NI Hepatitis B and C Network:
Diagnosis and Treatment
• Developments in 2011/12
– Introduction of new treatments for hepatitis C
– Near patient testing for ethnic groups
– Treatment of HBV in pregnancy
– Closing the gap
Annual incidence of new hepatitis C cases
(antibody positive) in N Ireland 1994-2011
160
Number of positive tests
140
134
135
120
132
106
100
100
116
115
114
86
75
80
65
63
55
60
65
54
54
46
43
40
20
0
1994
1995
1996
1997
1998
1999
2000
2001
Years
2002
2003
2004
2005
2006
2007
2008
2009
2010
2011
Incidence of new hepatitis C antibody positive
and confirmed PCR positive cases in N Ireland
160
Number of HCV positve cases diagnosed
140
135
134
New cases of HCV
132
120
114
100
PCR Positive
116
115
106
103
95
80
86
86
79
73
74
2010
2011
60
40
20
0
Years
2005
2006
2007
2008
2009
Treatment of Chronic Hepatitis C
• Goal is to make patient PCR negative and
have Sustained Virological Response (SVR)
• SVR = PCR negative 6 months after
stopping treatment
• SVR affected by:
– Genotype
– Viral load
– Fibrosis score
– Obesity, gender, race, IL28B
Treatment of
Genotypes 2 and 3
• Current therapy:
• Pegylated interferon plus Ribavirin
• 16 to 24 weeks duration
• Success rate 80-85% SVR
• No good options for treatment failures
Treatment of
Genotype 1
• Best therapy up until 2012:
• Pegylated interferon plus Ribavirin
• 48 weeks duration
• SVR 40% (depending on profile)
New treatment for
Genotype 1 HCV
(Rx naïve patients)
Direct Acting Antivirals (DAAs)
• Telaprevir
• 12 weeks triple therapy, then dual therapy 12-36wks
• SVR 72-75% (v 44% PR control)
• Side effects: anaemia, rash
• Boceprevir
• 4 week lead in, then triple therapy for 24-44 wks
• SVR 63-66% (v 38% PR control)
• Side effects: anaemia, dysguesia
What about Genotype 1
patients with previous
treatment failure?
Definitions of failure on prior Peg-IFN/RBV therapy
HCV RNA level
Non-response
Null response
Relapse
2 log10 drop
Partial response
Detection limit
Treatment
Adapted from Shiffman M. Curr Gastroenterol Rep 2006;8:46–52
Neumann A, et al. Science 1998;282:103–7; De Bruijne J, et al. Neth J Med 2008;66:311–22
REALIZE (telaprevir): SVR in prior relapsers, partial
responders and null responders
Prior
relapsers
Prior
partial
responders
*
Prior null
responder
s
SVR (%)
*
*
*
*
PR48
n/N=
16/68
*p<0.001 vs PR48; post-hoc analysis
LI T12/
PR48
T12/
PR48
124/141
121/145
PR48
*
LI T12/
PR48
T12/
PR48
PR48
LI T12/
PR48
T12/
PR48
26/48
29/49
2/37
25/75
21/72
4/27
Foster GR, et al. Hepatol Int 2011;5(Suppl. 1):14
RESPOND-2 (boceprevir): SVR in prior relapsers
and partial responders
Prior
relapsers
Prior
partial
responders
SVR (%)
Prior null
responders were
excluded from
RESPOND-2
PR48
n/N=
15/51
BOC
RGT
BOC44/
PR48
72/105
77/103
PR48
BOC
RGT
BOC44/
PR48
23/57
30/58
2/29
Bacon BR, et al. Hepatology 2010;52(Suppl.):430A
DAA use in Northern Ireland
• Commenced August 2012
• For all treatment naïve AND treatment experienced
genotype 1 HCV patients (NICE)
• Backlog treated first
• Cost: approx £20,000 per patient
• NOT applicable to genotypes 2/3
The Future…
• Next generation DAAs
•
•
•
•
Protease inhibitors
Polymerase inhibitors
Nucleoside analogues
NS5A inhibitors
• Interferon-free regimens