Hépatites Virales B Epidemiologie Mahiou. H Service de Gastro-entérologie CHU BAB EL OUED 21 Journées D’hepatogastoenterologie Alger le 09 et 10 décembre 2009 emes

Le VHB :Introduction Problème majeur de santé publique Environ 25 % meurent d’une cirrhose ou d’un cancer du foie 2 milliards de personnes exposées au virus 350 millions atteints d’hépatite chronique B L’Afrique compte 60 millions Population mondiale 6 milliards 500.000 à 1.200.000 décès chaque année dus à des complications du VHB dans le monde 1. Lavanchy D; Hepatitis B virus epidemiology, disease burden, treatment, and current and emerging prevention and control measure; J Viral Hepatitis 2004; 11: 97-107. 2. WHO. World Health Organization, Department of communicable Disease Surveillance and response. Hepatitis B. 2002; 1-76. 2

Virus B Famille des Hepadnaviridaes 100 fois plus contagieux que HIV 10 fois plus contagieux que HCV carcinogene connu Présent dans le sang et les fluides organiques capable de survivre dans le sang séché > 1 semaine KEY TAKEAWAY HBV is 100 times more infectious than HIV and 10 times more infectious than HCV It is a recognised carcinogen in humans Hepatitis B virus (HBV) is the prototype of the Hepadnaviridae family of viruses. HBV is 100 times more infectious than the human immunodeficiency virus (HIV) and 10 times more infective than HCV and can live outside the body on clothing and other surfaces for more than one week. Full Reference National Institutes of Health. Report on Carcinogens, Eleventh Edition; US Department of Health and Human Services, Public Health Service, National Toxicology Program. Available at: http://ntp.niehs.nih.gov/ntp/roc/eleventh/profiles/s092thpb.pdf. Accessed September, 2006. Ott, et al. J Pediatr Health Care. 1999;13:211-216. CDC. MMWR. 2003;52(RR01):1-33. Ribeiro, et al. Microbes Infect. 2002;4:829-835. NIH 11th Report on Carcinogens, 2004.

Hépatite B : présence d’ADN VHB dans une momie Coréenne du XVI siècle Prélèvement laparoscopique d’un fragment hépatique chez une momie du XVI siècle identifiée par C14 Extraction ADN VHB par 3 méthodes différentes dans 3 labos en Corée, GB et Israël Extraction et amplification d’un fragment de la région préC Génotype C AASLD 2007 – Klein A - Israel, Abstract 925

Distribution géographique de l’infection chronique par le VHB Prévalence de l’AgHBs > 8 %-Forte (Risque sup à 60%) 2%-7%-Moyenne (Risque 20%- 60%) 88% DE LA POPULATION Source: CDC <2%-Faible (Risque inf. à 20%) 36 5

La prevalence de l’hépatite chronique B est en changement au niveau de la région méditéranéenne ALLEMAGNE Prevalence <2% Incidence a chuter de 2.9 cas/ 100,000 (2001) à 1.6 cas/100,000 FRANCE Prevalence <2%, mais afflux à partir des zones de haute endimicité TURKIE Prevalence ~ 6% globale, mais varie de ~3% à l’Ouest à ~9% en Est Prevalence chez les donneurs de sang (Ouest) 1.2% (1998-2002) vs 2.3% (1993-1997) ESPAGNE Prevalence 2-8% ARABIE SAUDITE Prevalence >8% MAIS varie de 17% au sud à 7% au nord CDC data present national HBsAg(+) prevalence rates in three broad categories: <2%, 2-8%, and >8% WHO provides more specific estimates of national HBsAg(+) prevalence rates: Germany: 0.62% France: 0.2% Spain: 1.2% Algeria: 2.15% (general population in 1998); 0.90% (blood donors in 2000); 0.78% (blood donors in 2002)‏ Egypt: 10.1% (older study)‏ Turkey: 6.6% Saudi Arabia: incidence has fallen from 30 cases/100,000 (1990) to 15 cases/100,000 In Turkey, the prevalence of HBV is highly variable in different geographical regions: Carriage is estimated at ~ 6% in western Turkey to 12.5-14.3% in eastern and southeastern Turkey (Leblebicioglu et al. 2004)‏ In western and central Anatolia HBV carriage rate is 3.1-10.3%; in eastern Anatolia it is 8.3-13% (Űner et al. 2001)‏ Overall HBsAg seropositivity rate is 6.1% in the adult population of Turkey (Balik et al. 1998) References CDC data. Available at: http://www.cdc.gov/ncidod/hepatitis/b/country_listing.htm; http://www.cdc.gov/ncidod/diseases/hepatitis/slides/hepb WHO data. Available at: http://www.who.int/vaccines-surveillance/graphics/htmls/hepbprev.htm; http://www.who.int/emc- documents/hepatitis/docs/whocdscsrlyo20022/disease/prevalence_various_areas.html; http://www.who/cds/csr/lyo/2002.2 Custer B, et al. J Clin Gastroenterol 2004; 38 (Suppl. 3): S158-68 Qirbi N, et al. East Mediterr Health J 2001; 7: 1034-45 BMS Colloquia 2003-2004 Turkey: Űner A, et al. Eastern J Med 2001; 6: 40-2 Leblebicioglu H, et al. Clin Microbiol Infect 2004; 10: 537-41 Sakarya S, et al. Saudi Med J 2004; 25: 1070-2 Balik I, et al. In: Viral Hepatitis, Nobel Tip Kitabevi, Istanbul 1998, pp. 10-39 http://www.vhpb.org/files/html/Meetings_and_publications/presentations/IST23EngCiblakbadur. pdf ALGERIE Prevalence 2-8% EGYPTE Prevalence ≤8% globale, mais varie de 3% à 11% CDC data. Available at: http://www.cdc.gov/ncidod/hepatitis/b/country_listing.htm; http://www.cdc.gov/ncidod/diseases/hepatitis/slides/hepb

