Hepatitis C“Hidden Harm”

Prof Suzanne Norris

Consultant Hepatologist

St James’s Hospital

Trinity College Dublin

Trinity College Dublin

Global burden of Hepatitis C virus infection: Europe

Cornberg M et al Liver International 2011; 31 (Suppl 2):30-60

Global Burden of HCV:Barriers to Testing, Care, Treatment

• Developed countries– Most HCV-infected persons are unaware of their infection

– Inadequate knowledge and awareness of HCV among healthcare providers and their patients

– Cost-related factors

– Lack of HCV screening policies

• Developing countries– Same barriers as in developed countries, plus

• Low political, provider, and community awareness of HCV as a significant health threat

• Lack of understanding among public health officials on the true burden of disease

• One-third of the WHO Member Countries do not collect prevalence data for viral hepatitis

Averhoff FM, et al. Clin Infect Dis. 2012;55(suppl 1):S10-S15.

Number of notifications of hepatitis C 2004-2010, by sex and mean age

Hepatitis C in Ireland

By 2013, 12,365 diagnosedPrevalence is 20,000-50,000

Mean annual notification rates per 100,000 for hepatitis C by age and sex, 2004-2012

Most likely risk factor (%) for cases of hepatitis C notified 2007-2010 (where data available, n=2772, 50%)

Most likely risk factor (%) for cases of hepatitis C notified 2007-2010 (where data available, n=2772, 50%)

HCV genotypes 1 and 3 are the most common

Prevalence of HCV among injection drug users in Ireland

In Ireland, 62–79% of injection drug users are positive for anti-HCV

62–79%

Fitzgerald et al. IMJ 2001;170:32Grogan et al. IMJ 2005;174(2):14Smyth et al. Addiction 1998;93(11):1649Smyth et al. J Epid Com Health 2003;57;310Cullen et al. IMJ 2003;172(3):1213

Epidemiology in Ireland: Prisons

Prevalence rate

Prison census survey

(n=1205)

Committal survey(n=607)

HBV 9% 6%

HCV 37% (81% IDU) 22% (72% IDU)

HIV 2% 2%

Department of Community Health and General Practice, Trinity College, Dublin. Hepatitis B, Hepatitis C and HIV In Irish Prisoners, Part II: Prevalence and Risk in Committal Prisoners 1999

17–21% started injecting drugs in prison

EpidemiologyEpidemiology: Ireland: Ireland

– No seroprevalence data from general population

– Of 62,667 women screened in the anti-D RhIg Programme, seroprevalence of HCV Ab positivity was 1.1% Kenny-Walsh et al, NEJM1999;340:1228

– Optional HCV Screening Programme of transfusion recipients, 1995 – 2002: 14,917 individuals screened (85% female) with seroprevalence rate of 0.3%

Davoren et al, Transfusion

2002;42:1501

HCV and the individual

• 10–20% of patients with HCV will develop cirrhosis after 20–30 years

EASL. J Hepatol 2014;60:392–42

Risk factors that may affect progression of HCV Infection

Factors contributing added risk to developing cirrhosis or HCC

Steatohepatitis/obesity1 Diabetes2

HIV coinfection1 Presence of varices2

Hepatitis B coinfection1 Low platelet count2

Alcohol intake1 Increasing age2

Smoking1 Black ethnic group2

Hepatic FibrosisHepatic Fibrosis

CirrhosisCirrhosis Liver CancerLiver Cancer

Healthy LiverHealthy Liver

Foster GR et al. Hepatology 1998;27:209–12

0102030405060708090

100

Physical functioning

Socialfunctioning

Role –physical

Role –emotional

Mentalhealth

Energy andfatigue

Pain General health

perception

Controls

Mild disease

Severe disease

Effect of chronic HCV infection on QoL measured using SF36 questionnaire

Change in quality of life following interferon therapy

Bonkovsky HL et al. Hepatology 1999;29:264–70

* p<0.05 **p<0.01

Responder (n=41)

Non-responder (n=396)

*

* *

*** *

Ch

an

ge

fro

m b

ase

line

in H

RQ

oL

(SF

-36

scal

e)

–505

101520253035

Physicalfunction

Role physical

Bodilypain

Generalhealth

Vitality Social function

Roleemotional

Mentalhealth

US multicentre randomised double-blind controlled study of 704 patients receiving 3µg inteferon, 9µg consensus interferon or 15µg interferon-alfa-2b 3 times a week for 24 weeks. Responder =undetectable HCV RNA at 24 weeks’ post-treatment

Indirect economic costs of HCV

• Data from the 2009 US National Health and Wellness Survey showed patients with HCV were significantly less likely to be employed vs controls (p<0.0001). HCV in the EU population significantly impacts several domains of HRQL (p<0.05)

