Hepatitis C
Last updated November 2014
Hepatitis C virus (1)
• Virus first identified in 19891
• No vaccine
• Routine screening of blood donations in Ireland started in 1991
• Approximately 1,700 people were infected through
contaminated blood/blood products prior to this2
• Most new cases of hepatitis C in developed countries like Ireland
are in injecting drug users1
• Hepatitis C can also be transmitted sexually and from an infected
mother to her baby – but these routes are less common1
• Most cases are initially asymptomatic or mildly symptomatic,
but approx. 75% of those infected develop chronic infection3
Hepatitis C virus (2)
• Chronic infection can cause cirrhosis, liver cancer (HCC), liver
failure and death3
• 5%-20% develop cirrhosis after 20-30 years3
• Of those with cirrhosis, approximately 4% progress to
decompensated liver disease annually, 1.5-2.5% develop HCC
annually and approximately 80% of those with HCC die annually3
• Disease progression is faster in males, people who were older at
infection, those who are co-infected with HIV or HBV and those
who consume high levels of alcohol5
• Disease progression is also influenced by metabolic (high BMI,
diabetes) and host genetic factors5
Worldwide prevalence hepatitis C infection
(source: WHO)
Epidemiology of hepatitis C in Ireland
• Hepatitis C became notifiable in 2004
• 2004-2013: 12,148 cases notified, peak 2007 (n=1539), significant
decrease in recent years – 786 cases notified in 20136
• Notifications include some (but not all) cases diagnosed before 2004 and
not previously notified, and some duplicates (full names not always given)
• 2012: case definitions altered to explicitly exclude cases known to be
resolved (no longer viraemic). Prior to this, laboratory results were
frequently insufficient to distinguish chronically infected and resolved cases
• 66% of cases notified 2004-2013 were male
• Age at notification 2004-2013: median 34 years, mean 36 years
• Risk factor data collected 2007-2013 (avail 52%)
• 82% of cases with risk factor data were injecting drug users
1800
45
1600
40
1400
35
1200
1000
1400
1119
1539
1506
30
1235
1209
1220
1240
800
25
894
600
786
20
15
400
10
200
5
0
0
2004
2005
2006
2007
2008
2009
2010
2011
2012
2013
Year
Male
Female
Unknown sex
Mean age males
Mean age females
Mean age
Number of notifications
Number of notifications of hepatitis C 2004-2013, by
sex and mean age
Average annual notification rates per
100,000
Average annual age and sex specific notification rates
per 100,000 for hepatitis C, 2010-2013
80
70
60
50
40
30
20
10
0
0-4
5-9
10-14
15-19
20-24
25-34
Age group (years)
Male
Female
35-44
45-54
55-64
65+
Notification rates of hepatitis C per 100,000
population by HSE area, 2010-2013
Notificaiton rate per 100,000
70
60
50
40
30
20
10
0
E
M
MW
NE
NW
SE
S
HSE area
2010
2011
2012
2013
W
Most likely risk factor (%) for cases of hepatitis C notified
2010-2013 (where data available, n=2354, 57%)
Other and no
known risk factor,
5.9%
Vertical
transmission, 2.7%
Possible sexual
transmission, 5.7%
Blood or blood
products, 3.2%
Injecting drug user,
82.5%
Risk factor trends for cases of hepatitis C notified 2010-2013
Number of notifications
700
Injecting drug user
600
Blood or blood products
500
400
Possible sexual
transmission
300
Vertical transmission
200
Other
100
Unknown
0
2010
2011
Year
2012
2013
Hepatitis C laboratory diagnostic data 1989-2004, and estimated
prevalence of chronic hepatitis C in Ireland at the end of 2009
•
•
Hepatitis C testing began in 1989. Approx. 95% of confirmatory HCV testing between
1989 and 2004 carried out by the National Virus Reference Laboratory (NVRL)
Study to convert NVRL laboratory information management system (LIMS) specimenbased data into person-based data and estimate prevalence chronic HCV in Ireland at
the end of 2009 based on NVRL diagnostic and HPSC notifications data7
Thornton L, Murphy N, Jones L, Connell J, Dooley S, Gavin S, Hunter K, Brennan A.
Determination of the burden of hepatitis C virus infection in Ireland.
