Primary Prophylaxis against Variceal Hemorrhage Pharmacotherapy vs Endoscopic Band Ligation

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1 Primary Prophylaxis against Variceal Hemorrhage Pharmacotherapy vs Endoscopic Band Ligation Siwaporn Chainuvati, MD Faculty of Medicine Siriraj Hospital

2 Outline Natural history of esophageal varices Which cirrhotic patient needs prophylaxis, how? Current data on roles of pharmacotherapy and endoscopic band ligation Cautions of beta-blocker use in cirrhosis

3 Natural History of EV Variceal hemorrhage occurs in 25-35% of cirrhotics and accounts for 70-80% of UGIB in these patients 50% of cirrhotics will have varices at the time of diagnosis

4 Guidelines for Screening for Esophageal Varices Gold standard: Esophagogastroduodenoscopy Diagnosis of cirrhosis Baveno IV consensus (2005) AASLD, ACG Guideline (2007)

5 No varices 7-8%/year Small varices Pre-Primary Prophylaxis Predictor of EV:HVPG > 10 mmhg 7-8%/year Large varices Primary Prophylaxis 5-15%/year Variceal bleeding 20% Mortality Secondary Prophylaxis Rebleeding Merli et al. J Hepatol 2003;38:266

6 Risk Indicators of First Bleeding from Esophageal Varices Variceal size Severity of liver disease (CPT) Presence of red signs Hepatic venous pressure gradient

7 Variceal Wall Tension (T) is a Major Determinant of Variceal Rupture Esophagus Wall thickness (w) Radius (r) Transmural pressure (tp) Varix Tension (T) T = tp x r w Groszmann, Gastroenterology 1984; 80:1611

8 ? Simvastatin? ARB? VEGF-R inhibitor Pathophysiology of Portal Hypertension Vasodilator :ISMN Endoscopic therapies? VEGF-R inhibitor Antiviral Rx TIPS Β-blockers Terlipressin Somatostatin Bosch et al., Journal of Hepatology 2008

9 Therapy for Primary Prophylaxis Non-selective betablockers (NSBB) Endoscopic variceal ligation (EVL) Isosorbide mononitrate (ISMN) NSBB+ EVL NSBB+ ISMN Sclerotherapy Recommend Not recommend Garcia-Tsao et al. ACG guideline 2007

10 Non-selective Beta-blockers for Primary Prophylaxis Bleeding rate (2 yr) All varices (11 trials) Control NSBB Absolute rate difference 25% (n=600) 15% (n=590) -10% Large varices (8 trials) 30% (n=411) 14% (n=400) -16% (-24 to-8) Small varices (3 trials) 7% (n=100) 2% (n=91) -5% D Amico et al. Sem Liv Dis 1999

11 ISMN + Propranolol vs Propranolol alone for primary prophylaxis Free of a first variceal bleeding Survival ns 75 ns % Propranolol + ISMN Propranolol + placebo Propranolol + ISMN Propranolol + placebo 0 1 Years Years 2 García-Pagán et al., Hepatology 2003

12 Endoscopic variceal ligation plus propranolol vs endoscopic variceal ligation alone in primary prophylaxis of variceal bleeding Sarin et al, Am J Gastroenterol 2005;100:

13 Primary Prophylaxis 20 mg twice a day Baveno IV consensus (2005) AASLD Guideline (2007) WCOG guideline Endoscopic band ligation q 2-4 weeks

14 Banding Ligation versus Beta-blockers for Primary Prevention in Esophageal Varices Cochran Review (1504 pts) Gludd LL, Krag A Cochran Database Systemic Review 2012

15 Esophageal Variceal Bleeding Rate Abillos et al. Clin Liver Dis 2010 HVPG response on NSBB, only 50% of patients were HVPG responder

16 Carvedilol for Primary Prophylaxis of Variceal Bleeding in Cirrhotic Patients with Hemodynamic non-response to Propranolol Patients (n) All (104) Propranolol responder 37 (36%) Carvedilol responder 38 (37%) Non-responder (EBL) 29 (28%) P value Follow-up, months Variceal bleeding,n(%) Hepatic decompensation (13%) 4 (11%) 3 (8%) 7 (24%) (38%) 14 (38%) 10 (26%) 16 (55%) Death, n(%) 18 (17%) 5 (14%) 4 (11%) 9 (31%) Bleeding related death, n(%) 8 (7%) 2 (5%) 1 (2%) 5 (17%) <0.01 Reiberger et al. Gut 2013

17 Double-Blind Randomized Controlled Trial of Simvastatin vs Placebo for Portal Hypertension in Cirrhosis + Simvastatin Albrades et al, Gastroenterology 2009

18 Effects of the Combined Administration of Propranolol plus Sorafenib on Portal Hypertension in Cirrhotic rats

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20 Primary Prophylaxis Large varices Small varices with red signs or in Child-C Non-selective ß-blocker EVL q 2-4 weeks patient s preference, contraindication or intolerance to BB No follow up EGD once on BB Titrate to keep HR 55/min, avoid hypotension (MAP < 82 mmhg) Bosch et al., Journal of Hepatology 2008 Garcia-Tsao et al, Hepatology 2007

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