DiBonaventura M et al. J Med Econ 2011;14:253–61

DiBonaventura M et al. Eur J Gastroenterol Hepatol 2012;24:869–77

Pa

tient

s (%

)

Absenteeism Presenteeism Overall work impairment

Activity impairment

20

30

10

0

Patients with HCV

Controls

REVEAL Study: risk of chronic HCV infection on hepatic and extrahepatic deaths

• Community based, long-term, prospective study– Invited 89,293 residents (aged 30-65 years) from 7

townships in Taiwan• 23,820 (26.7%) agreed to participate

• Current analysis (n=19,636 HBsAg-negative)– Anti-HCV seronegative (n=18,541)

– Anti-HCV seropositive (n=1095)• Detectable HCV RNA: 69.4%

• 2394 deaths over 317,742 person-years of follow-up– Average follow-up: 16.2 years

– Overall mortality: 753.4 per 100,000 person-years

REVEAL: Risk Evaluation of Viral Load Elevation and Associated Liver Disease/Cancer.Enrollment 1991-1992. Last follow-up: 12/2008. Lee M-H, et al. J Infect Dis. 2012; 206:469-477.

REVEAL Study Mortality: Liver Cancer and Cirrhosis

Lee M-H, et al. J Infect Dis. 2012; 206:469-477.

0 2 4 6 8 10 12 14 16 18 20

Liver Cancer(n=115)

Cu

mu

lati

ve M

ort

alit

y (%

)

Follow-Up (Years)

10.4%*

1.6%

0.3%

0 2 4 6 8 10 12 14 16 18 20

Chronic Liver Diseasesand Cirrhosis

(n=76)

Cu

mu

lati

ve M

ort

alit

y (%

)

Follow-Up (Years)

2.8%†

0.3%0%

REVEAL: Risk Evaluation of Viral Load Elevation and Associated Liver Disease/Cancer.*P<0.001 for comparison among all 3 groups and P<0.001 for HCV RNA detectable versus undetectable.†P<0.001 for comparison among all 3 groups and P=0.005 for HCV RNA detectable versus undetectable.

Anti-HCV+, HCV RNA detectableAnti-HCV+, HCV RNA undetectableAnti-HCV-

Anti-HCV+, HCV RNA detectableAnti-HCV+, HCV RNA undetectableAnti-HCV-

UK hospital admissions due to HCV-related ESLD and HCC are increasing

HPA report 2012 Available at: www.hpa.org.uk/webw/HPAweb&HPAwebStandard/HPAweb_C/1317135237627 Accessed June 2013

Annual number of individuals in England, Scotland and Wales hospitalised with HCV-related ESLD or HCV-related HCC:1998-2010

UK deaths from HCV-related ESLD and HCC are increasing

HPA report 2012 Available at: www.hpa.org.uk/webw/HPAweb&HPAwebStandard/HPAweb_C/1317135237627 Accessed June 2013

Deaths from HCV-related ESLD or HCV-related HCC mentioned on the death certificate in the UK:1996-2010

Burden of HCC in Ireland

HCV-related transplants 2001-2011

We apologise that this information is not able to shared online as it is unpublished data

A viral cure can be achieved in HCV infection

Achievement of a sustained virologic response (SVR) following completion of treatment is indicative of successful therapy and is synonymous with a cure

Soriano V, et al. J Antimicrob Chemother. 2008;62:1–4. Smith BD, et al. MMWR. 2012;61(4):1-32. Metzner KJ. Future Virol. 2006;1:377-91

Acute Infection

Chronic Infection

Successful Therapy

Does SVR equal cure of liver disease?

• Viral eradication stops progression of diseaseViral eradication stops progression of disease• Mild Disease - long-term outcome = popMild Disease - long-term outcome = pop’’n riskn risk

Veldt Gut 2002

286 pts with SVR after IFN therapy

Follow-up post SVR (n=286)

Pro

port

ion

of p

atie

nts

Time [yrs]

Decompensation/HCC

Survival

Matched generalpopulation

SVRs (n=286)

% s

urvi

val

Time [yrs]

SVR saves lives

0 1 2 3 4 5 6 7 8 9 100

10

20

30 10-year occurence SVR: 8.9% (95%CI 3.3-14.5) non-SVR: 26.0% (95%CI 20.2-28.4)

p<0.001

Follow-up time, years

Ove

rall

Mo

rtal

ity,

%

Van de Meer et al 2012

Long-term follow-up of patients with cirrhosis post-treatment

SVR

Non-SVR

SVR eliminates liver failure

Benefits of SVR: reduction in liver-related disease

Nu

mb

er o

f ev

ents

Mortality Rates and Hospital Episode Rates (Per 100 Person Years) by SVR Status Observed Among 1,215 Post-Treatment HCV Patients in Scotland, 1996-2007

Innes HA et al. Hepatology 2011;54:1547-1558.

