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The effect of improved HCV The effect of improved HCV diagnosis and treatment on diagnosis and treatment on
public health public health
P MathurinHôpital Claude Huriez Lille
Yoshida H et al., Gut 2004
Gain in hepatocellular carcinoma-free Gain in hepatocellular carcinoma-free survival by Interferonsurvival by Interferon
Yoshida H et al., Gut 2004
Gain in hepatocellular carcinoma-free Gain in hepatocellular carcinoma-free survival by Interferonsurvival by Interferon
• 6 months’ interferon monotherapy was the main protocol with a 7% SVR rate for type 1b genotype high viral load
• Peginterferon and ribavirin for 48 weeks with a response rate of 40% or better will provide
- 5 additional years of gain in HCC-free survival in 40-year old patients with fibrosis stage F4
- 1 additional year of gain in HCC-free survival in 60-year old patients with fibrosis stage F2
Gain in hepatocellular carcinoma-free Gain in hepatocellular carcinoma-free survival by Interferonsurvival by Interferon
Yoshida H et al., Gut 2004
Impact of viral eradication on Impact of viral eradication on mortality related to hepatitis C mortality related to hepatitis C
using a modeling approachusing a modeling approach
Deuffic-Burban S, Deltenre P, Louvet A, Canva V, Dharancy S, Hollebecque A, Boitard J, Henrion J, Yazdanpanah Y, Mathurin P
J Hepatol 2008
• Our first aim: quantify the impact of alcohol abuse, present screening policy and antiviral therapy on HCV mortality
• Second aim: estimate the impact of viral eradication in terms of lives saved, according to different scenarios of progress in HCV screening and treatment practice
AimsAims
Recovery from
infection
LiverLiver failurefailure
Death from other causes
CirrhosisCirrhosis
F4F4
25%
75% Ps,a,i Ps,a,i Ps,a,i Ps,a,i
PLF
PHCC
PDHCC
PDLF
Infection
HCCHCC
F3 F2 F1 F0
HCVHCV-relatedrelated HCCHCC deathdeath
HCVHCV-related lrelated liveriver
failure failure deathdeath
Model simulates HCV progression of Model simulates HCV progression of infected cohorts with acute hepatitis Cinfected cohorts with acute hepatitis C
Model assumptions Model assumptions
• Screening assumptions in % of individuals aware of their function
- 5% of HCV individuals aware of their HCV infection in 1991 when antiviral treatment became available
- linear increase to 24% in 1994 (Dubois F Hepatology 1997) and to 56% in 2004 (Meffre C et al., Prevalence of hepatitis C in France, 2003-2004. EASL 2006)- that, according to the same second linear progression, it will reach 75% (French government objective)
• Assumption for excessive drinking
- excessive alcohol intake starts at 20 years of age
• Main assumptions for treatment were:
1) Patients eligible for treatment were those aware of their infection, between 18 and 70 years of age
2) The annual likelihood of treatment was independent of age and sex
3) The annual likelihood of treatment for patients with fibrosis stage F<2 was 80% lower than for patients with fibrosis stage F2
4) For patients with alcohol abuse, the annual likelihood of treatment was 80% lower than for patients without alcohol abuse
5) Patients achieving SVR were withdrawn from the number of patients in the different stages, except for patients with cirrhosis (F4) who remain at risk of developing complications of cirrhosis
Model assumptions Model assumptions
Proportion of treated patients Proportion of sustained viral responder
Genotypes 1/4 Genotypes 2/3 Genotypes 1/4 Genotypes 2/3 References
Naive patients (first treatment) F ≤ 2 F > 2 F ≤ 2 F > 2
1991-1994 8% 8% 3% 2% 20% 14% (35, 36)
1995-1998 16% 16% 7% 5% 29% 21% (35, 36)
1999-2001 21% 42% 38% 27% 64% 46% (3, 35, 36)
2002* 21% 42%53% 38% 79% 68% (3)
Annual likelihood of treatment for patients with fibrosis stage F<2 was 80% 80% lowerlower than for patients with fibrosis stage F2
Annual likelihood of treatment among Annual likelihood of treatment among patients aware of their infectionpatients aware of their infection
0
100
200
300
400
500
600
700
800
900
1979 1981 1983 1985 1987 1989 1991 1993 1995 1997 1999 2001 2003
YearYear
An
nu
al in
cid
ence
of
HC
C d
eath
