1. Surveillance of hepatitis C Infection in France JC Desenclos, Département des Maladies Infectieuses Institut de Veille Sanitaire

2. Outline Background Ongoing Surveillance –HCV screening activity –newly treated patients in reference centres –blood donors & residual risk –indicators of arm reduction activities –nosocomial HCV infections Repeated surveys –HIV-HCV co-infection –prevalence and % of HCV infected screened –HCV associated deaths Other projects

3. HCV national prevention and control plan National plan initiated by the Ministry of Health Planned at the regional level Secondary and tertiary prevention –screening of at risk groups (goal : 70% in 2002) –early follow up, management and treatment Primary prevention –blood (NAT, 2001 ) and organ donation safety –harm reduction policy among IV drug users –control of iatrogenic transmission health care related (standard precautions…) tattooing, piercing…

4. Epidemiolgical profile Prevalence : 1.1%; 500 000 - 650 000 with HCV antibodies of whom 80% are HCV RNA+ (1994) Source of past infection: Blood transfusion : 1/3 IV drug use : 1/3 iatrogenic : ?? 10-15% Genotype : “0bservatoire VHC” 2000-2001 Incidence : ? 1 2 3 4 5

5. Lyon : 1,3% Fécamp : 1,9% Prevalence of HCV serum antibodies in 4 regions, France, 1994

6. % Year Proportion of HCV positive subjects who knew their status when screened, Social security examination center, Région Centre, France, 1993-2000 Source : Dubois et al, Concours Médical

7. Objectives of HCV surveillance Data for decision making –burden –trends –risk factors Evaluate prevention and control programs –screening activities –blood safety –IVDU harm reduction Disease control : outbreak detection, investigation and control Link and interaction with public health research

8. Surveillance of laboratory HCV antibody screening activity RENAVHC : network of hospitals and public laboratories nationally distributed (N = 257) Initiated in 2000 Activity by quarter –monitor screening activities –number of serologic tests done and of positive –test confirmation activity –basic characteristics of positive tests Analysis by quarter and region (n = 22)

9. Screening activity by quarter, RENAVHC network (n=257), France 2000

10. Newly referred patients in hepatitis C reference centers 30 reference centers –hepatology or gastro-enterology centers –designated by the ministry of health –coordinate a regional network of clinical care, information, treatment, prevention, training… National surveillance network –reference centers-InVS (23 in 2000; 25 in 2001) –trend overtime in patient characteristics –case definition : newly referred hepatitis C –data : clinical, epidemiological and virological

11. Newly referred HCV patients, “pôles de référence, 2000” : mode of discovery of HCV

12. Newly referred HCV patients, “pôles de référence, 2000” : clinical stage 9,8 * * 1991-1993 : 20%; F. Roudot-Thoraval et al. Hepatology 1997 ; 26 : 485-90

13. Newly referred HCV patients, “pôles de référence, 2000” : source of infection Suspected source of Women Men infection n (%) n (%) Transfusion 359 46,2 281 27,1 IV drug use 183 23,2 518 49,5 Nasal drug use 37 5,1 131 4,1 Professional exposure † 35 4,5 20 1,9 Nosocomial exposure ‡ 146 18,4 136 12,9 Other factors ¶ 146 18,7 202 19,4 No risk factors 99 12,3 115 10,7 total >100%, > to more than 1 risk factorr; †health care related ; ‡ dialysis, surgery, endoscopy ; ¶ acupuncture, injections, piercing, sexual partner HCV+ * : in 1991-2003 : 34 and 25%, respectively 34* 38* HCV-HIV co-infection : 7%

14. Surveillance of blood safety Collaborative surveillance between blood centers & InVS HBV, HCV and HIV markers –all donors –repeat donors –denominators –characteristics of positive patients Incidence among repeat donors Estimate of residual risk

15. Incidence of HIV, HBV, HCV and HTLV among repeat blood donors, France, 1992-2000 0,0 1,0 2,0 3,0 4,0 5,0 6,0 1992-941993-951994-961995-971996-981997-991998-00 HCV HTLV HIV HBV Source : GATT, InVS, INTS Cases per 100 000 person year 3 years moving period

