Journal of Hepatology
Volume 48 , Pages S68-S92 , 2008

The management of portal hypertension: Rational basis, available treatments and future options

  • Jaime Bosch

      Affiliations

    • Hepatic Hemodynamic Laboratory, Liver Unit, Institut d’Investigacions Biomediques August Pi i Sunyer (IDIBAPS), University of Barcelona, Hospital Clínic, C.Villarroel 170, 08036 Barcelona, Spain
    • Centro de Investigación, Biomédica en Red de Enfermedades Hepáticas y Digestivas (Ciberehd), Spain
    • Corresponding Author InformationCorresponding author. Fax: +34 93 451 5522.
    • ,
  • Annalisa Berzigotti

      Affiliations

    • Hepatic Hemodynamic Laboratory, Liver Unit, Institut d’Investigacions Biomediques August Pi i Sunyer (IDIBAPS), University of Barcelona, Hospital Clínic, C.Villarroel 170, 08036 Barcelona, Spain
    • Centro de Investigación, Biomédica en Red de Enfermedades Hepáticas y Digestivas (Ciberehd), Spain
    • Centre Diagnostic per la Imatge, Hospital Clinic, Barcelona, Spain
    • ,
  • Juan Carlos Garcia-Pagan

      Affiliations

    • Hepatic Hemodynamic Laboratory, Liver Unit, Institut d’Investigacions Biomediques August Pi i Sunyer (IDIBAPS), University of Barcelona, Hospital Clínic, C.Villarroel 170, 08036 Barcelona, Spain
    • Centro de Investigación, Biomédica en Red de Enfermedades Hepáticas y Digestivas (Ciberehd), Spain
    • ,
  • Juan G. Abraldes

      Affiliations

    • Hepatic Hemodynamic Laboratory, Liver Unit, Institut d’Investigacions Biomediques August Pi i Sunyer (IDIBAPS), University of Barcelona, Hospital Clínic, C.Villarroel 170, 08036 Barcelona, Spain
    • Centro de Investigación, Biomédica en Red de Enfermedades Hepáticas y Digestivas (Ciberehd), Spain