Prevalence de L’AgHbe(-) est en augmentation dans la region EMEA DENMARK ~50% ALLEMAGNE~90% (1999) POLOGNE En augmentation,surtout ages GRECE ~90% FRANCE 57% (2002) 72% (2006) TURQUIE~66% Espagne 63% (1996) LIBAN et EAU En augmentation Maroc 94%(2004) 96¨%(2008) The prevalence of HBeAg-negative chronic hepatitis B is increasing worldwide. In the EMEA region, the prevalence of HBeAg-negative disease is reportedly 50-90% Throughout the Mediterranean region, North Africa and Middle East most cases of chronic hepatitis B are HBeAg-negative. Turkish studies reported HBeAg(-) rates of 54% (2001) and 62.5% (2005) Features of HBeAg-negative disease: HBeAg-negative chronic hepatitis B is not acquired as a de novo infection; instead, the mutant HBV form emerges during the course of infection with wild-type virus. HBeAg-negative chronic hepatitis B occurs throughout the world and has become a major public health concern due to its high endemicity and chronicity. Current data indicates that liver disease is more active and advanced in HBeAg-negative patients than in HBeAg-positive patients. This form of CHB is usually progressive and sustained spontaneous remission is rare; long-term prognosis is poor. The hallmarks of the disease include persistent intermittent HBV replication, severe liver necroinflammation, and progressive fibrosis. It is estimated in some studies that approximately 40% of HBeAg-negative CHB patients have histologically confirmed cirrhosis. References Cadranel JF, et al. Hepatology 2003;38(Suppl 1):616A. Zarski JP, et al. J Hepatol 2006;Apr 18 (Epub ahead of print). Funk ML, et al. J Viral Hepatitis 2002;9:52-61. Keefe EB, et al. Clin Gastroenterol Hepatol 2004;2:87-106. Turkey: Sunbul M, et al. Viral hepatit Dergisi 2001; 2: 286-9 Sunbul M, et al. World J Gastroenterol 2005; 11: 1976-80 (62.5% of patients HBeAg-negative) EGYPTE ~90–95% ITALIE 89% (1997) Cadranel et al. Hepatology 2003;38(Suppl 1):616A; Zarski et al. J Hepatol 2006;Apr 18 (Epub ahead of print); Funk et al. J Viral Hepatitis 2002;9:52-61; Keefe et al. Clin Gastroenterol Hepatol 2004;2:87-106 7

Genotypes HBV A et D sont les plus frequents dans la region EMEA A,B,C,D A C,H D C Bj D D D H Ba E The prevalence of the various HBV genotypes varies across the world and shows a strong correlation with ethnicity. Genotype A is mainly found in northwestern Europe and North America Genotypes B and C are the predominant strains in the indigenous population of Southeast Asia, China, Japan and the South Pacific islands Genotype D (the most widely distributed genotype) is most common in southern Europe, North Africa, the Middle East and India Genotype E is found in western and southern Africa Genotype F (believed to be the original genotype of the New World) is found in Central and South America and the Eskimo populations of northern Canada and Alaska . Genotype H is found in Japan and Central America In many countries where well-known waves of migration have occurred in recent recorded history (e.g. Australia, South Africa, the United States), the HBV genotype pattern largely reflects the origins of the migrants. References Fung SK, Lok AS. Hepatology 2004; 40:790–792. Chu CJ, Keeffe EB, Han SH, et al. Gastroenterology. 2003;125:444–451. Kidd-Ljunggren K, et al. J Gen Virol 2002;83:1267-80. Meilleure Pc F F A A,B,C,D Graves Difficiles a traiter Fung et al. Hepatology 2004;40:790–792; Chu et al. Gastroenterology 2003;125:444–451; Kidd-Ljunggren et al. J Gen Virol 2002;83:1267-80 8

