HCV Guidelines

Dr Saeed Hamid
 STATUS OF HEPATITIS C HCV

Incidence:
1.75 million new infections / year
(Unsafe health care and injection drug use)

Prevalence:
71 million infected, all regions

Sources – WHO (Center for Disease Analysis )

 Globally, Pakistan is estimated to have the one
of the highest number of viremic HCV infections
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Total Viremic Infections, All Ages (millions)

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12

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Gower E, et al. J Hepatology 2014.

BLOOD AND INJECTION SAFETY

Proportion of unsafe injections by region:

challenges remain, particularly in
the Eastern Mediterranean region

Source: Pepin et al, 2013

 Global Health Sector Strategy on Viral
Hepatitis (2016): Roadmap to Elimination

Goal = Eliminate viral hepatitis as a major public health threat by 2030

 WHO Global Health Sector Strategy
2016-2030

Targets for Hepatitis B and C prevention

diagnosis, and treatment

• 90% infants to receive a birth dose of HBV vaccine.

• All blood donations to be screened for HBV and HCV.
• 90% of people to have access to safe injections.
• 90% of people diagnosed by 2030;
• 90% of eligible people treated by 2030;
• 90% of those treated are cured by 2030.
 How are WHO guidelines different
from other guidelines?
Feature WHO Guideline Other Guidelines

TARGET AUDIENCE National programme managers Prescribing clinicians

SETTINGS • Low and middle income countries High income countries

• Variable access to laboratory
testing (e.g. viral load, genotyping,
transient elastography)
EVIDENCE-BASED • Strength and quality of evidence Variable use of evidence-
GRADE APPROACH Feasibility, equity, based framework
• resource use considered
APPROACH The “Public health approach” Individualised treatment
 WHO guidelines development process
WHO Steering Committee
Constitute Guideline Development Group

Formulate questions (PICO format)

Conduct systematic reviews of data

Evaluate quality of evidence (GRADE)

Formulate recommendations

Disseminate, Adapt, Evaluate

 WHO released its first HCV treatment
guidelines in April 2014
• Recommendations along continuum of
care:
– Screening:
• Whom to test
• Confirmation testing
– Care:
• Screening for high alcohol use
• Fibrosis assessment
– Treatment:
• PEG-IFN/RBV, boceprevir, telaprevir,
simeprevir and sofosbuvir
WHO released updated HCV care and
treatment guidelines in 2016

Topic Recommendation

Staging  Use non-invasive tests (APRI or FIB4) for

assessment of liver fibrosis
Treatment  Assessment of all adults and children with
chronic HCV, including PWID for antiviral
treatment
Considerations  Increased risk of death/fibrosis; extrahepatic
for manifestations; psychosocial morbidity;
prioritisation: maximising reduction in transmission.
WHO released updated HCV care and
treatment guidelines in 2016
Few Countries are on track to Eliminate
HCV by 2030
Cascade of Care for HCV in Pakistan

Polaris Observatory, CDA

 What has happened since release of WHO
2016 guidelines?
• Price reductions and wider availability of generics (WHO
Progress Report on Access to HCV Treatment, March 2018)
• New pan-genotypic DAA regimens approved:
– Sofosbuvir/Velpatasvir
– Glecaprevir/Pibrentasvir
• Accumulating evidence on safety and effectiveness of DAA
regimens in real world (e.g., Daclatasvir/Sofosbuvir)

 Further guidance needed on when to start treatment and

what treatment to use
 Whom to treat and when to start?
• New WHO guidance recommends treating all those infected above 12
years of age (with exception of pregnant women)
• DAAs lead to high rates of cure (SVR) and SVR is associated with
reduced all cause mortality, liver related mortality, and reduced
incidence of HCC (based primarily on IFN data),

• SVR is associated with improvement of co-morbidities like diabetes,

depression and chronic renal disease
• Treatment of HCV-infected adolescents is effective and well tolerated
 Treating all: Balance of benefits versus
harms
• Benefits
• Substantial decrease in liver-related complications and deaths
• Prevention of co-morbidities
• Leads to a modest reduction in incident HCV infections
• Clear support among the community of HCV infected persons
• Public health approach to implementation

• Potential harms
• More side-effects potentially if larger-scale use of DAAs
(need pharmaco-vigilance)
• Possibility of reactivation for HBV co-infected persons
• Perception that harm reduction among PWID would be unnecessary

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 What treatment to use?