16. Residual risk of transmission of blood-borne viruses per million blood donations, 1992-2000 (Transfusion; 2002, in press ) Source : GATT, InVS, INTS 0,0 1,0 2,0 3,0 4,0 5,0 6,0 7,0 8,0 9,0 1992-941993-951994-961995-971996-981997-991998-00 HCV HTLV HIV HBV 3 years moving period Risk per 1 000 000

17. Harm reduction activities : SIAMOIS National data-base, stratified by district Delivery indicators –number of syringes sold –number of steribox  kit sold –amount of subutex  sold –methadone Impact indicators –overdose deaths –arrests for drug offense National and local monitoring Sharp drop in 1ml syringe sale in last year

18. Notification of nosocomial infection events Introduced in 2001 Nosocomial sentinel events –based on criteria; no positive nor negative list –HCV and HBV infection following medical care Notification –to local district health offices –inter-regional nosocomial coordination centers –national coordination : RAISIN-InVS

19. Examples of notification of HCV iatrogenic transmission since July 2001 Outbreak in an haemodialysis center, 2001 –22 new infections; incidence : 52%person years –3 genotypes –major breaches in hygiene procedures –case-control study: infection associated with : care by a nurse who had just cared for an HCV+ patient not to dialysis on a machine used previously by an HCV positive patient Seroconversions associated with : –endoscopy (1) –inappropriate use of a glucometer (1)

20. Surveys Seroprevalence and behavioral surveys of IV drug users (InVS, INED, ANRS) –multi-city (5 to 6 large urban area) –cluster (multi site) probability sample –blood (finger) taken for HIV, HCV and HBV –questionnaire –pilot done in Marseille (April 2002) Prevalence of HIV-HCV co-infection National seroprevalence survey

21. HIV-HCV co-infection National probability sample of HIV wards –one day survey (June 2001) –in- and out- HIV positive patients –basic epidemiological and clinical characteristics Results –N = 1744 –co-infecion : 28% (25-30 000 patients) Among HCV patients, HIV infection : 7% New survey planned in 2003 –hepatitis B markers –include hepatology wards

22. % HCV infection among HIV patients, France, June 2001

23. Population survey Aim : evaluate HCV prevention plan –prevalence by age (18-80), gender, region (5 inter-regions) and social status (low vs others) –% of HCV+ subjects who knew HCV status –% of HCV+ patient that are taken in charge Stratified probability cluster sample of social security affiliated –N = 15 000 –HCV and HBV –Planned for last quarter of 2002

24. Mortality associated with hepatitis C Vital statistics Specific viral hepatitis included in 10th ICD Not available in the 9th ICD: –chronic hepatitis –cirrhosis –carcinoma Survey of death certificates (CépiDC-InVS) –retrospective survey of certifiers and medical records –random sample of certificates with mention of liver conditions and HIV –done in 1997 and planned in 2003 for (HCV and HBV)

25. Death associated with chronic hepatitis per 100 000 population, by gender, France, 1979-1998. Source : CépiDC-INSERM

26. Representative sample of death certificates with mention of liver disease (N = 360), France, 1997 Source : CépiDC

27. Estimate of the number of deaths associated with HCV in 1997 By applying sampling fraction Deaths : 1 837, 95% CI : 1 740 - 1 930 Death per 100 000 : 3,2; 95% CI : 2,9 - 3,3 Initial versus associated cause of death : –initial : 630 –associated cause : 1207 major role : 564 not major : 643 –Total : 1837 Source : CépiDC

28. Age Death per 100 000 Death rate associated to HCV infection by age and gender, France, 1997 Source : CépiDC

29. Disease registries Cancer registriy (Francim) –all cancers (liver cancer included) –covers 10 districts (12% of population) –certified, coordinated and funded jointly by InVS and INSERM –being strengthened to monitor long term trends Cirrhosis registry –no registry in France –interaction between HCV, HBV and alcohol

30. Public health research conducted under the auspices of ANRS Case control study of HCV seroconversions –plan to include 70 cases and 280 controls –ongoing Cohort study of HCV- intravenous drug users –north and east of France –one year follow up –basic incidence rate : ~ 10% person year Sociological research : perception, barriers to screening, follow up, treatment; quality of life... Cost-efficacy studies...