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Primary prophylaxis of gastroesophageal variceal bleeding: consensus recommendations of the Asian Pacific Association for the Study of the Liver

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Abstract

The Asian Pacific Association for the Study of the Liver (APASL) set up a Working Party on Portal Hypertension in 2002, with a mandate to develop consensus guidelines on various clinical aspects of portal hypertension relevant to disease patterns and clinical practice in the Asia-Pacific region. Variceal bleeding is a consequence of portal hypertension, which, in turn, is the major complication of liver cirrhosis. Primary prophylaxis to prevent the first bleed from varices is one of the most important strategies for reducing the mortality in cirrhotic patients. Experts predominantly from the Asia-Pacific region were requested to identify the different aspects of primary prophylaxis and develop the consensus guidelines. The APASL Working Party on Portal Hypertension evaluated the various therapies that have been used for the prevention of first variceal bleeding. A 2-day meeting was held on January 12 and 13, 2007, at New Delhi, India, to discuss and finalize the consensus statements. Only those statements that were unanimously approved by the experts were accepted. These statements were circulated to all the experts and were subsequently presented at the annual conference of the APASL at Kyoto, Japan, in March 2007.

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Abbreviations

APASL:

Asian Pacific Association for the Study of the Liver

UGIE:

Upper gastro-intestinal endoscopy

HVPG:

Hepatic venous pressure gradient

IAP:

Intra-abdominal pressure

VBL:

Variceal band ligation

ISMN:

Isosorbide-5-mononitrate

EIS:

Endoscopic injection sclerotherapy

B-RTO:

Balloon-occluded retrograde transvenous obliteration

BO-EIS:

Balloon-occluded endoscopic injection sclerotherapy

References

  1. de Franchis R. Evolving Consensus in Portal Hypertension Report of the Baveno IV Consensus Workshop on methodology of diagnosis and therapy in portal hypertension. J Hepatol 2005;43:167–176

    PubMed  Google Scholar 

  2. Garcia-Tsao G, Sanyal AJ, Grace ND, Carey W. Practice Guidelines Committee of the American Association for the Study of Liver Diseases. Practice Parameters Committee of the American College of Gastroenterology. Prevention and management of gastroesophageal varices and variceal hemorrhage in cirrhosis. Hepatology 2007;46(3):922–938. doi:10.1002/hep.21907

    PubMed  CAS  Google Scholar 

  3. Grace ND. Diagnosis and treatment of gastrointestinal bleeding secondary to portal hypertension. Am J Gastroenterol 1997;92:1081–1091

    PubMed  CAS  Google Scholar 

  4. Centre for evidence-based medicine. Levels of evidence. 2001. http://www.cebm.net/index.aspx?o=1047. Accessed 23 Aug 2008

  5. de Franchis R, Pascal JP, Burroughs AK, Henderson JM, Fleig W, Groszmann RJ, et al. Definitions, methodology and therapeutic strategies in portal hypertension. A consensus development workshop. J Hepatol 1992;15:256–261. doi:10.1016/0168-8278(92)90044-P

    PubMed  Google Scholar 

  6. Grace ND, Groszmann RJ, Garcia-Tsao G, Burroughs AK, Pagliaro L, Makuch RW, et al. Portal hypertension and variceal bleeding: an AASLD single topic symposium. Hepatology 1998;28:868–880. doi:10.1002/hep.510280339

    PubMed  CAS  Google Scholar 

  7. D’Amico G, Garcia-Tsao G, Cales P, Escorsell A, Nevens F, Cestari R, et al. Diagnosis of portal hypertension: how and when. In de Franchis R, editor. Portal Hypertension III. Proceedings of the Third Baveno International Consensus Workshop on Definitions, Methodology and Therapeutic Strategies. Oxford, UK: Blackwell Science; 2001. 36–64

  8. The North Italian Endoscopic Club for the Study and Treatment of Esophageal Varices. Prediction of the first variceal hemorrhage in patients with cirrhosis of the liver and esophageal varices. A prospective multicenter study. N Engl J Med 1988;319:983–989

    Google Scholar 

  9. El-Serag HB, Everhart JE. Improved survival after variceal hemorrhage over an 11-year period in the Department of Veterans Affairs. Am J Gastroenterol 2000;95:3566–3573. doi:10.1111/j.1572-0241.2000.03376.x

    PubMed  CAS  Google Scholar 

  10. D’Amico G, de Franchis R. Upper digestive bleeding in cirrhosis. Posttherapeutic outcome and prognostic indicators. Hepatology 2003;38:599–612. doi:10.1053/jhep.2003.50385

