Advertisement

Prevention of the First Gastrointestinal Bleeding

  • Didier Lebrec
  • Jean-Pierre Benhamou

Abstract

Esophageal variceal bleeding may occur in patients with portal hypertension who have developed superior portosystemic circulation. Thus, the ideal way to prevent bleeding esophageal varices is to avoid the development of portal hypertension or esophageal varices themselves. Alcohol abstinence and hepatitis vaccines are the best measures of prevention of the development of portal hypertension; however, this syndrome may occur for other reasons. In addition to antiviral drugs, other substances may also limit the development of liver disease and thus prevent portal hypertension and its complications. For example, we recently showed that chronic oral administration of ursodeoxycholic acid or colchicine in rats with bile duct ligation reduces the development of secondary biliary cirrhosis when compared to rats receiving a placebo [1,2]. Accordingly, portal intrahepatic resistance was lower in treated rats than in the placebo group. In this experimental study, the degree of portal hypertension was significantly lower in the rats receiving ursodesoxycholic acid or colchicine than in the control rats. Similarly, preliminary results showed that the development of portosystemic shunts was less severe in mice with induced murine schistosomiasis receiving propranolol than in mice receiving a placebo [3]. Since these different pharmacologic treatments have not yet been evaluated in patients with chronic liver disease, clinical studies are obviously needed.

