Hepatitis C When, how and which patients should be treated
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Transcript of Hepatitis C When, how and which patients should be treated
Hepatitis CWhen, how and which patients
should be treated Graham R Foster
Professor of Hepatology Queen Marys School of Medicine
Barts and The London
JC
• 34 year old man
• Infected with genotype 1 HCV (ALT 120)
• Refuses liver biopsy
JC
• 34 year old man
• Infected with genotype 1 HCV
• Refuses liver biopsy
• Single
• Lives in a rented flat does not drink
JC
• 34 year old man
• Infected with genotype 1 HCV
• Refuses liver biopsy
• Single
• Lives in a rented flat does not drink
• Methadone prescription – 80 mls/day
JC
• 34 year old man• Infected with genotype 1 HCV• Refuses liver biopsy • Single• Lives in a rented flat does not drink• Methadone prescription – 80 mls/day• Injects heroin x3 per week/ crack ‘ occasionally’
JC
Should we treat him ?
HCV in 2006
• Not treating Jason
• Good reasons/Bad reasons
HCV in 2006
• Not treating Jason
• Good reasons/ Bad reasons
• He does not have bad disease
HCV in East LondonPrevalence of cirrhosis in Pakistani/Bangladeshi
patients presumably infected at birth
0-10 11-20 21-30 31-40 41-50 51-60 61-70 >700
10
20
30
40
50
60
70
80
90
Age of Patients
Per
cen
t o
f P
atie
nts
wit
hC
irrh
osi
s
D’Souza et al Clin Gastro Hep 2005
HCV in East LondonPrevalence of cirrhosis in Pakistani/Bangladeshi
patients presumably infected at birth
0-10 11-20 21-30 31-40 41-50 51-60 61-70 >700
10
20
30
40
50
60
70
80
90
Age of Patients
Per
cen
t o
f P
atie
nts
wit
hC
irrh
osi
s
D’Souza et al Clin Gastro Hep 2005
HCV in East LondonPrevalence of cirrhosis in Pakistani/Bangladeshi
patients presumably infected at birth
0-10 11-20 21-30 31-40 41-50 51-60 61-70 >700
10
20
30
40
50
60
70
80
90
Age of Patients
Per
cen
t o
f P
atie
nts
wit
hC
irrh
osi
s
D’Souza et al Clin Gastro Hep 2005
HCV in East London
0-10 11-20 21-30 31-40 41-50 51-60 61-70 >700
10
20
30
40
50
60
70
80
90
Caucasians
Age of Patients
Per
cen
t o
f P
atie
nts
wit
hC
irrh
osi
s
Therapy for HCV:Who should receive therapy?
Risk of liver damage
Need for biopsy
Therapy
Young people
Low Low If they wish!
Therapy for HCV:Who should receive therapy?
Risk of liver damage
Need for biopsy
Therapy
Young people
Low Low If they wish!
Middle
aged
Moderate High If they wish or have fibrosis
Therapy for HCV:Who should receive therapy?
Risk of liver damage
Need for biopsy
Therapy
Young people
Low Low If they wish!
Middle
aged
Moderate High If they wish or have fibrosis
Elderly High High Only if they have bad disease
HCV in 2006 ()
• I am seeing increasing numbers of patients from Bangladesh and Pakistan with advanced liver disease from HCV
HCV in 2006 ()Are we missing something ?
• The government tells us that this is a drug users disease
• I am seeing non-drug users with liver cancer secondary to HCV
• Are we missing something important ?
HCV in 2006
• Not treating Jason
• Good reasons/ Bad reasons
• He does not have bad disease – but he will get it!
HCV in 2006
• Not treating Jason
• Good reasons/ Bad reasons
• He does not have bad disease – but he will get it!
• He is unlikely to respond
Sustained Response Rates in HCVGenotype 1 – 40 KD PEG IFNα2a + Ribavirin
0
10
20
30
40
50
60
24 weeks 48 weeks
SV
R (
%)
29%
41% 40%
51%
n=101 n=118 n=250 n=271
PEG IFNRBV 800
PEG IFNRBV 1000/1200
PEG IFNRBV 800
PEG IFNRBV 1000/1200
Hadziyannis et al Ann Intern Med 2004:140;346-355
Effects of age and SVR(Data from patients treated with 40 KD PEG IFNα2a and Ribavirin)
2060
Age (completed life-years)55 50 45 35 25 20
30
40
50
60
70
80
90C
alcu
late
d S
VR
Rat
e (%
)
40 30
Foster et al AASLD 2003
Sustained Response Rates in HCVGenotype non 1 – 40 KD PEG IFNα2a + Ribavirin
SV
R (
%)
0
10
20
30
40
50
60
70
80
90
24 weeks 48 weeks
78% 78% 73% 77%
n=106 n=162 n=111 n=165
PEG IFNRBV 800
PEG IFN RBV 1000/1200
PEG IFNRBV 800
PEG IFNRBV 1000/1200
Hadziyannis et al Ann Intern Med 2004:140;346-355
Treating the non-1 patientCan we use shorter durations of therapy ?
• Pilot study of 14 weeks therapy in patients with an early virological response
• Used Peg-Intron 1.5g/kg + Normal dose ribavirin
Dalgard et al Hepatology 2004:40:1260-1265
Treating the non-1 patientCan we use shorter durations of therapy ?
SVR (by per protocol analysis) of patients with an early virological response receiving 14 weeks therapy
Peg-IFN and Ribavirin Today
• The standard algorithms are being revised
• Easy to treat patients may need shorter durations of therapy
Peg-IFN and Ribavirin Today
• The standard algorithms are being revised
• Easy to treat patients may need shorter durations of therapy
• Easy to treat patients are young with no fibrosis!
HCV therapy tomorrow
BILN 2061
New protease and polymerase inhibitors are on the way
HCV in 2006
• Not treating Jason
• Good reasons/ Bad reasons
Therapy in difficult patient groups
•
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)
HCV in drug users - evidence
Treatment of chronic hepatitis C in injecting drug users: 5 years' follow-up.Dalgard O, Bjoro K, Hellum K, Myrvang B, Skaug K, Gutigard B, Bell H; The Construct Group.Eur Addict Res 2002 Jan;8(1):45-9
Treatment of hepatitis C infection in injection drug users Markus Backmund, Kirsten Meyer, Michael Von Zielonka, Dieter Eichenlaub Hepatology July 2001 • Volume 34 • p188 to p193
HCV in drug users
• Drug users infect others !
• Not treating drug users encourages the spread of HCV
Treating the untreatable
27 patients started therapy (13 Genotype 1)
Completed = 10Early cessation = 2 Completed 3 months = 11
4 PCR +ve7 PCR -veETR = 9 (SVR 3/3)
i.e. by Intent to treat analysis 16/23 = 70% have an EVR
Treating the untreatable
27 patients started therapy (13 Genotype 1)
Completed = 10Early cessation = 2 Completed 3 months = 11
4 PCR +ve7 PCR -veETR = 9 (SVR 3/3)
ALL patients have benefited from the attention – two are looking for work!
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
Therapy for HCV Summary (II)
• We have effective therapies available and these can be given to ALL patients with chronic HCV
Therapy for HCV
• Who would treat Jason ?
Therapy for HCV Post Script
• JC was offered therapy
• He agreed to undergo therapy and has completed 9 months treatment
• He has not injected for 3 months
• He has been offered a job in his brothers shop