Patrizia FARCI

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

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

HDV Highly Pathogenic HDV 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 HBV HCV 0 Fibrosis Cirrhosis 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 Therapy Liver Transplantation

(12 months)

HDV RNA Quantification

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

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

: 12 years)

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

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 D Shortcomings 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 D How to Improve the Response Rate Continuous therapy Combination therapy Pegylated Interferon

Pegylated Interferon Alpha

et al., 2006

P. Farci, Hepatology 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 D Summary 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 D Summary 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 RoskamsValeer Desmet