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Hepatitis C Last updated November 2014. Hepatitis C virus (1) Virus first identified in 1989 1 No vaccine Routine screening of blood donations in Ireland.

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Presentation on theme: "Hepatitis C Last updated November 2014. Hepatitis C virus (1) Virus first identified in 1989 1 No vaccine Routine screening of blood donations in Ireland."— Presentation transcript:

1 Hepatitis C Last updated November 2014

2 Hepatitis C virus (1) Virus first identified in 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 this 2 Most new cases of hepatitis C in developed countries like Ireland are in injecting drug users 1 Hepatitis C can also be transmitted sexually and from an infected mother to her baby – but these routes are less common 1 Most cases are initially asymptomatic or mildly symptomatic, but approx. 75% of those infected develop chronic infection 3

3 Hepatitis C virus (2) Chronic infection can cause cirrhosis, liver cancer (HCC), liver failure and death 3 5%-20% develop cirrhosis after years 3 Of those with cirrhosis, approximately 4% progress to decompensated liver disease annually, % develop HCC annually and approximately 80% of those with HCC die annually 3 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 alcohol 5 Disease progression is also influenced by metabolic (high BMI, diabetes) and host genetic factors 5

4 Worldwide prevalence hepatitis C infection (source: WHO)

5 Epidemiology of hepatitis C in Ireland Hepatitis C became notifiable in : 12,148 cases notified, peak 2007 (n=1539), significant decrease in recent years – 786 cases notified in 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 were male Age at notification : median 34 years, mean 36 years Risk factor data collected (avail 52%) 82% of cases with risk factor data were injecting drug users

6 Number of notifications of hepatitis C , by sex and mean age

7 Average annual age and sex specific notification rates per 100,000 for hepatitis C,

8 Notification rates of hepatitis C per 100,000 population by HSE area,

9 Most likely risk factor (%) for cases of hepatitis C notified (where data available, n=2354, 57%)

10 Risk factor trends for cases of hepatitis C notified

11 Hepatitis C laboratory diagnostic data , and estimated prevalence of chronic hepatitis C in Ireland at the end of 2009 Hepatitis C testing began in 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) specimen- based data into person-based data and estimate prevalence chronic HCV in Ireland at the end of 2009 based on NVRL diagnostic and HPSC notifications data 7 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 Aug;140(8): ,384 cases of hepatitis C diagnosed by NVRL, % 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: % (20,000-50,000) More recent estimates of levels of underdiagnosis 8 indicate that prevalence in Ireland is more likely to be % (20,000-30,000)

12 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% 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 positive 18 Antenatal females: Universal HCV screening studies in 2 large maternity hospitals in Dublin: 0.7% & 0.9% anti-HCV positive 19,20 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 infection 21

13 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 decompensation 22, liver tranplantation 23 and all-cause mortality 23

14 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 IFN 24 Factors associated with better response to treatment – Genotype 2/3 rather than genotype 1 25,26 – Younger age at treatment 26 – Lower viral load at treatment 25, 26 – Disease stage: non-cirrhotic 25 – host genetics: IL28B CC genotype, rather than TT 26

15 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

16 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)