    PubMed  Google Scholar 

  11. Carbonell N, Pauwels A, Serfaty L, Fourdan O, Levy VG, Poupon R. Improved survival after variceal bleeding in patients with cirrhosis over the past two decades. Hepatology 2004;40:652–659. doi:10.1002/hep.20339

    PubMed  Google Scholar 

  12. Moitinho E, Escorsell A, Bandi JC, Salmeron JM, Garcia-Pagan JC, Rodes J, et al. Prognostic value of early measurements of portal pressure in acute variceal bleeding. Gastroenterology 1999;117:626–631. doi:10.1016/S0016-5085(99)70455-5

    PubMed  CAS  Google Scholar 

  13. Groszmann RJ, Garcia-Tsao G, Bosch J, Grace ND, Burroughs AK, Planas R, et al. Portal Hypertension Collaborative Group. Betablockers to prevent gastroesophageal varices in patients with cirrhosis. N Engl J Med 2005;353:2254–2261. doi:10.1056/NEJMoa044456

    PubMed  CAS  Google Scholar 

  14. D’Amico G, Morabito A. Noninvasive markers of esophageal varices: another round, not the last. Hepatology 2004;39:30–34. doi:10.1002/hep.20018

    PubMed  Google Scholar 

  15. Eisen GM, Eliakim R, Zaman A, Schwartz J, Faigel D, Rondonotti E, et al. The accuracy of PillCam ESO capsule endoscopy versus conventional upper endoscopy for the diagnosis of esophageal varices: a prospective three-center pilot study. Endoscopy 2006;38:31–35. doi:10.1055/s-2005-921189

    PubMed  CAS  Google Scholar 

  16. Lapalus MG, Dumortier J, Fumex F, Roman S, Lot M, Prost B, et al. Esophageal capsule endoscopy versus esophagogastroduodenoscopy for evaluating portal hypertension: a prospective comparative study of performance and tolerance. Endoscopy 2006;38:36–41. doi:10.1055/s-2006-924975

    PubMed  Google Scholar 

  17. Reliability of endoscopy in the assessment of variceal features: the Italian Liver Cirrhosis Project. J Hepatol 1987;4:93–98. doi:10.1016/S0168-8278(87)80015-6

  18. Sarin S, Lamba GS, Kumar M, Misra A, Murthy NS. Comparison of endoscopic ligation and propranolol for the primary prevention of variceal bleeding. N Engl J Med 1999;340:988–993. doi:10.1056/NEJM199904013401302

    PubMed  CAS  Google Scholar 

  19. Merli M, Nicolini G, Angeloni S, Rinaldi V, De Santis A, Merkel C, et al. Incidence and natural history of small esophageal varices in cirrhotic patients. J Hepatol 2003;38:266–272. doi:10.1016/S0168-8278(02)00420-8

    PubMed  Google Scholar 

  20. Conn HO, Grace ND, Bosch J, Groszmann J, Rodes J, Wright SC, et al. Propranolol in the prevention of the first hemorrhage from esophagogastric varices: a multicenter, randomized clinical trial. Hepatology 1991;13:902–912

    PubMed  CAS  Google Scholar 

  21. The PROVA Study Group. Prophylaxis of first hemorrhage from esophageal varices by sclerotherapy, propranolol or both in cirrhotic patients. A randomized multicenter trial. Hepatology 1991;14:1016–1024

    Google Scholar 

  22. Angelico M, Carli L, Piat C, Gentile S, Capocaccia L. Effects of isosorbide-5-mononitrate compared with propranolol on first bleeding and long-term survival in cirrhosis. Gastroenterology 1997;113:1632–1639. doi:10.1053/gast.1997.v113.pm9352866

    PubMed  CAS  Google Scholar 

  23. Garcia-Pagan JC, Villanueva C, Vila MC, Albillos A, Genesca J, Ruiz del Arbol L, et al. Mononitrato Varices Esofagicas: isosorbide mononitrate in the prevention of first variceal bleed in patients who cannot receive beta-blockers. Gastroenterology 2001;121:908–914. doi:10.1053/gast.2001.27993

    PubMed  CAS  Google Scholar 

  24. Merkel C, Marin R, Sacerdoti D, Donada C, Cavallarin G, Torboli P, et al. Long-term results of a clinical trial of nadolol with or without isosorbide mononitrate for primary prophylaxis of variceal bleeding in cirrhosis. Hepatology 2000;31:324–329. doi:10.1002/hep.510310210

