Jahresinzidenz in der Schweiz Meldungen von Laboratorien und Ärzten

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2 Hepatitis C Jahresinzidenz in der Schweiz Meldungen von Laboratorien und Ärzten Total Drogen Sexueller/Nicht-sexueller Kontakt, andere Medizinisches Personal, Transfusionen, Dialyse, Operation Unbekannt Schweizerisches Bundesamtes für Gesundheitswesen;

3 Scoring of Hepatic Fibrosis Fibrosis Knodell 1 Ishak 2 METAVIR 3 No fibrosis some, septal 1 Mild 1 1 most, septal 2 Moderate occasional bridging Severe marked bridging Incomplete cirrhosis Cirrhosis Knodell et al, Hepatology 1981;1: Ishak K. et al., J Hepatol 1995;22: Bedossa et al., Hepatology 1996;24:

4 Histologic Activity Index (HAI) or necroinflammatory scores Knodell 1 Ishak 2 METAVIR 3 A. Periportal or periseptal inerface hepatitis (piecemeal necrosis) B. Confluent necrosis or 1 C. Lobular degeneration or focal lytic necrosis/apoptosis D. Portal inflammation HAI A1 - A3 1 Knodell et al, Hepatology 1981;1: Ishak K. et al., J Hepatol 1995;22: Bedossa et al., Hepatology 1996;24:

5 Langzeit-Verlauf nach akuter Transfusionshepatitis Transfusion-Associated NANBNC-Hepatitis (n=314, median age at infection 49 +/-13 years Follow-up 25 Jahre [Drop out: n=132 (59%)] Cirrhosis 7/222 only = 3% 71% Anti-HCV + (n=222) 77% PCR + (n=69) 35% Zirrhose (n=7) 49% ALT + (n=34) 17% Anti-HCV + (n=15) 29% Anti-HCV - (n=92) 51% ALT - (n=35) 7% Anti-HCV - (n=6) 65% Chronische Hepatitis +/- Fibrose METAVIR 1-2 (n=13) Spontaneously recovered 21 (23%) 1 Seeff et al., Hepatology 2001;33:

6 Langzeit-Verlauf nach akuter Transfusionshepatitis Anti-HCV + Cases Controls (n=222) (n=377) Anti-HCV - Cases Controls (n=92) (n=168) All deaths Liver related deaths - HCC - Decompensated cirrhosis - Hepatitis - Hepatic failure 67.1% 65.0% 4.1% p = % (n=9) (n=5) 51.1% 54.8% 3.3% p = n.s. 0.6% (n=3) (n=1) 1 Seeff et al., Hepatology 2001;33:

7 Anti-D-kontaminierte Frauen 1 (Genotyp 1b) 1.1% Anti-HCV + (N=704) 98.9% Anti-HCV - (N=704) Follow-up 17 Jahre 55% HCV-RNA + (N=390) Evaluation (N=376): 81% Symptomatisch 47% ALT + 66% Müdigkeit 45% 38% HCV-RNA Myo-Arthralg - ien 16% (N=704) Angst & Depression 6% Oberbauchschmerz rechts 5% rashes 98% Histologie mit chronischer Hepatitis C - 51% Fibrose - 2% Zirrhose 1 Kenny-Walsh E. et al., NEJM 1999;340:

8 Prognosis of Chronic Hepatitis C: Results of a Large, Prospective Study 1 (N=838; Follow-up 50±27months) Without cirrhosis (n=696) Cirrhosis without complication Cirrhosis with complication Years 1 Niederau C. et al., Hepatology 1998;28:1687-5

9 Prognosis of Chronic Hepatitis C: Results of a Large, Prospective Study 1 1 (N=838; Follow-up 50±27months) General population Chronic HCVinfection Years 1 Niederau C. et al., Hepatology 1998;28:1687-5

10 Typ C Zirrhose - Hepatische Dekompensation 1 Erste Episode mit Aszites, Varizenblutung, Enzephalopathie, Ikterus 50% Jährliche Inzidenz 3.9% 25% Kumulative Prävalenz: 3 Jahre 12% 5 Jahre 18% 10 Jahre 29% Monate nach Diagnose Child A Zirrhose 1 Fattowich et al., Gastroenterology 1997;112:

11 Typ C Zirrhose - HCC 1 Kompatible Histologie oder AFP >400 + Sonografiebefund 50% Jährliche Inzidenz : 1.4% 25% Kumulative Prävalenz: 3 Jahre 4% 5 Jahre 7% 10 Jahre 14% Monate nach Diagnose Child A Zirrhose 1 Fattowich et al, Gastroenterology 1997;112:

12 Typ C Zirrhose - Survival 1 Tod durch Leberversagen, Oesophagusvarizenblutung, HCC 100% Alle Patienten 50% Nach 1. Dekompensation Kumulatives Überleben: Monate nach Diagnose Child A Zirrhose 5 Jahre 91% 10 Jahre 79% Jährliche Letalität : 1.9% 1 Fattowich et al., Gastroenterology 1997;112:

