Journal of Hepatology
Volume 53, Issue 4 , Pages 616-623 , October 2010

Low virological response and high relapse rates in hepatitis C genotype 1 patients with advanced fibrosis despite adequate therapeutic dosing

  • Wendy S.C. Cheng

      Affiliations

    • Royal Perth Hospital, Perth, Australia
  • ,
  • Stuart K. Roberts

      Affiliations

    • Alfred Hospital, Melbourne, Australia
  • ,
  • Geoffrey McCaughan

      Affiliations

    • Royal Prince Alfred Hospital, Sydney, Australia
  • ,
  • William Sievert

      Affiliations

    • Monash Medical Centre and Monash University, Melbourne, Australia
  • ,
  • Martin Weltman

      Affiliations

    • Nepean Hospital, Sydney, Australia
  • ,
  • Darrell Crawford

      Affiliations

    • Greenslopes Hospital, Brisbane, Australia
  • ,
  • William Rawlinson

      Affiliations

    • SEALS Microbiology, Prince of Wales Hospital, Sydney, Australia
  • ,
  • Philippa S. Marks

      Affiliations

    • National Centre in HIV Epidemiology and Clinical Research, University of New South Wales, Sydney, Australia
  • ,
  • James Thommes

      Affiliations

    • Roche Products, Nutley, NJ, USA
  • ,
  • Bishoy Rizkalla

      Affiliations

    • Roche Products, Sydney, Australia
  • ,
  • Motoko Yoshihara

      Affiliations

    • Roche Products, Sydney, Australia
  • ,
  • Gregory J Dore

      Affiliations

    • National Centre in HIV Epidemiology and Clinical Research, University of New South Wales, Sydney, Australia
    • St. Vincent’s Hospital, Sydney, Australia
    • Corresponding Author InformationCorresponding author. Address: National Centre in HIV Epidemiology and Clinical Research, University of New South Wales, CFI Building, Corner Boundary and West Streets, Darlinghurst, NSW 2010, Australia. Tel.: +61 2 9385 0900; fax: +61 2 9385 0876.
  • ,
  • on behalf of the CHARIOT Study Group

Received 12 November 2009 ,Revised 19 March 2010 ,Accepted 11 April 2010.