    PubMed  CAS  Google Scholar 

  25. Cales P, Oberti F, Payen JL, Naveau S, Guyader D, Blanc P, et al. Lack of effect of propranolol in the prevention of large oesophageal varices in patients with cirrhosis: a randomized trial. French-speaking Club for the study of portal hypertension. Eur J Gastroenterol Hepatol 1999;11:741–745. doi:10.1097/00042737-199907000-00011

    PubMed  CAS  Google Scholar 

  26. Merkel C, Marin R, Angeli P, Zanella P, Felder M, Bernardinello E, et al. A placebo-controlled clinical trial of nadolol in the prophylaxis of growth of small esophageal varices in cirrhosis. Gastroenterology 2004;127:476–484. doi:10.1053/j.gastro.2004.05.004

    PubMed  CAS  Google Scholar 

  27. Staritz M, Poralla T, Meyer zum Büschenfelde KH. Intravascular oesophageal variceal pressure (IOVP) assessed by endoscopic fine needle puncture under basal conditions, Valsalva’s manoeuvre and after glyceryltrinitrate application. Gut 1985;26(5):525–530. doi:10.1136/gut.26.5.525

    PubMed  CAS  Google Scholar 

  28. Kravetz D, Romero G, Argonz J, Guevara M, Suarez A, Abecasis R, et al. Total volume paracentesis decreases variceal pressure, size, and variceal wall tension in cirrhotic patients. Hepatology 1997;25(1):59–62. doi:10.1002/hep.510250111

    PubMed  CAS  Google Scholar 

  29. Luca A, Feu F, García-Pagán JC, Jiménez W, Arroyo V, Bosch J, et al. Favorable effects of total paracentesis on splanchnic hemodynamics in cirrhotic patients with tense ascites. Hepatology 1994;20(1 Pt 1):30–33

    PubMed  CAS  Google Scholar 

  30. Escorsell A, Ginès A, Llach J, García-Pagán JC, Bordas JM, Bosch J, et al. Increasing intra-abdominal pressure increases pressure, volume, and wall tension in esophageal varices. Hepatology 2002;36(4 Pt 1):936–940

    PubMed  Google Scholar 

  31. Luca A, Cirera I, García-Pagán JC, Feu F, Pizcueta P, Bosch J, et al. Hemodynamic effects of acute changes in intra-abdominal pressure in patients with cirrhosis. Gastroenterology 1993;104(1):222–227

    PubMed  CAS  Google Scholar 

  32. García-Pagàn JC, Santos C, Barberá JA, Luca A, Roca J, Rodriguez-Roisin R, et al. Physical exercise increases portal pressure in patients with cirrhosis and portal hypertension. Gastroenterology 1996;111(5):1300–1306. doi:10.1053/gast.1996.v111.pm8898644

    PubMed  Google Scholar 

  33. Bandi JC, García-Pagán JC, Escorsell A, François E, Moitinho E, Rodés J, et al. Effects of propranolol on the hepatic hemodynamic response to physical exercise in patients with cirrhosis. Hepatology 1998;28(3):677–682. doi:10.1002/hep.510280312

    PubMed  CAS  Google Scholar 

  34. Feu F, Bordas JM, Luca A, García-Pagán JC, Escorsell A, Bosch J, et al. Reduction of variceal pressure by propranolol: comparison of the effects on portal pressure and azygos blood flow in patients with cirrhosis. Hepatology 1993;18(5):1082–1089

    PubMed  CAS  Google Scholar 

  35. Luca A, García-Pagán JC, Bosch J, Feu F, Caballería J, Groszmann RJ, et al. Effects of ethanol consumption on hepatic hemodynamics in patients with alcoholic cirrhosis. Gastroenterology 1997;112(4):1284–1289. doi:10.1016/S0016-5085(97)70142-2

    PubMed  CAS  Google Scholar 

  36. Ready JB, Hossack KF, Rector WG Jr. The effects of ethanol administration on portal pressure and gastroesophageal collateral blood flow in patients with alcoholic cirrhosis. Hepatology 1990;11(4):674–677. doi:10.1002/hep.1840110422

    PubMed  CAS  Google Scholar 

  37. Albillos A, Bañares R, González M, Catalina MV, Pastor O, Gonzalez R, et al. The extent of the collateral circulation influences the postprandial increase in portal pressure in patients with cirrhosis. Gut 2007;56(2):259–264. doi:10.1136/gut.2006.095240

