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Lawrence Serfaty
Service d’Hépatologie, UMR_S 938
Hôpital Saint-Antoine, Paris
Who, when and how to treat:
summary and take home messages
4th European Young Hepatologist Workshop, Bendor, 10-12th July
Approval of 1st generation PIs
Approval of new DAAs
Access to new HCV treatments
Market approval/early access program
for new DAAs in Europe in 2014
Sofosbuvir
Simeprevir
Daclatasvir
Sofosbuvir
Daclatasvir
Sofosbuvir
Simeprevir
Daclatasvir
EASL guidelines:
Treatment regimen in genotypes 1/2/3
G1a G1b G2 G3 Patient profile
Naïve Recommended Alternative option
SOF+ PR 12w SOF+DCV 12w ±R(cirrh) SOF+ SIM 12w ±R(cirrh) SIM 12w+PR 24w Q80K- SOF+R 24w
SOF+ PR 12w SOF+DCV 12w ±R(cirrh) SOF+ SIM 12w ±R(cirrh) SIM 12w+PR 24w DCV 12w +PR 24w SOF+R 24w
SOF + R 12w
SOF + PR 12w SOF + R 24w SOF+ DCV 12w
Relapsers Recommended Alternative option
SOF+ PR 12w SOF+DCV 24w ±R(cirrh) SOF+ SIM 12w ±R(cirrh) SIM 12S+PR 24w Q80K- SOF+R 24w
SOF+ PR 12w SOF+DCV 24w ±R(cirrh) SOF+ SIM 12w ±R(cirrh) SIM 12/24w+PR 24w DCV 12w+PR 24w SOF+R 24w
SOF + R 12w SOF + PR 12w SOF + R 24w SOF+ DCV 24w
Non responders Recommended Alternative option
SOF+ PR 12w or longer? SOF+DCV 24 w ±R SOF+ SIM 12 w ±R
SOF+ PR 12w or longer? SOF+DCV 24w ±R SOF+ SIM 12w ±R
SOF + R 16 -20w SOF + PR 12s SOF + R 24w SOF+ DCV 24w ±R(cirrh)
G1 PI failure SOF+DCV 24w SOF+DCV 24w
G4 G5 or 6
Patient profile
Naïve Recommended Alternative option
SOF+ PR 12w SOF+DCV 12 w ±R(cirrh) SOF+ SIM 12 w ±R(cirrh) SIM 12w+PR 24w DCV 12/24w+PR 24w SOF+R 24w
SOF+ PR 12w SOF+R 24w
Relapsers Recommended Alternative option
SOF+ PR 12w SOF+DCV 24w ±R(cirrh) SOF+ SIM 12 w ±R(cirrh) SIM 12w+PR 24w DCV 12/24w+PR 24w SOF+R 24w
SOF+ PR 12w SOF+R 24w
Non responders Recommended Alternative option
SOF+ PR 12w SOF+DCV 24 w ±R(cirrh) SOF+ SIM 12 w ±R(cirrh) SIM 12w+PR 24w DCV 12/24w+PR 24w SOF+R 24w
SOF+ PR 12w ? SOF+R 24w
EASL guidelines:
Treatment regimen in genotypes 4/5/6
Re-treatment of DAA-failure patients (EASL)
DAA failure regimen Retreatment
Sofosbuvir as only DAA Sofosbuvir + Simeprevir (G1 or G4)
Sofosbuvir + Daclatasvir
Boceprevir/telaprevir/simeprevir as
only DAA
Sofosbuvir + Daclatasvir
Daclatasvir as only DAA Sofosbuvir + Simeprevir (G1 or G4)
Sofosbuvir + simeprevir Sofosbuvir + Daclatasvir
Sofosbuvir + daclatasvir Sofosbuvir + Simeprevir (G1 or G4)
Who to treat (EASL)
• All treatment-naïve and -experienced patients with compensated
disease due to HCV should be considered for therapy
• Treatment should be prioritized for patients with significant fibrosis
(METAVIR score F3 to F4)
• Treatment is justified in patients with moderate fibrosis (METAVIR
score F2)
• In patients with no or mild disease (METAVIR score F0-F1), the
indication for and timing of therapy can be individualized
• Patients with decompensated cirrhosis who are on the transplant list
should be considered for IFN-free, ideally ribavirin-free therapy
High proportion of patients with no or mild
fibrosis included in phase 3 Pis trials
Jacobson IM, N Engl J Med 2011
Zeuzem S, N Engl J Med 2011
Treatment access
HCV screening rates in Europe
Belgium France Germany Italy Spain UK
HCV Screening, %
Observed, % (yr) 37
(2000)
57
(2004)
40
(2004)
40
(2005)
33
(2008–9)
30
(2004)
