Post on 19-Jan-2016
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Hepatitis C Nonresponders
Prakash Zacharias
Proportion of Genotypes in India
Hissar
et al (N
)
Singh
et al (N
)
Panigr
ahi e
t al (N
)
Amarapurka
r et a
l(W)
Chaudhuri e
t al (E
)
Chaudhury
et al(E
)
Raghuram
an et a
l (S&E)
Veliammai
(S)
Khaja et a
l (S)
PVS0%
10%20%30%40%50%60%70%80%90%
100%
MixedOther GenotypesGenotype3Genotype2Genotype1
Modified from Mukhopadhya A; J. Biosci.2008, 33 465–473
Genotypes & Duration of therapy
Genotype I,4,5,6
Genotype 2, 3
48weeks
24weeks
SVR
SVRVirologic ‘‘cure’’Improves morbidity and mortality
Evolution of Hepatitis C Treatment
IFN α 2b x 24 wks
IFN α 2b x 48 wks
IFN α 2b x tiw + Ribavirin
PEG IFN
PEG IFN QW + Ribavirin
PEG IFN QW + wt based Ribavirin
0%
18%
41%
24-36%
54%
61%
Treatment Response
SVR on Treatment on PEG IFN + Ribavirin therapy
Series10
10
20
30
40
50
60
70
80
90
Geno 2,3Geno I
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 RNAreplication & virion assembly
Boceprevir (BOC) and Telaprevir(TVR)
Non Responders
Null ResponderNo decline (by at
least 2 log) in HCV RNA wk12
RelapserHCV RNA undetectable
during treatment; Reappear after stopping
At least 2 log IU/ml at wk 12; Detectable wk 24
Partial Responder
Boceprevir in previously treated cases- RESPOND-2 Trial
Overall Relapser Partial responder0
10
20
30
40
50
60
70
80
66
75
52
59
69
40
21
29
7
BOC/PR48BOC RGTSOC
Bacon BR et al; N Engl J Med 2011;364: 1207-1217.
Boceprevir in previously treated cases- RESPOND-2 Trial
Overall Relapser Partial responder0
10
20
30
40
50
60
70
80
66
75
52
59
69
40
21
29
7
BOC/PR48BOC RGTSOC
Bacon BR et al; N Engl J Med 2011;364: 1207-1217.
4-wk lead-in phase of PegIFN +RBV → fixed duration triple therapyx 44wks
Boceprevir in previously treated cases- RESPOND-2 Trial
Overall Relapser Partial responder0
10
20
30
40
50
60
70
80
66
75
52
59
69
40
21
29
7
BOC/PR48BOC RGTSOC
Bacon BR et al; N Engl J Med 2011;364: 1207-1217.
4-wk lead-in phase → RGT (BOC +PegIFN + RBV x32 wks; If detectable HCV RNA wk 8, SOC for additional 12 weeks
Boceprevir in previously treated cases- RESPOND-2 Trial
Overall Relapser Partial responder0
10
20
30
40
50
60
70
80
66
75
52
59
69
40
21
29
7
BOC/PR48BOC RGTSOC
Bacon BR et al; N Engl J Med 2011;364: 1207-1217.
Teleprevir in previously treated cases (REALIZE study)
Overall Relapser Partial Responder Null Responder0
10
20
30
40
50
60
70
80
90
100
64
83
59
29
66
88
54
33
17
24
15
5
T12PR48L1-T12PR48SOC
Zeuzem S et al.N Engl J Med 2011;364: 2417-2428
Teleprevir in previously treated cases (REALIZE study)
Overall Relapser Partial Responder Null Responder0
10
20
30
40
50
60
70
80
90
100
64
83
59
29
66
88
54
33
17
24
15
5
T12PR48L1-T12PR48SOC
Zeuzem S et al.N Engl J Med 2011;364: 2417-2428
Triple therapy x 12 wks → SOC x
36 wks
Teleprevir in previously treated cases (REALIZE study)
Overall Relapser Partial Responder Null Responder0
10
20
30
40
50
60
70
80
90
100
64
83
59
29
66
88
54
33
17
24
15
5
T12PR48L1-T12PR48SOC
Zeuzem S et al.N Engl J Med 2011;364: 2417-2428
Lead-in treatment with
SOC x 4 weeks → triple therapy x
12 wks
Teleprevir in previously treated cases (REALIZE study)
Overall Relapser Partial Responder Null Responder0
10
20
30
40
50
60
70
80
90
100
64
83
59
29
66
88
54
33
17
24
15
5
T12PR48L1-T12PR48SOC
Zeuzem S et al.N Engl J Med 2011;364: 2417-2428
Recommendation
Virological relapse or Partial responders
( Evidence - Class 1,Level A)
GHANY ET AL.,HEPATOLOGY, October 2011
Re-treatment with Boceprevir or Telaprevir,+ PEG IFN alfa and weight-basedribavirin
Recommendation
Virological relapse or Partial responders
( Evidence - Class 1,Level A)
GHANY ET AL.,HEPATOLOGY, October 2011
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)
Recommendation
GHANY ET AL.,HEPATOLOGY, October 2011
Evidence Class 2b, Level B
Re-treatment with telaprevir + PEG IFN alfa +
wt based ribavirin
Null Responder
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
THANKS
IL28B Testing & SVR in Gen 1 (SOC)
Caucasians Blacks0
10
20
30
40
50
60
70
80
69
48
33
15
27
13
CCCTTT
Thompson AJ et al. Gastroenterology 2010;139:120-129.