Keywords

Portal Hypertension Gastrointestinal Bleeding Cirrhotic Patient Esophageal Varix Variceal Bleeding 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Poo JL, Erlinger S, Feldmann G, Dumont M, Braillon A, Lebrec D (1989) Uesodeoxycholic acid prevents biliary cirrhosis and the hyperkinetic circulation induced by bile duct ligation in the rat (abstract). Hepatology 10: 584Google Scholar
  2. 2.
    Poo JL, Feldmann G, Cailmail S, Gaudin C, Braillon A, Lebrec D (1989) Colchicine reduces the development of portal hypertension and liver dysfunctions induced by bile duct ligation in the rat (abstract). Hepatology 10: 713Google Scholar
  3. 3.
    Sarin SK, Stadeker M, Groszmann RJ (1989) Propranolol prevents the development of portal-systemic shunting in chronic murine schistosomiasis (abstract). Gastroenterology 96: A654Google Scholar
  4. 4.
    Conn HO, Lindenmuth WW, May CL, Rambsy GR (1972) Prophylactic portacaval anastomosis. A tale of two studies. Medicine 51: 27–40PubMedCrossRefGoogle Scholar
  5. 5.
    Jackson FC, Perin EB, Smith AG, Dagradi AE, Nadal HM (1968) A clinical investigation of the portocaval shunt. II. Survival analysis of the prophylactic operation. Am J Surg 115: 22–42PubMedCrossRefGoogle Scholar
  6. 6.
    Resnick RH, Chalmers TC, Ishihara A, Garceau JA, Callow AD, Schimmel EM, O’Hara ET, the Boston Inter-Hospital Liver Group (1969) A controlled study of the prophylactic portacaval shunts. A final report. Ann Int Med 70: 675–688PubMedCrossRefGoogle Scholar
  7. 7.
    Inokuchi K (1984) Prophylactic portal nonde-compression surgery in patients with esophageal varices. Ann Surg 200: 61–65PubMedCrossRefGoogle Scholar
  8. 8.
    Rector WG, Reynolds TB (1985) Risk factors for haemorrhage from oesophageal varices and acute gastric erosions. Clin Gastroenterol 14: 139–153PubMedGoogle Scholar
  9. 9.
    Baker LA, Smith C, Lieberman G (1959) The natural history of esophageal varices. A study of 115 cirrhotic patients in whom varices were diagnosed prior to bleeding. Am J Med 26: 228–237PubMedCrossRefGoogle Scholar
  10. 10.
    Beppu K, Inokuchi K, Koyanagi N, Nakayam S, Sakata H, Kitano S, Kobayashi M (1981) Prediction of variceal hemorrhage by esophageal endoscopy. Gastrointest Endosc 27: 213–218PubMedCrossRefGoogle Scholar
  11. 11.
    The North Italian Endoscopic Club for the Study and Treatment of Esophageal Varices (1988) Prediction of the first variceal hemorrhage in patients with cirrhosis of the liver and esophageal varices. A prospective multicenter study. N Engl J Med 319: 983–989CrossRefGoogle Scholar
  12. 12.
    Sauerbruch T, Wotzka R, Köpcke W, Härlin M, Heldwein W, Bayerdörffer E, Sander R, Ansari H, Starz I, Paumgartner G (1988) Prophylactic sclerotherapy before the first episode of variceal hemorrhage in patients with cirrhosis. N Engl J Med 319: 8–15PubMedCrossRefGoogle Scholar
  13. 13.
    Sayegh R, Bernuau J, Rueff B, Benhamou JP (1985) The risk of early recurrence of gastrointestinal bleeding is related to the degree of liver failure (abstract). J Hepatol 1: S127Google Scholar
  14. 14.
    Poynard T, Lebrec D, Hillon P, Sayegh R, Bernuau J, Naveau S, Chaput JC, Klepping C, Rueff B, Benhamou JP (1987) Propranolol for prevention of recurrent gastrointestinal bleeding in patients with cirrhosis: A prospective study of factor associated with rebleeding. Hepatology 7: 447–451PubMedCrossRefGoogle Scholar
  15. 15.
    Macdougall BRD, Williams R (1983) A controlled clinical trial of cimetidine in the recurrence of variceal hemorrhage: Implications about the pathogenesis of hemorrhage. Hepatology 3: 69–73PubMedCrossRefGoogle Scholar
  16. 16.
    Garcia-Tsao G, Groszmann RJ, Fisher RL, Conn HO, Atterbury CE, Glickman M (1985) Portal pressure, presence of gastroesophageal varices and variceal bleeding. Hepatology 5: 419–424PubMedCrossRefGoogle Scholar
  17. 17.
    Lebrec D, de Fleury P, Rueff B, Nahum H, Benhamou JP (1980) Portal hypertension, size of esophageal varices, and risk of gastrointestinal bleeding in alcoholic cirrhosis. Gastroenterology 79: 1139–1144PubMedGoogle Scholar
