Primary Prophylaxis against Variceal Hemorrhage Pharmacotherapy vs Endoscopic Band Ligation Siwaporn Chainuvati, MD Faculty of Medicine Siriraj Hospital
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
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
Guidelines for Screening for Esophageal Varices Gold standard: Esophagogastroduodenoscopy Diagnosis of cirrhosis Baveno IV consensus (2005) AASLD, ACG Guideline (2007)
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
Risk Indicators of First Bleeding from Esophageal Varices Variceal size Severity of liver disease (CPT) Presence of red signs Hepatic venous pressure gradient
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
? 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
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
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
ISMN + Propranolol vs Propranolol alone for primary prophylaxis Free of a first variceal bleeding Survival 100 100 75 ns 75 ns % 50 25 Propranolol + ISMN Propranolol + placebo 50 25 Propranolol + ISMN Propranolol + placebo 0 1 Years 2 0 1 Years 2 García-Pagán et al., Hepatology 2003
Endoscopic variceal ligation plus propranolol vs endoscopic variceal ligation alone in primary prophylaxis of variceal bleeding Sarin et al, Am J Gastroenterol 2005;100:797-804
Primary Prophylaxis 20 mg twice a day Baveno IV consensus (2005) AASLD Guideline (2007) WCOG guideline Endoscopic band ligation q 2-4 weeks
Banding Ligation versus Beta-blockers for Primary Prevention in Esophageal Varices Cochran Review (1504 pts) Gludd LL, Krag A Cochran Database Systemic Review 2012
Esophageal Variceal Bleeding Rate Abillos et al. Clin Liver Dis 2010 HVPG response on NSBB, only 50% of patients were HVPG responder
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 19.5 + 9.7 20.9+ 9.2 18.9+ 9.5 19.5+ 10.4 0.391 14 (13%) 4 (11%) 3 (8%) 7 (24%) 0.043 40 (38%) 14 (38%) 10 (26%) 16 (55%) 0.079 Death, n(%) 18 (17%) 5 (14%) 4 (11%) 9 (31%) 0.018 Bleeding related death, n(%) 8 (7%) 2 (5%) 1 (2%) 5 (17%) <0.01 Reiberger et al. Gut 2013
Double-Blind Randomized Controlled Trial of Simvastatin vs Placebo for Portal Hypertension in Cirrhosis + Simvastatin Albrades et al, Gastroenterology 2009
Effects of the Combined Administration of Propranolol plus Sorafenib on Portal Hypertension in Cirrhotic rats
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