44 th 44 th Annual AISF Meeting Rome, February 23 rd -26 th th, 2011 Update on the Baveno Consensus Conference Roberto de Franchis Department of of Clinical Sciences, University of of Milan, Head, Gastroenterology Unit, Luigi Sacco University Hospital Milan On behalf of the Baveno V Faculty
Update on the Baveno Consensus Conference Contents What is Baveno Topics addressed at Baveno I-VI For each topic: Baveno I-IV I IV recommendations New evidence after Baveno IV Baveno V recommendations Application of the Baveno recommendations in clinical practice
International Consensus Workshops on Portal Hypertension 1986 Groningen 2007 - Atlanta 1990 - Baveno I 2010 Baveno V 1992 Milano 1995 - Baveno II 1996 - Reston 2000 - Baveno III 2005 - Baveno IV
Update on the Baveno Consensus Conference Baveno V (21-22 22 May, 2010) Was the most recent of of a series of of meetings of of world experts to to review the scientific evidence and issue recommendations for the diagnosis and management of of portal hypertension Baveno IV-V V recommendations Whenever applicable, the level of of existing evidence was ranked - and the recommendations were graded - according to to the Oxford System* (i.e.: level of of evidence from 1 = highest to to 5 = lowest; grade of of recommendation from A = strongest, to to D = weakest) *http://www.cebm.net/index.aspx?o=1025
Update on the Baveno Consensus Conference The Baveno V consensus report is is available online at: http://dx.doi.org/10.1016/j.jhep.2010.06.004 And is is published in the October 2010 issue of the Journal of Hepatology ((2010;53:762-768) 768) The Baveno V Proceedings book is is published by Wiley-Blackwell and has been released in January 2011
Update on the Baveno Consensus Conference Contents What is Baveno Topics addressed at Baveno I-VI For each topic: Baveno I-IV I IV recommendations New evidence after Baveno IV Baveno V recommendations Application of the Baveno recommendations in clinical practice
Topics addressed at Baveno I-VI Definition of key events Diagnostic evaluation of patients with portal Because of time constraints, this presentation hypertension does not include all the Baveno V recommendations concerning the management of portal hypertension. Prognostic factors for first bleeding, rebleeding and death Therapeutic strategies in patients with portal hypertension Methodological requirements of trials
Update on the Baveno Consensus Conference Therapeutic strategies in patients with Portal Hypertension Pre-primary and primary prophylaxis Treatment of acute bleeding and prevention of early rebleeding Prevention of late rebleeding
Possible Times of Inception of the Prevention of the First Variceal Haemorrhage Pre-primary prophylaxis When portal hypertension is is present, but varices have not yet appeared, aiming at preventing variceal formation. When small varices are present, aiming at preventing variceal growth. Primary prophylaxis When medium-large varices are present, aiming at preventing variceal rupture.
