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This study investigates the proportions of hepatitis C genotypes among nonresponders in India and evaluates treatment outcomes associated with different therapy regimens. The analysis includes examination of sustained virologic response (SVR) rates for various genotypes and therapy durations, revealing that genotype I and advanced fibrosis present significant treatment challenges. The emergence of direct-acting antiviral agents has changed the landscape of hepatitis C treatment, necessitating the reevaluation of therapy strategies for individual patient responses, particularly in nonresponders.
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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’’ Improves morbidity and mortality SVR
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%
Question HCV Genotype I with advanced fibrosis – PEG IFN + Ribavirin non responder -> What next ?
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
HCV NS3/4A serine protease required for RNA replication & virion assembly Boceprevir (BOC) and Telaprevir (TVR)
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
Boceprevir in previously treated cases- RESPOND-2 Trial Bacon BR et al; N Engl J Med 2011;364: 1207-1217.
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.
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.
Boceprevir in previously treated cases- RESPOND-2 Trial Bacon BR et al; N Engl J Med 2011;364: 1207-1217.
Teleprevir in previously treated cases (REALIZE study) Zeuzem S et al.NEngl J Med 2011;364: 2417-2428
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
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
Teleprevir in previously treated cases (REALIZE study) Zeuzem S et al.NEngl J Med 2011;364: 2417-2428
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
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
Recommendation Re-treatment with telaprevir + PEG IFN alfa + wt based ribavirin Null Responder Evidence Class 2b, Level B GHANY ET AL.,HEPATOLOGY, October 2011
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
IL28B Testing & SVR in Gen 1 (SOC) Thompson AJ et al. Gastroenterology 2010;139:120-129.