13 1 Aktuelle Indikation - Replizierende HCV- Infektion HCV-RNA positiv - Transaminasen über >6 Monate - Leberbiopsie Entzündliche Aktivität Aktuell keine Indikation - Akute HCV-Infektion - Normale Transaminasen - HBV/HIV-Koinfektion 1 SASL/SEVHEP/SGGH/FAGAS 1996

14 Randomised trial comparing three different regimens of alpha-2a-interferon in chronic hepatitis C (Virological SR after 52 weeks) Genotyp I 47-54%, II 32-38%, III 13-16%) % MU tiw 24 W (n=54) 3 MU tiw 52 W (n=61) 6-9 MU tiw W, 3 MU tiw up to 52 W(n=59) 1 Chemello et al., Hepatology 1995;22:

15 % Interferon alpha alone or in combination with ribavirin as initial treatment for chronic hepatitis C 1-3 (Virological SR; IFN 3x3 MIU tiw/riba mg/d) IFN 24w IFN-RIBA 24w IFN 48w IFN-RIBA 48w Poynard (n=832) McHutchinson (n=912) Reichard (n=100) 1 Poynard T.et al. Lancet 1998;352: McHutchinson J.G. et al. NEJM 1998;339: Reichard O.et al. Lancet 1998;351:83-87.

16 Interferon Alfa 2a With and Without Amantadine-Sulphate as Initial Treatment for Chronic Hepatitis C 1 (Randomized, double-blind, Placebo-Controlled Trial) % ETR ALT - ETR PCR - SR ALT - SR PCR - IFN+AMA (n=59) IFN (n=60) 1 Zeuzem S et al., Hepatology 2000;32:

17 Interferon Alfa 2a With and Without Amantadine-Sulphate as Initial Treatment for Chronic Hepatitis C 1 (Randomized, double-blind, Placebo-Controlled Trial) % ETR ALT - ETR PCR - SR ALT - SR PCR - IFN+AMA (n=121) IFN (n=125) 1 SASL-Study N 10. Hepatology 2002;35:

18 Interferon alfa alone vs. Pegylated Interferons as initial treatment for chronic hepatitis C 1,2 (Virolgical SR after 24 weeks) % IFN alfa 2b 3MU tiw (Standard, n=303) - IFN alfa 2a 6/3MU tiw (Induction, n=264) 12kD-PEG-IFN (PegIntron 1.5ug/kg weekly, n=304) 40kD-PEG-IFN (PEGASYS 180ug weekly, n=267) 1 Lindsay et al., Hepatology 2001;34: Zeuzem et al., N Engl J Med 2000;343:

19 % PegInterferon alfa-2a plus ribavirin as initial treatment (48 weeks) for chronic hepatitis C 1 (Virolgical SR depending on genotyp and cirrhosis; n=1121) PegIFN+RIBA IFN+RIBA PegIFN+PLC All patients Genotyp 1 Genotyp 4 Genotyp 2 or 3 Cirrhosis 21 1 Fried M. et al., N Engl J Med 2002;347:

20 100 PegInterferon alfa-2a plus ribavirin as initial treatment (48 weeks) for chronic hepatitis C 1 (Virolgical SR depending on genotyp and viral load; n=1121) % PegIFN+RIBA IFN+RIBA PegIFN+PLC 13 Genotyp 2,3; <2 Mio copies/ml Genotyp 1,4; <2 Mio copies/ml Genotyp 2,3; >2 Mio copies/ml Genotyp 1,4; >2 Mio copies/ml 1 Fried M. et al., N Engl J Med 2002;347:

21 % PegInterferon alfa-2a plus ribavirin as initial treatment fo chronic hepatitis C 1 (Virolgical relapse rate; n=1121) PegIFN+RIBA IFN+RIBA PegIFN+PLC Virological relapse rate after ETR 1 Fried M. et al., N Engl J Med 2002;347:

22 Predictability of sustained virologic response Sustained virologic response N = 253 (65%) Week 12 (n=453) 2-log drop or undetectable HCV RNA Yes No N = 390 (86%) N = 63 (14%) No sustained virologic response Sustained virologic response No sustained virologic response N = 137 (35%) N = 2 (3%) N = 61 (97%) 1 Fried M. et al., N Engl J Med 2002;347:

23 Interferon alfa-2a alone vs. pegylated Interferons as initial treatment for patients with chronic hepatitis C and cirrhosis % Sustained virologic response Histologic response (Knodell-Index - 2 Pts.) IFN alfa 2a 3MU tiw (n=88) for 48 W 40kD-PEG-IFN 180ug weekly (N=87) for 48 W 1 Heathcote J. et al., N Engl J Med 2000;343:

24 Erstbehandlung Genotyp 1 (4) PegIFN mg RIBA 12 Monate Genotyp 2,3 PegIFN + 800mg RIBA 6 Monate Relapse nach IFN-Monotherapie Non-Responder PegIFN + RIBA analog Erstbehandlung PegIFN + RIBA+AMA+PHLEBO* *im Rahmen von Studien