National Hepatitis C Database Dr Lelia Thornton Health

National Hepatitis C Database Dr Lelia Thornton Health Protection Surveillance Centre December 2012

Background • The National Hepatitis C Database was set up in 2004 in association with eight specialist hepatology units • Any person (alive or dead) who contracted HCV infection through the administration of blood or blood products within the state is eligible to be included • 4 th Round of data collection completed (contains data to 31 st December 2009)

Hepatitis C RNA results for all participants and by source of infection 100 3, 8 1, 2 0, 9 5, 5 90 % of participants 80 34, 3 43, 5 45, 3 70 60 50 16, 0 42, 5 0, 9 18, 1 22, 4 23, 4 12, 7 20, 6 8, 5 12, 0 40 30 20 46, 0 47, 1 41, 5 45, 2 57, 6 44, 2 10 6, 9 0 All participants Anti-D all Anti-D 77 -79 Anti-D 91 -94 RNA status and source of infection Currently chronically infected Chronically infected in past Transfusion or renal Never chronically infected Clotting factors No RNA results

Distribution of hepatitis C genotypes by source of infection (n=722, genotype 4&5 omitted, n=4) % of participants with genotype results 120 100 18, 5 80 10 0, 2 31, 3 4, 7 10, 1 10 60 40 22, 5 76, 8 100 89, 8 100 58, 7 67, 4 20 0 All participants Anti-D all Anti-D 77 -79 Anti-D 91 -94 Source of infection and genotype Genotype 1 Genotype 2 Genotype 3 Blood transfusion Blood clotting factors

Summary of age at infection, age at end of latest follow -up, years since infection by source of infection Source of infection and RNA status Age at infection Age at end of follow up Duration of infection (years since infection) Median (range) Anti-D 28 (16 -44) 57 (26 -76) 32 (4 -45) Anti-D 1977 -1979 28 (17 -44) 58 (33 -76) 32 (17 -33) Anti-D 1991 -1994 30 (18 -39) 46 (26 -56) 16 (4 -18) Transfusion or renal 32 (0 -77) 61 (16 -91) 23 (1 -48) Clotting factors 13 (0 -59) 42 (12 -81) 27 (8 -50)

Distribution of the highest reported alcohol consumption by gender for participants who became chronically infected (where data available, n=761, 93%) % of chronically infected patients 70 65, 9 60 50 45, 1 40 30 24, 4 23, 1 20 14, 9 10 4, 4 5, 3 0 Female Male Alcohol consumption and gender Non drinker Within recommended limits Moderately high High 16, 9

Liver related outcomes for participants who are currently RNA positive

Cirrhosis • 137 ever chronically infected participants had developed cirrhosis* – 86 (14. 5%) were female and 51 (23. 2%) were male – Median duration of RNA positivity at the estimated date of cirrhosis was 24 years – Median age at cirrhosis was 53 years – There was no cases of cirrhosis in those who never developed chronic HCV infection – After RNA status, alcohol consumption was the biggest determinant of risk of cirrhosis

Hepatocellular carcinoma (HCC) • 32 ever chronically infected participants had developed HCC • Prevalence was significantly higher in males (n=20, 9%) • Median duration of infection at time of HCC diagnosis was 27. 5 yrs and the median age at diagnosis of HCC was 63 yrs • The median time from estimated date of diagnosis of cirrhosis to estimated date of diagnosis of HCC was three years

Comparison of rates of cirrhosis

Summary of main outcomes by hepatitis C RNA status for all participants (excludes n=50 with no RNA results) Outcomes All (n=1316) Ever chronically infected * (n=815) Never chronically infected † (n=451) Num % 187 14. 2 175 21. 5 5 1. 1 142 10. 8 137 16. 8 0 0. 0 Liver tumours or HCC 34 2. 6 32 3. 9 0 0. 0 High fibrosis score on biopsy ‡ 167 12. 7 160 19. 6 4 0. 9 212 16. 1 145 17. 8 26 5. 8 55 4. 2 45 5. 6 2 0. 4 Signs of liver disease Cirrhosis Deceased Died from liver disease §