  18. 18.
    Lin HC, Tsai YT, Lee FY, Chang TT, Wang SS, Lay CS, Lee SD, Lo KJ (1989) Comparison between portal vein pressure and wedged hepatic vein pressure in hepatitis B-related cirrhosis. J Hepatol 9: 326–330PubMedCrossRefGoogle Scholar
  19. 19.
    Gaiani S, LiBassi S, Siringo S, Zironi G, Di Febo G, Bolondi L, Barbara L (1989) Relationship between portal venous flow assessed by Doppler US and oesophageal varices in patients with cirrhosis and portal hypertension (abstract). J Hepatol 9 (Suppl 1): S152Google Scholar
  20. 20.
    Calès P, Pascal JP (1988) Histoire naturelle des varices oesophagiennes au cours de la cirrhose (de la naissance à la rupture). Gastroenterol Clin Biol 12: 245–254PubMedGoogle Scholar
  21. 21.
    Christensen E, Fauerholdt L, Schlichting P, Juhl E, Poulsen H, Tygstrup N, Copenhagen Study Group for Liver Diseases(CSL) (1961) Aspects of the natural history of gastrointestinal bleeding in cirrhosis and the effect of prednisone. Gastroenterology 81: 944–952Google Scholar
  22. 22.
    Calès P, Braillon A, Jiron MI, Lebrec D (1984) Superior portosystemic collateral circulation estimated by azygos blood flow in patients with cirrhosis. Lack of correlation with oesophageal varices and gastrointestinal bleeding. Effect of propranolol. J Hepatol 1: 37–46CrossRefGoogle Scholar
  23. 23.
    Koch H, Henning H, Grimm H, Soehendra N (1986) Prophylactic sclerosing of esophageal varices—Results of a prospective controlled study. Endoscopy 18: 40–43PubMedCrossRefGoogle Scholar
  24. 24.
    Paquet KJ (1982) Prophylactic endoscopic sclerosing treatment of the esophageal wall in varices—a prospective controlled randomized trial. Endoscopy 14: 4–5PubMedCrossRefGoogle Scholar
  25. 25.
    Piai G, Cipolletta L, Claar M, Marone G, Bianco MA, Forte G, Iodice G, Mattera D, Minieri M, Rocco P, Santoro LM, Mazzacca G (1988) Prophylactic sclerotherapy of high-risk esophageal varices: results of a multicentric prospective controlled trial. Hepatology 8: 1495–1500PubMedCrossRefGoogle Scholar
  26. 26.
    Pötzi R, Bauer P, Reichel W, Kerstan E, Renner F, Gangl A (1986) Prophylactic endoscopic sclerotherapy of oesophageal varices in liver cirrhosis. A multicentre prospective controlled randomised trial in Vienna. Gut 30: 873–879CrossRefGoogle Scholar
  27. 27.
    Russo A, Giannone G, Magnano A, Passanisi G, Longo C (1989) Prophylactic sclerotherapy in nonalcoholic liver cirrhosis: Preliminary results of a prospective controlled randomized trial. World J Surg 13: 149–153PubMedCrossRefGoogle Scholar
  28. 28.
    Santangelo WC, Dueno M, Estes BL, Krejs GJ (1988) Prophylactic sclerotherapy of large esophageal varices. N Engl J Med 318: 814–818PubMedCrossRefGoogle Scholar
  29. 29.
    Witzel L, Wolbergs E, Merki H (1985) Prophylactic endoscopic sclerotherapy of oesophageal varices. A prospective controlled study. Lancet I: 773–775CrossRefGoogle Scholar
  30. 30.
    Andréani T, Poupon RE, Balkau B, Trinchet JC, Grangé JD, Peigney N, Poupon R (1990) Prophylaxie de la première hémorragie digestive chez le cirrhotique: Etude prospective randomisée comparant sclérise endoscopique, propranolol et placebo (abstract). Gastroenterol Clin Biol 14 (Suppl 2): A5Google Scholar
  31. 31.
    De Franchis R, the North Italian Endoscopic Club for the Study and Treatment of Esophageal Varices (1989) Prophylactic sclerotherapy (ST) in highrisk cirrhotics selected by endoscopie criterial: Long term-follow-up of a multicenter randomized controlled trial (abstract). J Hepatol 9 (Suppl 1): S24CrossRefGoogle Scholar
  32. 32.
    Duhamel O, Carle JP, Daures JP, Boyer A, Cassan P, Dubois A, Raffanel C, Balmes JL, Nalet B, Vaucher E, Blanc F, Bauret P, Parelon G, Michel H (1990) Sclèrothèrapie prophylactique des ruptures de varices oesophagiennes chez le cirrhotique (Etude contrôlée multicentrique à propos de 116 malades) (abstract). Gastoenterol Clin Biol 14 (Suppl 2): A186Google Scholar