Beta-blockers to Prevent Gastroesophageal Varices in Patients with Cirrhosis 50 Placebo 105 pts. Timolol 108 pts. % with event 40 30 20 10 0 40 39 varices formation 2,9 2,8 14,3 9,3 p = 0.006 5,7 18,5 variceal bleeding death adverse events Placebo Timolol Groszmann RJ et al. N Engl J Med 2005;353:2288-2290 2290
Pre-primary Prophylaxis (Preventing the Formation of Varices) Baveno IV Recommendation There is no indication, at this time, to treat patients to prevent the formation of varices (1b;A) de Franchis R J Hepatol 2005;43:167-176 176
Baveno V recommendations: Pre-Primary Primary Prophylaxis Confirmed Prevention of the development of complications of portal hypertension is is an important area of research. ((5;D) All cirrhotic patients should be screened for varices at diagnosis ((5;D) There is is no indication, at this time, to use beta-blockers blockers to prevent the formation of varices. ((1b;A) de Franchis R, J Hepatol 2010;53:762-768 768
Hepatic vein pressure gradient predicts clinical decompensation in patients with compensated cirrhosis 75 50 25 0 % w ith e v e n t 100 53 47 Remained compensated HVPG > 10 mmhg 87 13 Developed decompensation HVPG < 10 mmhg Ripoll C et al. Gastroenterology 2007;133:481-488 488
Antiviral therapy reduces portal pressure in patients with cirrhosis due to HBeAg negative chronic hepatitis B and significant portal hypertension 19 patients with HBV cirrhosis and HVPG > 10 mmhg treated with lamivudine HVPG measured at baseline and at 6 months HVPG decreased in all but one patient 20 20 15 15 10 10 5 0 HVPG (mmhg) 14,4 14,4 12,4 12,4 p = 0.007 Baseline 12 12 months Manolakopoulos S et al. J Hepatol 2009;51:468-474 474
Baveno V Recommendations Pre-primary Prophylaxis New Hepatic venous pressure gradient (HVPG) 10 mmhg is is predictive of varices formation and decompensation. ((1b;A) Treatment of underlying liver disease may reduce portal hypertension and prevent its clinical complications. ((1b;A) HVPG measurement in pre-primary primary prophylaxis may be recommended only in the context of clinical trials. ((5;D) de Franchis R, J Hepatol 2010;53:762-768 768
Possible Times of Inception of the Prevention of the First Variceal Haemorrhage Pre-primary prophylaxis When portal hypertension is is present, but varices have not yet appeared, aiming at preventing variceal formation. When small varices are present, aiming at preventing variceal growth. Primary prophylaxis When medium-large varices are present, aiming at preventing variceal rupture.
Beta-blockers in the Prevention of Aggravation of Esophageal Varices in Patients With Cirrhosis and Small Varices: a Placebo-controlled controlled Clinical Trial Placebo 78 pts. Nadolol 83 pts. % with event 50 40 30 20 10 0 p < 0.001 37,1 growth of varices 10,8 10 3 40 p 30 = 0.02 p = 0.025 p = 0.03 variceal bleeding 1 11 6 17 death side effects regression of varices Placebo Nadolol Merkel C et al. Gastroenterology 2004;127:476-484 484
Risk of Bleeding Increases with Variceal Size, RWM and Child Class (Data from NIEC N Engl J Med 1988;319:983-989) 989) 100 % risk of bleeding 75 50 25 0 76 52 44 42 34 28 26 20 16 15 10 6 Child A Child B Child C Small varices without RWM Small varices with severe RWM Large varices without RWM Large varices with severe RWM Bosch J, J Hepatol 2006;45:174-177 177
Pre-primary Prophylaxis (Preventing the Growth of Varices) Baveno IV Recommendation Patients with small varices with red wale signs or of Child C class have an increased risk of bleeding and may benefit from treatment (5;D) Patients with small varices could be treated with non-selective beta-blockers blockers to prevent progression of varices and bleeding, but further studies, especially as relates to prevention of bleeding, are required before a formal recommendation on their use can be made. (5;D) de Franchis R J Hepatol 2005;43:167-176 176
Baveno V Recommendations Pre-primary Prophylaxis New Patients with small varices with red wale marks or Child C class have an increased risk of bleeding ((1b;A) ) and should be treated with nonselective beta blockers (NSBB) ((5;D). Confirmed Patients with small varices without signs of increased risk may be treated with NSBB to prevent progression of varices and bleeding. (1b;A) ) Further studies are required to confirm their benefit. de Franchis R, J Hepatol 2010;53:762-768 768
Possible Times of Inception of the Prevention of the First Variceal Haemorrhage Pre-primary prophylaxis When portal hypertension is is present, but varices have not yet appeared, aiming at preventing variceal formation. When small varices are present, aiming at preventing variceal growth. Primary prophylaxis When medium-large varices are present, aiming at preventing variceal rupture.
