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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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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 Self-cleavage of RNA by internal ribozyme elements Transcribed by host RNA Polymerase II Features of the HDV RNA
HDVHighly PathogenicHDV causes the least common but most severe form of chronic viral hepatitis leading to cirrhosis in about 80% of the cases
Evolution of Hepatitis D Compared to Hepatitis B and C HDV Fibrosis Cirrhosis HBV HCV 0 Years
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
Hepatitis D Virus Infection-not a vanishing disease in Europe! HH. Wedemeyer, B. Heidrich and M.P. Manns Hepatology 2007, in press
Therapy of Chronic Hepatitis D Antiviral TherapyLiver Transplantation
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
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
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
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
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
Treatment of Chronic Hepatitis DHow to Improve the Response Rate Continuous therapy Combination therapy Pegylated Interferon
et al., 2006 2006 2006
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
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
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
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