Epidemiol Infect. 2012 Aug;140(8):1461-8
•
10,384 cases of hepatitis C diagnosed by NVRL, 1989-2004
- 55% genotype 1, 4% genotype 2, 39% genotype 3, 1% genotype 1&3, 1
other mixed genotypes and genotypes 4 and 5
- Risk factor available for 76%: 80% were current of former drug users, 16%
received blood or blood products in the past
•
Estimated national prevalence chronic hepatitis C end 2009: 0.5-1.2% (20,000-50,000)
•
More recent estimates of levels of underdiagnosis8 indicate that prevalence in Ireland
is more likely to be 0.5-0.7% (20,000-30,000)
Studies of hepatitis C prevalence in Ireland
Injecting drug users
• Studies of injecting drug users (mostly heroin) in Ireland, between 1992 and
2006: hepatitis C antibody (anti-HCV) prevalence in this population 52-84%9-17
• 2011 prison study found that 54% of prisoners with a history of injecting heroin
were anti-HCV positive and 41.5% of prisoners with a history of injecting any
drugs were anti-HCV positive18
Antenatal females: Universal HCV screening studies in 2 large maternity hospitals in
Dublin: 0.7% & 0.9% anti-HCV positive19,20
New blood donors: Irish Blood Transfusion Service: 0.02% of new donors tested
1997 to 2012 were anti-HCV positive (personal communication: IBTS)
Asylum seekers: Balseskin reception centre: 1% of those tested, under the
voluntary health screening programme, between 2004 and 2012, were positive for
chronic HCV infection21
Hepatitis C anti-viral treatment
• Anti-viral treatments are available for hepatitis C
• Goal of treatment is to eradicate the virus from the patient’s
blood and prevent long-term liver damage and death
• Treatment success is measured by SVR12 or SVR24 – sustained
virological response – undetectable RNA at 12 or 24 weeks after
completion of treatment
• SVR is associated with a reduction in liver-related mortality,22,23
hepatocellular carcinoma,22,23 hepatic decompensation22, liver
tranplantation23 and all-cause mortality23
Treatment standard of care in Ireland prior to 2012
• Pegylated interferon (Peg-IFN) & ribavirin (RBV)24
– 24 weeks for genotype 2 or 3 HCV
SVR: >75%
– 48 weeks for genotype 1 HCV
SVR: 40-50%
• Significant side effects - mainly from IFN24
• Factors associated with better response to treatment
– Genotype 2/3 rather than genotype 125,26
– Younger age at treatment26
– Lower viral load at treatment25, 26
– Disease stage: non-cirrhotic25
– host genetics: IL28B CC genotype, rather than TT26
New treatments currently available in Ireland: Direct
acting antivirals (DAA)
• In 2012 two protease inhibitors (Boceprevir (Boc) and Telaprevir
(Tel) were recommended by NCPE for reimbursement in Ireland.
These were for use in patients with Genotype 1 hepatitis C
infection in combination with Peg-IFN and RBV
• Response guided treatment – clear stopping rules – based on viral
load
• Additional side effects –rash, haematological, gastrointestinal
• SVR in genotype 1 patients –improvement on previous treatments
- Boceprevir + Peg-IFN + RBN: 54-75%27
- Telaprevir + Peg-IFN + RBN: 61-75%27
Newer Direct Acting Antivirals
• Many new therapies in development and undergoing licensing and
reimbursement decisions
• Various combination therapies using new direct acting antivirals,
with and without RBV, and with and without Peg-IFN (all-oral
treatment possible)
• Achieving high SVRs in clinical trials, even among patients with
cirrhosis and those who have previously failed treatment
• Daclatasvir, sofosbuvir and simeprevir are currently licensed in
Europe and reimbursement recommendations in respect of these
drugs are under review by the National Centre for
Pharmacoeconomics (NCPE) www.ncpe.ie
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Thornton L, Murphy N, Jones L, Connell J, Dooley S, Gavin S, Hunter K, Brennan A. Determination of the burden of hepatitis C virus
infection in Ireland. Epidemiol Infect. 2012 Aug;140(8):1461-8
Public Health England. Hepatitis C in the UK: 2013 report. Available at:
http://www.hpa.org.uk/webc/HPAwebFile/HPAweb_C/1317139502302
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Martyn F, Phelan O, O'Connell M. Hepatitis C: is there a case for universal screening in pregnancy? Ir Med J. 2011 May;104(5):144-6
Lambert J, Jackson V, Coulter-Smith S, Brennan M, Geary M, Kelleher TB, O'Reilly M, Grundy K, Sammon N, Cafferkey M. Universal
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Brennan M, Boyle PJ, O'Brien AM, Murphy K. Health of Asylum seekers - are we doing enough? ICGP Forum magazine, November 2013
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