Prophylactic treatments for the first variceal bleeding β-blockers vs. Placebo 10 RCTs, 1154 patients Bleeding EVL vs. no treatment 5 RCTs, 601 patients Bleeding Plac. β-bl. ARR NNT No Rx EVL ARR NNT 25% 15% -10% 10 Mortality 32% 12% -20% 5 Mortality Plac. β-bl. ARR NNT No Rx EVL ARR NNT 27% 23% -4% 25 35% 20% -15% 6 D Amico G et al. Sem Liver Dis 1999;19:475-505 505 Imperiale TF et al. Hepatology 2001;33:802-807 807
Prevention of the first bleeding episode Baveno IV Recommendations Nonseletive beta-blockers blockers reduce the risk of first variceal bleeding ((1a;A) Prophylactic endoscopic band ligation (EBL) is is useful in the prevention of the first variceal hemorrhage in patients with medium-large esophageal varices (1a;A) de Franchis R J Hepatol 2005;43:167-176 176
Prevention of the First Bleeding Episode Baveno IV Recommendations EBL is is more effective than non-selective beta blockers in preventing first variceal bleeding but does not improve survival. However the long-term benefits of EBL are uncertain because of the short duration of follow-up (1a;A) EBL should be offered to patients with medium/large varices and contraindications or intolerance to beta- blockers. (5;D) de Franchis R J Hepatol 2005;43:167-176 176
Variceal band ligation vs. beta blockers for primary prevention of variceal bleeding: a meta-analysis analysis Meta-analysis analysis of 9 RCTs published in full (734( pts; 356VBL, 378 BB) First bleeding: EBL better - PRR 0.63 (0.43-0.92), 0.92), NNT 13 Treatment withdrawal for SAEs: EBL better PRR 0.24 (0.12-0.47), 0.47), NNT 10 Overall mortality: no difference Bleeding related mortality: no difference Iatrogenic bleeding with EBL: 6 ((1.6%), fatality 2 (0.56%) Tripathi D et al. Eur J Gastroenterol Hepatol 2007;19:835-845 845
Randomized controlled trial of carvedilol versus variceal band ligation for the prevention of the first variceal bleed 152 patients randomized to to Carvedilol 12.5 mg per day (n (n = 77) EBL every 2 weeks until eradication (n (n = 75) % with event Median follow-up 20 months 10 But: Mean interval between randomization and treatment Carvedilol: 1 day; ; EBL 21 days EBL eradication of varices 58% 50 p = 0.04 p = 0.71 25 0 35 37 23 Bleeding Mortality Carvedilol EBL Tripathi D et al. Hepatology 2009;50:825-833 833
Baveno V Recommendations Primary Prophylaxis New Either NSBB or endoscopic band ligation (EBL) is is recommended for the prevention of first variceal bleeding of medium or large varices. ((1a;A) Choice of treatment should be based on local resources and expertise, patient preference and characteristics,, side effects and contraindications. ((5;D) Carvedilol is is a promising alternative ((1b;A) which needs to be further explored. de Franchis R, J Hepatol 2010;53:762-768 768
Algorithm for primary prevention of variceal bleeding in cirrhosis - 2011 Diagnosis of cirrhosis Endoscopic screening No varices Small varices, No red signs Child A-B Small varices, Red signs + Child C Mediumlarge varices Surveillance endoscopy at 3 years intervals Surveillance Endoscopy At 1-2 years? Nonselective Beta blockers? Treat with Nonselective Beta blockers Treat with Nonselective Beta blockers or band ligation
Update on the Baveno Consensus Conference Therapeutic strategies in patients with Portal Hypertension Pre-primary and primary prophylaxis Treatment of acute bleeding and prevention of early rebleeding Prevention of late rebleeding
Setting Steps in the management of the acute haemorrhage and prevention of early rebleeding Resuscitation Transfusion policy Vasoactive drugs and antibiotic therapy Endoscopic diagnosis and therapy
