SCREENING POLICIES

ANGELOS HATZAKISProfessor of Epidemiology & Preventive Medicine, Athens University

Medical School/ Co-Chair, Hepatitis B & C Public Policy Association

1st European Roundtable on Hepatitis Cure & Eradication

Frankfurt, 9 September 2015

Disclosures

Research Grants: Gilead

Advisory Boards: BMS, Gilead

Unrestricted Grants: AbbVie, BMS, Gilead, Novartis

Co-Chair, Hepatitis B & C Public Policy Association,

supported by AbbVie, BMS, Gilead

Back to Basics

Challenges for a Screening Programme to Control or

Eliminate HCV/HBV

Is Elimination of HCV/HBV possible?

Recommendations

Conclusions

Back to Basics

Continuum of HCV diagnosis, care and treatment

HCV infected

Unaware of HCV

Screening offered

Screening accepted

Screening diagnosis

Screening results offered

Linked to care

Retained to care

Need treatment

No contraindication

Treatment cost covered

On treatment

Sustained viral response (cure)

Yehia BR et al. PlosOne 2014: 9, 7

Goals of a Hepatitis Screening, Care and Treatment

Programme

To control HCV/HBV: To decrease incidence of cirrhosis

and HCC following reduction of HCV incidence.

To eliminate HCV/HBV: Zero or near zero incidence of

HCV infection with major reduction in the incidence of

cirrhosis and HCC in a specific area.

To eradicate HCV/HBV: Zero or near zero incidence of

HCV infection with major reduction in the incidence of

cirrhosis and HCC at global level.

WHO, 2015

Challenges for a Screening Programme to

Control or Eliminate HCV/ HBV

Challenges for designing an efficient screening

programme to control or eliminate HCV/HBV

1) Knowledge of HCV/HBV epidemiology and burden of disease.

2) Issues related to the screening process (goals, testing

algorithms, testing strategy, operational and ethical problems).

3) Improvements in all steps of treatment cascade.

4) Availability of resources for testing, care and treatment (health

infrastructure, affordable care and treatment).

HCV epidemiology

1) Observational studies (prevalence, incidence, risk factors,

mortality).

2) Modelling studies for prediction of natural history, burden

of disease and economic burden.

HCC, Decompensated Cirrhosis and Transplant, 1950-2030

England, France, Germany and Portugal

Razavi H, et al. J Viral Hepat 2014; 21 Suppl 1: 34-59.

Cirrhosis, 2013-2030

England, France, Germany and Portugal

Wedemeyer H, Duberg AS, Buti M, et al. .J Viral Hepat 2014; 21 Suppl 1: 60-89.

Estimated Viremic Infections, 2013-2030

Czech Republic, Denmark and Egypt

Wedemeyer H, Duberg AS, Buti M, et al. JVH 2014; 21 Suppl 1: 60-89.

Is Elimination of HCV/HBV

possible?

Is elimination of HCV/HBV possible?

Important parametres

1) Viremic prevalence

2) Age and sex distribution of HCV/HBV

3) Diagnostic rate

4) Distribution of CHC/CHB by fibrosis stage

5) Status of primary prevention

6) Treatment rate

7) Increase in the future treatment coverage

8) Efficient testing strategy

9) Availability of resources for testing, care and treatment

infrastructure

10) Ethical issues

Historical Distribution by Age and Gender

Canada, Czech Republic, Denmark and Egypt

Bruggmann P, Berg T, Ovrehus AL, et al. Historical epidemiology of hepatitis C virus (HCV) in select countries. J Viral Hepat 2014; 21 Suppl 1: 5-33.

Historical Distribution by Age and Gender

Argentina, Finland, Greece and India

Saraswat V, Norris S, de Knegt RJ, et al. Historical epidemiology of hepatitis C virus (HCV) in select countries – volume 2. J Viral Hepat 2015; 22 Suppl S1: 6-25.

Wedemeyer et al. JVH, 2014. 21 (Suppl S1), 60-89

Distribution of CHC by fibrosis stage

Status of Primary Prevention

It is reflected in the assumed number of new HCV/HBV

infections per year in the past and up to 2030.

Past infections are estimated by various methods (back-

calculation, population surveys etc).

HBV vaccination initiation and coverage.

Increase in the future treatment coverage

Efficient testing strategy (1)

1) Risk groups

2) Age-based or birth cohort screening

3) Combination of the above

WHO Recommendation on Screening

(risk-based)

It is recommended that HCV serology testing be offered to

individuals who are part of a population with high HCV

seroprevalence, or who have a history of HCV risk

exposure/behaviour.

It is suggested that nucleic acid testing for the detection of HCV

RNA be performed directly, following a positive HCV serological

test to establish the diagnosis of chronic HCV infection, in

addition to nucleic acid testing for HCV RNA as part of the

assessment for starting treatment for HCV infection.

