The effect of improved HCV diagnosis and treatment on public health The effect of improved HCV diagnosis and treatment on public health P Mathurin Hôpital

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



• 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



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


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


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

Documents

The effect of improved HCV diagnosis and treatment on public health The effect of improved HCV diagnosis and treatment on public health P Mathurin Hôpital