Vasoactive drugs and antibiotic therapy Baveno IV recommendations The best approach in the management of acute esophageal variceal haemorrhage is is the combination of a vasoactive drug and antibiotic prophylaxis from admission followed by endoscopic therapy ((1a;A) Terlipressin, somatostatin, octreotide or vapreotide may be used as vasoactive drugs ((1b;A) de Franchis R J Hepatol 2005;43:167-176 176
RCTs of of combination of of vasoactive drugs + endoscopic treatments vs. endoscopic treatment alone for acute variceal bleeding: a meta-analysis analysis 10 RCTs, 1995-2001; 1273 pts. Immediate bleeding control O.R. O.R. 3.41 3.41 (95% C. C. I. I. 2.24-5.20) 5 days bleeding control O.R. O.R. 2.30 2.30 (95% C.I. C.I. 1.70-3.11) 5 days mortality O.R. O.R. 0.73 0.73 (95% C.I. C.I. 0.44-1.22) 42 days mortality O.R. 0.76 (95% C.I. 0.54-1.09) + 13.7% + 14.1% - 2.2% -5.9% - 0.25 0.0 + 0.25 Pooled rate differences Updated from Bañares ares R et al. Hepatology 2002;35:609-615 615
Low dose terlipressin plus banding ligation vs. low dose terlipressin alone in the prevention of very early rebleeding of esophageal varices 93 93 patients with inactive acute variceal bleeding randomized to to EBL EBL + terlipressin 1 mg mg q. q. 6 h for for 48 48 h (n (n = 47) 47) Terlipressin 1 mg mg i.v. i.v. q. q. 6 h for for 5 days days (n (n = 46) 46) End points: treatment failure and very early rebleeding But: Extremely selected population Low Low dose dose terlipressin in in the the drug drug alone arm arm % with event 30 20 10 0 p = 0.002 p = 0.006 p = N.S. 2 24 Treatment failure EBL + Ter. 0 15 Very early rebleeding 2 6,5 Mortality Terlipressin Lo GH et al. Gut 2009;58:1275-1280 1280
Optimal management of variceal bleeding Questions Which vasoactive drug? Which antibiotic regimen?
Comparison of individual vasoactive drugs + endoscopic therapy vs. endoscopic therapy for variceal bleeding : a meta-analysis analysis Pooled rate differences control of bleeding a) Terlipressin + sclero. vs. b) sclerotherapy [2 trials, (1 f.p.) 139 pts.] a) worse a) better PRD + 22.2% a) Somatostatin + sclero. vs. b) sclerotherapy [2 trials, (1 f.p.) 268 pts.] a) Vapreotide + endo. vs. b) endoscopic therapy [4 trials (1 f.p.); 623 pts.] a) Octreotide + endo. vs. b) endoscopic therapy [6 trials (5S, 1L) 696 pts.] -0.4-0.2 0.0 + 0.2 + 0.4 PRD + 19.7% PRD + 9.8% PRD + 9.6%
Terlipressin vs. octreotide in bleeding esophageal varices as an adjuvant therapy with endoscopic band ligation: a randomized double blind placebo-controlled controlled study 324 patients with acute variceal bleeding randomized to to Terlipressin 1 mg mg i. i. v. v. q. q. 6 h for for 72 72 h (n (n = 163) 163) Octreotide 50 50 µg/h i. i. v. v. for for 72 72 h (n (n = 161) 161) Non-inferiority design- primary end point: bleeding control But: Only 5 days days figures available Extremely selected population Low Low dose dose terlipressin Extremely low low failure rates Abid S et Very al. Am low low J Gastroenterol mortality 2009;104:617-623 623 % with event 30 20 10 0 p = 0.107 p = 0.626 p = 0.034 7,4 4,4 Treatment failure Terlipressin 5,5 4,3 16 25,5 5-day mortality Active bleeding at endoscopy Octreotide
Baveno V Treatment of of Acute Bleeding Which vasoactive drug do you prefer in combination with endoscopic therapy for the therapy of patients with acute variceal bleeding? 100 1. Terlipressin 2. Somatostatin % 75 50 61,8 3. Octreotide 25 22,7 13,6 4. Vapreotide 0 1,8 Terlipressin Somatostatin Octreotide Vapreotide
Optimal management of variceal bleeding Questions What is the optimal duration of vasoactive treatment?
