Dr Helen Harris Presentation - Uniting Voices for HCV elimination Meeting, 4/7/16

1. New Treatments for hepatitis C:
Impact on morbidity and mortality
– What could possibly go wrong..?
DR HELEN HARRIS – NIS, PUBLIC HEALTH ENGLAND
Uniting Voices for HCV Elimination, Royal Society of Medicine: 4 July 2016, London

2. Globaldiseaseburden
• Global burden of viral hepatitis: increasing since 1990,
reaching 1.46 million deaths in 2013.*
– Viral hepatitis is a leading cause of death globally with a toll exceeding
that of HIV (1.3 million deaths), tuberculosis (1.2 million deaths) and
malaria (0.5 million deaths)*
• WHO European region: More than 15 million people are
estimated to be living with chronic HCV infection**
• UK: 214,000 people estimated to be living with chronic
HCV infection***
* WHO. Combating HCV and HBV to reach elimination by 2030, May 2016
** Epidemiol Infect 2014;142:270-86
*** PHE. Hepatitis C in the UK 2015 report. London, 2015.

3. TheWHO goalof elimination…
• World Health Organisation’s (WHO) Global
Health Sector Strategy (GHSS) on Viral
Hepatitis, 2016-2021*
– Working towards eliminating hepatitis C as a major
public health threat by 2030
• Reduce the number of
new HCV infections
• Drive down HCV-related
morbidity & mortality
30%
10%
By 2020
* http://www.who.int/hepatitis/strategy2016-2021/Draft_global_health_sector_strategy_viral_hepatitis_13nov.pdf?ua=1
90%
65%
By 2030

4. NewDirectActingAntiviralDrugs
• A milestone. New direct-acting antivirals (DAAs) have the
potential to transform the hepatitis C treatment landscape;
SVR (~ Cure) > 90%
– All-oral
– Shorter treatment durations
– Improved side effect profiles
• Practical reality. New DAAs are expensive…
Q. What are the consequences of focusing on
minimizing the results of severe liver disease vs.
reducing transmission via ‘treatment as prevention’?
Easier to roll out in
community/outreach
settings
This
matters!

5. Modellingmethodsinbrief…
• A back-calculation model was used to estimate
the impact of treatment of mild, moderate and
compensated cirrhosis on new (incident) cases
of HCV-related end-stage liver
disease/hepatocellular carcinoma (ESLD/HCC).
• A dynamic model was used to determine the
impact on incidence and prevalence of chronic
infection in people who inject drugs (PWID), the
main risk group in England.
J Viral Hepat 2016 Mar 29. doi: 10.1111/jvh.12529.

6. PredictedannualincidentcasesofHCV-
relatedESLDorhepatocellularcarcinoma
0
500
100015002000
2010 2015 2020 2025 2030
Year
Current treatment DAAs cirrhosis only, IFN mild/moderate
DAAs cirrhosis/moderate, IFN mild DAAs all stages
J Viral Hepat 2016 Mar 29. doi: 10.1111/jvh.12529.

7. Results,part1
• Treating 3500 cirrhotics per year, for example,
was predicted to reduce ESLD/HCC incidence
from 1100 (95% CrI 970–1240) cases per year in 2015
to 630 (95% CrI 530–770) in 2020, around half that
currently expected.
– Although treating moderate-stage
disease will also be needed to
sustain this reduction beyond 2020
J Viral Hepat 2016 Mar 29. doi: 10.1111/jvh.12529.
0
500
100015002000
IncidentESLD/HCC 2010 2015 2020 2025 2030
Year
Current treatment DAAs cirrhosis only, IFN mild/moderate
DAAs cirrhosis/moderate, IFN mild DAAs all stages
X
X

8. Treating10,000 patientsperyear…
If diagnosed, we
would quickly treat
those with cirrhosis
HCV in the UK, 2015 report
Speed
ODNs can
tackle this
will vary

9. Treatingthosewithcirrhosis
• We cannot treat those who do not attend
treatment services
– Finding undiagnosed (N?) and re-engaging already diagnosed
patients will be important
– Outreach settings will be key (inequalities)
– Strategies, like peer support, to help engagement
• Those with moderate stage disease will need to
be tackled quickly too
– Some groups are more likely to disengage with watchful waiting
programmes, so may become lost to follow-up (inequalities)
Projections for reducing HCV disease
burden will not be met if we fail to treat at
least 70% of those with cirrhosis

10. Monitoringoutcomes
• Mortality: Deaths from HCV-related
ESLD/HCC
• Morbidity: Estimated incidence of
HCV-related ESLD/HCC
• Number initiating treatment
– Outcome of treatment
– Disease stage
Death
data
(ONS)
Hospital
episode
statistics
(HES)
National
Treatment
Monitoring
DatasetAssess impact on
future burden via
modelling
IMPACT

