National Hepatitis C Database for infection acquired through blood and blood products Dr Lelia Thornton, HPSC European Hepatitis C Conference 5-7 June 2015

National Hepatitis C Database Database project Approx. 1,700 people infected with hepatitis C in Ireland through: Anti-D immunoglobulin Blood transfusion/treatment for renal disease Blood clotting factors Database established in 2004 HPSC and 8 specialist hepatology units Steering Committee – including patient support groups Database includes antibody pos and RNA pos

Objectives of the database National Hepatitis C Database Objectives of the database To follow the natural history of hepatitis C infection in people infected through blood/blood products administered in Ireland To evaluate the impact of host factors on disease progression To evaluate the outcomes of treatment To provide information for planning health services To serve as a resource for research

Confidentiality and security National Hepatitis C Database Confidentiality and security No names or addresses Consent required except for deceased Ethics approval from hospitals Eligible patients identified by hepatology units Data from medical records in hepatology units – no direct contact with patients High levels of database security

National Hepatitis C Database Type of data collected Demographic and lifestyle data Infection details Laboratory results Clinical status Cause and date of death Treatment details Clinical management

National Hepatitis C Database 5 rounds of data collection: Baseline 2005 Follow-up 2007, 2008, 2009, 2013

National Hepatitis C Database Latest data period 2010-2013 Definitions/assumptions: Year of infection or year first received clotting factors or year of diagnosis HCV RNA status Ever chronic infection Current chronic infection (includes deceased) Alive and current chronic infection Chronic infection in past Never chronic infection (liver disease rare) No RNA results (22% haemophiliacs, all deceased)

National Hepatitis C Database

National Hepatitis C Database Number of haemophiliac participants by data collection period (latest participation=73.3%, 165/225)

National Hepatitis C Database 225 people identified as infected with hepatitis C through blood clotting factors in Ireland

Haemophiliac cohort by year of HCV infection and RNA status National Hepatitis C Database Haemophiliac cohort by year of HCV infection and RNA status

HCV infection status – Haemophiliac cohort National Hepatitis C Database HCV infection status – Haemophiliac cohort RNA status – most recent All haemophiliacs Currently alive No. % Current chronic infection 61 37.0 28 30.8 Past chronic infection 46 27.9 43 47.2 Never chronic infection 21 12.7 20 22.0 No RNA results 37 22.4 Total 165 100 91

Hepatitis C status at diagnosis National Hepatitis C Database Hepatitis C status at diagnosis

Profile of haemophiliac cohort (n=165) National Hepatitis C Database Profile of haemophiliac cohort (n=165) Males 154 (93%); females 11 (7%) Median age at infection: 13 years Median age now of those alive and chronically infected = 50 years HIV co-infection: n=69 (42%) 22 HIV co-infected are alive 9 currently HCV infected 12 have cleared HCV through treatment 1 never had chronic HCV infection Genotype 1=65%, genotype 3=22%, other=13%

Profile of haemophiliac cohort National Hepatitis C Database Profile of haemophiliac cohort All haemophiliacs (n=165) Alive, chronic infection (n=28) No. % Age at infection <20 20-39 40+ 111 45 9 67.3 27.3 5.5 21 6 1 75.0 21.4 3.6 Age at latest follow-up 0-44 45-64 65+ 83 70 12 50.3 42.4 7.3 10 15 3 35.7 53.6 10.7 Time since infection <20 years 20-29 years 30+ years 24 54 87 14.5 32.7 52.7 4 14.3 85.7

National Hepatitis C Database Alcohol consumption Moderately high – 8% of chronically infected High (>40 units) – 10% of chronically infected Males>females Younger>older Differences by source of infection may be attributable to age and sex distribution: Blood transfusion/renal: 21% Haemophiliacs: 35% Anti-D: 11%

Main outcomes – haemophiliac cohort National Hepatitis C Database Main outcomes – haemophiliac cohort Outcomes Ever chronic infection Alive and chronic infection No. % Clinical signs of serious liver disease* 39 36.5 11 39.3 Cirrhosis 21 19.6 4 14.3 Liver tumour/HCC 10 9.4 2 7.1 High fibrosis score on biopsy** 12 11.2 Deceased 36 33.6 Died from liver disease 13 12.4 *Cirrhosis, HCC, varices, portal hypertension, ascites, decompensated liver disease, encephalopathy, hepatosplenomegaly, hepatopulmonary syndrome, hepatic synthetic dysfunction, hepatorenal syndrome, portal gastropathy

Liver-related diagnostic procedures National Hepatitis C Database Liver-related diagnostic procedures

National Hepatitis C Database Liver-related outcomes in database participants who are alive with chronic infection

National Hepatitis C Database Changes in the prevalence of outcomes for chronically infected haemophiliacs since 2007

National Hepatitis C Database Outcomes in haemophiliacs (ever chronic infection or no RNA results), by HIV status

National Hepatitis C Database Ever chronically infected participants with clinical signs of serious liver disease, by duration of infection and alcohol

Clinical signs of serious liver disease – all database participants National Hepatitis C Database Clinical signs of serious liver disease – all database participants Mainly cirrhosis, varices, portal hypertension and ascites The factors independently associated with having serious liver disease were: High alcohol intake Longer duration of infection Male sex Older age at end of follow-up Genotype 3 High alcohol intake - >5 times higher odds of having signs of serious liver disease

Cirrhosis – all database participants National Hepatitis C Database Cirrhosis – all database participants High alcohol intake, being 50 years or older at last follow-up, being HCV infected for 20 years or longer and male sex were all independently associated with cirrhosis in those who had ever developed chronic infection. Those with a high alcohol intake had 5 times higher odds of having cirrhosis

National Hepatitis C Database Cirrhosis in ever chronically infected participants: age at diagnosis and duration of infection Source of infection Number (%) with cirrhosis Median age at cirrhosis diagnosis Median duration of infection at cirrhosis Anti-D 77 (18%) 56 30 Transfusion/renal 82 (29.9%) 57 22 Haemophilia 21 (19.6%) 45

HCC – all database participants National Hepatitis C Database HCC – all database participants Male sex and genotype 3 (vs genotype 1) were independently associated with HCC in chronically infected participants Those infected through blood transfusion or clotting factors were significantly more likely to develop HCC than anti-D cohort

Deaths in haemophilia cohort National Hepatitis C Database Deaths in haemophilia cohort 74 had died by latest follow-up 47 were HIV positive, 27 HIV negative Liver-related death in 23% HIV positive and 39% HIV negative Many HIV positive had died from HIV-related causes prior to effective antiretroviral treatments

National Hepatitis C Database HCV Treatment courses by type and %SVR, 1992-2013 - All database participants

HCV treatment in haemophiliac cohort National Hepatitis C Database HCV treatment in haemophiliac cohort Sixty (56%) haemophiliacs had received anti-viral treatment for HCV by latest follow-up Treatment outcome available for 55 – SVR 65.5% for last treatment Peg-IFN & RBV in treatment naïve haemophiliacs SVR 36% for genotype 1 SVR 69% for genotype 2/3

National Hepatitis C Database Acknowledgements All database participants Patient support groups: Irish Haemophilia Society, Transfusion Positive, Positive Action, Irish Kidney Association Staff in the eight hepatology units Database Steering Committee My colleagues in HPSC: Paula Flanagan, Niamh Murphy, Margaret McIver

National Hepatitis C Database www.hcvdatabase.ie