References 

  1. Garcia-Pagan JC, Groszmann RJ, Bosch J. Portal hypertension. In:  Weinstein WM,  Hawkey CJ,  Bosch J editor. Clinical gastroenterology and hepatology. 1st ed.. Philadelphia: Elsevier Mosby; 2005;p. 707–716
  2. Bosch J, Garcia-Pagan JC, Berzigotti A, Abraldes JG. Measurement of portal pressure and its role in the management of chronic liver disease. Semin Liver Dis. 2006;26:348–362
  3. Bosch J, Navasa M, Kravetz D, Pizcueta MP, Garcia-Pagan JC, de Lacy AM, et al. Diagnosis and evaluation of portal hypertension. Z Gastroenterol. 1988;26:8–14
  4. Groszmann RJ, Garcia-Tsao G, Bosch J, Grace ND, Burroughs AK, Planas R, et al. Beta-blockers to prevent gastroesophageal varices in patients with cirrhosis. N Engl J Med. 2005;353:2254–2261
  5. Casado M, Bosch J, Garcia-Pagan JC, Bru C, Banares R, Bandi JC, et al. Clinical events after transjugular intrahepatic portosystemic shunt: correlation with hemodynamic findings. Gastroenterology. 1998;114:1296–1303
  6. Groszmann RJ, Bosch J, Grace ND, Conn HO, Garcia-Tsao G, Navasa M, et al. Hemodynamic events in a prospective randomized trial of propranolol versus placebo in the prevention of a first variceal hemorrhage. Gastroenterology. 1990;99:1401–1407
  7. Valla DC, Condat B. Portal vein thrombosis in adults: pathophysiology, pathogenesis and management. J Hepatol. 2000;32:865–871
  8. Bargallo X, Gilabert R, Nicolau C, Garcia-Pagan JC, Bosch J, Bru C. Sonography of the caudate vein: value in diagnosing Budd-Chiari syndrome. AJR Am J Roentgenol. 2003;181:1641–1645
  9. Bargallo X, Gilabert R, Nicolau C, Garcia-Pagan JC, Ayuso JR, Bru C. Sonography of Budd-Chiari syndrome. AJR Am J Roentgenol. 2006;187:W33–W41
  10. Valla D, Benhamou JP. Obstruction of the hepatic veins or suprahepatic inferior vena cava. Dig Dis. 1996;14:99–118
  11. Plessier A, Sibert A, Consigny Y, Hakime A, Zappa M, Denninger MH, et al. Aiming at minimal invasiveness as a therapeutic strategy for Budd-Chiari syndrome. Hepatology. 2006;44:1308–1316
  12. Bosch J. Vascular deterioration in cirrhosis. The big picture. J Clin Gastroenterol. 2007;41(Suppl. 3):S247–S253
  13. Fernandez M, Vizzutti F, Garcia-Pagan JC, Rodes J, Bosch J. Anti-VEGF receptor-2 monoclonal antibody prevents portal–systemic collateral vessel formation in portal hypertensive mice. Gastroenterology. 2004;126:886–894
  14. Bosch J, Abraldes JG, Groszmann RJ. Current management of portal hypertension. J Hepatol. 2003;38:S54–S68
  15. Schrier RW, Arroyo V, Bernardi M, Epstein M, Henriksen JH, Rodes J. Peripheral arterial vasodilation hypothesis: a proposal for the initiation of renal sodium and water retention in cirrhosis. Hepatology. 1988;8:1151–1157
  16. Arroyo V, Colmenero J. Ascites and hepatorenal syndrome in cirrhosis: pathophysiological basis of therapy and current management. J Hepatol. 2003;38:S69–S89
  17. Rodriguez-Roisin R, Roca J, Agusti AG, Mastai R, Wagner PD, Bosch J. Gas exchange and pulmonary vascular reactivity in patients with liver cirrhosis. Am Rev Respir Dis. 1987;135:1085–1092
  18. Rodriguez-Roisin R, Agusti AG, Roca J. The hepatopulmonary syndrome: new name, old complexities. Thorax. 1992;47:897–902
  19. Rodriguez-Roisin R, Krowka MJ, Herve P, Fallon MB. Pulmonary-hepatic vascular disorders (PHD). Eur Respir J. 2004;24:861–880
  20. Fallon MB. Portopulmonary hypertension: new clinical insights and more questions on pathogenesis. Hepatology. 2003;37:253–255
  21. Al Hamoudi W, Lee SS. Cirrhotic cardiomyopathy. Ann Hepatol. 2006;5:132–139
  22. Ruiz-del-Arbol L, Urman J, Fernandez J, Gonzalez M, Navasa M, Monescillo A, et al. Systemic, renal, and hepatic hemodynamic derangement in cirrhotic patients with spontaneous bacterial peritonitis. Hepatology. 2003;38:1210–1218
  23. Rios R, Sangro B, Herrero I, Quiroga J, Prieto J. The role of thrombopoietin in the thrombocytopenia of patients with liver cirrhosis. Am J Gastroenterol. 2005;100:1311–1316
  24. D’Amico G, Pagliaro L, Bosch J. The treatment of portal hypertension: a meta-analytic review. Hepatology. 1995;22:332–354
  25. D’Amico G, Luca A. Natural history clinical-haemodynamic correlations. Prediction of the risk of bleeding. Baillieres Clin Gastroenterol. 1997;11:243–256
  26. Christensen E, Fauerholdt L, Schlichting P, Juhl E, Poulsen H, Tygstrup N. Aspects of the natural history of gastrointestinal bleeding in cirrhosis and the effect of prednisone. Gastroenterology. 1981;81:944–952
  27. 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
  28. 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
  29. Garcia-Tsao G, Groszmann RJ, Fisher RL, Conn HO, Atterbury CE, Glickman M. Portal pressure, presence of gastroesophageal varices and variceal bleeding. Hepatology. 1985;5:419–424
  30. Zoli M, Merkel C, Magalotti D, Gueli C, Grimaldi M, Gatta A, et al. Natural history of cirrhotic patients with small esophageal varices: a prospective study. Am J Gastroenterol. 2000;95:503–508
  31. de Franchis R. Evaluation and follow-up of patients with cirrhosis and oesophageal varices. J Hepatol. 2003;38:361–363
  32. 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
  33. Vorobioff J, Groszmann RJ, Picabea E, Gamen M, Villavicencio R, Bordato J, et al. Prognostic value of hepatic venous pressure gradient measurements in alcoholic cirrhosis: a 10-year prospective study. Gastroenterology. 1996;111:701–709
  34. NIEC. Prediction of the first variceal hemorrhage in patients with cirrhosis of the liver and esophageal varices. A prospective multicenter study. The North Italian Endoscopic Club for the Study and Treatment of Esophageal Varices. N Engl J Med. 1988;319:983–989
  35. 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
  36. Viallet A, Marleau D, Huet M, Martin F, Farley A, Villeneuve JP, et al. Hemodynamic evaluation of patients with intrahepatic portal hypertension. Relationship between bleeding varices and the portohepatic gradient. Gastroenterology. 1975;69:1297–1300
  37. D’Amico G, Garcia-Pagan JC, Luca A, Bosch J. Hepatic vein pressure gradient reduction and prevention of variceal bleeding in cirrhosis a systematic review. Gastroenterology. 2006;131:1611–1624
  38. Abraldes JG, Tarantino I, Turnes J, Garcia-Pagan JC, Rodes J, Bosch J. Hemodynamic response to pharmacological treatment of portal hypertension and long-term prognosis of cirrhosis. Hepatology. 2003;37:902–908
  39. Wiest R, Groszmann RJ. The paradox of nitric oxide in cirrhosis and portal hypertension: too much, not enough. Hepatology. 2002;35:478–491
  40. Pinzani M, Gentilini P. Biology of hepatic stellate cells and their possible relevance in the pathogenesis of portal hypertension in cirrhosis. Semin Liver Dis. 1999;19:397–410
