Where are we on the path to eliminate hepatitis C virus ?

Are <strong>we</strong> on the path to eliminate
hepatitis C virus ?
Mona Amin
Professor of internal medicine
Hepato-gastroenterology
Cairo University
1

The Life cycle of an Infectious Disease
1. Discovery √
2. Reliable Diagnostic Test √
3. Effective Therapy √
4. Protective Vaccination
5. Control Of Disease Burden
6. Elimination Of Infection
7. Global Eradication Of Infection
2

Control vs. Elimination vs. Eradication
‣Control: Reduction In Prevalence,
Morbidity/Mortality Of An Infectious Disease To A
Locally Acceptable Level.
‣Elimination: Reduction To Zero Of The
Incidence Of Disease Or Infection In A Defined
Geographical Area, But Requires Continued
Measures To Prevent Re-establishment Of
Transmission
‣Eradication: Permanent Reduction To Zero Of
The Worldwide Incidence Of Infection, With No
Further Control Measures Required WHO 1998
CDC, 1993; Dowdle, 1998.
3

• World Health Organization goal is to eliminate
hepatitis C virus (HCV) as a public health threat
• Specifically, the goal is dramatic and large scale
reductions in new transmissions of HCV, as <strong>we</strong>ll
as in the number of people becoming ill and
dying from HCV, to a level where HCV no longer
represents a major health concern
• In numeric terms, the WHO has proposed
reductions of 60% in HCV related mortality and
90% in HCV transmission globally and in
member countries
John W. Ward, Gastroenterology & Hepatology 2016
4

Why HCV Is A Tractable Target For
Eradication ?
• No known non-human reservoir
• There is no latent cellular reservoir
• Pharmacologic treatment with direct
acting antivirals can truly cure an
infected person, treatment-based
elimination is an option
5

Barriers To Elimination
• Hepatitis C is generally asymptomatic both during the acute
and chronic phase.
• Heavy concentration of HCV infections in difficult-to reach
populations, including people who inject drugs and the
homeless, as <strong>we</strong>ll as marginalized groups such as the
incarcerated.
• The treatment cost is expensive. This expense raises
concerns about the feasibility of widespread treatment
• A prophylactic vaccine may be an essential missing piece of
the effort to eliminate hepatitis C.
• Reinfection is a possibility
6

Nearly Everyone With HCV Can Now Be Treated
Successfully
• Very high SVR rates; therapies highly tolerable
• All-oral therapy for almost every pt
• Treatment generally just 12 wks
100
80
60
40
Standard
Interferon
1991
Ribavirin
1998
34
Peginterferon
2001
42 39
55
Direct-Acting
Antivirals
2011
70+
2013
90+
All-Oral
Therapy
Current
95+
20
0
6
IFN
6 Mos
16
IFN
12 Mos
IFN/RBV
6 Mos
IFN/RBV
12 Mos
PegIFN
12 Mos
PegIFN/
RBV
12 Mos
PegIFN/
RBV +
DAA
DAA +
RBV ±
PegIFN
All–Oral
DAA±
RBV
7

We Now Have the Tools . . . What Do
We Do With Them?
‣Should We Focus Primarily On Pts With
Cirrhosis?
‣Should We Try To Cure Everyone?
8

9

10

Viremic Infections (by Stage)
Impact of HCV: What Happens If We Do
Nothing?
• Change in the number of HCV-related liver transplants,
decompensated cirrhosis cases, and HCC cases over time
HCC
Decompensated cirrhosis
Liver transplant
England
Yr
S<strong>we</strong>den
3500
1000
900
3000
800
2500
700
600
2000
500
1500
400
1000
300
200
500
100
0
0
1950 1960 1970 1980 1990 2000 2010 2020 2030 1950 1960 1970 1980 1990 2000 2010 2020 2030
Yr
Razavi H, et al. J Viral Hepat. 2014;21(suppl 1):34-59.
11

Deaths (n)
Focusing on Pts With Cirrhosis:
The English Experience
• Deaths caused by end-stage liver disease or HCC in pts with HCV
mentioned on death certificate: UK 2005-2015
500
450
400
350
300
250
200
150
100
50
0
2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015*
Yr
*2015 data provisional for England/Wales, missing for Northern Ireland.
Office for National Statistics for England and Wales; Deaths registration
data supplied by NISRA for Northern Ireland; Health Protection Scotland
in association with Information Services Division.
12

Focusing on Cirrhosis
Rapid reduction in mortality
But
– Means forever playing “catch up”
– People with cirrhosis remain at risk of
HCC and must remain under
surveillance—they <strong>are</strong> the most
expensive to treat
Slide credit:
13

Can We Do More?
Should <strong>we</strong> try to find and treat
everyone with HCV infection?
14

Pts (%)
HCV in the US: Gaps in Current Practice
100
100%
80
60
50%
43%
40
27%
20
17% 16%
9%
0
Chronic
HCV
Infected
Diagnosed
and
Aw<strong>are</strong>
Access
to
C<strong>are</strong>
HCV RNA
Confirmed
Liver
Biopsy
Prescribed
HCV
Treatment
Achieved
SVR
n = 3,500,000 1,743,000 1,514,667 952,726 581,632 555,883 326,859
Yehia BR, et al. PLoS One. 2014;9:e101554.
15