    PubMed  CAS  Google Scholar 

  38. Albillos A, Rossi I, Iborra J, Lledó JL, Calleja JL, Barrios C, et al. Octreotide prevents postprandial splanchnic hyperemia in patients with portal hypertension. J Hepatol 1994;21(1):88–94. doi:10.1016/S0168-8278(94)80142-8

    PubMed  CAS  Google Scholar 

  39. Ludwig D, Schädel S, Brüning A, Schiefer B, Stange EF. 48-hour hemodynamic effects of octreotide on postprandial splanchnic hyperemia in patients with liver cirrhosis and portal hypertension: double-blind, placebo-controlled study. Dig Dis Sci 2000;45(5):1019–1027. doi:10.1023/A:1005553914878

    PubMed  CAS  Google Scholar 

  40. Buonamico P, Sabbá C, Garcia-Tsao G, Berardi E, Antonica G, Ferraioli G, et al. Octreotide blunts postprandial splanchnic hyperemia in cirrhotic patients: a double-blind randomized echo-Doppler study. Hepatology 1995;21(1):134–139

    PubMed  CAS  Google Scholar 

  41. de Lédinghen V, Mannant PR, Foucher J, Perault MC, Barrioz T, Ingrand P, et al. Non-steroidal anti-inflammatory drugs and variceal bleeding: a case-control study. J Hepatol 1996;24(5):570–573. doi:10.1016/S0168-8278(96)80142-5

    PubMed  Google Scholar 

  42. de Lédinghen V, Heresbach D, Fourdan O, Bernard P, Liebaert-Bories MP, Nousbaum JB, et al. Anti-inflammatory drugs and variceal bleeding: a case-control study. Gut 1999;44(2):270–273

    PubMed  Google Scholar 

  43. Colle I, De Vriese AS, Van Vlierberghe H, Lameire NH, DeVos M. Systemic and splanchnic haemodynamic effects of sildenafil in an in vivo animal model of cirrhosis support for a risk in cirrhotic patients. Liver Int 2004;24(1):63–68. doi:10.1111/j.1478-3231.2004.00892.x

    PubMed  CAS  Google Scholar 

  44. Poynard T, Cales P, Pasta L, Ideo G, Pascal JP, Pagliaro L, et al. Betaadrenergic-antagonist drugs in the prevention of gastrointestinal bleeding in patients with cirrhosis and esophageal varices. An analysis of data and prognostic factors in 589 patients from four randomized clinical trials, Franco-Italian Multicenter Study Group. N Engl J Med 1991;324:1532–1538

    PubMed  CAS  Google Scholar 

  45. Pagliaro L, D’Amico G, Sorensen TI, Lebrec D, Burroughs AK, Morabito A, et al. Prevention of first bleeding in cirrhosis. A meta-analysis of randomized trials of nonsurgical treatment. Ann Intern Med 1992;117:59–70

    PubMed  CAS  Google Scholar 

  46. D’Amico G, Pagliaro L, Bosch J. Pharmacological treatment of portal hypertension: an evidence-based approach. Semin Liver Dis 1999;19:475–505

    PubMed  CAS  Google Scholar 

  47. Merkel C, Bolognesi M, Sacerdoti D, et al. The hemodynamic response to medical treatment of portal hypertension as a predictor of clinical effectiveness in the primary prophylaxis of variceal bleeding in cirrhosis. Hepatology 2000;32:930–934. doi:10.1053/jhep.2000.19322

    PubMed  CAS  Google Scholar 

  48. Bosch J. A la carte or menu fixed: improving pharmacologic therapy of portal hypertension. Hepatology 2002;36:1330–1332

    PubMed  Google Scholar 

  49. Feu F, Garcia-Pagan JC, Bosch J, Luca A, Teres J, Escorsell A, et al. Relation between portal pressure response to pharmacotherapy and risk of recurrent variceal haemorrhage in patients with cirrhosis. Lancet 1995;346:1056–1059. doi:10.1016/S0140-6736(95)91740-3

    PubMed  CAS  Google Scholar 

  50. Villanueva C, Balanzo J, Novella MT, Soriano G, Sainz S, Torras X, et al. Nadolol plus isosorbide mononitrate compared with sclerotherapy for the prevention of variceal rebleeding. N Engl J Med 1996;334:1624–1629. doi:10.1056/NEJM199606203342502

    PubMed  CAS  Google Scholar 

  51. Bureau C, Peron JM, Alric L, Morales J, Sanchez J, Barange K, et al. “A la carte” treatment of portal hypertension: adapting medical therapy to hemodynamic response for the prevention of bleeding. Hepatology 2002;36:1361–1366

