Hépatite C Prise en charge de l’adulte

Programme sur l’hépatite C au Sud bilan et perspectivesdu groupe de travail

Réunion de l’AC 12, ANRS, 28 février 2008

Réunion ANRS, hépatites virales en PED, 17 janvier 2007

Aspects prise en charge• Outils virologiques pour le VHC (J. Izopet)• Evaluation et traitement de la fibrose hépatique en Afrique (P. Cales)• Evaluation de la fibrose hépatique au Burkina Faso (P. Bonnard & L.

Slama)• Traitement des hépatites B chroniques au Sénégal (P.S. M’Baye & M.

Vray)• Etudes sur le VHC au Cameroun

– Epidémiologie et études phylogénétiques du VHC au Cameroun (R. Njouom & C. Pasquier)

– Histoire médicale du Cameroun et épidémiologie historique du VHC (ANRS 1299) (G. Lachenal)

– Traitement du VHC au Cameroun (O. Njoya)• Etudes sur le VHC en Egypte

– ANRS viral hepatitis research site in Cairo (M. Mohamed & A. Fontanet)– Immunological markers of HCV clearance (M. Albert & J. Decalf).– Transmission intra-familiale de l'infection par le VHC (L. Abel & S.

Plancoulaine)

Cameroun

Richard Njouom, Centre Pasteur du CamerounOudou Njoya Hépatologue, CHU de Yaoundé

Ntem 1997 Pop: 408 (14,4%)

400 10 20 30 40 50 60 70

0

20

40

60

80

100

Mekas 1993 Pop: 644 (16,7%)

0 10 20 30 40 50 60 70

0

20

40

60

80

100

Yokadouma 1994 Pop: 646 (3,3 %)

0 10 20 30 40 50 60 70

0

20

40

60

80

100

Nditam 1994 Pop: 368 (2,9%)

0 10 20 30 40 50 60 70

0

20

40

60

80

100

HCV sero-prevalence in Cameroun

Nerrienet et al. J Med Virol 2005

Yaounde 2003N=1434 6.9%

Hétérogénéité et distribution des génotypes HCV à Yaoundé

Richard Njouom, Centre Pasteur du CamerounChristophe Pasquier, Laboratoire de Virologie, CHU Toulouse

• n = 156– Génotype : 1 70 45%– Génotype : 2 37 24%– Génotype : 4 49 31%– nombreux sous-types (pour 1 et 4)– Nombreux sous-types non classifiés– Concordance parfaite des clusters NS5b et E2

(n=144)

Pasquier, J Med Virol 2005; 77:390-8

HCV genotypes and sub-

types n =156

Suivi virologique des patients VHC positifs sous traitement antiviral

Début TT S12 (RVP) M6-12 (RVFT) M12-18 (RVS)

Génotype 1

34 22/34 (64,7%) 13/26 (50%) 10/23 (43,5%)

Génotype 2

14 14/14 (100%) 12/13 (92,3%) 12/13 (92,3%)

Génotype 4

22 13/22 (59,1%) 9/18 (50%) 7/16 (43,8%)

Total 70 49/70 (70%) 34/57 (59,6%) 29/52 (55,8%)

Résultats : : de 2003 à nos jours (résultats au 17/01/2007)

O. Njoya Hépatologue, CHU de YaoundéRichard Njouom, Centre Pasteur du Cameroun17/01/2007

Egypt

EgyptNetwork participants

• In Egypt:– Most of activities are based at the National Hepatology and Tropical Medicine Research

Institute (NHTMRI) in Cairo and involve:• Ain Shams University: epidemiology (Prof Mostafa K Mohamed) and immunology (Prof Mona Rafik).• Cairo university: clinical expertise (Prof Gamal Esmat),• Minia University: virology (Prof Mohamed Abdel Hamid),• University of Mansoura: pathology (Prof Khaled Zalata).

Under the guidance of the Ministry of Health through the National Committee for the prevention and control of viral hepatitis in Egypt.

