1 / 24

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’’

sarah-jacobs
Download Presentation

Hepatitis C Nonresponders

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  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.

More Related