    PubMed  Google Scholar 

  52. Aracil C, Lopez-Balaguer JM, Monfort D, Piqueras M, Gonzalez B, Minana J, et al. Hemodynamic response to beta-blockers and prediction of clinical efficacy in the primary prophylaxis of variceal bleeding in patients with cirrhosis. Hepatology 2003;38:296A. abstract doi:10.1016/S0270-9139(03)80334-8

  53. Sarin SK, Guptan RC, Jain AK, Sundaram KR. A randomized controlled trial of endoscopic variceal band ligation for primary prophylaxis of variceal bleeding. Eur J Gastroenterol Hepatol 1996;8:337–342. doi:10.1097/00042737-199604000-00010

    PubMed  CAS  Google Scholar 

  54. Lo GH, Chen WC, Chen MH, Lin CP, Lo CC, Hsu PI, et al. Endoscopic ligation vs. nadolol in the prevention of first variceal bleeding in patients with cirrhosis. Gastrointest Endosc 2004;59:333–338. doi:10.1016/S0016-5107(03)02819-0

    PubMed  Google Scholar 

  55. Schepke M, Kleber G, Nurnberg D, Willert J, Koch L, Veltzke-Schlieker W, et al. Ligation versus propranolol for the primary prophylaxis of variceal bleeding in cirrhosis. Hepatology 2004;40:65–72. doi:10.1002/hep.20284

    PubMed  Google Scholar 

  56. Lay CS, Tsai YT, Lee FY, Lai YL, Yu CJ, Chen CB, et al. Endoscopic variceal ligation versus propranolol in prophylaxis of first variceal bleeding in patients with cirrhosis. J Gastroenterol Hepatol 2006;21:413–419. doi:10.1111/j.1440-1746.2005.04071.x

    PubMed  Google Scholar 

  57. Jutabha R, Jensen DM, Martin P, Savides T, Han SH, Gornbein J. Randomized study comparing banding and propranolol to prevent initial variceal hemorrhage in cirrhotics with high-risk esophageal varices. Gastroenterology 2005;128:870–881. doi:10.1053/j.gastro.2005.01.047

    PubMed  CAS  Google Scholar 

  58. Imperiale TF, Chalasani N. A meta-analysis of endoscopic variceal ligation for primary prophylaxis of oesophageal variceal bleeding. Hepatology 2001;33:802–807. doi:10.1053/jhep.2001.23054

    PubMed  CAS  Google Scholar 

  59. Teran JC, Imperiale TF, Mullen KD, Tavill AS, McCullough AJ. Primary prophylaxis of variceal bleeding in cirrhosis: a cost-effectiveness analysis. Gastroenterology 1997;112:473–482. doi:10.1053/gast.1997.v112.pm9024301

    PubMed  CAS  Google Scholar 

  60. Shaheen NJ, Stuart E, Scmidt SM, Mitchell K, Fried M, et al. Pantoprazole reduces the size of post banding ulcers after variceal band ligation: a randomized controlled trial. Hepatology 2005;41:588–594. doi:10.1002/hep.20593

    PubMed  CAS  Google Scholar 

  61. Yoshida H, Mamada Y, Taniai N, Yamamoto K, Kawano Y, Mizuguchi Y, et al. A randomized control trial of bi-monthly versus bi-weekly endoscopic variceal ligation of oesophageal varices. Am J Gastroenterol 2005;100(9):2005–2009. doi:10.1111/j.1572-0241.2005.41864.x

    PubMed  Google Scholar 

  62. De Franchis R. Endoscopy critics vs endoscopy enthusiasts for primary prophylaxis of variceal bleeding. Hepatology 2006;43:24–26. doi:10.1002/hep.21026

    PubMed  Google Scholar 

  63. Chen CY, Sheu MZ, Su SY. Prophylactic endoscopic variceal ligation (EVL) with multiple band ligator for esophageal varices. Gastroenterology 1998;114(Suppl):A1224. abstract

    Google Scholar 

  64. De BK, Ghoshal UK, Das T, Santra A, Biswas PK. Endoscopic variceal ligation for primary prophylaxis of oesophageal variceal bleed: preliminary report of a randomized controlled trial. J Gastroenterol Hepatol 1999;14:220–224. doi:10.1046/j.1440-1746.1999.01800.x

    PubMed  CAS  Google Scholar 

  65. Lui HF, Stanley AJ, Forrest EH, Jalan R, Hislop WS, Mills PR, et al. Primary prophylaxis of variceal haemorrhage: a randomized controlled trial comparing band ligation, propranolol, and isosorbide mononitrate. Gastroenterology 2002;123:735–744. doi:10.1053/gast.2002.35385

