management of hepatitis c in alcohol and other drug services greg dore viral hepatitis clinical...
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Management of Hepatitis C in Alcohol and Other Drug Services
Greg Dore
Viral Hepatitis Clinical Research Program
National Centre in HIV Epidemiology and Clinical Research
Overview
HCV epidemiology
HCV treatment
HCV treatment among methadone clients and current IDU
Strategies to improve HCV treatment outcomes
Hepatitis C management in AOD services
Hepatitis C epidemiology
Hepatitis C notifications: 1990-2005
0
5000
10000
15000
20000
25000
1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005
NCHECR 2006
Hepatitis C notifications 15-19 years: 1996-2005
0
100
200
300
400
500
600
700
1996 1997 1998 1999 2000 2001 2002 2003 2004 2005
Male
Female
Hepatitis C epidemiology
NCHECR 2006Heroin shortage
HCV prevalence among IDUs in annual NSP survey
0
10
20
30
40
50
60
70
1999 2000 2001 2002 2003 2004 2005
Females
Males
NCHECR 2006
%
Hepatitis C epidemiology
HCV prevalence among IDUs in NSP survey (< 20 years)
0
10
20
30
40
50
60
70
2001 2002 2003 2004 2005
Females
Males
NCHECR 2006
%
Hepatitis C epidemiology
HCV HIV
HBV
264,000
90,000 – 160,000
17,000
Estimates of BBV prevalence in Australia
Hepatitis C epidemiology
ORT40,000
HCV RNA+20,000
HCV Ab+30,000
Estimates of HCV population on opiate pharmacotherapy
Hepatitis C epidemiology
HBV HCV Description D SMR 95% CI D SMR 95%CI All 896 1.4 1.3 - 1.5 3342 3.1 3.0 - 3.2
All liver 227 12.2 10.7 - 13.9 503 16.8 15.4 - 18.3
HCC 131 27.8 23.4 - 33.0 117 16.7 14.0 - 20.1
HIV 35 9.2 6.6 - 12.9 49 5.2 4.0 - 6.9
Lymphoid 35 1.7 1.2 - 2.4 62 1.9 1.5 - 2.5
Drug 31 1.4 1.0 - 2.0 989 19.3 18.1 - 20.5
HBV and HCV stand. mortality rates: NSW linkage study
Amin et al Lancet 2006
Hepatitis C epidemiology
0
50
100
150
200
250
300
0-19 20 25 30 35 40 45 50 55 60 65 70 75 80+
Drug
Liver
Drug and liver-related deaths in people with HCV
Deaths
Hepatitis C epidemiology
Trends in HCV deaths: NSW linkage study
0
50
100
150
200
250
300
1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002
Liver disease
Drug
Hepatitis C epidemiology
Estimates of people with HCV cirrhosis: 1990-2020
0
5000
10000
15000
20000
25000
30000
35000
1990 1995 2000 2005 2010 2015 2020
Dore et al J Clin Virol 2003
Hepatitis C epidemiology
IFN-α2b24 weeks
8%-12%
PEG-IFN48 weeks
25%-29%IFN-α2b 48 weeks
15%-22%
IFN-α2b+RBV 48 weeks
41%
PEG-IFN+RBV 24-48 weeks 61%-65%
10 years
Sustained Virological Response
Hepatitis C treatment
?
Issues
Positive
Curative potential (50 – 80%)
Improving response rates and clinical experience
Government-subsidized
Some expansion of access – removal of liver biopsy
Negative
Toxicity: flu-like symptoms, depression, anaemia, lethargy
Requirement for contraception during and 6 months following
Re-emergence of guilt, shame for some, and ongoing stigma
Tertiary hospital – focused
Hepatitis C treatment
0
500
1000
1500
2000
2500
3000
3500
2005(03)
2005(04)
2005(05)
2005(06)
2005(07)
2005(08)
2005(09)
2005(10)
2005(11)
2005(12)
2006(01)
2006(02)
2006(03)
2006(04)
2006(05)
2006(06)
2006(07)
2006(08)
2006(09)
2006(10)
2006(11)
PEG/RBV HCV treatment (sales): Mar 2005 – Nov 2006
Hepatitis C treatment
Removal of mandatory liver biopsy
patients
Sustained virological response (PEG-IFN-α2a/RBV)
0
10
20
30
40
50
60
70
80
PEG-IFN 2a + placebo IFN + RBV PEG-IFN 2a + RBV
Fried et al NEJM 2002
%
29%
44%
65%
Hepatitis C treatment
SVR for HCV genotype 1
0
10
20
30
40
50
60
70
80
PEG-IFN 2a + placebo IFN + RBV PEG-IFN 2a + RBV
%
21%
36%
46%
Fried et al NEJM 2002
Hepatitis C treatment
SVR for HCV genotype 2,3
0
10
20
30
40
50
60
70
80
90
PEG-IFN 2a + placebo IFN + RBV PEG-IFN 2a + RBV