  41. Rockey DC, Weisiger RA. Endothelin induced contractility of stellate cells from normal and cirrhotic rat liver: implications for regulation of portal pressure and resistance. Hepatology. 1996;24:233–240
  42. Hernandez-Guerra M, Garcia-Pagan JC, Bosch J. Increased hepatic resistance: a new target in the pharmacologic therapy of portal hypertension. J Clin Gastroenterol. 2005;39:S131–S137
  43. Rodriguez-Vilarrupla A, Fernandez M, Bosch J, Garcia-Pagan JC. Current concepts on the pathophysiology of portal hypertension. Ann Hepatol. 2007;6:28–36
  44. Gupta TK, Toruner M, Chung MK, Groszmann RJ. Endothelial dysfunction and decreased production of nitric oxide in the intrahepatic microcirculation of cirrhotic rats. Hepatology. 1998;28:926–931
  45. Rockey DC, Chung JJ. Reduced nitric oxide production by endothelial cells in cirrhotic rat liver: endothelial dysfunction in portal hypertension. Gastroenterology. 1998;114:344–351
  46. Matei V, Rodriguez-Vilarrupla A, Deulofeu R, Colomer D, Fernandez M, Bosch J, et al. The eNOS cofactor tetrahydrobiopterin improves endothelial dysfunction in livers of rats with CCl4 cirrhosis. Hepatology. 2006;44:44–52
  47. Yu Q, Shao R, Qian HS, George SE, Rockey DC. Gene transfer of the neuronal NO synthase isoform to cirrhotic rat liver ameliorates portal hypertension. J Clin Invest. 2000;105:741–748
  48. Morales-Ruiz M, Cejudo-Martn P, Fernandez-Varo G, Tugues S, Ros J, Angeli P, et al. Transduction of the liver with activated Akt normalizes portal pressure in cirrhotic rats. Gastroenterology. 2003;125:522–531
  49. Loureiro-Silva MR, Cadelina GW, Iwakiri Y, Groszmann RJ. A liver-specific nitric oxide donor improves the intra-hepatic vascular response to both portal blood flow increase and methoxamine in cirrhotic rats. J Hepatol. 2003;39:940–946
  50. Fiorucci S, Antonelli E, Brancaleone V, Sanpaolo L, Orlandi S, Distrutti E, et al. NCX-1000, a nitric oxide-releasing derivative of ursodeoxycholic acid, ameliorates portal hypertension and lowers norepinephrine-induced intrahepatic resistance in the isolated and perfused rat liver. J Hepatol. 2003;39:932–939
  51. Zafra C, Abraldes JG, Turnes J, Berzigotti A, Fernandez M, Garca-Pagan JC, et al. Simvastatin enhances hepatic nitric oxide production and decreases the hepatic vascular tone in patients with cirrhosis. Gastroenterology. 2004;126:749–755
  52. Abraldes JG, Rodriguez-Vilarrupla A, Graupera M, Zafra C, Garcia-Caldero H, Garcia-Pagan JC, et al. Simvastatin treatment improves liver sinusoidal endothelial dysfunction in CCl4 cirrhotic rats. J Hepatol. 2007;46:1040–1046
  53. Hernandez-Guerra M, Garcia-Pagan JC, Turnes J, Bellot P, Deulofeu R, Abraldes JG, et al. Ascorbic acid improves the intrahepatic endothelial dysfunction of patients with cirrhosis and portal hypertension. Hepatology. 2006;43:485–491
  54. Lavina B, Gracia-Sancho J, Rodriguez-Vilarrupla A, Chu Y, Heistad DD, Bosch J, et al. Extracellular superoxide dismutase gene transfer reduces porta pressure and improves intrahepatic endothelial dysfunction in cirrhotic rat livers by diminishing superoxide and increasing nitric oxide bioavailability. J Hepatol. 2007;46:51A
  55. Graupera M, March S, Engel P, Rodes J, Bosch J, Garcia-Pagan JC. Sinusoidal endothelial COX-1-derived prostanoids modulate the hepatic vascular tone of cirrhotic rat livers. Am J Physiol Gastrointest Liver Physiol. 2005;288:G763–G770
  56. Graupera M, Garcia-Pagan JC, Pares M, Abraldes JG, Rosello J, Bosch J, et al. Cyclooxygenase-1 inhibition corrects endothelial dysfunction in cirrhotic rat livers. J Hepatol. 2003;39:515–521
  57. Graupera M, Garcia-Pagan JC, Abraldes JG, Peralta C, Bragulat M, Corominola H, et al. Cyclooxygenase-derived products modulate the increased intrahepatic resistance of cirrhotic rat livers. Hepatology. 2003;37:172–181
  58. Fiorucci S, Antonelli E, Mencarelli A, Orlandi S, Renga B, Rizzo G, et al. The third gas: H2S regulates perfusion pressure in both the isolated and perfused normal rat liver and in cirrhosis. Hepatology. 2005;42:539–548
  59. Vorobioff J, Bredfeldt J, Groszmann RJ. Hyperdynamic circulation in a portal hypertensive rat model: a primary factor for maintenance of chronic portal hypertension. Am J Physiol. 1983;244:G52–G56
  60. Benoit JN, Barrowman JA, Harper SL, Kvietys PR, Granger DN. Role of humoral factors in the intestinal hyperemia associated with chronic portal hypertension. Am J Physiol. 1984;247:G486–G493
  61. Pizcueta MP, Piqué JM, Bosch J, Whittle BJR, Moncada S. Effects of inhibiting nitric oxide biosynthesis on the systemic and splanchnic circulation of rats with portal hypertension. Br J Pharmacol. 1992;105:105–184
  62. Pizcueta P, Piqué JM, Fernández M, Bosch J, Rodés J, Whittle BJR, et al. Modulation of the hyperdynamic circulation of cirrhotic rats by nitric oxide inhibition. Gastroenterology. 1992;103:1909–1915
  63. Wiest R, Groszmann RJ. Nitric oxide and portal hypertension: its role in the regulation of intrahepatic and splanchnic vascular resistance. Semin Liver Dis. 1999;19:411–426
  64. Groszmann RJ. Hyperdynamic circulation of liver disease 40 years later: pathophysiology and clinical consequences. Hepatology. 1994;20:1359–1363
  65. Garcia-Pagan JC, Salmeron JM, Feu F, Luca A, Gines P, Pizcueta P, et al. Effects of low-sodium diet and spironolactone on portal pressure in patients with compensated cirrhosis. Hepatology. 1994;19:1095–1099
  66. Garcia-Pagan JC, Escorsell A, Moitinho E, Bosch J. Influence of pharmacological agents on portal hemodynamics: basis for its use in the treatment of portal hypertension. Semin Liver Dis. 1999;19:427–438
  67. Fernandez M, Mejias M, Angermayr B, Garcia-Pagan JC, Rodes J, Bosch J. Inhibition of VEGF receptor-2 decreases the development of hyperdynamic splanchnic circulation and portal–systemic collateral vessels in portal hypertensive rats. J Hepatol. 2005;43:98–103
  68. Fernandez M, Mejias M, Garcia-Pras E, Mendez R, Garcia-Pagan JC, Bosch J. Reversal of portal hypertension and hyperdynamic splanchnic circulation by combined vascular endothelial growth factor and platelet-derived growth factor blockade in rats. Hepatology. 2007;46:1208–1217
  69. Garcia-Pagan JC, Bosch J. The resistance of the cirrhotic liver: a new target for the treatment of portal hypertension 1985. J Hepatol. 2004;40:887–890
  70. 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
  71. Panes J, Teres J, Bosch J, Rodes J. Efficacy of balloon tamponade in treatment of bleeding gastric and esophageal varices. Results in 151 consecutive episodes. Dig Dis Sci. 1988;33:454–459
