. View at Publisher · View at Google Scholar
  23. Panel AIHG, “Hepatitis C guidance: AASLD-IDSA recommendations for testing, managing, and treating adults infected with hepatitis C virus,” Hepatology, vol. 62, no. 3, pp. 932–954, 2015. View at Google Scholar
  24. E. Huchet, “Varying efficacy of sofosbuvir treatment regimens in real life settings,” in Proceedings of the 4th Canadian Symposium on Hepatitis C, Banff, Canada, 2015.
  25. G. J. Dore and J. J. Feld, “Hepatitis C virus therapeutic development: in pursuit of “perfectovir”,” Clinical Infectious Diseases, vol. 60, no. 12, pp. 1829–1836, 2015. View at Publisher · View at Google Scholar
  26. V. Lohmann, “Viral and host factors of hepatitis C virus RNA replication,” in Proceedings of the 4th Canadian Symposium on Hepatitis C Virus, Banff, Canada, 2015.
  27. V. Lohmann, F. Körner, J.-O. Koch, U. Herian, L. Theilmann, and R. Bartenschlager, “Replication of subgenomic hepatitis C virus RNAs in a hepatoma cell line,” Science, vol. 285, no. 5424, pp. 110–113, 1999. View at Publisher · View at Google Scholar · View at Scopus
  28. C. Berger, I. Romero-Brey, D. Radujkovic et al., “Daclatasvir-like inhibitors of NS5A block early biogenesis of hepatitis C virus-induced membranous replication factories, independent of RNA replication,” Gastroenterology, vol. 147, no. 5, pp. 1094–1105.e5, 2014. View at Publisher · View at Google Scholar · View at Scopus
  29. K. H. Barakat, A. Anwar-Mohamed, J. A. Tuszynski, M. J. Robins, D. L. Tyrrell, and M. Houghton, “A refined model of the HCV NS5A protein bound to daclatasvir explains drug-resistant mutations and activity against divergent genotypes,” Journal of Chemical Information and Modeling, vol. 55, no. 2, pp. 362–373, 2015. View at Publisher · View at Google Scholar · View at Scopus
  30. S. Reiss, C. Harak, I. Romero-Brey et al., “The lipid kinase phosphatidylinositol-4 kinase III alpha regulates the phosphorylation status of hepatitis C virus NS5A,” PLoS Pathogens, vol. 9, no. 5, Article ID e1003359, 2013. View at Publisher · View at Google Scholar · View at Scopus
  31. I. Khan, D. S. Katikaneni, Q. Han et al., “Modulation of hepatitis C virus genome replication by glycosphingolipids and four-phosphate adaptor protein 2,” Journal of Virology, vol. 88, no. 21, pp. 12276–12295, 2014. View at Publisher · View at Google Scholar · View at Scopus
  32. H. Wang, J. W. Perry, A. S. Lauring, P. Neddermann, R. De Francesco, and A. W. Tai, “Oxysterol-binding protein is a phosphatidylinositol 4-kinase effector required for HCV replication membrane integrity and cholesterol trafficking,” Gastroenterology, vol. 146, no. 5, pp. 1373–1385.e11, 2014. View at Publisher · View at Google Scholar · View at Scopus
  33. M. Götte, “Resistance to HCV NS5A and NS5B inhibitors: significance and mechanisms,” in Proceedings of the 4th Canadian Symposium on Hepatitis C Virus, Banff, Canada, 2015.
  34. E. S. Svarovskaia, H. Dvory Sobol, N. Parkin et al., “Infrequent development of resistance in genotype 1-6 hepatitis C virus-infected subjects treated with sofosbuvir in phase 2 and 3 clinical trials,” Clinical Infectious Diseases, vol. 59, no. 12, pp. 1666–1674, 2014. View at Publisher · View at Google Scholar · View at Scopus
  35. M. D. Miller and H. Mo, “HCV NS5B polymerase inhibitors: nucleoside analogs,” in Proceedings of the International Workshop on Antiviral Drug Resistance: Meeting the Global Challenge, Antiviral Therapy, Berlin, Germany, June 2014.