    PubMed  CAS  Google Scholar 

  66. Thuluvath PJ, Maheshwari A, Jagannath S, Arepally A. A randomized controlled trial of β-blockers versus endoscopic band ligation for primary prophylaxis: a large sample size is required to show a difference in bleeding rates. Dig Dis Sci 2005;50:407–410. doi:10.1007/s10620-005-1619-8

    PubMed  CAS  Google Scholar 

  67. Psilopoulos D, Galanis P, Goulas S, Papanikolaou IS, Elefsiniotis I, Liatsos C, et al. Endoscopic variceal ligation vs. propranolol for prevention of first variceal bleeding: a randomized controlled trial. Eur J Gastroenterol Hepatol 2005;17(10):1111–1117. doi:10.1097/00042737-200510000-00016

    PubMed  Google Scholar 

  68. Khuroo MS, Khuroo NS, Farahat KLC, Khuroo YS, Sofi AA, Dahab ST. Meta-analysis: endoscopic variceal ligation for primary prophylaxis of oesophageal variceal bleeding. Aliment Pharmacol Ther 2005;21:347–361. doi:10.1111/j.1365-2036.2005.02346.x

    PubMed  CAS  Google Scholar 

  69. Sarin SK, Wadhawan M, Agarwal SR, Tyagi P, Sharma BC. Endoscopic variceal ligation plus propranolol versus endoscopic variceal ligation alone in primary prophylaxis of variceal bleeding. Am J Gastroenterol 2005;100:797–804. doi:10.1111/j.1572-0241.2005.40468.x

    PubMed  Google Scholar 

  70. Angelico M, Carli L, Piat C, Gentile S, Rinaldi V, Bologna E, et al. Isosorbide-5-mononitrate versus propranolol in the prevention of first bleeding in cirrhosis. Gastroenterology 1993;104:1460–1465

    PubMed  CAS  Google Scholar 

  71. Groszmann RJ. Beta-adrenergic blockers and nitrovasodilators for the treatment of portal hypertension: the good, the bad, the ugly. Gastroenterology 1998;113:1794–1797. doi:10.1053/gast.1997.v113.agast971131794

    Google Scholar 

  72. Borroni G, Salerno F, Cazzaniga M, Bissoli F, Lorenzano E, Maggi A, et al. Nadolol is superior to isosorbide mononitrate for the prevention of the first variceal bleeding in cirrhotic patients with ascites. J Hepatol 2002;37:315–321. doi:10.1016/S0168-8278(02)00174-5

    PubMed  CAS  Google Scholar 

  73. Merkel C, Marin R, Enzo E, Donada C, Cavallarin G, Torboli P, et al. Randomised trial of nadolol alone or with isosorbide mononitrate for primary prophylaxis of variceal bleeding in cirrhosis. Lancet 1996;348:1677–1681. doi:10.1016/S0140-6736(96)05406-2

    PubMed  CAS  Google Scholar 

  74. Garcia-Pagan JC, Morillas R, Banares R, Albillos A, Villanueva C, Vila C, et al. Propranolol plus placebo versus propranolol plus isosorbide-5-mononitrate in the prevention of a first variceal bleed: a double-blind RCT. Hepatology 2003;37:1260–1266. doi:10.1053/jhep.2003.50211

    PubMed  CAS  Google Scholar 

  75. D’Amico G, Pasta L, Politi F, Vizzini G, Traina M, Caltagirone M, et al. Isosorbide mononitrate with nadolol compared to nadolol alone for prevention of the first bleeding in cirrhosis. A double-blind placebo-controlled randomized trial. Gastroenterol Int 2002;15:40–50

    Google Scholar 

  76. Sarin SK, Lahoti D, Saxena SP, Murthy NS, Makwana UK. Prevalence, classification and natural history of gastric varices: a long-term follow-up study in 568 portal hypertension patients. Hepatology 1992;16:1343–1349. doi:10.1002/hep.1840160607

    PubMed  CAS  Google Scholar 

  77. Sarin SK, Primignani M, Agarwal SR. Gastric varices. In: De Franchis R, editor. Proceedings of the third Baveno international consensus workshop on definitions, methodology and therapeutic strategies. Oxford: Blackwell Science; 2001. p. 76–96

  78. Hosking SW, Johnson AG. Gastric varices: a proposed classification leading to management. Br J Surg 1988;75:195–196. doi:10.1002/bjs.1800750303