Les mouvements de populations modifient profils regionaux genotype VHB … les mouvements de population sont l’evolution des profiles des patients F D A,B,C,D A C,H D C Bj D D D H Ba E Globalization and increasing movement of people between countries and continents – particularly from areas of high HBV endemicity to areas of low endemicity - is likely to have an impact on the prevailing geographical distribution of HBV genotypes in the EMEA region. Blurring of regional differences in HBV genotype patterns may lead to greater homogeneity in HBV-disease outcomes. References Chu CJ, et al. Hepatology 2002;35:1274-6. Kao JH, et al. J Clin Microbiol 2002;40:1207-9. Fujie H, et al. Gastroenterology 2001;120:1564-5. Chu CJ, et al. Gastroenterology 2002;122:1756-62. Mahtab MA, et al. ISVHLD 2006, Poster P077 (Bangladeshis) F F A A,B,C,D 9

Transmission du HBV Transmission perinatale Transmission Horizontale 90% des enfants infectés le deviennent de façon chronique 6% des sujets infectés après l’age de 5 ans le deviennent de façon chronique Mère Hote enfant KEY TAKEAWAY The HBV infection can be acquired through numerous routes of transmission In vertical transmission—including perinatal transmission from mother to child—90% of those infected develop chronic infection. Horizontal transmission includes child-to-child transmission and other sources as listed in the slide—only 6% of people infected over the age of 5 develop chronic infection. Full Reference Centers for Disease Control and Prevention. Viral hepatitis B fact sheet. Available at: http://www.cdc.gov/ncidod/diseases/hepatitis/b/fact.htm. Accessed September 2006. Receveur Enfant à enfant Aiguilles contaminées Contacts sexuels Professionnels de santé Transfusion sanguine CDC Viral hepatitis B fact sheet. Lee. N Engl J Med. 1997;337:1733-1745. Lavanchy. J Viral Hepat. 2004;11:97-107.

Quoique l’HCB est transmise par voie horizontale, dans plusieurs pays la voie verticale et intra-familiale sont importantes ALLEMAGNE, AUSTRALIE, SUISSE Horizontale (contact sexuel, UDIV, invasive, chirurgie) RUSSIE Horizontale (intra-familiale, UDIV)‏ ESPAGNE généralement horizontale TURKIE généralement horizontale; plus de transmission perinatale/enfance précoce à l’Est ALGERIE généralement horizontale (sexuel, transfusion sanguine, UDIV)‏ The mode of transmission of hepatitis B infection varies throughout the world. In underdeveloped nations or areas of high endemicity such as Southeast Asia, China, and Africa, the most common route of transmission is by perinatal transmission (vertical) or transmission from one child to another (horizontal). In more developed nations—areas with lower endemicity—including North America, Western Europe and Australia, most HBV infections are acquired in early adult life via horizontal transmission (sexual transmission, blood transfusion, IV drug use). Increasing frequency of IV drug use in Russia, central Asia and parts of Eastern Europe (Belarus, Moldova, Ukraine) has implications for HBV transmission IV drug use is a significant mode of transmission of HIV infection (and, by implication, HBV infection) in certain parts of the Middle East and north Africa (Libya, Bahrain, Tunisia)‏ Some countries in Eastern Europe and the Middle East, as well as certain ethnic communities within Western Europe, have high rates of intra-familial transmission during early childhood. In Turkey, exposure to blood is the main source of HBV infection; however, high seroprevalence rates (~10%) and low vaccination rates (7.5%) reported in children in eastern Anatolia suggest significant vertical transmission in this region. For individuals who acquire HBV infection during early childhood, disease progression continues after HBeAg seroconversion, and complications of cirrhosis and hepatocellular carcinoma may develop even with low-level viraemia. The risk of HBV-related death is highest in those individuals who acquire infection in the perinatal and early childhood periods. Current treatment guidelines do not adequately address these high- risk individuals. References 1. CDC Fact Sheet. http://www.cdc.gov/ncidod/diseases/hepatitis/b/. Accessed: October 2, 2004. 2. Lee WM. N Engl J Med. 1997;337(24):1733–1745. Lavanchy D. J Viral Hepat. 2004;11(2):97–107. United Nations Office on Drugs and Crime. Extent of HIV/AIDS and intravenous drug use across the globe. http://www.unodc.org/unodc/drug_demand_hiv_aids_extend.html. Accessed September 11, 2006 Turkey: Űner A, et al. Eastern J Med 2001; 6: 40-2 Leblebicioglu H, et al. Clin Microbiol Infect 2004; 10: 537-41 ARABIE SAUDITE transmission périnatale en Sud ITALIE Transmision Intra-familiale fréquente http://www.cdc.gov/ncidod/diseases/hepatitis/b/; Lee WM. N Engl J Med 1997;337:1733–45; Lavanchy D. J Viral Hepat 2004;11:97–107