Estimated in 2011, % 50 64 48 46 35 34
HCV Genotype
G1, % 60 56 60 62 65 44
G2/3, % 27 32 37 34 23 53
Other
genotypes, %
13 12 3 4 12 3
Deuffic-Burban S, et al. Gastroenterology 2012
Proportion of patients ever treated with peginterferons per
100 prevalent HCV cases by country until end of 2005
Lettmeier B, et al J Hepatol 2008
16
12 12 11
1 < 1
Reduction in cumulative incidence of genotype 1
HCV-related deaths, 2012–2021 R
ed
ucti
on
in
cu
mu
lati
ve i
ncid
en
ce (
%)
25
20
10
5
0 Belgium France Germany Italy Spain UK
15
Greater reduction in HCV-related deaths with PI-based triple therapy than with dual therapy
-24%
-27%
-28%
-37%
-21%
-38%
Deuffic-Burban S, et al. Gastroenterology 2012
Dual therapy PI-based triple
therapy
Belgium France Germany Italy Spain UK
Red
ucti
on
in
cu
mu
lati
ve i
ncid
en
ce (
%)
Country
25
20
15
10
5
0
PI-based triple therapy with increased
screening and treatment access*
Dual therapy PI-based triple
therapy
Deuffic-Burban S, et al. Gastroenterology 2012
Reinforcing screening and treatment access: cumulative
incidence of genotype 1 HCV-related deaths, 2012–2021
*Assumes 75% of HCV-infected patients will be screened by 2015 and
one G1-infected patient in 2 will be treated in 2015 with PI-based triple therapy
-58%
-150%
-128%
-264%
-107%
-50%
Dramatic reduction in HCV-related deaths with PI-based triple therapy + reinforced screening and treatment access
2 889 385 veterans screened for HCV in 2011
Birth cohort screening: prevalence of HCV
infection by birth year in US veterans
Backus LI, et al; JAMA Intern Med 2013
Birth cohort vs current risk-based screening:
cost-effective in US
Compensated
cirrhosis
Decompensated
cirrhosis
HCC LT HCV-related
mortality
McGarry L, Hepatology 2012
Lifetime incremental reductions
Incremental cost effectiveness ratio (ICER) of $37,700
per quality-adjusted life year gained
Mena A, et al AASLD 2013, Abs. 2241
HCV seroprevalence by year of screening HCV seroprevalence by birth year
12
10
8
6
4
2
0 ≤ 1930 1931-
1940
1941-
1950
1951-
1960
1961-
1970
1971-
1980
1981-
1990
> 1990 0
2
4
6
10
8
12
2008 2012 2011 2010 2009
Pre
va
len
ce
(%
)
Year
Birth cohort screening in Europe? Prevalence of HCV by birth year in a Spanish hospital
92 143 HCV screening between 2008-2012
Rapid HCV diagnostic test
SAMPLE TYPE
Oral fluid
Venipuncture
Whole blood
Serum
Plasma
Fingerstick
Whole blood
MIX
TEST
INTERPRETATION
20 min
OraQuick® HCV Rapid Antibody Test Device
Accuracy of rapid HCV diagnostic tests Fingerstick whole blood
Specificity (CI95%)
Sensitivity (CI95%)
PPV NPV
OraQuick® HCV Rapid Ab Test
100% (97.9-100.0)
99.4% (97.7-99.9)
100% 98.4%
TOYO® anti-HCV test
98.2% (94.8-99.4)
96.2% (93.3-98.0)
99.0% 93.1%
Labmen® HCV test 100%
(94.4-100.0) 62.7%
(54.8-69.5) 100% 49.6%
Accuracy of OraQuick® Oral fluid
Specificity (CI95%)
Sensitivity (CI95%)
PPV NPV
OraQuick® HCV Rapid Ab Test
100% (97.9-100.0)
98.2% (95.9-99.1)
100% 96.6%
The present The future
HCV treatment challenge: simplicity
• Genotype
• Naïve or tt experienced
• Cirrhosis
• 8, 12 or 24 w
• RBV or no RBV
• BID or QD
• Drug-drug interaction
One pill a day for 4 weeks
100%
20%
10%
Screened
and treated
Cured
All HCV
patients
PEG-IFN/RBV
100%
20%
95% SVR
19%
100%
90%
85%
95% SVR
and improved screening
Courtesy M. Manns