%45%
61%
76%
Fried et al NEJM 2002
Hepatitis C treatment
0
10
20
30
40
50
60
70
80
Backmund etal (n=50)
Sylvestre et al (n=66)
Schaefer et al (n=21)
Mausss et al (n=50)
Matthews et al (n=12)
Jeffrey et al(n=50)
SVR
SVR rates in AOD service settings
%
Hepatitis C treatment
Impact of IDU status on HCV referral
0
10
20
30
40
50
60
70
80
90
100
Non-IDU Past-IDU Current-IDU
Stoove et al Drug & Alcohol Depend 2005
%
Hepatitis C treatment
Impact of IDU status on HCV treatment
0
10
20
30
40
50
60
70
80
90
100
Non-IDU Past-IDU Current-IDU
Stoove et al Drug & Alcohol Depend 2005
%
Hepatitis C treatment
HCV treatment consideration (Rankin Court / KRC, n=100)
0
10
20
30
40
50
60
70
80
90
100
20% efficacy 40% efficacy 70% efficacy
Consider
Strongly consider
Doab et al CID 2005
%
Hepatitis C treatment
Factors to consider in treatment decision-making
Prognosis / stage of liver disease
Efficacy of treatment
Toxicity of treatment
Presence of co-morbidities
Stage of opiate dependency treatment
Work and Family
Treatment eligibility
Hepatitis C treatment
Treatment eligibility (S100 Criteria)
18 years or older
No evidence of de-compensated cirrhosis
Chronic HCV infection
Use of dual contraception if potential for pregnancy
No prior IFN-based HCV treatment
Hepatitis C treatment
IDU on drug treatment (n=237)
Referral criteria -ve (n=58)
Chronic HCV (n=121)
HCV positive (n=178, 75%)
Referral criteria +ve (n=63)
Referred to clinic (n=43)
Attended clinic (n=27)
HCV referral and treatment (Byrne Surgery, Redfern)
HCV treatment (n=14)
Referral criteria:
>10 years duration of HCV
ALT elevation
Clinical evidence of cirrhosis
Hepatitis C treatment
Hallinan R et al Drug & Alcohol Dependence 2007
Patient HCV genotype Fibrosis stage HCV treatment / outcome
58M 1 NA PEG/RBV ceased, no EVR
38F 3a 3 PEG/RBV completed, ETR
42M 1/3a 4 (cirrhosis) PEG/RBV completed, SVR
29M 3a 2 PEG/RBV completed, SVR
37M 3a 2 PEG/RBV completed, SVR
39M 3a 4 (cirrhosis) PEG/RBV completed, SVR
43M 3a 3 PEG/RBV completed, SVR
39M 2a/2c 4 (cirrhosis) PEG/RBV completed, SVR
33M 3a 3 PEG/RBV completed, ETR
44M 3a 3 PEG/RBV commenced, EVR
44M 3a 3 PEG/RBV commenced
45M 3a 2 PEG/RBV commenced
33M 3a NA PEG/RBV commenced
HCV treatment (Byrne Surgery, Redfern)
Hepatitis C treatment
Improving HCV treatment uptake and outcomes
HCV screening and treatment clinics in D&A treatment settings
Education and training of AOD HCWs in HCV treatment
Education and training of HCV treatment HCWs in AOD
Research on models of treatment delivery
New therapeutic agents with greater efficacy, reduced toxicity, and shortened duration of therapy
Hepatitis C treatment
1
2
3
4
5
6
7
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14
Study Time (in Days)
Med
ian
HC
V R
NA
(L
og
10 IU
/mL
)
Placebo VX-950 450 mg q8h VX-950 750 mg q8h VX-950 1250 mg q12h
Reesink et al DDW. 2005.
Protease Inhibitor: VX 950
Advances in HCV Therapy
Week 0 12 24 36 48 72
Phase II studies with Telaprevir (PROVE 1 and 2): HCV genotype 1
PEG/RBV
PEG/RBV
PEG/RBV
PEG
D
C
B
A
TPV
TPV
TPV
TPV
PEG/RBV
E
Advances in HCV Therapy
PROVE studies (Telaprevir) interim efficacy analysis (week 12)
0
10
20
30
40
50
60
70
80
90
100
PEG/RBV (n=33) PEG/RBV/TPV (n=74)
<10 IU/ml
%
Vertex press release Dec 13, 2006
Advances in HCV Therapy
Histamine Hcl
Levovirin
Phase II
On market
Phase III
Phase I
Research
Preclinical
Protease inhibitors
HCV vaccines
Other IFNs
IFN & PEG-IFN
Many others includingAntisense
AntifibroticsImmune stimulants
Gene therapy
Ribozymes
Ribavirin
Polymerase inhibitorsAntisense
HCV immunotherapy
Viramidine
IL 10 & IL 12Others
Apoptosis inhibitors
Therapies in development
Hepatitis C treatment