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Hepatitis C Nonresponders

Hepatitis C Nonresponders. Prakash Zacharias. Proportion of Genotypes in India. Modified from Mukhopadhya A; J. Biosci.2008, 33 465–473. Genotypes & Duration of therapy. 48weeks. Genotype I,4,5,6. 24weeks. Genotype 2, 3. SVR. Virologic ‘‘ cure’’

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Hepatitis C Nonresponders

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  1. Hepatitis C Nonresponders Prakash Zacharias

  2. Proportion of Genotypes in India Modified from Mukhopadhya A; J. Biosci.2008, 33 465–473

  3. Genotypes & Duration of therapy 48weeks Genotype I,4,5,6 24weeks Genotype 2, 3

  4. SVR Virologic‘‘cure’’ Improves morbidity and mortality SVR

  5. Evolution of Hepatitis C Treatment IFN α 2b x 24 wks 0% 18% IFN α 2b x 48 wks IFN α 2b x tiw + Ribavirin 41% PEG IFN 24-36% PEG IFN QW + Ribavirin 54% PEG IFN QW + wt based Ribavirin 61%

  6. SVR on Treatment on PEG IFN + Ribavirin therapy

  7. Question HCV Genotype I with advanced fibrosis – PEG IFN + Ribavirin non responder -> What next ?

  8. Developments in HCV treatment • Direct-acting antiviral (DAA) agents • Identification of several single-nucleotide polymorphisms associated with spontaneous and treatment-induced clearance of HCV infection

  9. HCV NS3/4A serine protease required for RNA replication & virion assembly Boceprevir (BOC) and Telaprevir (TVR)

  10. Non Responders At least 2 log IU/ml at wk 12; Detectable wk 24 Partial Responder Null Responder No decline (by at least 2 log) in HCV RNA wk12 Relapser HCV RNA undetectable during treatment; Reappear after stopping

  11. Boceprevir in previously treated cases- RESPOND-2 Trial Bacon BR et al; N Engl J Med 2011;364: 1207-1217.

  12. Boceprevir in previously treated cases- RESPOND-2 Trial 4-wk lead-in phase of PegIFN +RBV → fixed duration triple therapyx 44wks Bacon BR et al; N Engl J Med 2011;364: 1207-1217.

  13. Boceprevir in previously treated cases- RESPOND-2 Trial 4-wk lead-in phase → RGT (BOC +PegIFN + RBV x32 wks; If detectable HCV RNA wk 8, SOC for additional 12 weeks Bacon BR et al; N Engl J Med 2011;364: 1207-1217.

  14. Boceprevir in previously treated cases- RESPOND-2 Trial Bacon BR et al; N Engl J Med 2011;364: 1207-1217.

  15. Teleprevir in previously treated cases (REALIZE study) Zeuzem S et al.NEngl J Med 2011;364: 2417-2428

  16. Teleprevir in previously treated cases (REALIZE study) Triple therapy x 12 wks → SOC x 36 wks Zeuzem S et al.NEngl J Med 2011;364: 2417-2428

  17. Teleprevir in previously treated cases (REALIZE study) Lead-in treatment with SOC x 4 weeks → triple therapy x 12 wks Zeuzem S et al.NEngl J Med 2011;364: 2417-2428

  18. Teleprevir in previously treated cases (REALIZE study) Zeuzem S et al.NEngl J Med 2011;364: 2417-2428

  19. Recommendation Re-treatment with Boceprevir or Telaprevir, + PEG IFN alfa and weight-based ribavirin Virological relapse or Partial responders ( Evidence - Class 1,Level A) GHANY ET AL.,HEPATOLOGY, October 2011

  20. Recommendation Response-guided therapy using either a boceprevir- or telaprevir- based regimen for relapsers (Class 2a, Level B for boceprevir; Class 2b, Level C for telaprevir), & partial responders (Class 2b, Level B for boceprevir; Class 3, Level C for telaprevir) Virological relapse or Partial responders ( Evidence - Class 1,Level A) GHANY ET AL.,HEPATOLOGY, October 2011

  21. Recommendation Re-treatment with telaprevir + PEG IFN alfa + wt based ribavirin Null Responder Evidence Class 2b, Level B GHANY ET AL.,HEPATOLOGY, October 2011

  22. Recommendation Treatment should be withdrawn because of the high likelihood of developing antiviral resistance Patients re-treated with telaprevir + PEG IFN + Ribavirin who continue to have detectable HCV RNA > 1,000 IU at weeks 4 or 12

  23. Thanks

  24. IL28B Testing & SVR in Gen 1 (SOC) Thompson AJ et al. Gastroenterology 2010;139:120-129.

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