Management of Hepatitis C in Alcohol and Other Drug Services Greg Dore Viral Hepatitis Clinical Research Program National Centre in HIV Epidemiology and

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


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

%


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

%


HCV HIV

HBV

264,000

90,000 – 160,000

17,000

Estimates of BBV prevalence in Australia


ORT40,000

HCV RNA+20,000

HCV Ab+30,000

Estimates of HCV population on opiate pharmacotherapy


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


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


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


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


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


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


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%


SVR for HCV genotype 1

0

10

20

30

40

50

60

70

80


%

21%

36%

46%



SVR for HCV genotype 2,3

0

10

20

30

40

50

60

70

80

90


%45%

61%

76%



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

%


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

%


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

%


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

%


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


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


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


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


39M 3a 4 (cirrhosis) 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)


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


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


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


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


Documents

Management of Hepatitis C in Alcohol and Other Drug Services Greg Dore Viral Hepatitis Clinical Research Program National Centre in HIV Epidemiology and