1. Hépatite Delta Epidémiologie, Histoire Naturelle Vlad Ratziu Hôpital Pitié Salpêtrière, Paris

2. Epidemiology of HDV Infection

12. Age Specific Prevalence of HDV in 1556 Italian HBsAg Carriers (Sagnelli, J Hepatol 1992) 0-19 20-29 30-39 40-49 >50 yrs. HDV+ (p<0.01) 73 56 % under 40 yrs HDV - % with HDV

16. Epidemiology of HDV Infection Current Trends in the 90’s : a decline in HDV prevalence 3.1/100000 to 1.2/100000

17. Declining Prevalence of HDV Super-infection in HBsAg Carriers in Spain (Navascues, Am J Gastroenterol 1995) Overall anti-HDV % HBsAg prevalence in IV drug addicts (%) 1979-1985 1986-1992

18. Decline of Acute HDV Infection in Taiwan 1983-1996 (Huo, J Gastro Hepatol 1997) 83 86 89 92 95 88 91 96 year Anti-HDV in HBsAg carriers HBsAg in prostitutes p<0.001 p<0.02 %

21. Age-specific Prevalence of anti-HDV in HBsAg Carriers (Gaetta, Hepatology 2000) 1997 1992 1987 23 14 8 Overall prevalence % % with HDV 0-29 yrs 30-49 yrs > 50 yrs

24. Clinical Impact of HDV Infection Acute HDV Infection

28. HBsAg HDVRNA anti-HBs ALT anti-HDV IgM anti-HDV 2 3 4 6 months Acute HDV Coinfection

29. HBsAg HDVRNA ALT anti-HDV IgM anti-HDV Acute and Chronic HDV Superinfection

30. Outcome of Acute HDV COINFECTION SUPERINFECTION Fulminant Recovery Chronicity Chronicity Recovery Fulminant CIRRHOSIS HEPATOCELLULAR CARCINOMA 2-20% 10-20% 90-95% 5-10% 2-7% 90-95% 70-80% 40%??

33. Influence of HDV on Severity of Acute Hepatitis B (Smedile Lancet 1982) Govindarajan Gastroenterology 1984) EUROPE LOS ANGELES p<0.01 p<0.01 N Europe 111 Los Angeles 71 Europe 532 Los Angeles 118 FULMINANT BENIGN % anti-HDV

34. Clinical Impact of HDV Infection Chronic HDV Infection

36. Outcome in Chronic Hepatitis Delta (Rizzetto Ann Intern Med 1983) NO CIRRHOSIS INITIALLY Follow-up: 4.1 y (n=75) CIRRHOSIS INITIALLY Follow-up : 3.7 y (n=26) 31% 23% 46% 45% 43% 12% Developed cirrhosis Improved Stable Died Complicated Stable

42. Clinical Impact of HDV Infection “ Asymptomatic” HDV Infection

44. HDV Infection in Asymptomatic HBsAg Carriers (Arico Lancet 1985) Abnormal LFT Active hepatitis Cirrhosis Anti-HDV positive Anti-HDV negative p<0.001 %

45. “ Healthy Carrier State” of HDV 2479 screened 260 ( 10.5%) 71 ( 27 %) 42 ( 59 %) 29 ( 41 %) Population survey on Rhodes AgHBs positive Anti-HDV positive Liver disease Normal ALT and biopsy Hadziyannis, 1991

46. Clinical Impact of HDV Infection Current Trends in the 90’s

47. Trends in Histological/Clinical Severity of Chronic HDV (Rosina, Gastroenterology 1999) 1977-1986 1987-1996 mild hepatitis severe hepatitis histological cirrhosis clinical cirrhosis 8 17 31 44 6 65 28

49. PCR Detection of HDVRNA in Delta Superinfection (Wu Gastroenterology 1995) % % years 100 75 50 8 2 4 6 HDV RNA ALT HDVRNA HBVDNA

50. Decline of HDV Replication during Hepatitis Delta Progression mild hepatitis severe hepatitis cirrhosis histological cirrhosis clinical % HDVRNA pos entry end of f/u (Rosina, Gastroenterology 1999)

51. Virologic Correlates of Liver Disease Progression in HDV Superinfection LOBULAR HEPATITIS CAH CPH REMISSION CIRRHOSIS HCC HDVRNA HBVDNA ALT

55. TRAITEMENT DE L’HEPATITE CHRONIQUE DELTA

56. Traitement par l’IFN  de l’HDV Important Taux de Rechute a l’Arrêt 25 3 71 43 36 0 % ALT =N Fin Trt (12m) Fin Suivi (32m) Rosina 1991 3M; N=31 Farci 1994 9 M; N=14 Farci 1994 3 M; N=14

57. Traitement par l’IFN  de l’HDV L’Effet Antiviral est Dose Dépendant 27 45 71 36 0 Rosina 1991 3M Non traites 9M 3M Non traites % PCR neg Farci, 1994

60. TRAITEMENT PAR INTERFERON RESULTATS EN FONCTION DE LA DOSE Fin du traitement 6 mois après ARN Delta négatif ARN Delta négatif Non traités 0% 8% 3 MU 36% 14% 9 MU 71% 43% Farci, N Engl J Med 1994

64. Baisse Durable de la Charge Virale HDV après Forte Dose IFN  Fin Trt Fin Suivi Farci, Gastroenterology 1994

74. Efficacité Virologique de l’Interféron dans l’Hépatite Chronique B Farci , Hepatology 2006