  36. M. H. Powdrill, E. P. Tchesnokov, R. A. Kozak et al., “Contribution of a mutational bias in hepatitis C virus replication to the genetic barrier in the development of drug resistance,” Proceedings of the National Academy of Sciences of the United States of America, vol. 108, no. 51, pp. 20509–20513, 2011. View at Publisher · View at Google Scholar · View at Scopus
  37. T. C. Appleby, J. K. Perry, E. Murakami et al., “Structural basis for RNA replication by the hepatitis C virus polymerase,” Science, vol. 347, no. 6223, pp. 771–775, 2015. View at Publisher · View at Google Scholar · View at Scopus
  38. B. Simmons, J. Saleem, K. Heath, G. S. Cooke, and A. Hill, “Long-term treatment outcomes of patients infected with hepatitis C virus: a systematic review and meta-analysis of the survival benefit of achieving a sustained virological response,” Clinical Infectious Diseases, vol. 61, no. 5, pp. 730–740, 2015. View at Publisher · View at Google Scholar · View at Scopus
  39. C. Cooper, “HCV Care Clarity and Chaos in Canada,” in Proceedings of the 4th Canadian Symposium on Hepatitis C Virus, Banff, Canada, 2015.
  40. H. A. Shah, J. Heathcote, and J. J. Feld, “A Canadian screening program for hepatitis C: is now the time?” Canadian Medical Association Journal, vol. 185, no. 15, pp. 1325–1328, 2013. View at Publisher · View at Google Scholar · View at Scopus
  41. R. P. Myers, M. Krajden, M. Bilodeau et al., “Burden of disease and cost of chronic hepatitis C virus infection in Canada,” Canadian Journal of Gastroenterology and Hepatology, vol. 28, no. 5, pp. 243–250, 2014. View at Publisher · View at Google Scholar · View at Scopus
  42. A. J. van der Meer, B. J. Veldt, J. J. Feld et al., “Association between sustained virological response and all-cause mortality among patients with chronic hepatitis C and advanced hepatic fibrosis,” The Journal of the American Medical Association, vol. 308, no. 24, pp. 2584–2593, 2012. View at Publisher · View at Google Scholar · View at Scopus
  43. C. A. F. J. J. Cooper, “Debate: ‘be it resolved that new HCV treatments should only be used on the sickest patients (F2 and above)’,” in Proceedings of the 4th Canadian Symposium on Hepatitis C Virus, Banff, Canada, 2015.
  44. Z. M. Younossi, M. E. Singer, H. M. Mir, L. Henry, and S. Hunt, “Impact of interferon free regimens on clinical and cost outcomes for chronic hepatitis C genotype 1 patients,” Journal of Hepatology, vol. 60, no. 3, pp. 530–537, 2014. View at Publisher · View at Google Scholar · View at Scopus
  45. M. Krajden, P. Bacon, P. Bourgois et al., “Panel discussion,” in Proceedings of the 4th Canadian Symposium on Hepatitis C Virus Infection, Banff, Canada, February 2015.
  46. D. Luster, “The role for patient advocacy in building a Canadian HCV action plan,” in Proceedings of the 4th Canadian Symposium on Hepatitis C Virus, Banff, Canada, 2015.
  47. M. Kuczynski, “Beyond the medication—resources needed for successful treatment,” in Proceedings of the 4th Canadian Symposium on Hepatitis C Virus, Banff, Canada, 2015.
  48. Public Health Agency of Canada, Hepatitis C in Canada: 2005–2010 Surveillance Report: Centre for Communicable Diseases and Infection Control, Infectious Disease Prevention and Control Branch, Public Health Agency of Canada, 2011.
  49. R. Remis, “Modelling the incidence and prevalence of hepatitis C infection and its sequelae in Canada, 2007,” Final Report, Health Canada, Ottawa, Canada, 2007. View at Google Scholar
  50. I. M. Jacobson, R. S. Brown Jr., B. Freilich et al., “Peginterferon alfa-2b and weight-based or flat-dose ribavirin in chronic hepatitis C patients: a randomized trial,” Hepatology, vol. 46, no. 4, pp. 971–981, 2007. View at Publisher · View at Google Scholar
  51. P. Bourgois, “Confronting the contradictions between law enforcement and public health: an anthropological perspective on the hepatitis C risk environment in teh US inner-city with notes from Canada,” in Proceedings of the 4th Canadian Symposium on Hepatitis C Virus, Banff, Canada, 2015.