  72. Hubmann R, Bodlaj G, Czompo M, Benko L, Pichler P, Al Kathib S, et al. The use of self-expanding metal stents to treat acute esophageal variceal bleeding. Endoscopy. 2006;38:896–901
  73. Bosch J, Thabut D, Bendtsen F, D’Amico G, Albillos A, Gonzalez AJ, et al. Recombinant factor VIIa for upper gastrointestinal bleeding in patients with cirrhosis: a randomized, double-blind trial. Gastroenterology. 2004;127:1123–1130
  74. Bosch J, Thabut D, Albillos A, Carbonell N, Spicak J, Massard J, et al. Recombinant Factor VIIA (RFVIIA) for active variceal bleeding in patients with advanced cirrhosis: a multi-centre randomized double-blind placebo-controlled trial. J Hepatol. 2007;46(Suppl. 1):295A
  75. D’Amico G, Garcia-Tsao G, Pagliaro L. Natural history and prognostic indicators of survival in cirrhosis: a systematic review of 118 studies. J Hepatol. 2006;44:217–231
  76. D’Amico G, Morabito A. Noninvasive markers of esophageal varices: another round, not the last. Hepatology. 2004;39:30–34
  77. de Franchis R. Noninvasive diagnosis of esophageal varices: is it feasible?. Am J Gastroenterol. 2006;101:2520–2522
  78. Chalasani N, Imperiale TF, Ismail A, Sood G, Carey M, Wilcox CM, et al. Predictors of large esophageal varices in patients with cirrhosis. Am J Gastroenterol. 1999;94:3285–3291
  79. Giannini E, Botta F, Borro P, Risso D, Romagnoli P, Fasoli A, et al. Platelet count/spleen diameter ratio: proposal and validation of a non-invasive parameter to predict the presence of oesophageal varices in patients with liver cirrhosis. Gut. 2003;52:1200–1205
  80. McCormick PA, Nolan N. Palpable epigastric liver as a physical sign of cirrhosis: a prospective study. Eur J Gastroenterol Hepatol. 2004;16:1331–1334
  81. de BG, Graviss EA. A systematic review of the diagnostic accuracy of physical examination for the detection of cirrhosis. BMC Med Inform Decis Mak. 2001;1:6
  82. Braillon A, Cales P, Valla D, Gaudy D, Geoffroy P, Lebrec D. Influence of the degree of liver failure on systemic and splanchnic haemodynamics and on response to propranolol in patients with cirrhosis. Gut. 1986;27:1204–1209
  83. Gluud C, Henriksen JH, Nielsen G. Prognostic indicators in alcoholic cirrhotic men. Hepatology. 1988;8:222–227
  84. Stanley AJ, Robinson I, Forrest EH, Jones AL, Hayes PC. Haemodynamic parameters predicting variceal haemorrhage and survival in alcoholic cirrhosis. QJM. 1998;91:19–25
  85. Qamar AA, Grace ND, Groszmann RJ, Garcia-Tsao G, Bosch J, Burroughs AK, et al. Platelet count is not a predictor of the presence or development of gastroesophageal varices in cirrhosis. 46th ed.; 2007.
  86. Schepis F, Camma C, Niceforo D, Magnano A, Pallio S, Cinquegrani M, et al. Which patients with cirrhosis should undergo endoscopic screening for esophageal varices detection?. Hepatology. 2001;33:333–338
  87. Zaman A, Hapke R, Flora K, Rosen HR, Benner K. Factors predicting the presence of esophageal or gastric varices in patients with advanced liver disease. Am J Gastroenterol. 1999;94:3292–3296
  88. Cottone M, D’Amico G, Maringhini A, Amuso M, Sciarrino E, Traina M, et al. Predictive value of ultrasonography in the screening of non-ascitic cirrhotic patients with large varices. J Ultrasound Med. 1986;5:189–192
  89. Bolondi L, Gandolfi L, Arienti V, Caletti GC, Corcioni E, Gasbarrini G, et al. Ultrasonography in the diagnosis of portal hypertension: diminished response of portal vessels to respiration. Radiology. 1982;142:167–172
  90. Zoli M, Iervese T, Merkel C, Bianchi G, Magalotti D, Marchesini G, et al. Prognostic significance of portal hemodynamics in patients with compensated cirrhosis. J Hepatol. 1993;17:56–61
  91. Moriyasu F, Nishida O, Ban N, Nakamura T, Sakai M, Miyake T, et al. “Congestion index” of the portal vein. AJR Am J Roentgenol. 1986;146:735–739
  92. van Leeuwen MS. Doppler ultrasound in the evaluation of portal hypertension. Clin Diagn Ultrasound. 1990;26:53–76
  93. Bolondi L, Li BS, Gaiani S, Zironi G, Benzi G, Santi V, et al. Liver cirrhosis: changes of Doppler waveform of hepatic veins. Radiology. 1991;178:513–516
  94. Sacerdoti D, Merkel C, Bolognesi M, Amodio P, Angeli P, Gatta A. Hepatic arterial resistance in cirrhosis with and without portal vein thrombosis: relationships with portal hemodynamics. Gastroenterology. 1995;108:1152–1158
  95. Iwao T, Toyonaga A, Oho K, Tayama C, Masumoto H, Sakai T, et al. Value of Doppler ultrasound parameters of portal vein and hepatic artery in the diagnosis of cirrhosis and portal hypertension. Am J Gastroenterol. 1997;92:1012–1017
  96. Bolognesi M, Sacerdoti D, Merkel C, Bombonato G, Gatta A. Noninvasive grading of the severity of portal hypertension in cirrhotic patients by echo-color-Doppler. Ultrasound Med Biol. 2001;27:901–907
  97. Berzigotti A, Casadei A, Magalotti D, Castaldini N, Losinno F, Rossi C, et al. Renovascular impedance correlates with portal pressure in patients with liver cirrhosis. Radiology. 2006;240:581–586
  98. Taourel P, Blanc P, Dauzat M, Chabre M, Pradel J, Gallix B, et al. Doppler study of mesenteric, hepatic, and portal circulation in alcoholic cirrhosis: relationship between quantitative Doppler measurements and the severity of portal hypertension and hepatic failure. Hepatology. 1998;28:932–936
  99. Materne R, Annet L, Dechambre S, Sempoux C, Smith AM, Corot C, et al. Dynamic computed tomography with low- and high-molecular-mass contrast agents to assess microvascular permeability modifications in a model of liver fibrosis. Clin Sci (Lond). 2002;103:213–216
  100. Van Beers BE, Materne R, Annet L, Hermoye L, Sempoux C, Peeters F, et al. Capillarization of the sinusoids in liver fibrosis: noninvasive assessment with contrast-enhanced MRI in the rabbit. Magn Reson Med. 2003;49:692–699
  101. Annet L, Materne R, Danse E, Jamart J, Horsmans Y, Van Beers BE. Hepatic flow parameters measured with MR imaging and Doppler US: correlations with degree of cirrhosis and portal hypertension. Radiology. 2003;229:409–414
  102. Ziol M, Handra-Luca A, Kettaneh A, Christidis C, Mal F, Kazemi F, et al. Noninvasive assessment of liver fibrosis by measurement of stiffness in patients with chronic hepatitis C. Hepatology. 2005;41:48–54
  103. Corpechot C, El Naggar A, Poujol-Robert A, Ziol M, Wendum D, Chazouilleres O, et al. Assessment of biliary fibrosis by transient elastography in patients with PBC and PSC. Hepatology. 2006;43:1118–1124
  104. Carrion JA, Navasa M, Bosch J, Bruguera M, Gilabert R, Forns X. Transient elastography for diagnosis of advanced fibrosis and portal hypertension in patients with hepatitis C recurrence after liver transplantation. Liver Transpl. 2006;12:1791–1798