    PubMed  CAS  Google Scholar 

  79. Kim T, Shijo H, Kokawa H, Tokumitsu H, Kubara K, Ota K, et al. Risk factors for hemorrhage from gastric fundal varices. Hepatology 1997;25:307–312. doi:10.1002/hep.510250209

    PubMed  CAS  Google Scholar 

  80. Hashizume M, Kitano S, Yamaga H, Koyanagi N, Sugimachi K. Endoscopic classification of gastric varices. Gastrointest Endosc 1990;36:276–280

    PubMed  CAS  Google Scholar 

  81. Arakawa M, Masuzaki T, Okuda K. Pathology of fundic varices of the stomach and rupture. J Gastroenterol Hepatol 2002;17:1064–1069. doi:10.1046/j.1440-1746.2002.02855.x

    PubMed  Google Scholar 

  82. D’Amico G, Pagliaro L, Bosch J. The treatment of portal hypertension: a meta-analytic review. Hepatology 1995;22:332–354

    PubMed  CAS  Google Scholar 

  83. Ramond MJ, Valla D, Mosnier JF, Degott C, Bernuau J, Rueff B, et al. Successful endoscopic obturation of gastric varices with butyl cyanoacrylate. Hepatology 1989;10:488–493. doi:10.1002/hep.1840100415

    PubMed  CAS  Google Scholar 

  84. Oho K, Iwao T, Sumino M, Toyonaga A, Tanikawa K. Ethanolamine oleate versus butyl cyanoacrylate for bleeding gastric varices: a nonrandomized study. Endoscopy 1995;27:349–354

    PubMed  CAS  Google Scholar 

  85. Sarin SK, Jain AK, Jain M, Gupta R. A randomized controlled trial of cyanoacrylate versus alcohol injection in patients with isolated fundic varices. Am J Gastroenterol 2002;97:1010–1015. doi:10.1111/j.1572-0241.2002.05622.x

    PubMed  CAS  Google Scholar 

  86. Rengstorff DS, Binmoeller KF. A pilot study of 2-octyl-cyanoacrylate injection for treatment of gastric fundal varices in humans. Gastrointest Endosc 2004;59:553–558. doi:10.1016/S0016-5107(03)02865-7

    PubMed  Google Scholar 

  87. Roesch W, Rexroth G. Pulmonary, cerebral and coronary emboli during bucrylate injection of bleeding fundic varices. Endoscopy 1998;30:S89–S90

    PubMed  CAS  Google Scholar 

  88. See A, Florent C, Lamy P, Levy VG, Bouvry M. Cerebrovascular accidents after endoscopic obturation of oesophageal varices with isobutyl-2-cyanoacrylate in 2 patients. Gastroenterol Clin Biol 1986;10:604–607

    PubMed  CAS  Google Scholar 

  89. Kanagawa H, Mima H, Kouyama H, Gotoh K, Uchida T, Okuda K. Treatment of gastric fundal varices by balloon-occluded retrograde transvenous obliteration. J Gastroenterol Hepatol 1996;11:51–58. doi:10.1111/j.1440-1746.1996.tb00010.x

    PubMed  CAS  Google Scholar 

  90. Hamamoto N, Matsumoto A, Nomura T, Kayazawa M, Hirata I, Morikawa H, et al. Treatment of gastric fundal varices by balloon endoscopic sclerotherapy. Gastrointest Endosc 1999;49:115–118. doi:10.1016/S0016-5107(99)70459-1

    PubMed  CAS  Google Scholar 

  91. Shiba M, Higuchi K, Nakamura K, Itani A, Kuga T, Okazaki H, et al. Efficacy and safety of balloon-occluded endoscopic injection for sclerotherapy as a prophylactic treatment for high-risk gastric varices: a prospective, randomized, comparative clinical trial. Gastrointest Endosc 2002;56:522–528. doi:10.1016/S0016-5107(02)70437-9

    PubMed  Google Scholar 

  92. Matsumoto A, Hamamoto N, Kayazawa M. Balloon endoscopic sclerotherapy, a novel treatment for high-risk gastric fundal varices: a pilot study. Gastroenterology 1999;117:515–516. doi:10.1053/gast.1999.0029900515

    PubMed  CAS  Google Scholar 

  93. Fukuda T, Hirota S, Sugimura K. Long-term results of balloon occluded retrograde transvenous obliteration for the treatment of gastric varices and hepatic encephalopathy. J Vasc Interv Radiol 2001;12:327–336. doi:10.1016/S1051-0443(07)61912-5