What is the minimum duration of pharmacological therapy? The minimum duration used in a RCT is 8 hours (Levacher 1995) The optimal duration is unknown, since no direct comparison has been made
Duration of vasoactive drug therapy in RCTs for the treatment of acute variceal bleeding 20 All vasoactive drugs combined: 46 RCTs N RCTs 15 10 5 0 15 11 12 2 1 1 1 1 1 1 8 h 12 h 24h 30 h 32 h 2 d 3 d 4 d 5 d 6 d Duration of vasoactive treatment
Baveno V Recommendations Pharmacological treatment Confirmed In suspected variceal bleeding, vasoactive drugs should be started as soon as possible, before endoscopy. ((1b;A) Vasoactive drugs (terlipressin, somatostatin, octreotide, vapreotide) should be used in combination with endoscopic therapy and continued for up to 5 days. ((1a;A)
Antibiotic Prophylaxis Rationale Cirrhotic patients are at increased risk of infection Bleeding increases the risk of sepsis Hemorrhagic shock increases bacterial translocation
Occurrence of Bacterial Infection in Bleeding Cirrhotic Patients Distribution of the date of occurrence of the first bacterial infection N patients 12 10 8 6 4 2 0 1 2 3 4 5 6 7 hospitalization day Bernard B et al. Gastroenterology 1995;108:1828-1834 1834
Effect of Antibiotic Treatment on GI Bleeding Outcome in Cirrhosis Rimola Soriano Blaise Pauwels Hsieh OVERALL Risk difference - 32% - 9.1% 0.2-0.0-0.2-0.4-0.6-0.8 + 0.1 0.0-0.1-0.2-0.3-0.4 Bacterial infection development Mortality Bernard B et al. Hepatology 1999;29:1655-61 61
Gastrointestinal bleeding Questions Which antibiotic regimen?
Norfloxacin vs. Ceftriaxone in the Prophylaxis of Infections in Patients with Advanced Cirrhosis and Hemorrhage 111 patients randomized to oral norfloxacin, 400 mg b.i.d. (n (n = 57) i.v. ceftriaxone, 1 g q.d. for 7 days (n (n = 54) End point: prevention of bacterial infections within 10 days % with event 50 25 0 p = 0.003 p = 0.03 p = 0.03 33 11 Proved or possible infections Norfloxacin 26 Proved infections 11 12 2 Spontaneous bacteremia or SBP Ceftriaxone Fernandez J et al. Gastroenterology 2006;131:1049-1056 1056
Baveno V Recommendations Antibiotic prophylaxis Confirmed Antibiotic prophylaxis is is an integral part of therapy for patients with cirrhosis presenting with upper gastrointestinal bleeding and should be instituted from admission ((1a;A). de Franchis R, J Hepatol 2010;53:762-768 768
Baveno V Recommendations Antibiotic prophylaxis New Oral quinolones are recommended for most patients ((1b;A). Intravenous ceftriaxone should be considered in patients with advanced cirrhosis ((1b;A), in hospital settings with high prevalence of quinolone-resistant bacterial infections and in patients on previous quinolone prophylaxis ((5;D) de Franchis R, J Hepatol 2010;53:762-768 768
Setting Steps in the management of the acute haemorrhage and prevention of early rebleeding Resuscitation Transfusion policy Vasoactive drugs and antibiotic therapy Endoscopic diagnosis and therapy
Gastrointestinal bleeding Questions Which endoscopic therapy?