  33. 33.
    Fleig WE, Stange EF, Wördehoff D, Jenns H, Preclik G, Nuber R, Rainer K, Ditschuneit H (1988) Prophylactic (PS) therapeutic sclerotherapy (TS) in cirrhotic patients with large esophageal varices and no previous hemorrhage: A randomized clinical trial (abstract). Hepatology 8: 1242Google Scholar
  34. 34.
    Gregory P, Hartigan P, Amodeo D, Baum R, Camara D, Colcher H, Fye C, Gebhard R, Goff J, Kruss D, McPhee M, Meier P, Rankin R, Reichelderfer J, Sonowsky R, Shields D, Silvis S, Weesner R, Winship D, Young H (1987) Prophylactic sclerotherapy for esophageal varices in alcoholic liver disease: Results of a VA cooperative randomized trial (abstract). Gastroenterology 92: 1414Google Scholar
  35. 35.
    Planas R, Boix J, Dominguez M, Abad A, Quer JC, de Léon R, Villagrasa M, Gassull MA (1989) Prophylactic sclerosis of esophageal varices (EV). Prospective trial (abstract). J Hepatol 9 (Suppl 1) S73Google Scholar
  36. 36.
    Triger DR, Johnson AG (1985) Prophylactic sclerotherapy of oesophageal varices: A preliminary report (abstract). Gut 26: A1102–A1103Google Scholar
  37. 37.
    Pagliaro L, Burroughs AK, Sorensen TIA, Lebrec D, Morabito A, D’Amico G, Tiné F (1989) Therapeutic controversies and randomised controlled trials (RCTs): Prevention of bleeding rebleeding cirrhosis. Gastroenterol Int 2: 71–84Google Scholar
  38. 38.
    Idéo G, Bellati G, Fesce E, Grimoldi D (1988) Nadolol can prevent the first gastrointestinal bleeding in cirrhotics: A prospective, randomized study. Hepatology 8: 6–9PubMedCrossRefGoogle Scholar
  39. 39.
    Lebrec D, Poynard T, Capron JP, Hillon P, Geoffroy P, Roulot D, Chaput JC, Rueff B, Benhamou JP (1988) Nadolol for prophylaxis of gastrointestinal bleeding in patients with cirrhosis. A randomized trial. J Hepatol 7: 118–125PubMedCrossRefGoogle Scholar
  40. 40.
    Pascal JP, Calès P, and a Multicenter Study Group (1987) Propranolol in the prevention of first upper gastrointestinal tract hemorrhage in patients with cirrhosis of the liver and esophageal varices. N Engl J Med 317: 856–861PubMedCrossRefGoogle Scholar
  41. 41.
    The Italian Multicenter Project for Propranolol in Prevention of Bleeding (1989) Propranolol prevents first gastrointestinal bleeding in non-ascitic cirrhotic patients. Final report of a multicenter randomized trial. J Hepatol 9: 75–83Google Scholar
  42. 42.
    Bosch J, Groszmann RJ, Grace N, Navasa M, Mastai R, Conn HO, Rodes J (1988) Propranolol in the prevention of the first hemorrhage from esophageal varices: Results of a randomized, double-blind, cooperative clinical trial (abstract). J Hepatol 7 (Suppl 1): S12Google Scholar
  43. 43.
    Hayes PC, Crichton S, Shepherd AN, Bouchier IAD (1987) Propranolol in chronic liver disease: A controlled trial of its effect and safety over twelve months. Q J Med 65: 823–834PubMedGoogle Scholar
  44. 44.
    Groszmann RJ, Bosch J, Grace N, Conn HO, Garcia-Tsao G, Navassas M, Albert J, Bermann M, Patrick M, Ródes J (1988) Hemodynamic events in a prospective randomized trial of propranolol vs placebo in the prevention of the first variceal hemorrhage (abstract). Hepatology 8: 1242CrossRefGoogle Scholar
  45. 45.
    Valla D, Jiron MI, Poynard T, Braillon A, Lebrec D (1987) Failure of haemodynamic measurements to predict recurrent gastrointestinal bleeding in cirrhotic patients receiving propranolol. J Hepatol 5: 144–148PubMedCrossRefGoogle Scholar
  46. 46.
    Westaby D, Poison RJ, Gimson AES, Hayes PC, Hayllar K, Williams R (1990) A controlled trial of oral propranolol compared with injection sclerotherapy for the long-term management of variceal bleeding. Hepatology 11: 353–359PubMedCrossRefGoogle Scholar

Copyright information

© Springer Japan 1991

Authors and Affiliations

  • Didier Lebrec
  • Jean-Pierre Benhamou
    • 1
  1. 1.Unité de Recherches de Physiopathologie Hépatique, INSERM U24 et Service d’HépatologieHôpital BeaujonClichyFrance

Personalised recommendations