Bottom lineBottom lineNon-Cirrhotics•SVR = cure normal life expectancy

Cirrhotics•SVR eliminates liver failure•SVR greatly reduces the risk of HCC•SVR improves liver-related AND overall survival

In a cost curtailed environment is curing a disease more effective than managing a disease - diabetes versus HCV?

Case-finding criticalCase-finding critical

24

30

13

18

8

14

8

16

34

24

10

18

12

27

37

20

3431

0

5

10

15

20

25

30

35

40Peg/RBV Peg/RBV/PI Peg/RBV/PI + Screening

Belgium France Germany Italy Spain UK

Red

uct

ion

in

cu

mu

lati

veIn

cid

ence

of

dea

th

Deuffic-Burban et al Gastro 2012

Treatment only effective for those who receive it…

Modelled number of IDUs in Scotland with liver failure with different uptake rates of HCV therapy, 2008-2030

Assuming uptake of HCV antiviral therapy by:

0 former IDUs per year

225 former IDUs per year

1,000 former IDUs per year

(up to) 2,000 former IDUs per year

Number of patients ever treated with PEG per 100 prevalent HCV cases* by country until end of 2005

Lettmeier et al JHepatol 2008

16

1

3

HCV mono-infection landscape in Ireland

We apologise that this information is not able to shared online as it is unpublished data

HCV mono-infection treatment programme in St James’s Hospital

We apologise that this information is not able to shared online as it is unpublished data

Current Challenges - unmet need

We apologise that this information is not able to shared online as it is unpublished data

HCV in Ireland: where is it?

Three big reservoirs• Current injectors• Ex-injectors

• Hidden• Finding them may take a screening campaign

(‘baby boomers’)

• Immigrants• Pattern of infection unpredictable (‘healthy migrant’ effect)

• Access can be difficult

• Not everyone wants to be associated with these virus

HCV Infection

Diagnosis

Referral to Specialist

Barriers to HCV Care

HCV Infection

Diagnosis

Referral to Specialist

Patient factors

Social supporthomelessness, social isolation,

culture, stigmatisation, language and ethnicity

Treatment side-effectsPatient fears and impact on quality

of life and career

CostFinancial concerns around

treatment and daily living costs and lack of funding support

HCP factors

Lack of educationLack of awareness of HCV among

primary care staffLack of screening and referral

facilitiesLack of communication with

specialist services

Clinician bias

Lack of urgency from the Department of Health and HSE.

What will it take to overcome current barriers?

Future: better treatments

• Simpler therapy• Shorter duration• More tolerable• Efficacious

Opportunity to reduce morbidity, mortality and associated healthcare costs

What will it take to overcome current barriers?

• Advocacy

• Leadership

• Political partnership

I.C.O.R.N.

• Irish Hepatitis C Outcomes Research Network. Established February 2012.

• Collaboration between ISG, IDSI, NCPE and HPSC, research networks, and pharma.

• The goal of this collaboration is to optimise the quality of care of patients with hepatitis C (HCV) treated with direct-acting antiviral therapy.

I.C.O.R.N.

• to provide a governance structure and stewardship programme for clinicians and clinical nurse specialists

• develop national treatment guidelines

• establishment of national treatment HCV registry

• platform for HCV clinical trials and HCV related research

• R&D models of care to enhance equitable access to services for all assess differing treatment models

DAAs – decision to reimburse

We apologise that this information is not able to shared online as it is unpublished data

Outputs from registry

• Real time e-data capture tool developed by ICORN (A O’Leary) in conjunction with DCCR (J. McCourt, R. Gaur)

• Real-world, observational data• Effectiveness vs efficacy

– Analysis of response modifiers• Quantitative analysis of adverse events• Economic consequences• PROMs and PREMs

ICORN HCV Roadmap 2014

• Development of Model of Care

- Network of treatment sites

• Expansion of Registry

• Advocacy for Implementation of National HCV Strategy– Education and awareness– Surveillance and screening

• Infrastructural programmatic support to consolidate national programme

• 36 recommendations across four key areas:

– Surveillance– Education &

Prevention– Screening– Treatment access &

delivery

Reality or Fantasy

• Will screening be acceptable in primary and care?

• Who will pay?

• Does infrastructure exist for referral and treatment?

• New models for care? Who will treat?

Lessons from Scottish HCV Plan

• Epidemiologic data KEY factor, data linkage techniques developed

• Clinician and Public Health leadership • Advocacy and support groups• Strong governance • Programme managed• Political partnership

Challenge for Ireland 2014

Thank you