References 

  1. Fried MW, Shiffman ML, Reddy KR, Smith C, Marinos G, Goncales FL, et al. Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection. N Engl J Med. 2002;347:975–982
  2. Hadziyannis SJ, Sette H, Morgan TR, Balan V, Diago M, Marcellin P, et al. Peginterferon-alpha2a and ribavirin combination therapy in chronic hepatitis C: a randomized study of treatment duration and ribavirin dose. Ann Intern Med. 2004;140:346–355
  3. Manns MP, McHutchison JG, Gordon SC, Rustgi VK, Shiffman M, Reindollar R, et al. Peginterferon alfa-2b plus ribavirin compared with interferon alfa-2b plus ribavirin for initial treatment of chronic hepatitis C: a randomised trial. Lancet. 2001;358:958–965
  4. Marrache F, Consigny Y, Ripault MP, Cazals-Hatem D, Martinot M, Boyer N, et al. Safety and efficacy of peginterferon plus ribavirin in patients with chronic hepatitis C and bridging fibrosis or cirrhosis. J Viral Hepat. 2005;12:421–428
  5. Abergel A, Hezode C, Leroy V, Barange K, Bronowicki JP, Tran A, et al. Peginterferon alpha-2b plus ribavirin for treatment of chronic hepatitis C with severe fibrosis: a multicentre randomized controlled trial comparing two doses of peginterferon alpha-2b. J Viral Hepat. 2006;13:811–820
  6. Roffi L, Colloredo G, Pioltelli P, Bellati G, Pozzpi M, Parravicini P, et al. Pegylated interferon-alpha2b plus ribavirin: an efficacious and well-tolerated treatment regimen for patients with hepatitis C virus related histologically proven cirrhosis. Antivir Ther. 2008;13:663–673
  7. Bruno S, Camma C, Di Marco V, Rumi M, Vinci M, Camozzi M, et al. Peginterferon alfa-2b plus ribavirin for naive patients with genotype 1 chronic hepatitis C: a randomized controlled trial. J Hepatol. 2004;41:474–481
  8. Serfaty L, Aumaitre H, Chazouilleres O, Bonnand AM, Rosmorduc O, Poupon RE, et al. Determinants of outcome of compensated hepatitis C virus-related cirrhosis. Hepatology. 1998;27:1435–1440
  9. Benvegnu L, Gios M, Boccato S, Alberti A. Natural history of compensated viral cirrhosis: a prospective study on the incidence and hierarchy of major complications. Gut. 2004;53:744–749
  10. Fattovich G, Giustina G, Degos F, Tremolada F, Diodati G, Almasio P, et al. Morbidity and mortality in compensated cirrhosis type C: a retrospective follow-up study of 384 patients. Gastroenterology. 1997;112:463–472
  11. Shiratori Y, Ito Y, Yokosuka O, Imazeki F, Nakata R, Tanaka N, et al. Antiviral therapy for cirrhotic hepatitis C: association with reduced hepatocellular carcinoma development and improved survival. Ann Intern Med. 2005;142:105–114
  12. Bruno S, Stroffolini T, Colombo M, Bollani S, Benvegnu L, Mazzella G, et al. Sustained virological response to interferon-alpha is associated with improved outcome in HCV-related cirrhosis: a retrospective study. Hepatology. 2007;45:579–587
  13. Veldt BJ, Heathcote EJ, Wedemeyer H, Reichen J, Hofmann WP, Zeuzem S, et al. Sustained virologic response and clinical outcomes in patients with chronic hepatitis C and advanced fibrosis. Ann Intern Med. 2007;147:677–684
  14. Shiratori Y, Imazeki F, Moriyama M, Yano M, Arakawa Y, Yokosuka O, et al. Histologic improvement of fibrosis in patients with hepatitis C who have sustained response to interferon therapy. Ann Intern Med. 2000;132:517–524
  15. Poynard T, McHutchison J, Manns M, Trepo C, Lindsay K, Goodman Z, et al. Impact of pegylated interferon alfa-2b and ribavirin on liver fibrosis in patients with chronic hepatitis C. Gastroenterology. 2002;122:1303–1313
  16. Roberts SK, Weltman MD, Crawford DH, McCaughan GW, Sievert W, Cheng WS, et al. Impact of high-dose peginterferon alfa-2A on virological response rates in patients with hepatitis C genotype 1: a randomized controlled trial. Hepatology. 2009;50:1045–1055
  17. Bedossa P, Poynard T. An algorithm for the grading of activity in chronic hepatitis C. The METAVIR Cooperative Study Group. Hepatology. 1996;24:289–293
  18. Fried MW, Shiffman ML, Reddy KR, Smith C, Marinos G, Goncales FL, et al. Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection. N Engl J Med. 2002;347:975–982
  19. Pal S, Shuhart MC, Thomassen L, Emerson SS, Su T, Feuerborn N, et al. Intrahepatic hepatitis C virus replication correlates with chronic hepatitis C disease severity in vivo. J Virol. 2006;80:2280–2290
  20. Medeiros-Filho JE, de Carvalho Mello IM, Pinho JR, Neumann AU, de Mello Malta F, da Silva LC, et al. Differences in viral kinetics between genotypes 1 and 3 of hepatitis C virus and between cirrhotic and non-cirrhotic patients during antiviral therapy. World J Gastroenterol. 2006;12:7271–7277
  21. Dahari H, Layden-Almer JE, Kallwitz E, Ribeiro RM, Cotler SJ, Layden TJ, et al. A mathematical model of hepatitis C virus dynamics in patients with high baseline viral loads or advanced liver disease. Gastroenterology. 2009;136:1402–1409
  22. Napoli J, Bishop GA, McGuinness PH, Painter DM, McCaughan GW. Progressive liver injury in chronic hepatitis C infection correlates with increased intrahepatic expression of Th1-associated cytokines. Hepatology. 1996;24:759–765
  23. Sarasin-Filipowicz M, Oakeley EJ, Duong FH, Christen V, Terracciano L, Filipowicz W, et al. Interferon signaling and treatment outcome in chronic hepatitis C. Proc Natl Acad Sci USA. 2008;105:7034–7039
  24. Ge D, Fellay J, Thompson AJ, Simon JS, Shianna KV, Urban TJ, et al. Genetic variation in IL28B predicts hepatitis C treatment-induced viral clearance. Nature. 2009;461:399–401
  25. Suppiah V, Moldovan M, Ahlenstiel G, Berg T, Weltman M, Abate ML, et al. IL28B is associated with response to chronic hepatitis C interferon-alpha and ribavirin therapy. Nat Genet. 2009;41:1100–1104
  26. Ferenci P, Laferl H, Scherzer TM, Gschwantler M, Maieron A, Brunner H, et al. Peginterferon alfa-2a and ribavirin for 24 weeks in hepatitis C type 1 and 4 patients with rapid virological response. Gastroenterology. 2008;135:451–458
  27. Jensen DM, Morgan TR, Marcellin P, Pockros PJ, Reddy KR, Hadziyannis SJ, et al. Early identification of HCV genotype 1 patients responding to 24 weeks peginterferon alpha-2a (40kd)/ribavirin therapy. Hepatology. 2006;43:954–960
  28. Mangia A, Minerva N, Bacca D, Cozzolongo R, Ricci GL, Carretta V, et al. Individualized treatment duration for hepatitis C genotype 1 patients: a randomized controlled trial. Hepatology. 2008;47:43–50
  29. Sanchez-Tapias JM, Diago M, Escartin P, Enriquez J, Romero-Gomez M, Barcena R, et al. Peginterferon-alfa2a plus ribavirin for 48 versus 72 weeks in patients with detectable hepatitis C virus RNA at week 4 of treatment. Gastroenterology. 2006;131:451–460
  30. Ferenci P, Laferl H, Scherzer TM, Maieron A, Hofer H, Stauber R, et al. Peginterferon alfa-2a/ribavirin for 48 or 72 weeks in hepatitis C genotypes 1 and 4 patients with slow virologic response. Gastroenterology. 2010;138:503–512
  31. Hezode C, Forestier N, Dusheiko G, Ferenci P, Pol S, Goeser T, et al. Telaprevir and peginterferon with or without ribavirin for chronic HCV infection. N Engl J Med. 2009;360:1839–1850
  32. McHutchison JG, Everson GT, Gordon SC, Jacobson IM, Sulkowski M, Kauffman R, et al. Telaprevir with peginterferon and ribavirin for chronic HCV genotype 1 infection. N Engl J Med. 2009;360:1827–1838

PII: S0168-8278(10)00540-4

doi: 10.1016/j.jhep.2010.04.024

Journal of Hepatology
Volume 53, Issue 4 , Pages 616-623 , October 2010