  105. Kazemi F, Kettaneh A, N’kontchou G, Pinto E, Ganne-Carrie N, Trinchet JC, et al. Liver stiffness measurement selects patients with cirrhosis at risk of bearing large oesophageal varices. J Hepatol. 2006;45:230–235
  106. Lemoine M, Katsahian S, Nahon P, Ganne-Carrie N, Kazemi F, Grando V, et al. Liver stiffness measurement is correlated with hepatic venous pressure gradient in patients with uncomplicated alcoholic and/or HVC related cirrhosis. Hepatology. 2006;44(Suppl. 1):204A
  107. Vizzutti F, Arena U, Romanelli RG, Rega L, Foschi M, Colagrande S, et al. Liver stiffness measurement predicts severe portal hypertension in patients with HCV-related cirrhosis. Hepatology. 2007;45:1290–1297
  108. Bureau C, Metivier S, Peron JM, Robic MA, Rouquet O, Dupuis E, et al. Prospective assessment of liver stiffness for the non-invasive prediction of portal hypertension. J Hepatol. 2007;46(Suppl. 1):34A
  109. Manduca A, Oliphant TE, Dresner MA, Mahowald JL, Kruse SA, Amromin E, et al. Magnetic resonance elastography: non-invasive mapping of tissue elasticity. Med Image Anal. 2001;5:237–254
  110. Huwart L, Peeters F, Sinkus R, Annet L, Salameh N, ter Beek LC, et al. Liver fibrosis: non-invasive assessment with MR elastography. NMR Biomed. 2006;19:173–179
  111. 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
  112. 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
  113. Frenette C, Kuldau JG, Hillebrand D, Lane J, Pockros PJ. Comparison of esophageal pill endoscopy and conventional endoscopy for variceal screening. Hepatology. 2006;44:445A
  114. 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
  115. Ripoll C, Banares R, Rincon D, Catalina MV, Lo Iacono O, Salcedo M, et al. Influence of hepatic venous pressure gradient on the prediction of survival of patients with cirrhosis in the MELD Era. Hepatology. 2005;42:793–801
  116. Saab S, DeRosa V, Nieto J, Durazo F, Han S, Roth B. Costs and clinical outcomes of primary prophylaxis of variceal bleeding in patients with hepatic cirrhosis: a decision analytic model. Am J Gastroenterol. 2003;98:763–770
  117. Spiegel BM, Targownik L, Dulai GS, Karsan HA, Gralnek IM. Endoscopic screening for esophageal varices in cirrhosis: is it ever cost effective?. Hepatology. 2003;37:366–377
  118. Arguedas MR, Heudebert GR, Eloubeidi MA, Abrams GA, Fallon MB. Cost-effectiveness of screening, surveillance, and primary prophylaxis strategies for esophageal varices. Am J Gastroenterol. 2002;97:2441–2452
  119. Sarin SK, Groszmann RJ, Mosca PG, Rojkind M, Stadecker MJ, Bhatnagar R, et al. Propranolol ameliorates the development of portal–systemic shunting in a chronic murine schistosomiasis model of portal hypertension. J Clin Invest. 1991;87:1032–1036
  120. D’Amico G, Pagliaro L, Bosch J. Pharmacological treatment of portal hypertension: an evidence-based approach. Semin Liver Dis. 1999;19:475–505
  121. Garcia-Pagan JC, Feu F, Bosch J, Rodes J. Propranolol compared with propranolol plus isosorbide-5-mononitrate for portal hypertension in cirrhosis. A randomized controlled study. Ann Intern Med. 1991;114:869–873
  122. 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 Gruppo-Triveneto per L’ipertensione portale (GTIP). Lancet. 1996;348:1677–1681
  123. 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
  124. Garcia-Pagan J, Morillas RM, Bañares R, Albillos A, Villanueva C, Vila C, et al. Propranolol plus placebo vs propranolol plus isosorbide-5-mononitrate in the prevention of the first variceal bleed. A double blind RCT. Hepatology. 2003;37:1260–1266
  125. Imperiale TF, Chalasani N. A meta-analysis of endoscopic variceal ligation for primary prophylaxis of esophageal variceal bleeding. Hepatology. 2001;33:802–807
  126. 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
  127. Chen CY, Sheu MZ, Tsai TL, Lin YL. Endoscopic variceal ligation with multiple band ligator for prophylaxis of first hemorrhage esophageal varices. Endoscopy. 1999;31:35A
  128. 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
  129. Song H, Shin JW, Kim HI, Choi J, Lim CY, Kim JW, et al. A prospective randomized trial between the prophylactic endoscopic variceal ligation and propranolol administration for prevention of first bleeding in cirrhotic patients with high risk esophageal varices. J Hepatol. 2000;32:41A
  130. Sarin SK, 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
  131. de la Mora, Farca-Belsaguy AA, Uribe M, de Hoyos-Garza A. Ligation vs propranolol for primary prophylaxis of variceal bleeding using multiple band ligator and objective measurements of treatment adequacy: preliminary results. Gastroenterology. 2000;118:6511A
  132. Lui HF, Stanley AJ, Forrest EH, Jalan R, Hislop WS, Mills PR, et al. Primary prophylaxis of variceal hemorrhage: a randomized controlled trial comparing band ligation, propranolol, and isosorbide mononitrate. Gastroenterology. 2002;123:735–744
  133. 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
  134. Thuluvath PJ, Maheshwari A, Jagannath S, Arepally A. A randomized controlled trial of beta-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
  135. De BK, Ghoshal UC, 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
  136. Drastich P, Lata J, Petrtyl J, Prochazka V, Vanasek T, Zdenek P, et al. Endoscopic variceal band ligation in comparison with propranolol in prophylaxis of first variceal bleeding in patients with liver cirrhosis. J Hepatol. 2005;42:202a
  137. 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
  138. 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;17:1111–1117
  139. Abdelfattah MH, Rashed MA, Elfakhry AA, Soliman MA, Shiha GH. Endoscopic variceal ligation versus pharmacological treatment for primary prophylaxis of variceal bleeding: a randomized study. J Hepatol. 2006;44:83A
  140. Gheorghe C, Gheorghe L, Vadan R, Hrehoret D, Popescu I. Prophylactic banding ligation of high-risk esophageal varices in patients on the waiting list for liver transplantation: an interim analysis. J Hepatol. 2002;36:38A
  141. Norberto L, Polese L, Cillo U, Grigoletto F, Burroughs AK, Neri D, et al. A randomized study comparing ligation with propranolol for primary prophylaxis of variceal bleeding in candidates for liver transplantation. Liver Transpl. 2007;13:1272–1278
  142. Tripathi D, Ferguson JW, Kochar N, Leithead JA, Therapondos G, McAvoy NC, et al. Multicenter randomized controlled trial of carvedilol versus variceal band ligation for the prevention of the first variceal bleed. Hepatology. 2007;46(Suppl. 1):269A
