Lelia Thornton Health Protection Surveillance Centre June 2009

1. Lelia Thornton Health Protection Surveillance Centre June 2009

2. Background to hepatitis C infection through blood/blood products in Ireland Anti-D • Approximately 1000 females infected through contaminated anti-D from 2 donors • ~90% infected 1977 to 1979 – genotype 1b • ~10% infected 1991 to 1994 – genotype 3a • Infected during child bearing years – expected to have been generally healthy when infected Blood transfusion/cross contamination in renal dialysis units • >400 people infected prior to the introduction of screening in 1991 • Heterogeneous group in terms of age and sex • Significant proportion likely to have had serious underlying illnesses when infected Blood clotting factors (for tx haemophilia, von Willebrand disease and other coagulation disorders) • >220 people infected – mostly between mid 1970s and early 1980s • Mostlymale, infected as children • Approximatelyone third co-infected with HIV

3. Background to the database • Specialist hepatology units set up in 8 hospitals • All living people infected with hepatitis C through blood/blood products referred to & assessed in a hepatology unit • Health (Amendment) Act 1996: ensures priority access to hepatology services and range of additional specialist hospital and primary care services – mostly through referrals from hepatology units • In 2000, the Consultative Council on Hepatitis C recommended that a database be developed to follow the natural history of hepatitis C disease in this group of patients • Database project started in 2004 – managed by HPSC • Eligible population identified through hepatology units

4. Who is included in the database and how is data collection done? Inclusion criteria • Infected with hepatitis C through blood/blood products in Ireland • Infection defined as Hepatitis C RNA positive and/or Hepatitis C antibody positive ( RIBA positive or indeterminate and/or EIA/ELISA positive or weak positive) Data collection • Consentrequiredto participate except where patient is deceased • Data collected from medical records in the 8 hepatology units by a HPSC research nurse • Baseline data collected 2005 to 2007 – all avail data up to end 2005 • First year of follow up data collected 2008 – data up to end 2007 • Ongoing project with annual follow up – Yr 2 follow up in progress

5. Data collected • Demographic and lifestyle data: date of birth, gender, height, weight, smoking, alcohol • Infection details: source & year of infection • Laboratory results: hepatitis C antibody & RNA results, hepatitis C genotype, LFT and biopsy results • Clinical status: signs of liver disease, other medical conditions • Cause and date of death for deceased patients • Treatment details: treatment regimes and outcomes • Clinical management: health services

6. Database population

7. Participation: % of eligible people currently in the database by source of infection

8. Number of database participants by source of infection and sex (n=1275)

9. Median age at infection and at end of latest follow up by source of infection

10. Distribution of age at infection and age at end of latest follow-up

11. % RNA positive at diagnosis by Source of infection

12. Viral clearance by time of diagnosis • At diagnosis: 64% RNA positive, 36% RNA negative • Females more likely to have cleared the virus 59% tested RNA positive compared to 85% of males • But, high spontaneous clearance rate in females should be interpreted with caution: • >20% of participants did not have positive confirmatory results for hepatitis C (RNA or RIBA positive), strongest results were EIA positive/weak positive/RIBA indeterminate • Some may have been false positives • Most common in females infected through anti-D • May have resulted in overestimation of viral clearance in this group

13. Distribution of duration of Hepatitis C RNA positivity for Anti-D participants

14. Distribution of duration of Hepatitis C RNA positivity for blood transfusion/renal & clotting factor participants

15. Hepatitis C genotype results: % of participants with each genotype by source of infection

16. Alcohol intake: highest recorded by sex – ever RNA positive participants only

17. Liver-related outcomes and medical conditions by end of latest follow-up

18. Liver-related outcomes by source of infection – ever RNA positive participants

19. Liver-related outcomes by sex – ever RNA positive participants

20. Liver-related outcomes by highest alcohol intake – ever RNA positive participants

21. Liver-related deaths • 43database participants had died directly from liver-related causes by the end of latest follow-up • 33 had tested RNA positiveat some stage, 8 had no RNA results in their charts and 2 had never tested RNA positive • Where alcohol consumption data available (n=34), 53% had high alcohol consumption • Cause of death: • Hepatitis C 19 • Liver cell carcinoma 12 • Liver failure 3 • Cirrhosis 3 • Other liver-related causes 6

22. Cumulative proportion of individuals surviving by RNA status & duration of infection RNA negative RNA positive

23. Disease severity • Participants were classified as having ‘more severe’ liver disease if they had: • Died from liver-related disease or • Had serious signs of liver disease – cirrhosis, HCC, ascites, varices, decompensated liver disease, portal hypertension, encephalopathy, hepatomegaly, splenomegaly or • Had a high fibrosis score on biopsy • All other participants were classified as having ‘less severe’ disease • By end of latest follow up 25% of ever RNA positive participants had ‘more severe’ liver disease (n=196) • Logistic regression modelling used to look at factors associated with disease severity

24. Factors associated with having more severe liver disease by end of latest follow-up:logistic regression model (n=682)

25. Most commonly recorded medical conditions

26. Medical conditions recorded significantly more often in charts of ever RNA positive participants • Without a control group, difficult to determine if prevalence of these medical conditions is different from the general population • Questionnaire looking general health sent to HAA card holders – questions based on national health and lifestyle questionnaire so responses can be compared

27. Anti-viral treatment

28. % of ever RNA positive participants treated (n=309) by source of infection & genotype

29. % SVR on first treatment by genotype, treatment type and treatment duration

30. Characteristics associated with SVR on first treatment

31. Logistic regression analysis of characteristics associated with SVR on first treatment

32. Change in fibrosis scores* after treatment by SVR status (n=106)

33. Concluding comments • Significant proportions of Irish people infected with hepatitis C through blood/blood products have now developed serious liver disease • Alcohol consumption has a large impact on disease progression • Treatment outcomes have improved substantially - Peg-IFN and Ribavirin • Database will be a source of valuable data on the natural history of hepatitis C over the next 5 to 10 years • Room for improvement: BMI data for most patients, recent alcohol consumption data & higher participation rate • Baseline and follow up reports available from: www.hcvdatabase.ie

34. Acknowledgements • Database participants • 8 Hepatology units • Patient Support Groups: Positive Action, Transfusion Positive, Irish Haemophilia Society & Irish Kidney Association • Hepatitis C Database Steering Committee • Hepatitis C Database Scientific & Technical Committee • Consultative Council on Hepatitis C Database Team in HPSC Dr Lelia Thornton, Specialist in Public Health Medicine (project coordinator) Niamh Murphy, Surveillance Scientist Paula Flanagan, Research Nurse Margaret McIver, Surveillance Assistant