WHO Guidelines , April 2014

AASLD Recommendation for HCV Testing (1)

One-time HCV testing is recommended for persons born between 1945 and 1965*,

without prior ascertainment of risk (birth-cohort screening)

Other persons should be screened for risk factors for HCV infection, and 1-time

testing should be performed for all persons with behaviors, exposures and

conditions associated with an increased risk of HCV infection (risk-based screening)

Risk exposures: • Long-term hemodialysis (ever)

• Getting a tattoo in an unregulated setting

• Healthcare, emergency medical and public safety workers after

needlesticks, sharps or mucosal exposures to HCV-infected blood

• Children born to HCV-infected women

• Prior recipients of transfusions or organ transplants, including persons who

1) were notified that they received blood from a

donor who later tested positive for HCV infection, 2) received a

transfusion of blood or blood components or underwent an organ

transplant before July 1992, 3) Received clotting factor

concentrates produced before 1987

• Persons who were ever incarcerated

*Regardless of country of birth

AASLD Recommendation for HCV Testing (2)

Risk behaviors: • Injection-drug use (current or ever, including those who inject once)

• Intranasal illicit drug use

Other: • HIV infection

• Unexplained chronic liver disease and chronic hepatitis, including

elevated alanine aminotransferase levels

• Solid organ donors (deceased and living)

Risk-based screening

Practitioner-based targeted (risk-group) screening is more

efficient in terms of screening uptake and cases detected.

The less efficient strategy is the media/information based

intervention.

(Aspinall et al. 2015)

Anti-HCV positive patients according to year of birth.

An increase in the anti-HCV prevalence cannot be observed either in

the US American or in the German baby boomer generation

Wolffram I et al. J Hepatol 2015; 62, 6: 1256

Efficient testing strategy (2)

Martin NK et al. Hepatol 2013. 58: 5

Treatment as prevention

Wedemeyer H et al. JVH. 2014, 21

Gane et al. JVH, 2015. 22, (Suppl S1), 46-73

Types of screening programmes

Integrated: Screening programmes that are integrated within

already existing health care facilities (STD clinics, HIV/STD

service providers, sexual and reproductive health clinics,

emergency departments, community centers, prisons, health

clinics, public laboratories, occupational physicians etc).

Non-integrated: Screening programmes that are exclusively

set up for screening (community health clinics, private practice

offices, outreach community screening, city programmes,

schools etc).

Cost and cost-effectiveness studies (1)

1) Increasing number of CE studies of chronic HCV

treatment with interferon free regimens.

2) Few cost-effectiveness (CE) studies with interferon free

regimens to assess HCV screening.

Cost and cost-effectiveness studies (2)

Intervention: PegIFN-Riba-Sofosbuvir or Sofosbuvir-Riba

compared to PegIFN-Riba-PI

Population: US population aged older than 20 (birth cohort

screening)

Result 1: Sofasbuvir regimens reduced deaths by 80682 at an

incremental cost of 26.2billion.

Result 2: The ICER was estimated 47,304 USD/QALY gained.

Result 3: The ICERs were decreasing with decrease cost of

treatment, better post-SVR quality of life, advanced fibrosis

stage.

Rein DB et al. CID 2015

Cost and cost-effectiveness studies (3)

Intervention: Sofosbuvir-Ledipasvir compared with PegIFN-Riba-PI

therapies, in the US population.

Result 1: Sofosbuvir-Ledipasvir therapies have an incremental cost-

effectiveness ratio (ICER) 55400 USD/QALY

Result 2: Sofosbuvir-Ledipasvir compared with interferon based

therapies would cost an additional 65 billion USD with savings of

16 billion USD.

Result 3: ICERs were decreasing with decreasing cost of treatment,

better post-SVR quality of life, advanced fibrosis stage, decreasing

age and in females.

Chhatwal J et al. Ann Intern Med. 2015

Ethical issues

1) Stigma

2) Inequalities

3) HCV/HBV screening should be connected with

affordable care and treatment

4) Screening and treatment in balance with primary

intervention

Recommendations

Considerations for the implementation of successful screening programmes for

HBV and HCV

Develop clear public awareness campaigns targeted at the general public and at risk groups.

Need a clear clinical strategy to deal with HBV- and HCV-infected persons.

Revise clinical guidelines to endorse HBV and HCV screening in specified risk groups and

reinforce dissemination of best practices for case finding.

Integrate screening into existing public health and care practices whenever possible.

Conduct HBV and HCV screening in HIV/AIDS clinics, prisons, drug user services as

well as in primary care clinics.

Simplify screening criteria, e.g. adopt age-based criteria for HCV, birth place for HBV with

the aim of providing clear guidance to GPs and those screening patients.

Educate providers about the needs for screening and about the management pathways for

HBV- and HCV- infected individuals.

Always carry out screening in an evidence-based way that defines when and how often

screening should be offered and respects the human rights of those screened.

Always accompany screening with appropriate counselling of the individual and his or her

family.

In the case of marginalized or stigmatized groups such as migrants or IDUs, one must

ensure that individuals are not stigmatized because of their group membership or their viral

hepatitis status.

Hatzakis A et al. JVH 2011, 18 (supp.1)

Conclusions

Conclusions

A screening/treatment strategy aiming to eliminate HCV/HBV should optimize all steps of treatment cascade.

The epidemiologic profile of HCV/HBV in many developed countries is favourable for elimination of new infections, cirrhosis and HCC, assuming increased screening uptake and treatment coverage of DAAs.

Elimination of new HCV infections by increased coverage of screening/treatment will be facilitated with an HCV vaccine, in groups where HCV is hyperendemic (IDUs).

The main barrier of screening/treatment expansion is cost, although the rapidly fallen treatment prices suggest that large and effective screening programmes are feasible in the near future.