Comparison of all-cause mortality rates

Comparison of liver-related mortality rates

Changes in the prevalence of all cause mortality and liver-related outcomes for chronically infected participants since baseline data were collected % of chronically infected patients 25 19, 1 20 17, 2 18, 0 17, 5 15 14, 8 11, 9 10 12, 2 10, 6 5 0 3, 5 1, 7 4, 2 2, 6 19, 2 16, 0 21, 5 19, 6 17, 8 16, 8 13, 8 4, 8 2, 9 5, 9 3, 9 Baseline: Yr 1 follow up: Yr 2 follow up: Yr 3 follow up: data up to end 2005 data up to end 2007 data up to end 2008 data up to end 2009 Changes in liver-related outcomes since the start of database project Signs liver disease Cirrhosis Liver tumour/HCC High fibrosis scores on biopsy Deceased Liver related deaths

Factors associated with severe liver disease in chronically infected participants-logistic regression model including gender (n=727) Factors associated with having severe liver disease (including Gender n=727) Odds Ratio P-value 95% Confidence interval 1 Reference 5. 6 <0. 001 3. 02 - 10. 52 1 2. 7 3. 7 Reference <0. 001 Reference 1. 60 - 4. 55 2. 11 - 6. 53 1 Reference 2. 8 <0. 001 1. 83 - 4. 37 1 0. 9 2. 2 Reference 0. 762 0. 002 Reference 0. 35 - 2. 14 1. 32 - 3. 61 <20 years 1 Reference 20+ years 2. 2 0. 002 1. 32 - 3. 58 Alcohol consumption Non drinker/within recommended limits/moderately high High (>40 units per week or alcohol abuse in chart) Age at end of latest follow-up <50 years 50 to 64 years 65+ years Gender Female Male Genotype 1 Genotype 2 Genotype 3 Duration of RNA positivity

Factors associated with severe liver disease in chronically infected participants-logistic regression model including source of infection (n=725) Odds Ratio P-value 95% Confidence interval 1 Reference 5. 5 <0. 001 2. 97 - 10. 36 1 Reference 50 to 64 years 2. 2 0. 003 1. 31 - 3. 66 65+ years 2. 6 0. 001 1. 47 - 4. 55 1 Reference Transfusion or renal 2. 8 <0. 001 1. 85 - 4. 35 Clotting factors 2. 1 0. 025 1. 09 - 3. 93 Genotype 1 1 Reference Genotype 2 0. 6 0. 286 0. 25 - 1. 51 Genotype 3 1. 9 0. 016 1. 12 - 3. 10 <20 years 1 Reference 20+ years 2. 4 0. 001 1. 47 - 4. 02 Factors associated with having severe liver disease Alcohol consumption Non drinker/within recommended limits/moderately high High (>40 units per week or alcohol abuse in chart) Age at end of latest follow-up <50 years Source of infection Anti-D Genotype Duration of RNA positivity

Treatment courses by type of treatment and percentage sustained virological response, 1992 -2009 80 70 50 60 40 50 30 40 30 20 20 10 10 0 0 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 Year of commencement of treatment Monotherapy with IFN or Peg-IFN Combination therapy with Peg-IFN & RBN Combination therapy with IFN & RBN % SVR Number of treatment courses 60

Percentage sustained virological response for treatment-naïve participants treated with combination therapy with Peg-IFN and RBN (n=124), by genotype and duration of therapy 90 80 80 68, 2 70 % SVR 75 57, 1 60 50 50 40 30 20 10 0 <24 weeks Treated =19 24 -47 weeks Treated =28 48+ weeks Treated =36 <24 weeks Treated = 22 Genotype 1 24 -47 weeks Treated =15 Genotypes 2 or 3 Genotype and duration of treatment 48+ weeks Treated =4