  143. Garcia-Pagan JC, Bosch J. Endoscopic band ligation in the treatment of portal hypertension. Nat Clin Pract Gastroenterol Hepatol. 2005;2:526–535
  144. Khuroo MS, Khuroo NS, Farahat KL, 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
  145. Abraczinskas DR, Ookubo R, Grace ND, Groszmann RJ, Bosch J, Garcia-Tsao G, et al. Propranolol for the prevention of first esophageal variceal hemorrhage: a lifetime commitment?. Hepatology. 2001;34:1096–1102
  146. Turnes J, Garcia-Pagan JC, Abraldes JG, Hernandez-Guerra M, Dell’Era A, Bosch J. Pharmacological reduction of portal pressure and long-term risk of first variceal bleeding in patients with cirrhosis. Am J Gastroenterol. 2006;101:506–512
  147. Imperiale TF, Klein RW, Chalasani N. Cost-effectiveness analysis of variceal ligation vs beta-blockers for primary prevention of variceal bleeding. Hepatology. 2007;45:870–878
  148. Longacre AV, Imaeda A, Garcia-Tsao G, Fraenkel L. A pilot project examining the predicted preferences of patients and physicians in the primary prophylaxis of variceal hemorrhage. Hepatology. 2008;47:169–176
  149. Garcia-Tsao G, Sanyal AJ, Grace ND, Carey W. Prevention and management of gastroesophageal varices and variceal hemorrhage in cirrhosis. Hepatology. 2007;46:922–938
  150. 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
  151. Merkel C, Bolognesi M, Sacerdoti D, Bombonato G, Bellini B, Bighin R, 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
  152. Aracil C, López-Balaguer J, Monfort D, Piqueras M, González B, Miñand 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
  153. Imperiale TF, Chalasani N, Klein RW. Measuring the hemodynamic response to primary pharmacoprophylaxis of variceal bleeding: a cost-effectiveness analysis. Am J Gastroenterol. 2003;98:2742–2750
  154. Hicken BL, Sharara AI, Abrams GA, Eloubeidi M, Fallon MB, Arguedas MR. Hepatic venous pressure gradient measurements to assess response to primary prophylaxis in patients with cirrhosis: a decision analytical study. Aliment Pharmacol Ther. 2003;17:145–153
  155. 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
  156. 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 esophageal varices. Am J Gastroenterol. 2005;100:2005–2009
  157. Bernard B, Lebrec D, Mathurin P, Opolon P, Poynard T. Beta-adrenergic antagonists in the prevention of gastrointestinal rebleeding in patients with cirrhosis: a meta-analysis. Hepatology. 1997;25:63–70
  158. Gournay J, Masliah C, Martin T, Perrin D, Galmiche JP. Isosorbide mononitrate and propranolol compared with propranolol alone for the prevention of variceal rebleeding. Hepatology. 2000;31:1239–1245
  159. 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
  160. Villanueva C, Minana J, Ortiz J, Gallego A, Soriano G, Torras X, et al. Endoscopic ligation compared with combined treatment with nadolol and isosorbide mononitrate to prevent recurrent variceal bleeding. N Engl J Med. 2001;345:647–655
  161. Patch D, Sabin CA, Goulis J, Gerunda G, Greenslade L, Merkel C, et al. A randomized, controlled trial of medical therapy versus endoscopic ligation for the prevention of variceal rebleeding in patients with cirrhosis. Gastroenterology. 2002;123:1013–1019
  162. Lo GH, Chen WC, Chen MH, Hsu PI, Lin CK, Tsai WL, et al. Banding ligation versus nadolol and isosorbide mononitrate for the prevention of esophageal variceal rebleeding. Gastroenterology. 2002;123:728–734
  163. Romero G, Kravetz D, Argonz J, Vulcano C, Suarez A, Fassio E, et al. Comparative study between nadolol and 5-isosorbide mononitrate vs endoscopic band ligation plus sclerotherapy in the prevention of variceal rebleeding in cirrhotic patients: a randomized controlled trial. Aliment Pharmacol Ther. 2006;24:601–611
  164. Karsan HA, Morton SC, Shekelle PG, Spiegel BM, Suttorp MJ, Edelstein MA, et al. Combination endoscopic band ligation and sclerotherapy compared with endoscopic band ligation alone for the secondary prophylaxis of esophageal variceal hemorrhage: a meta-analysis. Dig Dis Sci. 2005;50:399–406
  165. Garcia-Tsao G, Sanyal AJ, Grace ND, Carey WD. Prevention and management of gastroesophageal varices and variceal hemorrhage in cirrhosis. Am J Gastroenterol. 2007;102:2086–2102
  166. Lo GH, Lai KH, Cheng JS, Chen MH, Huang HC, Hsu PI, et al. Endoscopic variceal ligation plus nadolol and sucralfate compared with ligation alone for the prevention of variceal rebleeding: a prospective, randomized trial. Hepatology. 2000;32:461–465
  167. de la Peña J, Brullet E, Sanchez-Hernandez E, Rivero M, Vergara M, Martin-Lorente JL, et al. Variceal ligation plus nadolol compared with ligation for prophylaxis of variceal rebleeding: a multicenter trial. Hepatology. 2005;41:572–578
  168. Study Group Spanish Cooperative Variceal Rebleeding. Multicenter RCT comparing drug therapy vs the combination of drug therapy plus endoscopic band ligation in the prevention of rebleeding in patients with cirrhosis. Hepatology. 2007;44:202A
  169. Bosch J, Garcia-Pagan J. Prevention of variceal rebleeding. Lancet. 2003;361:952–954
  170. Gonzalez A, Augustin S, Perez M, Dot J, Saperas E, Tomasello A, et al. Hemodynamic response-guided therapy for prevention of variceal rebleeding: an uncontrolled pilot study. Hepatology. 2006;44:806–812
  171. Escorsell A, Banares R, Garcia-Pagan JC, Gilabert R, Moitinho E, Piqueras B, et al. TIPS versus drug therapy in preventing variceal rebleeding in advanced cirrhosis: a randomized controlled trial. Hepatology. 2002;35:385–392
  172. Burroughs AK, Vangeli M. Transjugular intrahepatic portosystemic shunt versus endoscopic therapy: randomized trials for secondary prophylaxis of variceal bleeding: an updated meta-analysis. Scand J Gastroenterol. 2002;37:249–252
  173. Rosemurgy AS, Serafini FM, Zweibel BR, Black TJ, Kudryk BT, Nord HJ, et al. Transjugular intrahepatic portosystemic shunt vs small-diameter prosthetic H-graft portacaval shunt: extended follow-up of an expanded randomized prospective trial. J Gastrointest Surg. 2000;4:589–597
  174. Henderson JM, Boyer TD, Kutner MH, Rikkers L, Jeffers L, Abu-Elmagd K. DSRS vs TIPS for refractory variceal bleeding: a prospective randomized controlled trial. Hepatology. 2004;40:725A
  175. Bureau C, Garcia-Pagan JC, Otal P, Pomier-Layrargues G, Chabbert V, Cortez C, et al. Improved clinical outcome using polytetrafluoroethylene-coated stents for tips: results of a randomized study. Gastroenterology. 2004;126:469–475
  176. Lo GH, Lai KH, Cheng JS, Chen MH, Chiang HT. A prospective, randomized trial of butyl cyanoacrylate injection versus band ligation in the management of bleeding gastric varices. Hepatology. 2001;33:1060–1064
