Hepatitis C: Disease Burden and Management Strategies for 2006

1
Hepatitis CDisease Burden and Management
Strategies for 2006

• Graham R Foster
• Professor of Hepatology
• Queen Marys School of Medicine
• Barts and The London

2
HCV in 2006

• Who is infected ?
• What does it do ?
• What should we do about it ?

3
HCV in 2006

• Who is infected ?
• What does it do ?
• What should we do about it ?

4
HCV in 2006

• We are told that
• HCV is common in drug users
• gt90 of patients with HCV have a past history of
  drug use

5
HCV in 2006
HCV is common in drug users
Find HCV in drug users
Only test for HCV in drug users
6
HCV in 2006

• We live on planet earth!

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Prevalence of HCV Infection Among Blood Donors
Anti-HCV Prevalence
gt5 - High
1.1-5 - Intermediate
0.2-1 - Low
?0.1 - Very Low
Unknown
Anti-HCV prevalence by EIA-1 or EIA-2 with
supplemental testing based on data available
in January, 1995
8
Prevalence of HCV Infection Among Blood Donors
Anti-HCV Prevalence
gt5 - High
1.1-5 - Intermediate
0.2-1 - Low
?0.1 - Very Low
Unknown
Anti-HCV prevalence by EIA-1 or EIA-2 with
supplemental testing based on data available
in January, 1995
9
HCV in 2006

• The prevalence of HCV in the Indian Subcontinent
  is unknown

10
HCV in 2006

• The prevalence of HCV in the Indian Subcontinent
  is unknown
• WHO estimates 3- 5

11
HCV in 2006

• The prevalence of HCV in the Indian Subcontinent
  is unknown
• WHO estimates 3- 5
• Studies in Bangladesh 0.9 - 13

12
HCV in 2006

• The prevalence of HCV in the Indian Subcontinent
  is unknown
• WHO estimates 3- 5
• Studies in Bangladesh 0.9 - 13
• Studies in Pakistan 3- 5

13
HCV in 2006

• The prevalence of HCV in the Indian Subcontinent
  is unknown
• WHO estimates 3- 5
• Studies in Bangladesh 0.9 - 13
• Studies in Pakistan 3- 5
• Anecdotes in Pakistan 20-50

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2002 census

• Ethnic origin
• Largest group 2.3 million (4.0) of ISC origin
• 1 million of Pakistani / Bangladeshi
• 1 million of Indian origin
• Born overseas 3 10
• Indian (570,000) 17100 57000
• Pakistani (336,000) 10080 33000
• Bangladeshi (152,000) 4560 15000

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HCV in 2006

• There may be a lot of HCV in the ethnic minority
  groups in the UK

16
HCV in 2006Whitechapel
17
HCV in 2006

• Pilot community screening project in the East
  London Mosque
• Took place at lunchtime prayers
• Screened exclusively Bangladeshi subjects

18
HCV Screening in East London
19
HCV Screening in East London
20
HCV Screening in East London
1 ve
21
HCV Screening in East London
1 ve
22
HCV Screening in East London

• In Bangladeshi patients born in Syllhet the
  prevalence is low (lt1)
• Further studies in Pakistani communities are in
  progress

23
HCV in 2006

• Who is infected ?
• What does it do ?
• What should we do about it ?

24
HCV ancien regime

• HCV is a mild disease in the majority of patients
• Treatment is ineffective and expensive
• We should only treat patients with biopsy proven
  bad disease

25
Natural History of HCVPatients infected when
young who get old ?

• What is the natural history of HCV after 50 years
  ???
• There is very little data

26
HCV in East LondonPrevalence of cirrhosis in
Pakistani/Bangladeshi patients presumably
infected at birth
DSouza et al Clin Gastro Hep 2005
27
HCV in East LondonPrevalence of cirrhosis in
Pakistani/Bangladeshi patients presumably
infected at birth
DSouza et al Clin Gastro Hep 2005
28
HCV in East LondonPrevalence of cirrhosis in
Pakistani/Bangladeshi patients presumably
infected at birth
DSouza et al Clin Gastro Hep 2005
29
Odds of end stage liver disease amongst episodes
in HCV infected individuals
30
HCV in East London
31
HCV Screening in East London
1 ve Platelets/WBC dec
32
HCV Screening in East London
1 ve FBC Normal
33
Natural History of HCV

• Benign in youngsters
• Progressive in the elderly
• If we wait long enough many patients will develop
  bad liver disease

34
HCV in 2006

• Who is infected ?
• What does it do ?
• What should we do about it ?