Predicted death from HCC for menObserved death from HCC for men
Predicted death from HCC for women
Observed death from HCC for women
Model fits the observed mortalityModel fits the observed mortality
0
500
1000
1500
2000
2500
1980 1985 1990 1995 2000 2005 2010 2015 2020 2025
Year
Ann
ual i
ncid
ence
of
HC
V-r
elat
ed m
orta
lity
Death from liver failure
Death from HCC
HCV-related mortality: liver failure vs HCCHCV-related mortality: liver failure vs HCC
• 37% of individuals recovered from their infection - 72% of them spontaneously- 28% of them after therapy
• 63% were HCV-RNA+- 17% of whom were previously treated- 38% of whom were aware of their infection but
never treated- 45% unaware of their HCV status
Model prediction in 2006Model prediction in 2006Virological patternVirological pattern
Impact of viral eradication on mortality Impact of viral eradication on mortality Influence of excessive alcohol intakeInfluence of excessive alcohol intake
of whom 13% were decompensated
of whom 42% were decompensated
23%
52%
0%
20%
40%
60%
80%
100%
% of severe fibrosis (F3-F4)
< 50 g/day alcohol
> 50 g/day alcohol
Age classAge class
0%
2%
4%
6%
8%
10%
12%
0-39 40-64 65+
Mor
tali
ty r
atio
(%
)M
orta
lity
rat
io (
%)
Alcohol < 50g per dayAlcohol < 50g per day
Alcohol > 50g per dayAlcohol > 50g per day
4%
0.37 %
11-fold increase
In 2001 mean age at death was earlier in alcohol+ patients: 69 vs 58 years
Impact of viral eradication on mortality Impact of viral eradication on mortality Influence of excessive alcohol intakeInfluence of excessive alcohol intake
In the modeling project mean age at death 69 years for HCV patients without alcohol consumption58 years for alcohol HCV patients
Marcellin J Hepatol 2007
Impact of viral eradication on mortality Impact of viral eradication on mortality Influence of excessive alcohol intakeInfluence of excessive alcohol intake
0
500
1000
1500
2000
2500
3000
1980 1985 1990 1995 2000 2005 2010 2015 2020 2025
YearYear
An
nual
inci
denc
e of
HC
V-r
elat
ed m
orta
lity
An
nual
inci
denc
e of
HC
V-r
elat
ed m
orta
lity In the absence of treatment
With current practice of treatment
-14% 7000 (6,700-7,300) deaths
-32%
G1/4
G2/37400 (7,200-7,700) deaths
Impact of current treatment on mortalityImpact of current treatment on mortalityAccording to genotypesAccording to genotypes
• In a scenario of new therapeutic guidelines supporting treatment regardless of fibrosis stages (same proportion for patients F<2 as those F2): - 700 (95%CI, 700-750) additional lives would be saved
• The model predicted that the French government objective of 75% of infected patients aware of their status would be reached in 2014.
• If the efforts of French public health authorities were increased so as to reach 75% in 2010 (4 years earlier)- 950 (95% CI, 900-1,000) lives could be saved over the next 20 years
Impact of scenarios of progress in HCV Impact of scenarios of progress in HCV screening and treatment practicescreening and treatment practice
Impact of scenarios of progress in HCV Impact of scenarios of progress in HCV screening and treatment practicescreening and treatment practice
• A scenario potential availability of new antiviral drug in 2010 (same improvement in SVR for G1/4 as previously obtained with pegylated bitherapy (40% increase in viral eradication)
– For naïve G1/4 patients, SVR of 74% in F<2 and 53 % in F2– For previously treated G1/4 patient, SVR of 24% in F<2 and 18% in F2
• New molecule will save - 1,500 (95% CI, 1,400-1,600) lives over the next 20 years.
• If, at the same time, the proportion of screening reached 75%, then the impact upon mortality in the next 20 years
- 1.7 times greater than the same new molecule without improved screening corresponding to a total of 2,600 (95%CI, 2,500-2,800) deaths avoided (-4.5%)
Modeling approach in Greece Modeling approach in Greece
V. Sypsa, J Viral Hepat 2005
ConclusionsConclusions
• In France current antiviral therapy will reduce HCV mortality from 2006-2025 by 20%
• Therapeutic guidelines must take into account their impact on HCV
mortality
• Public health policy is as important as treatment
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