16

HCV is not JUST a liver virus
‣People with HCV infection <strong>are</strong>
not just “livers on legs”
‣People with HCV infection have
MANY health concerns
17

Change in Summary PRO
Score From BL to EOT
(scale: 0-100)*
Pt-Reported Outcomes Improve With DAA
Therapy
• End-of-treatment changes from baseline in summary pt-reported outcomes
among 818 pts treated with SOF/VEL or SOF + RBV in ASTRAL-2 (GT2) and
ASTRAL-3 (GT3)
10
8
6
4
2
0
-2
-4
-6
-8
P = .16
SF-36:
Physical
Component
Summary
SOF + RBV
P = .0001
SF-36:
Mental
Component
Summary
SOF/VEL
P = .0001 P = .0009
FACIT-F:
Fatigue
FACIT-F:
Total
P = .0012
CLDQ-
HCV:
Total
P = .0024
WPAI:SHP:
Work
Productivity
P = .0002
WPAI:SHP:
Activity
*Changes of > 2 points represent significant difference from BL within treatment group (P < .05).
Younossi ZM, et al. Clin Infect Dis. 2016;63:1042-1048.
18

Pts (%)
HCV Affects Pts’ Lives Now: Indirect
Economic Costs of HCV
• 2010 EU National Health and Wellness Survey: HCV associated with
significantly lo<strong>we</strong>r scores vs controls in several HRQoL domains (P < .05) [1]
• 2009 US National Health and Wellness Survey: pts with HCV significantly less
likely to be employed vs controls (P < .0001) [2]
30
20
Pts with HCV
Controls
17
14
19
15
25
22
10
5
3
0
Absenteeism Presenteeism Overall Work
Impairment
Activity
Impairment
1. DiBonaventura Md, et al. Eur J Gastroenterol Hepatol. 2012;24:869-
877. 2. DiBonaventura Md, et al. J Med Econ. 2011;14:253-261.
19

In Every Country Analyzed, Treatment Is More Cost Saving
Estes C, Abdel-K<strong>are</strong>em M, Abdel-Razek W, Abdel-Sameea E, Abuzeid M, Gomaa A, et al. Economic burden of hepatitis C in
Egypt: the future impact of highly effective therapies. Aliment Pharmacol Ther 2015 Jul 22.
20

Treating Everyone
‣Encourages testing
‣Improves quality of life
‣Reduces onward transmission
21

Increasing SVR >90% without change in numbers treated
has small impact on morbidity & mortality -
22

Increasing SVR >90% with increase in numbers
treated 5-fold out could eliminate HCV by 2030
23

Global Call for HCV Elimination
• Vision: “A world where viral hepatitis transmission is stopped
and everyone has access to safe, affordable, and effective
treatment and c<strong>are</strong>”
– 2020 target: 3 million HCV infections treated
• Feasible by scaling up 6 key interventions to high coverage:
– Hepatitis B vaccination (including birth dose)
– Safe injection practices and safe blood
– Harm reduction for injecting drug users
– Safer sex (including condom promotion)
– Hepatitis B treatment
– Hepatitis C cure
2030 Targets
90% Diagnosed
WHO. Towards the elimination of hepatitis B and C by 2030.
Draft WHO Global Hepatitis Strategy, 2016-2021.
80% Treated
65% Reduced Mortality
24

Eliminating HCV Is Everyone’s Job
• Identify undiagnosed HCV
– HCV rapid testing
– Opiate replacement
therapy
– Syringe access
• Preventing infection and
reinfection
– Outreach and education
– Safer injection counseling
– Reinfection prevention
counseling
• Treatment access and
delivery
– Linkage to HCV c<strong>are</strong>
– Access to HCV drugs
– Primary c<strong>are</strong>–based
therapy
– Methadone-based directly
observed therapy
– Access to specialty c<strong>are</strong>
25

What Would It Take For Global Elimination Of HCV?
World Health Organisation Targets For 2030
26

WHAT needs to be done?
1
• Innovative treatment to be
affordable
2
• Diagnosis rate to be
efficient and effective
3
• Strategies to avoid infection
and reinfection
27

The Key Factor Of A Successful Strategy:
28

29

Member States with National Viral Hepatitis Plans
2016 (NVHP) (n=36)
30

Could HCV Be Eliminated Through Antiviral Therapy?
DAA Therapies Combined With Increased Uptake
31

WHO May 2016
32

Impact Of Prevention On Outcome Of Scenario .
33

HCV Control to Elimination (90/90/90)
34

35

Take Home Points
‣Treatment in 2016 is effective, becoming
simplified, and provides all-oral options for
almost every pt
– Next generation of therapy expected to be
pangenotypic, effective for previous DAA failure
‣Goals in HCV therapy expanding beyond
individual cure to HCV elimination; keys
include:
– Involving primary c<strong>are</strong>
– Addressing barriers to treatment
– Providing effective therapy to challenging pt groups
36

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