35
HCV therapy in 2005

• Standard of care is Peg-IFN plus ribavirin
• We are starting to become very sophisticated in
  the way we use these drugs

36
Sustained Response Rates in HCVGenotype non 1
40 KD PEG IFNa2a Ribavirin
78
78
77
73
SVR ()
n106
n162
n111
n165
PEG IFNRBV 800
PEG IFN RBV 1000/1200
PEG IFNRBV 800
PEG IFNRBV 1000/1200
24 weeks
48 weeks
Hadziyannis et al Ann Intern Med 2004140346-355
37
Treating the non-1 patientCan we use shorter
durations of therapy ?
78
78
77
73
SVR ()
n106
n162
n111
n165
PEG IFNRBV 800
PEG IFN RBV 1000/1200
PEG IFNRBV 800
PEG IFNRBV 1000/1200
24 weeks
48 weeks
Hadziyannis et al Ann Intern Med 2004140346-355
38
Super-responders
Viral load
1
2
3
Time (months)
39
Super-responders
Viral load
1
2
3
Time (months)
40
Super-responders
Viral load
1
2
3
Time (months)
41
Super-responders
Viral load
1
2
3
Time (months)
42
Mangia Study Formal Study

• Randomised 13
• Peg-Intron 1 mg/Kg weight adjusted riba
• Patients randomised to-
• A) Standard 24 weeks
• B) Variable therapy EVR 12 weeks
• No EVR 24
  weeks

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Results
44
Mangia Study

• Super responders with genotype 2
• SVR 24 weeks 89 (n31)
• SVR 12 weeks 87 (n89)

45
Mangia Study

• Super responders with genotype 3
• SVR 24 weeks 100 (n10)
• SVR 12 weeks 77 (n24)

46
Mangia Study

• The data shows that Italian patients with
  genotype 2 HCV do very well with 12 weeks therapy

47
Mangia Study

• There is insufficient data to comment on Italian
  patients with genotype 3!

48
Short duration for genotype 3

• We have large numbers of genotype 3 patients from
  Bangladesh and Pakistan
• Most have advanced disease
• Response rates to 24 weeks therapy are
  disappointing

49
Short duration for genotype 3

• What I do..
• Young drug users (super responders) get 12 weeks
• The rest get 24 weeks

50
Sustained Response Rates in HCVGenotype 1 40
KD PEG IFNa2a Ribavirin
51
41
40
29
SVR ()
n101
n118
n250
n271
PEG IFNRBV 800
PEG IFNRBV 1000/1200
PEG IFNRBV 800
PEG IFNRBV 1000/1200
24 weeks
48 weeks
Hadziyannis et al Ann Intern Med 2004140346-355
51
Can we improve results for genotype 1 patients ?
51
41
40
29
SVR ()
n101
n118
n250
n271
PEG IFNRBV 800
PEG IFNRBV 1000/1200
PEG IFNRBV 800
PEG IFNRBV 1000/1200
24 weeks
48 weeks
Hadziyannis et al Ann Intern Med 2004140346-355
52
Identifying patients who only need 24 weeks

• Sophisticated virological studies are under way
  to determine whether viral kinetic studies can
  identify early responders
• Early studies suggests that patients who are PCR
  negative (lt200 IU/ml) at week 4 can stop after 24
  weeks

53
Can we improve results for genotype 1 patients ?
51
41
40
29
SVR ()
n101
n118
n250
n271
PEG IFNRBV 800
PEG IFNRBV 1000/1200
PEG IFNRBV 800
PEG IFNRBV 1000/1200
24 weeks
48 weeks
Hadziyannis et al Ann Intern Med 2004140346-355
54
Extending treatment duration

• Increasing the length of therapy increases the
  response rates in patients who comply
• We now need to identify who will benefit from
  prolonged therapy

T. Berg et al data presented at AASLD 2004
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Peg-IFN and Ribavirin Today

• The standard algorithms are being revised
• Within 2 years we will have patient friendly
  treatment regimes

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Peg-IFN and Ribavirin tomorrow

• New direct antivirals are on the way
• In 5-10 years time we will have potent new drugs

57
HCV therapy tomorrow
BILN 2061
New protease and polymerase inhibitors are on the
way
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HCV therapy today

• Therapy is less effective as you get older

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Effects of age and SVR(Data from patients
treated with 40 KD PEG IFNa2a and Ribavirin)
Foster et al AASLD 2003
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Effects of age and SVR(Data from patients
treated with 40 KD PEG IFNa2a and Ribavirin)
Foster et al AASLD 2003
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The Clinicians Dilemma

• Treat early .
• Treat later ..

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The Clinicians Dilemma

• Treat early .
• Treat later ..
• Trust your patient patients respond better when
  they are in control

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HCV Who should we treat?(Opinion based
medicine)

• We should NOT treat active drug users
• They will not comply
• They will get reinfected
• (They are not worth it)

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HCV in drug users - evidence
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HCV in drug users

• Drug users infect others !
• Not treating drug users encourages the spread of
  HCV

66
Treating the untreatable
27 patients started therapy (13 Genotype 1)
Completed 10
Early cessation 2
Completed 3 months 11
4 PCR ve
7 PCR -ve
ETR 9 (SVR 3/3)
ALL patients have benefited from the attention
two are looking for work!
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How many patients with HCV should we treat ?
Davis GL et al Projecting future complications
of HCV in the US Liver Transplantation
20039331-338
68
Therapy for HCV Summary (I)

• The natural history of HCV is of glacial
  progression
• Many patients will eventually develop cirrhosis
• Delaying therapy may reduce response rates

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Therapy for HCV Summary (II)

• We have effective therapies available and these
  can be given to ALL patients with chronic HCV