17 References (1) 1.World Health Organization: Guidelines for the screening, care and treatment of persons with hepatitis C infection. Geneva; April Health Protection Surveillance Centre. National Hepatitis C database Report. Available at: Z/Hepatitis/HepatitisC/HepatitisCDatabase/BaselineandFollow-upReports/ 3. Global Burden of Hepatitis C Working Group: Global burden of disease (GBD) for hepatitis C. J Clin Pharmacol 2004, 44: Mohd Hanafiah K, Groeger J, Flaxman AD, Wiersma ST: Global epidemiology of hepatitis C virus infection: new estimates of age- specific antibody to HCV seroprevalence. Hepatology 2013, 57(4): Seeff LB. The history of the "natural history" of hepatitis C ( ). Liver Int Jan;29 Suppl 1: Health Protection Surveillance Centre. HPSC annual report 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 Aug;140(8): Public Health England. Hepatitis C in the UK: 2013 report. Available at: 9. Smyth R, Keenan E, Dorman A, O’Connor J: Hepatitis C infection among injecting drug users attending the National Drug Treatment Centre. Ir J Med Sci 1995, 164(4): Smyth BP, Keenan E, O’Connor JJ: Bloodborne viral infection in Irish injecting drug users. Addiction 1998, 93(11): Smyth BP, Keenan E, O’Connor JJ: Evaluation of the impact of Dublin’s expanded harm reduction programme on prevalence of hepatitis C among short-term injecting drug users. J Epidemiol Community Health 1999, 53: Cullen W, Bury G, Barry J and O’Kelly F (2000) Drug users attending general practice in the Eastern Regional Health Authority area. IMJ, 93(7): 214– Grogan L, Tiernan M, Geoghegan N, Smyth BP, Keenan E: Bloodborne virus infections among drug users in Ireland: a retrospective cross-sectional survey of screening, prevalence, incidence and hepatitis B immunisation uptake. Ir J Med Sci 2005, 174(2): Cullen W, Bury G, Barry J, O’Kelly FD: Hepatitis C infection among drug users attending general practice. Ir J Med Sci 2003, 172(3):

18 References (2) 15. Cullen W, Stanley J, Langton D, Kelly Y, Bury G: Management of hepatitis C among drug users attending general practice in Ireland: Baseline data from the Dublin area hepatitis C in general practice initiative. Eur J Gen Pract 2007, 13: Long, Jean (2006) Blood-borne viral infections among injecting drug users in Ireland, 1995 to Overview 4. Health Research Board, DublinBlood-borne viral infections among injecting drug users in Ireland, 1995 to Overview Allwright S, Bradley F, Long J, Barry J, Thornton L and Parry JV (2000) Prevalence of antibodies to hepatitis B, hepatitis C and HIV and risk factors in Irish prisoners: results of a national cross-sectional survey. BMJ, 321: 78– Drummond A, Codd M, Donnelly N, McCausland D, Mehegan J, Daly L, Kelleher C: Study on the prevalence of drug use, including intravenous drug use, and blood-borne viruses among the Irish prisoner population. Dublin: National Advisory Committee on Drugs and Alcohol; Martyn F, Phelan O, O'Connell M. Hepatitis C: is there a case for universal screening in pregnancy? Ir Med J May;104(5): Lambert J, Jackson V, Coulter-Smith S, Brennan M, Geary M, Kelleher TB, O'Reilly M, Grundy K, Sammon N, Cafferkey M. Universal antenatal screening for hepatitis C. Ir Med J May;106(5): Brennan M, Boyle PJ, O'Brien AM, Murphy K. Health of Asylum seekers - are we doing enough? ICGP Forum magazine, November Ng V, Saab S. Effects of a sustained virologic response on outcomes of patients with chronic hepatitis C. Clin Gastroenterol Hepatol Nov;9(11): Van der Meer AJ, Veldt BJ, Feld JJ, Wedemeyer H, Dufour JF, Lammert F et al. Association between sustained virological response and all-cause mortality among patients with chronic hepatitis C and advanced hepatic fibrosis. JAMA Dec 26;308(24): Manns MP, Wedemeyer H, Cornberg M. Treating viral hepatitis C: efficacy, side effects, and complications. Gut Sep;55(9): Asselah T, Estrabaud E, Bieche I, Lapalus M, De Muynck S, Vidaud M et al. Hepatitis C: viral and host factors associated with non- response to pegylated interferon plus ribavirin. Liver Int Oct;30(9): Chuang WL, Yu ML. Host factors determining the efficacy of hepatitis C treatment. J Gastroenterol Jan;48(1): Ramachandran P, Fraser A, Agarwal K, Austin A, Brown A, Foster GR et al. UK consensus guidelines for the use of the protease inhibitors boceprevir and telaprevir in genotype 1 chronic hepatitis C infected patients. Aliment Pharmacol Ther Mar;35(6):


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