Patrizia FARCI Hepatitis Delta Virus From HDV From

Patrizia FARCI

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

Features of the HDV RNA I 1. 7 kb, single-stranded, circular RNA Editing HDAg gene A Extensive base-pairing Transcribed by host RNA Polymerase II Self-cleavage of RNA by internal ribozyme elements

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

Cirrhosis Evolution of Hepatitis D Compared to Hepatitis B and C HDV Fibrosis 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 Infectionnot 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)

(12 months)

HDV RNA Quantification

Changes from Baseline in HDV RNA Levels in Interferon Treated and Untreated Patients End of Treatment vs. Baseline n = 13 n = 12 n = 11 p = 0. 009 Farci et al. , Gastroenterology, 2004

Changes in HDV RNA Levels from Baseline According to Biochemical Response in Patients Treated with 9 MU of IFN End of Treatment vs. Baseline (n = 9) (n = 4) p = 0. 003 Farci et al. , Gastroenterology, 2004

: 12 years)

Changes from Baseline in HDV RNA Levels in Interferon Treated and Untreated Patients End of Treatment vs. Baseline n = 13 p = 0. 009 n = 12 n = 11 Last Evaluation vs. Baseline n = 13 n = 11 n=9 p = 0. 008 Farci et al. , Gastroenterology, 2004

Farci et al. , Gastroenterology, 2004

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

2006

2006

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 HBs. Ag are lost, titrating the dose according to tolerance and serum ALT levels

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