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Patrizia FARCI

Patrizia FARCI. From HDV:. From HBV:. From HDV:. From HBV:. HDV RNA genome. Hepatitis B surface antigen (HBsAg). Hepatitis delta antigen (HDAg). 36 nm. Hepatitis Delta Virus. I. 1.7 kb, single-stranded, circular RNA. RNA Editing. A. HDAg gene. Extensive base-pairing.

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Patrizia FARCI

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  1. Patrizia FARCI

  2. From HDV: From HBV: From HDV: From HBV: HDV RNA genome Hepatitis B surface antigen (HBsAg) Hepatitis delta antigen (HDAg) 36 nm Hepatitis Delta Virus

  3. I 1.7 kb, single-stranded, circular RNA RNA Editing A HDAg gene Extensive base-pairing Self-cleavage of RNA by internal ribozyme elements Transcribed by host RNA Polymerase II Features of the HDV RNA

  4. HDVHighly PathogenicHDV causes the least common but most severe form of chronic viral hepatitis leading to cirrhosis in about 80% of the cases

  5. Evolution of Hepatitis D Compared to Hepatitis B and C HDV Fibrosis Cirrhosis HBV HCV 0 Years

  6. Changing Epidemiology of HDV • Although HDV incidence in Southern Europe has dramatically declined during the last 2 decades, new outbreaks are emerging in different areas of the world (Southern Russia, Albania, India, Japan, South America) • In the face of a declining prevalence in areas of old endemicity, immigration poses a threat of resurgence

  7. Hepatitis D Virus Infection-not a vanishing disease in Europe! HH. Wedemeyer, B. Heidrich and M.P. Manns Hepatology 2007, in press

  8. Therapy of Chronic Hepatitis D Antiviral TherapyLiver Transplantation

  9. (12 months)

  10. (12 months)

  11. HDV RNA Quantification

  12. End of Treatment vs. Baseline n = 13 n = 12 n = 11 p = 0.009 Farci et al., Gastroenterology, 2004 Changes from Baseline in HDV RNA Levels in Interferon Treated and Untreated Patients

  13. End of Treatment vs. Baseline (n = 9) (n = 4) p = 0.003 Farci et al., Gastroenterology, 2004 Changes in HDV RNA Levels from Baseline According to Biochemical Response in Patients Treated with 9MU of IFN

  14. : 12 years)

  15. End of Treatment vs. Baseline Last Evaluation vs. Baseline n = 13 n = 12 n = 11 n = 13 n = 11 n = 9 p = 0.009 p = 0.008 Farci et al., Gastroenterology, 2004 Changes from Baseline in HDV RNA Levels in Interferon Treated and Untreated Patients

  16. Farci et al., Gastroenterology, 2004

  17. Farci et al., Gastroenterology, 2004

  18. Our long-term study provided evidence that high doses of interferon alpha significantly improved the long-term clinical outcome and survival of patients with chronic hepatitis D

  19. Alpha-Interferon Therapy of Chronic Hepatitis DShortcomings • Limited efficacy • Relapses are common • Treatment is often poorly tolerated at the doses needed • Side effects are common • Treatment is contraindicated in patients with decompensated cirrhosis

  20. Treatment of Chronic Hepatitis DHow to Improve the Response Rate Continuous therapy Combination therapy Pegylated Interferon

  21. Pegylated Interferon Alpha

  22. et al., 2006 2006 2006

  23. 2006

  24. 2006

  25. 2006

  26. P. Farci , Hepatology 2006

  27. Peg-IFN in Chronic Hepatitis D • These preliminary studies indicate that Peg-IFN is well tolerated and effective in the treatment of CHD, even in the case of previous failure of standard IFN therapy • In analogy with the superior results achieved with Peg-IFN in CHB and CHC, these studies, albeit limited, also support the use of Peg-IFN as first-line therapy for CHD • Larger studies are needed to better evaluate the benefit of Peg-IFN and to define the optimal treatment schedule in patients with CHD

  28. Alpha-Interferon Therapy of Chronic Hepatitis DSummary • Alpha IFN represents the only therapy of proven benefit for chronic hepatitis D • IFN should be administered at high doses for at least one year • HDV RNA quantification is needed for monitoring and treatment assessment • Careful medical supervision is mandatory for the early detection of major medical and psychiatric complications

  29. Alpha-Interferon Therapy of Chronic Hepatitis DSummary • In responders IFN should be continued as long as possible until serum HDV RNA and HBsAg are lost, titrating the dose according to tolerance and serum ALT levels

  30. Acknowledgements Department of Medical Sciences University of Cagliari, Italy Eliana Lai Rita Strazzera Stefania Farci Alessandra Coiana Angelo Balestrieri Luchino Chessa Giancarlo Serra Cinzia Balestrieri Cristiana Cauli Rosetta Scioscia Maurizio Loy Department of Pathology, Leuven, Belgium Tania Roskams Valeer Desmet

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