11. DeathsfromESLD*orHCCinthosewithHCV
mentionedontheirdeathcertificateinEngland
PHE. HCV in the UK, 2015 report
EAP Cirrhosis, June 2015
EAP Severe/Decom, April, 2014
Note: 2015 mortality data will be released in
HCV in the UK report on July 28, 2016…we
should start to see an impact

12. Whatabouttreatmentasprevention?
• Main route of transmission of HCV in England is
via injecting drug use (when injecting equipment
is shared)*
• Theory. If we treat those who are transmitting
the virus (current PWID), we should reduce
prevalence in PWID (the numbers with HCV)
and therefore the incidence (numbers getting
newly infected)
– You are less likely to catch HCV when you share injecting
equipment if less PWID have the virus in the first place.
* PHE. HCV in the UK, 2015 report

13. Estimatedprevalenceandincidenceof
chronicHCVamongPWIDinEngland
J Viral Hepat 2016 Mar 29. doi: 10.1111/jvh.12529.

14. Results,part2
• Treating mild-stage PWID was required to make
a substantial impact on transmission:
– with 2500 treated per year,
for example, chronic
prevalence/annual incidence
in PWID was reduced from
34%/4.8% in 2015 to
11%/1.4% in 2030
J Viral Hepat 2016 Mar 29. doi: 10.1111/jvh.12529.
X
X
X
X

15. Treatmentasprevention...
• Strategies that focus on advanced disease are unlikely to have a
‘prevention impact’ as they don’t catch many current PWID.
• Modelling studies suggest that treatment as prevention has the
potential to reduce the prevalence and incidence of HCV in PWID*
– “The most that can be expected from
any model is that it can supply a useful
approximation to reality:
All models are wrong; some models are useful”
George Box, 1919-2013
• If we are to reduce the number of new infections, then the potential
of treatment as prevention, when combined with other harm
reduction measures (OST, NSP), needs to be tested urgently.
*J Viral Hepat 2016 Mar 29. doi: 10.1111/jvh.12529.

16. Monitoringoutcomes
• Incidence: Number of new HCV
infections
– Estimated incidence of HCV among PWID
– Estimated prevalence of anti-HCV among recent initiates to drug use
• Harm reduction:
– Estimated proportion of PWID reporting adequate needle/syringe
provision
– Access to treatment
UAM
Survey
of PWID
Sentinel
Surveillance
of Hepatitis
Testing
AND
Laboratory
Reports
UAM
Survey
of PWID
IMPACT
National
Treatment
Monitoring
Dataset

17. HCVprevalenceinthosewhobeganinjecting
inthelastthreeyears:England, 2004to2014
* PHE. HCV in the UK, 2015 report

18. Strategies
treating mild
stage
disease
Strategies
treating
advanced
disease
Potential impact
on transmission
Potential dramatic
reductions in severe
liver disease
BUT… virtually no
prevention impact
BUT… virtually no
impact on ESLD/HCC
within 15 years*
*The long timescale of liver disease means relatively few
PWID reach cirrhosis before cessation of injecting.
Impactofstrategies…

19. *Elimination ofHCVasamajorpublic
healththreatby2030..?
TARGET
AREA
2020
TARGETS
2030
TARGETS
Challenges and Opportunities
Impact targets
Incidence: New
cases of
chronic viral
hepatitis C
infection
30% reduction 90% reduction
Challenge: Targets represent a
significant challenge for UK health
services requiring a radical change in
the response to HCV among PWID.
• Improvements in harm reduction,
diagnosis and treatment of PWID.
Mortality: Viral
hepatitis C
deaths
10% reduction 65% reduction
Opportunity: Targets seem achievable
and could possibly be exceeded.
• More diagnosis and treatment,
particularly in those with
moderate/severe disease
*http://www.who.int/hepatitis/strategy2016-
2021/Draft_global_health_sector_strategy_viral_hepatitis_13nov.pdf?ua=1

20. Challenges…
• Currently no vaccine.
• New therapies may be cost
effective but are expensive.
• Hep C treatment services
need to continue to be re-structured country-wide so they are
accessible to all those who need them.
• Asymptomatic nature means many remain undiagnosed:
increased awareness, testing & diagnosis are required.
• We are endeavouring to drive forward improvements in the
prevention and control of HCV at a time when resources are
scarce, and in some areas diminishing.

21. Italways seemsimpossible until
itisdone!

22. Acknowledgements
Colleagues in: PHE’s Statistics, Modelling and Economics Department;
PHE’s Immunisation, Hepatitis and Blood Safety Department; and Bristol
University’s School of Social and Community Medicine.
In particular…
• Ross Harris
• Sema Mandal
• Matthew Hickman and Natasha Kaleta Martin