Avantages de la vaccination Réduction du pourcentage de porteurs de l’AgHBs 14,6% 15 avant vaccination 13 après vaccination 12,0% 9,8% 11 8,8% 9 AgHBs (%) 6,2% 7 5,2% 5,4% 5 3 2,0% 1,4% 0,7% 0,9% 0,8% 0,5% 0% 1 Alaska Thaïlande Indonésie Shanghai Taiwan Gambie Chine

Incidence tumeur cérébrale Avantages de la vaccination Réduction de l’incidence de carcinomes hépatocellulaires Incidence CHC Mortalité CHC Incidence tumeur cérébrale 1.6 1.4 1.2 1 Incidence par 100.000 0.8 0.6 0.4 0.2 < 1985- 1987- 1989- 1991- 1993- 1984 1986 1988 1990 1992 1994 Chang et al. N Engl J Med 1997; 336: 1855-9. Universal hepatitis B vaccination in Taiwan and the incidence of hepatocellular carcinoma in children.

Programmes de vaccination contre HBV varient largement en Europe Vaccination has reduced long-term burden of chronic hepatitis B, but there are still many untreated individuals. In the low endemic countries of Europe, hepatitis B is viewed as a limited public health problem and vaccination is in danger of losing its place on governments’ agendas. e.g., the UK, Ireland, Netherlands and Nordic countries adopt a risk-group approach Risk-group vaccination misses a substantial proportion of those in the targeted risk groups and often identifies individuals only when already infected The disease burden from hepatitis B in these countries is still substantial. Note: ‘other universal programme’ signifies adolescent vaccination programme. References CDC-UNICEF-VHPB-WHO Meeting, Istanbul 2006 Van Damme P, et al. Eurosurveillance 2004; 9 (Issue 10-12): 67-8 CDC-UNICEF-VHPB-WHO Meeting, Istanbul 2006 Based on 2002 data

La couverture vaccinale est menée en Afrique du nord

Maladie sous diagnostiguée et sous traitée Moins de 15% des patients diagnostiqués sont traités Moins de 20% des patients diagnostiqués Established practice guidelines provide direction for the diagnosis and management of chronic hepatitis B; however, not all patients with chronic hepatitis B are identified and many of those who are diagnosed do not receive adequate management and follow-up. An estimated 15 million people are chronically infected with HBV throughout Europe and up to 25% of hepatitis B carriers die prematurely from liver disease In Europe fewer than 20% of chronic hepatitis B patients are diagnosed and fewer than 15% of diagnosed patients are treated References Zoulim F. Virgil presentation EASL 2005. Available at: http://www.virgil- net.org/about-virgil/virgileasl2005.ppt (accessed June 2006). CDC. Hepatitis B. 2005. Available at: http://www.cdc.gov/nip/publications/pink/hepb.pdf (accessed November 2005). BMS. Data on file. Prevalence ~15 million d’hépatite chronique B en europe 3% traiter ! Zoulim F. Virgil presentation EASL 2005. Available at: http://www.virgil-net.org/about-virgil/virgileasl2005.ppt (accessed June 2006). CDC. Hepatitis B. 2005. Available at: http://www.cdc.gov/nip/publications/pink/hepb.pdf (accessed November 2005).