  177. 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
  178. Tan PC, Hou MC, Lin HC, Liu TT, Lee FY, Chang FY, et al. A randomized trial of endoscopic treatment of acute gastric variceal hemorrhage: N-butyl-2-cyanoacrylate injection versus band ligation. Hepatology. 2006;43:690–697
  179. Lo GH, Liang HL, Chen WC, Chen MH, Lai KH, Hsu PI, et al. A prospective, randomized controlled trial of transjugular intrahepatic portosystemic shunt versus cyanoacrylate injection in the prevention of gastric variceal rebleeding. Endoscopy. 2007;39:679–685
  180. D’Amico G, de Franchis R. Upper digestive bleeding in cirrhosis. Post-therapeutic outcome and prognostic indicators. Hepatology. 2003;38:599–612
  181. Graham D, Smith J. The course of patients after variceal hemorrhage. Gastroenterology. 1981;80:800–806
  182. 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
  183. Chalasani N, Kahi C, Francois F, Pinto A, Marathe A, Bini EJ, et al. Improved patient survival after acute variceal bleeding: a multicenter, cohort study. Am J Gastroenterol. 2003;98:653–659
  184. Stokkeland K, Brandt L, Ekbom A, Hultcrantz R. Improved prognosis for patients hospitalized with esophageal varices in Sweden 1969–2002. Hepatology. 2006;43:500–505
  185. Nidegger D, Ragot S, Berthelemy P, Masliah C, Pilette C, Martin T, et al. Cirrhosis and bleeding: the need for very early management. J Hepatol. 2003;39:509–514
  186. Abraldes JG, Bosch J. The treatment of acute variceal bleeding. J Clin Gastroenterol. 2007;41(Suppl. 3):S312–S317
  187. Cardenas A, Gines P, Uriz J, Bessa X, Salmeron JM, Mas A, et al. Renal failure after upper gastrointestinal bleeding in cirrhosis: incidence, clinical course, predictive factors, and short-term prognosis. Hepatology. 2001;34:671–676
  188. McCormick PA, Jenkins SA, McIntyre N, Burroughs AK. Why portal hypertensive varices bleed and bleed: a hypothesis. Gut. 1995;36:100–103
  189. Castaneda B, Debernardi-Venon W, Bandi JC, Andreu V, Perez-del-Pulgar S, Moitinho E, et al. The role of portal pressure in the severity of bleeding in portal hypertensive rats. Hepatology. 2000;31:581–586
  190. Villanueva C, Ortiz J, Minana J, Soriano G, Sabat M, Boadas J, et al. Somatostatin treatment and risk stratification by continuous portal pressure monitoring during acute variceal bleeding. Gastroenterology. 2001;121:110–117
  191. Morales J, Moitinho E, Abraldes JG, Fernandez M, Bosch J. Effects of the V1a vasopressin agonist F-180 on portal hypertension-related bleeding in portal hypertensive rats. Hepatology. 2003;38:1378–1383
  192. Ejlersen E, Melsen T, Ingerslev J, Andreasen RB, Vilstrup H. Recombinant activated factor VII (rFVIIa) acutely normalizes prothrombin time in patients with cirrhosis during bleeding from oesophageal varices. Scand J Gastroenterol. 2001;36:1081–1085
  193. Goulis J, Armonis A, Patch D, Sabin C, Greenslade L, Burroughs AK. Bacterial infection is independently associated with failure to control bleeding in cirrhotic patients with gastrointestinal hemorrhage. Hepatology. 1998;27:1207–1212
  194. Hou MC, Lin HC, Liu TT, Kuo BI, Lee FY, Chang FY, et al. Antibiotic prophylaxis after endoscopic therapy prevents rebleeding in acute variceal hemorrhage: a randomized trial. Hepatology. 2004;39:746–753
  195. Bernard B, Grange JD, Khac EN, Amiot X, Opolon P, Poynard T. Antibiotic prophylaxis for the prevention of bacterial infections in cirrhotic patients with gastrointestinal bleeding: a meta-analysis. Hepatology. 1999;29:1655–1661
  196. Rimola A, Garcia-Tsao G, Navasa M, Piddock LJ, Planas R, Bernard B, et al. Diagnosis, treatment and prophylaxis of spontaneous bacterial peritonitis: a consensus document International Ascites Club. J Hepatol. 2000;32:142–153
  197. Fernandez J, Ruiz-del-Arbol L, Gomez C, Durandez R, Serradilla R, Guarner C, et al. Norfloxacin vs ceftriaxone in the prophylaxis of infections in patients with advanced cirrhosis and hemorrhage. Gastroenterology. 2006;131:1049–1056
  198. Levacher S, Letoumelin P, Pateron D, Blaise M, Lapandry C, Pourriat JL. Early administration of terlipressin plus glyceryl trinitrate to control active upper gastrointestinal bleeding in cirrhotic patients. Lancet. 1995;346:865–868
  199. Abraldes JG, Bosch J. Somatostatin and analogues in portal hypertension. Hepatology. 2002;35:1305–1312
  200. Escorsell A, Ruiz-del-Arbol L, Planas R, Albillos A, Banares R, Cales P, et al. Multicenter randomized controlled trial of terlipressin versus sclerotherapy in the treatment of acute variceal bleeding: the TEST study. Hepatology. 2000;32:471–476
  201. Ioannou GN, Doust J, Rockey DC. Systematic review: terlipressin in acute oesophageal variceal haemorrhage. Aliment Pharmacol Ther. 2003;17:53–64
  202. Uriz J, Gines P, Cardenas A, Sort P, Jimenez W, Salmeron JM, et al. Terlipressin plus albumin infusion: an effective and safe therapy of hepatorenal syndrome. J Hepatol. 2000;33:43–48
  203. Escorsell A, Bordas JM, del Arbol LR, Jaramillo JL, Planas R, Banares R, et al. Randomized controlled trial of sclerotherapy versus somatostatin infusion in the prevention of early rebleeding following acute variceal hemorrhage in patients with cirrhosis. Variceal Bleeding Study Group. J Hepatol. 1998;29:779–788
  204. Villanueva C, Ortiz J, Sabat M, Gallego A, Torras X, Soriano G, et al. Somatostatin alone or combined with emergency sclerotherapy in the treatment of acute esophageal variceal bleeding: a prospective randomized trial. Hepatology. 1999;30:384–389
  205. Moitinho E, Planas R, Bañares R, Albillos A, Ruiz-del-Arbol L, Galvez C, et al. Multicenter randomized controlled trial comparing different schedules of somatostatin in the treatment of acute variceal bleeding. J Hepatol. 2001;35:712–718
  206. Escorsell A, Bandi JC, Andreu V, Moitinho E, Garcia-Pagan JC, Bosch J, et al. Desensitization to the effects of intravenous octreotide in cirrhotic patients with portal hypertension. Gastroenterology. 2001;120:161–169
  207. International Octreotide Varices Study Group Burroughs AK. Double blind RCT of 5 day octreotide versus placebo, associated with sclerotherapy for trial failures. Hepatology. 1996;24:352A
  208. Corley DA, Cello JP, Adkisson W, Ko WF, Kerlikowske K. Octreotide for acute esophageal variceal bleeding: a meta-analysis. Gastroenterology. 2001;120:946–954
  209. Lo GH, Lai KH, Cheng JS, Lin CK, Huang JS, Hsu PI, et al. Emergency banding ligation versus sclerotherapy for the control of active bleeding from esophageal varices. Hepatology. 1997;25:1101–1104