Endoscopic therapy Baveno IV recommendations Ligation is is the recommended form of endoscopic therapy, although sclerotherapy may be used in the acute setting when ligation is is technically difficult ((1b;A) de Franchis R J Hepatol 2005;43:167-176 176
A Randomized Controlled Trial Comparing Ligation and Sclerotherapy as Emergency Endoscopic Treatment Added to Somatostatin in Acute Variceal Bleeding 50 EBL 90 pts. ; EVS 89 pts. 40 p = 0.02 p = 0.02 p = 0.48 p = 0.01 p = 0. 25 % events 30 20 10 10 24 4 15 18 24 8 23 5 9 EBL EVS 0 Overall Failure Failure to control bleeding Active bleeding No active bleeding Early rebleeding Villanueva C et al. J Hepatology 2006;45:560-567 567
A Randomized Controlled Trial Comparing Ligation and Sclerotherapy as Emergency Endoscopic Treatment Added to Somatostatin in Acute Variceal Bleeding EBL 90 pts; EVS 89 pts. Transfusion requirements 100 p = 0.72 p = 0.17 p = 0.04 10 p = 0.05 % with event 75 50 25 0 3 3 5 days mortality 13 21 42 days mortality 14 28 Major complications N Units of blood 8 6 4 2 0 2 3,1 EBL EVS EBL EVS Villanueva C et al. J Hepatology 2006;45:560-567 567
Baveno V Recommendations Endoscopic treatment Confirmed Ligation (EVL) is is the recommended form of endoscopic therapy for acute esophageal variceal bleeding, although sclerotherapy may be used in the acute setting if if ligation is is technically difficult (1b;A) de Franchis R, J Hepatol 2010;53:762-768 768
Early HVPG measurement to direct the type of therapy of acute variceal bleeding 116 bleeding cirrhotic patients treated with 1 session of EVS HVPG measured within 24 h 64 patients: HVPG < 20 mmhg = low risk 52 patients: HVPG > 20 mmhg = high risk 26 randomized to TIPS 26 randomized to non-tips Monescillo A et al. Hepatology 2004;40:793-810 % with event 100 75 50 25 0 p = 0.003 p = 0.02 p = 0.01 11 12 50 Treatment failure 5 11 38 In hospital mortality 17 31 65 1 year Mortality Low risk HR-TIPS HR Non TIPS
Early use of TIPS in patients with cirrhosis and variceal bleeding 63 high risk cirrhotic patients with AVB treated with vasoactive drugs + EVL Randomized within 24 h to: PTFE-covered TIPS within 72 hrs (32) Continue vasoactive drugs + EVL (31), then beta blockers + Is5MN + EVL Criteria of admission: Child >10 or 7-9 + active bleeding End points: Treatment failure Survival % with event 100 75 50 25 0 p = 0.01 p = 0.001 p = 0.01 3,1 45,2 Early treatment failure TIPS 3 50 One year treatment failure EVL + drugs 14 40 One year Mortality Garcia-Pag Pagàn n JC et al. N Engl J Med 2010;362:2370-2379 2379
Baveno V Recommendations Early TIPS placement New An early TIPS within 72 hours (ideally < 24 hours) should be considered in patients at high-risk of treatment failure (e.g. Child-Pugh class C < 14 points or Child class B with active bleeding) after initial pharmacological and endoscopic therapy. ((1b;A)
Algorithm for treatment of acute variceal bleeding - 2011 Bleeding Initial assessment (history, physical exam, blood tests, cultures) Endoscopy Resuscitation (prevent aspiration, peripheral + central lines, blood gases, pulse oximetry, transfusion Ht 25-30%), start vasoactive drugs + antibiotic prophylaxis Nonvariceal bleed. Treat as appropriate according to the bleeding source Variceal bleeding High risk patients: Early PTFE-TIPS Perform band ligation or sclerotherapy and continue vasoactive drug for up to 5 days Success? Failure Start prophylaxis of rebleeding Emergency surgical shunt Emergency TIPS /Stent?