    PubMed  CAS  Google Scholar 

  94. Cho SK, Shin SW, Lee IH, Do YS, Choo SW, Park KB, et al. Balloon-occluded retrograde transvenous obliteration of gastric varices: outcomes and complications in 49 patients. AJR Am J Roentgenol 2007;189(6):W365–W372. doi:10.2214/AJR.07.2266

    PubMed  Google Scholar 

  95. Arai H, Abe T, Takagi H, Mori M. Efficacy of balloon-occluded retrograde transvenous obliteration, percutaneous transhepatic obliteration and combined techniques for the management of gastric fundal varices. World J Gastroenterol 2006;12(24):3866–3873

    PubMed  Google Scholar 

  96. Mittal SK, Kalra KK, Aggarwal V. Diagnostic upper GI endoscopy for hematemesis in children: experience from a pediatric gastroenterology centre in north India. Indian J Pediatr 1994;61:651–654. doi:10.1007/BF02751973

    PubMed  CAS  Google Scholar 

  97. Yachha SK, Khanduri A, Sharma BC, Kumar M. Gastrointestinal bleeding in children. J Gastroenterol Hepatol 1996;11:903–907

    PubMed  CAS  Google Scholar 

  98. Cox K, Ament ME. Upper gastrointestinal bleeding in children and adolescents. Pediatrics 1979;63:408–413

    PubMed  CAS  Google Scholar 

  99. Dilawari JB, Chawla YK. Extrahepatic portal venous obstruction. Gut 1988;29:554–555. doi:10.1136/gut.29.4.554

    PubMed  CAS  Google Scholar 

  100. Bernard O, Alvarez F, Brunelle F, Hadchouel P, Alagille D. Portal hypertension in children. Clin Gastroenterol 1985;14:33–55

    PubMed  CAS  Google Scholar 

  101. Howard ER, Stamatakis JD, Mowat AP. Management of esophageal varices in children by injection sclerotherapy. J Pediatr Surg 1984;19:2–5

    PubMed  CAS  Google Scholar 

  102. Howard ER, Stringer MD, Mowat AP. Assessment of injection sclerotherapy in the management of 152 children with esophageal varices. Br J Surg 1988;75:404–408

    PubMed  CAS  Google Scholar 

  103. Goncalves MEP, Cardoso SR, Maksoud JG. Prophylactic sclerotherapy in children with esophageal varices: long-term results of a controlled prospective randomized trial. J Pediatr Surg 2000;35:401–405

    PubMed  CAS  Google Scholar 

  104. Arora NK, Lodha R, Gulati S, et al. Portal hypertension in north Indian children. Indian J Pediatr 1998;65:585–591

    PubMed  CAS  Google Scholar 

  105. Celinska-Cedro D, Teisseyre M, Woynarowski M, et al. Endoscopic ligation of esophageal varices for prophylaxis of first bleeding in children and adolescents with portal hypertension: preliminary results of a prospective study. J Pediatr Surg 2003;38:1008–1011

    PubMed  Google Scholar 

  106. Shashidhar H, Langhans N, Grand RJ. Propanolol in prevention of portal hypertensive hemorrhage in children: a pilot study. J Pediatr Gastroenterol Nutr 1999;29:12–17

    PubMed  CAS  Google Scholar 

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  1. Department of Gastroenterology, G B Pant Hospital, Affiliated to University of Delhi, New Delhi, 110 002, India

    Shiv Kumar Sarin, Ashish Kumar, Peter W. Angus, Sanjay Saran Baijal, Yogesh Kumar Chawla, Radha Krishna Dhiman, H. Janaka de Silva, Saeed Hamid, Shozo Hirota, Ming-Chih Hou, Wasim Jafri, Mobin Khan, Laurentius A. Lesmana, Hock F. Lui, Veena Malhotra, Hitoshi Maruyama, Debendranath Guha Mazumder, Masao Omata, Ujjal Poddar, Amrinder S. Puri, Praveen Sharma, Huma Qureshi, Rizvi Moattar Raza, Peush Sahni, Puja Sakhuja, Mohammad Salih, Amal Santra, Barjesh Chander Sharma, Hasnain Ali Shah, Gamal Shiha & Jose Sollano

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APASL Working Party on Portal Hypertension

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Correspondence to Shiv Kumar Sarin.

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Sarin, S.K., Kumar, A., Angus, P.W. et al. Primary prophylaxis of gastroesophageal variceal bleeding: consensus recommendations of the Asian Pacific Association for the Study of the Liver. Hepatol Int 2, 429–439 (2008). https://doi.org/10.1007/s12072-008-9096-8

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