EN ALGERIE

Prévalence de l’Ag Hbs chez le donneur de sang Année 85 87 89 90 2003 2004 2005 2006 1,2 1,2 1,4 2,40 0,95 0,95 0,82 0,99 % 2006: Ag Hbs positif 0.99 pour 100 dons de sang Sur 334628 dons = 3313 dons positifs source: ANS 2006 CTS 18 18

Prévalence de l’Ag Hbs chez la femme enceinte 3500 femmes enceintes testées (1996*): 2,2% 6000 femmes enceintes testées (1998§): 1,8% *Mémoire: A. Aguercif, IPA Alger 1996 §IPA Alger 1998

Enquête Nationale Séro-Epidémiologique (1998) Prévalence de l’AgHbs: 2 8125 Sérums 2 sexes 2 - >65ans 1 1 1 2 2 3 Zones 2 Nord Hauts plateaux Sud 3 3 Recherche AgHBs 2 Techniques ELISA ≠

Taux de portage de l'Ag HBs selon les régions Moyenne = 2.15% 7 5.93 6 5 4 3.41 3.22 2.86 3 2.44 2 1.26 1.1 1 Haut Plateaux Ouest Haut Plateaux Centre Haut Plateaux Est Côte Ouest ô Côte centre Côte est Sud-Est - Sud-Ouest La répartition par région révèle des inégalités avec une différence statistiquement significative p < 0.005

La répartition du portage de l’Ag HBs par tranche d’âge est assez stable et ne révèle pas de différence significative

Enquête régionale: 6 Wilayas Est de l’Algérie (2006) 6049 prélèvements (1- >60ans) ELISA ● Annaba ■ Alger 1,70 2,29 ● Oran 0,70 2.68 0.89 1,31 (27.9-17.10.2005) Prévalence de l’Ag Hbs: 1,53% [0,70 -2,68%]

2OO5

COMMENTAIRES Prévalence AgHBs en Algérie : 1998 = 2.15 % 2006 = 1.53 % - Zone d’endémie moyenne Inégalité entre les régions: 1.61-4.4 Pas de différence significative : sexe et l’âge

INCIDENCE DR HANOUN INSP

Evolution de l’hépatite virale B par tranches d’âge Dr D. Hannoun, Institut National de Santé Publique

Evolution de l’hépatite virale B par tranches d’âge Dr D. Hannoun, Institut National de Santé Publique

INCIDENCE Dr D. Hannoun, Institut National de Santé Publique

Hépatite chronique virale B: n=126 Facteur de transmission le plus probable Transfusion 14,3% Portage familial 7,1% Exposition Pro. 5,5% 42,8% 3,9% S. Dentaires Tatouage 3,9% 2,4% Transfusio n Chirurgie Injections IM Berkane S. Thèse de Doctorat en Sciences Médicales, Mai 2003

Enquête santé bucco-dentaire Enquête menée en 2006 par l’INSP sur les connaissances et pratiques des chirurgiens dentistes Eau courante absente ds la ½ des cas Poupinel utilisé dans 92,8 % Près d’1/5ème des praticiens ne se lavent pas les mains entre 2 soins Moins des 2/3 des dentistes sont vaccinés contre l’HVB Dr D. Hannoun, Institut National de Santé Publique

Transmission perinatale Prevalence chez la femme encreinte:1.8% 800 000 naissances/an 14 400 grossesses à risque/an Depistage chez la femme enceinte n’est pas obligatoire Absence d’immunoglobuline anti HBS Vaccination depuis 2003

*série hospitalière, Hôpital Bologhine Statut Hbe (N= 673*) Sex-ratio: 1,75 Ag Hbe + 74 Anti-Hbe + 599 Age moyen: 39,2 ans [3-90] 11% 89% *série hospitalière, Hôpital Bologhine

S. Gourari, Service Microbiologie, CHU Mustapha 2008 Génotypes du VHB (2) N = 150 (82% Ag Hbe négatif) S. Gourari, Service Microbiologie, CHU Mustapha 2008

Génotypes du VHB (1) N =75 (87% Ag Hbe négatif) Khelifa F. Institut Pasteur. Constantine Constantine les 7 et 8 novembre 2007

Programme national vaccination Arrete du 10 septembre 2002 integrant la vaccination de l’HBV dans le calrndrier de l’enfant

Couverture vaccinale nationale Direction de la prévention MSPRH

Très peu de malades traites Hépatite B Ag HBs 2,15% [1,40-3,23] Enquête Nationale (IPA, INSP, OMS, 1998) 645 000 Porteurs chroniques Très peu de malades traites

Conclusion Prévalence de l’HBV situe notre pays parmi les pays à prévalence moyenne (2% – 8%) Tendance à la hausse de l’HBV ces dernières années 89% HVB chroniques sont Hbe (-) Essentiellement génotype D Très peu de malades traites Vaccination: 2003 Dépistage obligatoire des femmes enceintes Sérovaccination des NNE de mères AgHbs+ Respects des règles d’hygiènes universelles