Advances in Management of Portal Hypertension Therapeutic strategies in patients with Portal Hypertension Pre-primary and primary prophylaxis Treatment of acute bleeding and prevention of early rebleeding Prevention of late rebleeding
Randomized Controlled Trials Comparing Band Ligation With Medical Treatment (β-blockers + Is-5-Mn) for Prevention of Variceal Rebleeding 80 p = 0.04 p<0.01 p= 0.25 p= N.S. % events 60 40 20 49 33 20 42 53,8 43,7 46 47 Rebl. EBL 0 Villanueva 2001 Lo 2002 Patch 2002 Romero 2006 Rebl. BIs Villanueva et al. NEJM 2001;345:647-655 655 Patch et al. Gastroenterology 2002;123:1013-1019 1019 Lo et al. Gastroenterology 2002;123:728-734 734 Romero G et al. Aliment Pharmacol Ther2006;24:601-11 11
Variceal Ligation Plus Nadolol Compared With Ligation for Prophylaxis of Variceal Rebleeding: a Multicenter Trial EBL + Nad: 43 pts. EBL alone: 37 pts. 80 60 p = 0.006 % events 40 20 N.S. p = 0.06 EBL alone EBL + Nad 0 Bleeding recurrence Mortality Variceal recurrence de la Peña a J et al. Hepatology 2005;41: 572-578 578
Prevention of late rebleeding Baveno IV Recommendations Secondary prophylaxis should start as soon as possible from day 6 of the index variceal bleeding episode (5;( D) D Beta blockers ((1a,A), band ligation ((1a;A) ) or both ((1b;A) ) should be used for prevention of recurrent bleeding Combination of beta blockers and band ligation is is probably the best treatment but more trials are needed (1b;A) In patients with cirrhosis who are on beta blockers for primary prevention and bleed: band ligation should be added ((5;D) de Franchis R J Hepatol 2005;43:167-176 176
Nadolol plus isosorbide mononitrate alone or associated with band ligation in the prevention of recurrent bleeding: a multicentre RCT 150 patients, 9 centers - 80 randomized to Nadolol + Isosorbide- 5 mononitrate + EBL - 78 randomized to Nadolol +Isosorbide-5 mononitrate Mean follow-up 15 Months % with event 100 75 50 25 0 p = 0.3 31 46 2 yr GI rebleeding N + I + EBL N.S. p = 0.01 26 23 61 32 2 yr Mortality Adverse events N+I Garcia-Pag Pagàn n JC et al. Gut 2009;58: 1144-1150 1150
Addition of propranolol and isosorbide mononitrate to endoscopic variceal ligation does not reduce variceal rebleeding incidence 169 patients - 80 randomized to Nadolol + Isosorbide- 5 mononitrate + EBL - 89 randomized to EBL alone % with event 50 40 30 20 10 0 p = 0.72 24 30 2 yr GI rebleeding p = 0.682 2,53,4 p = N.S. 15 8 2 yr Mortality Adverse events Mean follow-up 15 months N + I + EBL EBL Kumar A et al. Gastroenterology 2009;137:892-901 901
Baveno V Recommendations Prevention of late rebleeding Confirmed Secondary prophylaxis should start as soon as possible from day 6 of the index variceal bleeding episode (5,( D) D In patients with cirrhosis who have contraindications or intolerance to beta- blockers, band ligation is is the preferred treatment ((5;D) de Franchis R, J Hepatol 2010;53:762-768 768
Baveno V Recommendations Prevention of late rebleeding New Combination of beta-blockers blockers and band ligation is is the preferred therapy as it it results in lower rebleeding compared to either therapy alone. ((1a;A) Beta-blockers with Isosorbide Mononitrate is is the preferred option for patients with cirrhosis who are unable or unwilling to be treated with EVL ((1a;A) de Franchis R, J Hepatol 2010;53:762-768 768