WHO recommends the use of pan-genotypic DAA

regimens for the treatment of persons with chronic
hepatitis C infection aged 18 years and above

•Pan-genotypic DAAs on the market:

– Sofosbuvir/Velpatasvir
– Glecaprevir/Pibrentasvir (no access policy yet announced)
– Daclatasvir/Sofosbuvir (based on real-world observational studies,
including MSF data for genotypes 5 and 6)
 Use of pan-genotypic regimens:
Balance of benefits versus harms
Benefits
• Remove the need for genotyping, which reduces cost and complexity
• Pan-genotypic DAA regimens may facilitate a rapid treatment scale-up,
especially in LMICs where the cost of genotyping can be prohibitively high
• Simplifies medicine procurement and supply chains

Potential harms
• There are countries where the recommended pan-genotypic regimens
may not yet be approved or available
• In addition, there are countries where the HCV epidemic is almost entirely
caused by one HCV genotype; thus, there may be a continued role for non-
pan-genotypic DAAs, while national programmes transition to using pan-
genotypic regimens.

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Exceptional Growth in Treatment Rate
Pakistan

Patient Treated 2015 2016 2017 2018

(estimate)
Private Market 72,500 154,300 195,000 250,000
Public Market 25,000 38,000 210,000 450,000
Total 97,500 192,300 405,000 700,000

Data is from ims for private market

Public Market data is from tender info
Recommended Regimens with Treatment
Durations for Patients without Cirrhosis
Genotype Regimen 1 Regimen 2 Regimen 3 Regimen 4
[Sofosbuvir/ [Sofosbuvir/ [Sofosbuvir/ [Sofosbuvir/
Ledipasvir] Ledipasvir/ Daclatasvir] Daclatasvir/
Ribavirin] Ribavirin]
Genotype 1 12 weeks No 12 weeks No
Genotype 2 No No 12 weeks No
Genotype 3 No No 12 weeks No
Genotype 4 12 weeks No 12 weeks No
Genotype 5 12 weeks No 12 weeks No
Genotype 6 12 weeks No 12 weeks No
MMPHCRF 2016
 Treatment of children < 12 years

Among children aged < 12 years with chronic hepatitis

C infection, WHO recommends:
• Deferring treatment until age 12 years

* Prior to approval of DAAs for children < 12 years old, exceptional treatment
with interferon+ribavirin may be considered for children with genotype 2 or 3
infection, and severe liver disease.
 Treatment of Adolescents (12-17 years)
Benefits vs Harms
Potential Benefits
• Curative, short-course DAA treatment is likely to be highly acceptable to
adolescents, as well as their parents or caregivers
• Cure will enable adolescents to live free of a socially stigmatising infection
• Earlier treatment may avoid the higher costs associated with treating
adults with advanced liver disease.

Potential Harms
• Some adolescents will be diagnosed and treated for HCV infection that is
currently causing no symptoms and this may create some anxiety
• LMICs with already significant financial constraints may be unwilling to
extend treatment to adolescents in the initial phase of scale-up.

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Simplified testing and management algorithms
 Conclusions
• WHO recommends use of DAAs to ‘treat all’ (with the
exception of pregnant women and children under age 12)
• Genotyping remains a barrier; thus, WHO is moving towards
recommending the use of pan-genotypic DAA regimens
• Very dynamic price scenario for DAA regimens; registration in
countries remains a barrier and needs to be a high priority
• Simplified algorithms for testing and treatment, adapted to
primary care, can greatly facilitate global scale-up
• Equity in access to DAAs is a critical guiding principle.
Thank you!