Variceal bleeding. Mainz,

Transcription

1 Variceal bleeding Mainz,

2 Risk of complications 5 years 10 years Ascites 10 % 25 % HCC 10 % 25 % Bleeding < 5 % 5-10 % Enceph. < 5 % < 5 %

3 Typical situation : Mortality 10 % to 40 %

4 Sequence Prevent Treat - Prevent

5 Portal hypertension Hepatic venous pressure gradient > 5 mm Hg (HVPG)

6 Pathogenesis of variceal bleeding Escorsell and Bosch, Kluwer 2004

7 Varices : Epidemiology % in patients with compensated cirrhosis and 60 % in patients with decompensated cirrhosis Annual incidence in patients with no varices : 5-10 % Groszmann and Abraldes, Montreal 2004

8 ? Development of varices

9 Prevention of first bleeding : Reduce portal pressure!? Ligatur

10 Patients with liver cirrhosis have a splanchnic blood pooling and a high cardiac index

11 Non selective ß-blockers reduce cardiac index and splanchnic blood flow

12 Non-selective ß-blocker for primary prophylaxis in patients with large varices N = 589, mean follow-up 2 years Placebo : bleeding rate 35 % Propranolol : bleeding rate 22 % Poynard et al, N Engl J Med 1991; 324:1532

13 Candidate for Propranolol

14 Problems with Propranolol for primary prophylaxis 40 % are hämodynamic non-responders. Around 25 % interrupt treatment. Around 5 % have contraindications. Lifelong therapy is necessary. Merkel et al Hepatology 2000; 32:930 Schepke et al Hepatology 2004

15 Is ligation an alternative?

16 Efficacy of primary prophylaxis Schepke et al Hepatology 2004

17 Ligation vs Propranolol : Metaanlysis Boyer Baveno IV Blackwell 2006

18 Carvedilol to prevent first bleeding Carvedilol Ligation N = 77 N = 75 Bleeding 13 % 22 % 6.25 or 12.5 mg 1 x per day, mean follow-up 24 months, mean Child-Pugh score 8.3 P, 13 % interruption of therapy (same group Propranolol 30 %) 6 bleedings due to ligation, no difference survival Tripathi et al AASLD Boston 2007, A 81

19 Baveno consensus suggests (Prevention of first variceal bleeding) Consider a non-selective ß-blocker first Use ligation, if the patient is noncompliant, does not tolerate the drug or has contraindications Carvedilol may be an alternative

20 Primary propylaxis in patients with small varices Nadolol 60 mg (n=83) vs Placebo (n = 78) Bleeding risk 12 vs 22 % after 5 years, NNT : 10 Merkel et al Gastroenterology 2004;127:476

21 Primary prophylaxis in patients with small varices You may suggest treatment with a non-selective ß-blocker but you must not!

22 Typical situation : Mortality 10 % to 40 %

23 Ligate the patient if ever possible!

24 Endoscopic hemostasis in acute variceal bleeding Villanueva et al J Hepatol 2006;45:560-7

25 Apply adjuvant vasoactive drugs that reduce portal inflow and esophageal pressure (flow)! Metaanalysis: de Franchis 2004

26 Use adjuvant antibiotics! They may decrease intrahepatic resistance Bernard et al Hepatology 1999;29 :1655

27 Fundic varices should be injected with glue

28 GOV Type I : Try to ligate!

29 How to treat refractory bleeding?

30 Local treatment of uncontrolled bleeding Lethal complications 5 %

31 Esophageal Stent for variceal hemostasis

32 Stent for compression of varices Hubmann et al Endoscopy 2006;38:896

33 TIPS - Rescue!? Immediate TIPS placement?

34 Early PTFE-TIPS vs. Drug+EBL. Composite endpoint: failure to control AVB or to prevent rebleeding Free of failure to control AVB or prevent rebleeding % 50% Early PTFE- TIPS p< Drugs + EBL months At risk: Early TIPS Drugs+E BL Garcia-Pagan, EASL Madrid

35 Rebleeding prophylaxis is necessary since 60 to 70 % rebleed after acute hemostasis

36 Rebleeding prophylaxis Ligation Betablocker + ISMN Villanueva 49 % 33% Patch 53 % 37 % Lo 38 % 57 % Romero 36 % 40 % Overall: 46 % 43 % 1) Villanueva et al., N Engl J Med 2001; 345: 647 2) Patch et al., Gastroenterology 2002; 123: ) Lo et al., Gastroenterology 2002; 123: 728 4) Romero et al., Aliment Pharm Ther 2006

37 Hemodynamic response and the risk of rebleeding Reduction of HVPG < 20 % bzw. >12 mm Hg > 20 % bzw. < 12 mm Hg Rebleeding 48 % 16 % N = 396 patients from 9 studies Garcia-Pagan u. Bosch, Correspondence Hepatology 2004, 39 :1746

38 Prevention of rebleeding : Ligation vs ligation and ß-blockers Verknüpfung mit neue seite.jpg.lnk Lo GH et al Hepatology 2000; 32 : and de La Pena et al Hepatology 2005; 41:572.

39 Luca et al, Radiology 1999; 212:411 TIPS vs endoscopic prevention of rebleeding : metaanlysis n= 750 bleeding risk (%) Rebleeding - 31 (- 39 bis - 23)* Encephalopathy +16 (+10 bis + 22)* Overall death + 2 (- 4 bis + 9) Lethal bleeding - 5 (-11 bis + 6 ) n= 11 RCT (ST 5, ST + ß-Bl. 3, Lig 3)

40 TIPS versus open shunt (DSRS) 140 Patienten; Child A/B; follow-up Monate Henderson JM, Gastroenterology 2006;130:1643

41 Summary: Rebleeding prophylaxis (Baveno) Secondary prophylaxis should start from day 6 of the index variceal bleed. Combination of beta-blockers and band ligation is probably the best treatment. Band ligation should be added in patients who were on beta-blockers for primary prevention. Patients with intolerance or contraindications to beta-blockers : ligation preferred treatment Patients who fail : TIPS or DSRS