Baveno V Recommendations Prevention of late rebleeding New For Patients who fail endoscopic and pharmacological treatment for the prevention of rebleeding, TIPS with PTFE-covered stents is is effective and is is the preferred option.. Surgical shunt in Child-Pugh A and B patients is is an alternative if if TIPS is is unavailable. ((2b;B) de Franchis R, J Hepatol 2010;53:762-768 768
Algorithm for prevention of late rebleeding - 2010 Patients surviving a variceal bleed Start prophylaxis as soon as possible (day 6) Patients previously on β-blockers Endoscopic band ligation + beta blockers Patients with contraindications or intolerance to β-blockers Patients unable or unwilling to undergo band ligation Add band ligation Success Success Continue + endoscopic follow-up TIPS; consider transplantation (poor risk) or H-graft PCS (good risk) Failure Band ligation Success β-blockers + Is-5-Mn Success Continue
Update on the Baveno Consensus Conference Contents What is Baveno Topics addressed at Baveno I-VI For each topic: Baveno I-IV I IV recommendations New evidence after Baveno IV Baveno V recommendations Application of the Baveno recommendations in clinical practice
Treatment administered in the acute setting of bleeding esophageal varices in a specialized unit compared with a community hospital % 100 80 60 40 20 0 p = 0.06 p = 0.04 79 67 55 Vasoactive drugs 27 86 74 p < 0.01 p < 0.01 5 21 Prophylactic antibiotics Endoscopic therapy Sengstaken-Blakemore tube Specialized unit Community hospital Hobolth L et al. Eur J Gastroenterol Hepatol 2010;22:1221-1227 1227
Secondary prophylaxis in patients surviving day 5 in a specialized unit compared with a community hospital % 100 80 60 40 20 0 91 p < 0.01 p = 0.02 p < 0.01 p < 0.01 74 82 71 71 64 47 45 Total Pharmacological therapy Endoscopic therapy Combined therapy Specialized unit Community hospital Hobolth L et al. Eur J Gastroenterol Hepatol 2010;22:1221-1227 1227
Adherence to the Baveno recommendations in clinical practice Although few data exist concerning the overall adherence to the Baveno recommendations in clinical practice, such adherence appears to be fair, at least in specialized units. However, even in this setting, there is is a wide margin for improvement. Strategies should be developed to increase the awareness of the recommendations and their application in clinical practice, both by hepatologists and generalists.
Acknowledgements Baveno V was possible thanks to the concerted efforts of the following: Scientific committee: J Bosch, AK AK Burroughs, G D Amico, D R de de Franchis, G Garcia-Tsao, ND ND Grace, R Groszmann, D Lebrec, C Merkel, M Primignani, F Salerno, SK SK Sarin,, TIA TIA Sørensen S Chairpersons: J Bosch, AK AK Burroughs, JC JC Garcia-Pagàn, G Garcia-Tsao, R Groszmann, L Laine, D Lebrec, C Merkel, SK SK Sarin, D Thabut, D Valla, C Villanueva. Panelists: S Abid, A Albillos, G Barosi, F Bendtsen, C Bureau, P Calès, YC YC Chawla, G D Amico, D A Dell Era, A Escorsell, ND ND Grace, P Hayes, H Janssen, P Kamath, A Kumar, GH GH Lo, Lo, M Merli, F Nevens, M Primignani, C Ripoll, T Sauerbruch, JP JP Vinel, J Vorobioff. Gave Lectures: JG JG Abraldes, R Bañares, ares, A Berzigotti, L Castéra, G D Amico, D R de de Franchis, JC JC Garcia-Pagàn, S Ling, B Mittmann, R Moreau, M Pinzani, M Senzolo, B Shneider, TIA TIA Sørensen, A Tripodi
Thank you for your attention! de Franchis 2010