  210. Villanueva C, Piqueras M, Aracil C, Gomez C, Lopez-Balaguer JM, Gonzalez B, et al. A randomized controlled trial comparing ligation and sclerotherapy as emergency endoscopic treatment added to somatostatin in acute variceal bleeding. J Hepatol. 2006;45:560–567
  211. Avgerinos A, Armonis A, Stefanidis G, Mathou N, Vlachogiannakos J, Kougioumtzian A, et al. Sustained rise of portal pressure after sclerotherapy, but not band ligation, in acute variceal bleeding in cirrhosis. Hepatology. 2004;39:1623–1630
  212. Avgerinos A, Nevens F, Raptis S, Fevery J. Early administration of somatostatin and efficacy of sclerotherapy in acute oesophageal variceal bleeds: the European Acute Bleeding Oesophageal Variceal Episodes (ABOVE) randomised trial. Lancet. 1997;350:1495–1499
  213. Cales P, Masliah C, Bernard B, Garnier PP, Silvain C, Szostak-Talbodec N, et al. Early administration of vapreotide for variceal bleeding in patients with cirrhosis French Club for the Study of Portal Hypertension. N Engl J Med. 2001;344:23–28
  214. Bosch J. Salvage transjugular intrahepatic portosystemic shunt: is it really life-saving?. J Hepatol. 2001;35:658–660
  215. Patch D, Nikolopoulou V, McCormick A, Dick R, Armonis A, Wannamethee G, et al. Factors related to early mortality after transjugular intrahepatic portosystemic shunt for failed endoscopic therapy in acute variceal bleeding. J Hepatol. 1998;28:454–460
  216. Monescillo A, Martinez-Lagares F, Ruiz-del-Arbol L, Sierra A, Guevara C, Jimenez E, et al. Influence of portal hypertension and its early decompression by TIPS placement on the outcome of variceal bleeding. Hepatology. 2004;40:793–801
  217. 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
  218. Teres J, Cecilia A, Bordas JM, Rimola A, Bru C, Rodes J. Esophageal tamponade for bleeding varices Controlled trial between the Sengstaken-Blakemore tube and the Linton-Nachlas tube. Gastroenterology. 1978;75:566–569
  219. Sarin SK, Agarwal SR. Gastric varices and portal hypertensive gastropathy. Clin Liver Dis. 2001;5:727–767
  220. Huang YH, Yeh HZ, Chen GH, Chang CS, Wu CY, Poon SK, et al. Endoscopic treatment of bleeding gastric varices by N-butyl-2-cyanoacrylate (Histoacryl) injection: long-term efficacy and safety. Gastrointest Endosc. 2000;52:160–167
  221. Chau TN, Patch D, Chan YW, Nagral A, Dick R, Burroughs AK. “Salvage” transjugular intrahepatic portosystemic shunts: gastric fundal compared with esophageal variceal bleeding. Gastroenterology. 1998;114:981–987
  222. Barange K, Peron JM, Imani K, Otal P, Payen JL, Rousseau H, et al. Transjugular intrahepatic portosystemic shunt in the treatment of refractory bleeding from ruptured gastric varices. Hepatology. 1999;30:1139–1143
  223. Lo GH, Liang HL, Chen WC, Chen MH, Lai KH, Hsu PI, et al. A prospective, randomized controlled trial of transjugular intrahepatic portosystemic shunt versus cyanoacrylate injection in the prevention of gastric variceal rebleeding. Endoscopy. 2007;39:679–685
  224. Matsumoto A, Hamamoto N, Nomura T, Hongou Y, Arisaka Y, Morikawa H, et al. Balloon-occluded retrograde transvenous obliteration of high risk gastric fundal varices. Am J Gastroenterol. 1999;94:643–649
  225. Primignani M, Carpinelli L, Preatoni P, Battaglia G, Carta A, Prada A, et al. Natural history of portal hypertensive gastropathy in patients with liver cirrhosis. The New Italian Endoscopic Club for the study and treatment of esophageal varices (NIEC). Gastroenterology. 2000;119:181–187
  226. Panes J, Bordas JM, Pique JM, Garcia-Pagan JC, Feu F, Teres J, et al. Effects of propranolol on gastric mucosal perfusion in cirrhotic patients with portal hypertensive gastropathy. Hepatology. 1993;17:213–218
  227. Panes J, Pique JM, Bordas JM, Llach J, Bosch J, Teres J, et al. Reduction of gastric hyperemia by glypressin and vasopressin administration in cirrhotic patients with portal hypertensive gastropathy. Hepatology. 1994;19:55–60
  228. Panes J, Pique JM, Bordas JM, Casadevall M, Teres J, Bosch J, et al. Effect of bolus injection and continuous infusion of somatostatin on gastric perfusion in cirrhotic patients with portal-hypertensive gastropathy. Hepatology. 1994;20:336–341
  229. Panes J, Casadevall M, Fernandez M, Pique JM, Bosch J, Casamitjana R, et al. Gastric microcirculatory changes of portal-hypertensive rats can be attenuated by long-term estrogen–progestagen treatment. Hepatology. 1994;20:1261–1270
  230. Kouroumalis EA, Koutroubakis IE, Manousos ON. Somatostatin for acute severe bleeding from portal hypertensive gastropathy. Eur J Gastroenterol Hepatol. 1998;10:509–512
  231. Perez-Ayuso RM, Pique JM, Bosch J, Panes J, Gonzalez A, Perez R, et al. Propranolol in prevention of recurrent bleeding from severe portal hypertensive gastropathy in cirrhosis. Lancet. 1991;337:1431–1434
  232. Abraldes JG, Villanueva C, Banares R, Aracil C, Catalina MV, Garca-Pagan JC, et al. HVPG and prognosis in patients with acute variceal bleeding treated with pharmacologic and endoscopic therapy. J Hepatol. 2008;48:229–236
  233. Bernard B, Cadranel JF, Valla D, Escolano S, Jarlier V, Opolon P. Prognostic significance of bacterial infection in bleeding cirrhotic patients: a prospective study. Gastroenterology. 1995;108:1828–1834
  234. Vivas S, Rodriguez M, Palacio MA, Linares A, Alonso JL, Rodrigo L. Presence of bacterial infection in bleeding cirrhotic patients is independently associated with early mortality and failure to control bleeding. Dig Dis Sci. 2001;46:2752–2757
  235. Ben Ari Z, Cardin F, McCormick AP, Wannamethee G, Burroughs AK. A predictive model for failure to control bleeding during acute variceal haemorrhage. J Hepatol. 1999;31:443–450
  236. Del Olmo JA, Pena A, Serra MA, Wassel AH, Benages A, Rodrigo JM. Predictors of morbidity and mortality after the first episode of upper gastrointestinal bleeding in liver cirrhosis. J Hepatol. 2000;32:19–24
  237. Gatta A, Merkel C, Amodio P, Bellon S, Bellumat A, Bolognesi M, et al. Development and validation of a prognostic index predicting death after upper gastrointestinal bleeding in patients with liver cirrhosis: a multicenter study. Am J Gastroenterol. 1994;89:1528–1536

☆ J. Bosch served as a consultant for Axcam-Nicox and Astellas in 2007. The article does not describe the use of products from these companies. This study was supported in part by grants from Plan Nacional de I+D, and the Ministries of University and Research, Health, Education and Science (SAF-07/61298), and from Instituto de Salud Carlos III (FIS 06/0623 and 05/0519).

PII: S0168-8278(08)00077-9

doi: 10.1016/j.jhep.2008.01.021

Journal of Hepatology
Volume 48 , Pages S68-S92 , 2008

Article Tools

* Image Usage & Resolution