• In France:– Institut Pasteur, Paris: epidemiology (Dr Arnaud Fontanet); immunology (Dr Matthew Albert), – INSERM U370, Paris: virology (Prof Christian Bréchot, Dr Valérie Thiers), – Necker Hospital, Paris: clinical expertise (Prof Stanislas Pol),– INSERM U707, Paris: mathematical modeling and cost-effectiveness studies (Prof Alain-

Jacques Valleron, Dr Bernard Larouzé, Dr Fabrice Carrat, and Dr Michaël Schwarzinger), – INSERM U550, Paris: genetic epidemiology (Dr Laurent Abel),– Beaujon Hospital, Paris: pathology (Prof Pierre Bedossa),– Saint Louis Hospital: virology HBV (François Simon),– Nantes Hospital: virology (Cyrille Féray)

• International collaborators:– U.S.A: Prof Stewart Cooper (clinical immunology), Dr Eric Delwart (virology), Dr Chris Loffredo

(epidemiology)– U.K.: Prof Nishi Charturvedi (epidemiology)

Research programme

6 months1 to 2 months 10 to 30 years

INCUBATION ACUTE PHASE CHRONIC PHASE

Chronic infection50-85%

Cirrhosis20%

Hepatocellular carcinoma

1 to 4 %/yearJaundice

25%

Asymptomatic

HCV infection

FeverHospitals

Villagecohort

HCV risk factors

Factors associated with HCV clearance:-epidemiology-lipids-virology-immunology-co-infection (HBV)

Treatment efficacy

Treatmentefficacy

Facteurs associated with transmission& chronicity /morbidity-genetic epidemiology-CV risk factors-virology

Mathematical modeling:Prediction, cost-effectiveness

0

10

20

30

40

50

600-

4

5-9

10-1

4

15-1

9

20-2

4

25-2

9

30-3

4

35-3

9

40-4

4

45-4

9

50-5

4

55-5

9

60+

malesfemales

HCV antibody prevalence (%)

Age group (in years)

HCV antibody prevalence (%) by age and sex Zwyat Razin, 2002 (n = 4020) (ANRS 1211).

(Arafa et al, J Hepatol, 2005)

0 20 40 60 80 100

HCV antibodies

Chronic HCVinfection

Chronic HCVinfection andelevated ALT

HCV-relatedadvanced liver

disease

18,5%

11,7%

4,5%

1,5%

HCV-related morbidity among adults(n= 2425, 18-65 yrs), Zwyat Razin, 2002.

(Mohamed MK, J Med Virol, 2006)

448

284

107/266

26 PBH*

* Cirrhose décompensée ou F3/F4 PBH

13 trt indications

Egyptian National Control Strategy for Viral Hepatitis

2008-2012• MOHP, National Committee on viral hepatitis

– Patient management • 9 liver centers where 10,050 patients where currently receiving

treatment as of Jan 2008, usually a wing in a MOHP hospital• Another 6 more centers in 2008• National headquarter is NHTMRI

– Collection of information on patient recruitment and follow-up in the centers

• Need to be standardized and computerized • Development of a web-based data entry system planned

To contribute to the evaluation of the network of treatment centers before proceeding further

Liver centers open in Egypt as of Jan 2008

SUDAN

†

Asyut ▲

Alexandria ▲

Tanta ▲

▲ Damietta

▲ Al Mansurah

Cairo ▲▲

Suhag ▲

▲ Az Zaqaziq

Currently,• 48 wks PEG IFN + Ribavirin at a total cost of 3000

euros. • 4 categories of patients

– Health insurance (HIO) (40%) : PEG-IFN– Contract patients (8%):

• not covered by HIO. • Private-sector employers have agreed to pay for trt in MOHP

facilities. PEG-IFN + Riba– Private patients (7%):

• pay for their own trt in MOHP or private clinics– Patients treated at government expense (45%): no

insurance; • preliminary evaluation (paid for by MOHP)• voucher for trt that covers 12 wks injections but not the cost of

ribavirin

Liver fibrosis evaluation among HCV genotype 4 infected patients in Egypt

P Bonnard, G Esmat

• To evaluate and compare – diagnostic accuracies of the non-invasive methods for fibrosis

assessment for the diagnosis of significant fibrosis • Non invasive methods have been validated in western

countries• In Egypt,

– Steatosis is more common,– Elevated BMI may compromise elastometry– Co-infection with S mansoni, HBV

• 400 patients referred to NHTMRI– Liver biopsy (routinely performed). “Gold standard”– Elastometry– Blood tests to calculate: APRI, Fib-4, Fibrometre, Fibrotest

• Expected start of the inclusions : October 2008

Key points to be discussed • Need of non-invasive markers of fibrosis

– Cost-effectiveness • Efforts on the cost of treatment including

– Antiviral therapy : • Generic?

– And monitoring : PCR • In the context of a National program

– Including screening strategies• Advanced liver diseases,

– Co-factors, – management– Epidemiological tools to follow-up trends?