  52. S. Larney, H. Kopinski, C. G. Beckwith et al., “Incidence and prevalence of hepatitis C in prisons and other closed settings: results of a systematic review and meta-analysis,” Hepatology, vol. 58, no. 4, pp. 1215–1224, 2013. View at Publisher · View at Google Scholar · View at Scopus
  53. J. Grebely and G. J. Dore, “Can hepatitis C virus infection be eradicated in people who inject drugs?” Antiviral Research, vol. 104, no. 1, pp. 62–72, 2014. View at Publisher · View at Google Scholar · View at Scopus
  54. A. A. M. Shaheen, A. F. Wan, and R. P. Myers, “FibroTest and FibroScan for the prediction of hepatitis C-related fibrosis: a systematic review of diagnostic test accuracy,” The American Journal of Gastroenterology, vol. 102, no. 11, pp. 2589–2600, 2007. View at Publisher · View at Google Scholar · View at Scopus
  55. J. Vergniol, J. Foucher, E. Terrebonne et al., “Noninvasive tests for fibrosis and liver stiffness predict 5-year outcomes of patients with chronic hepatitis C,” Gastroenterology, vol. 140, no. 7, pp. 1970–1979, 2011. View at Publisher · View at Google Scholar · View at Scopus
  56. S. Liu, M. Schwarzinger, F. Carrat, and J. D. Goldhaber-Fiebert, “Cost effectiveness of fibrosis assessment prior to treatment for chronic hepatitis C patients,” PLoS ONE, vol. 6, no. 12, Article ID e26783, 2011. View at Publisher · View at Google Scholar · View at Scopus
  57. J. Grebely, “LiveRLife: a liver health promotion campaign amoung people who inject drugs in the drug and alcohol setting,” in Proceedings of the 4th Canadian Symposium on Hepatitis C Virus, Banff, Canada, 2015.
  58. B. K. Moessner, T. R. Jørgensen, M. Skamling et al., “Outreach screening of drug users for cirrhosis with transient elastography,” Addiction, vol. 106, no. 5, pp. 970–976, 2011. View at Publisher · View at Google Scholar · View at Scopus
  59. J. Foucher, B. Reiller, V. Jullien et al., “FibroScan used in street-based outreach for drug users is useful for hepatitis c virus screening and management: a prospective study,” Journal of Viral Hepatitis, vol. 16, no. 2, pp. 121–131, 2009. View at Publisher · View at Google Scholar · View at Scopus
  60. R. P. Myers, “Burden of HCV in Canada and management strategies,” in Proceedings of the 4th Canadian Symposium on Hepatitis C Virus, Banff, Canada, 2015.
  61. S. Hutchinson, “Scotland's action plan on hepatitis C,” in Proceedings of the 4th Canadian Symposium on Hepatitis C Virus, Banff, Canada, 2015.
  62. S. J. Hutchinson, J. F. Dillon, R. Fox et al., “Expansion of HCV treatment access to people who have injected drugs through effective translation of research into public health policy: Scotland's experience,” International Journal of Drug Policy, vol. 26, no. 11, pp. 1041–1049, 2015. View at Publisher · View at Google Scholar · View at Scopus
  63. M. Ouellette, “CIHR funding for HCV research,” in Proceedings of the 4th Canadian Symposium on Hepatitis C Virus, Banff, Canada, 2015.
  64. M. Krajden, “Responding to hepatitis C in Canada: status and deliberations of the national HCV task group,” in Proceedings of the 4th Canadian Symposium on Hepatitis C Virus, Banff, Canada, 2015.
  65. B. D. Smith, R. L. Morgan, G. A. Beckett et al., “Recommendations for the identification of chronic hepatitis C virus infection among persons born during 1945–1965,” MMWR Recommendations and reports, vol. 61, pp. 1–32, 2012. View at Google Scholar · View at Scopus