Download PDF
Semin Liver Dis 2008; 28(1): 003-025
DOI: 10.1055/s-2008-1040318
© Thieme Medical Publishers

Portal Hypertension and Gastrointestinal Bleeding

Jaime Bosch1 , 2 , Juan G. Abraldes1 , 2 , Annalisa Berzigotti3 , 4 , Juan Carlos Garcia-Pagan1 , 2
  • 1Hepatic Hemodynamic Laboratory, Liver Unit, Institut d'Investigacions Biomediques August Pi i Sunyer (IDIBAPS), University of Barcelona, Spain
  • 2Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), University of Barcelona, Spain
  • 3Centre Diagnostic per la Imatge, Hospital Clinic, Barcelona, Spain
  • 4Department of Internal Medicine, Cardioangiology, Hepatology, Policlinico S. Orsola, University of Bologna, Italy
Further Information

Publication History

Publication Date:
22 February 2008 (online)

    Permissions and Reprints

ABSTRACT

Variceal bleeding is one of the most serious complications of portal hypertension. The driving force for the development of varices is an increase in portal pressure. As portal hypertension progresses, varices dilate until they finally rupture and bleed. This sequence of events might be prevented by achieving a sufficient decrease in portal pressure or by acting locally at the varices with endoscopic treatments. This article reviews the rationale for the management of portal hypertension and the current recommendations for the prevention and treatment of variceal bleeding.

KEYWORDS

Cirrhosis - varices - endoscopic band ligation - TIPS - β-adrenergic blockers - hepatic venous pressure gradient

REFERENCES

  • 1 Groszmann R J, Garcia-Tsao G, Bosch J et al.. Beta-blockers to prevent gastroesophageal varices in patients with cirrhosis.  N Engl J Med. 2005;  353 2254-2261
    CrossrefPubMedGoogle Scholar
  • 2 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
    CrossrefPubMedGoogle Scholar
  • 3 D'Amico G, Pagliaro L, Bosch J. The treatment of portal hypertension: a meta-analytic review.  Hepatology. 1995;  22 332-354
    CrossrefPubMedGoogle Scholar
  • 4 D'Amico G, Luca A. Natural history-clinical-haemodynamic correlations: prediction of the risk of bleeding.  Baillieres Clin Gastroenterol. 1997;  11 243-256
    CrossrefPubMedGoogle Scholar
  • 5 Garcia-Tsao G, Groszmann R J, Fisher R L, Conn H O, Atterbury C E, Glickman M. Portal pressure, presence of gastroesophageal varices and variceal bleeding.  Hepatology. 1985;  5 419-424
    CrossrefPubMedGoogle Scholar
  • 6 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
    CrossrefPubMedGoogle Scholar
  • 7 Merkel C, Marin R, Angeli P 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
    CrossrefPubMedGoogle Scholar
  • 8 Merli M, Nicolini G, Angeloni S et al.. Incidence and natural history of small esophageal varices in cirrhotic patients.  J Hepatol. 2003;  38 266-272
    CrossrefPubMedGoogle Scholar
  • 9 Zoli M, Merkel C, Magalotti D et al.. Natural history of cirrhotic patients with small esophageal varices: a prospective study.  Am J Gastroenterol. 2000;  95 503-508
    CrossrefPubMedGoogle Scholar
  • 10 de Franchis R. Evaluation and follow-up of patients with cirrhosis and oesophageal varices.  J Hepatol. 2003;  38 361-363
    CrossrefPubMedGoogle Scholar
  • 11 Cales P, Oberti F, Payen J L 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
    CrossrefPubMedGoogle Scholar
  • 12 Groszmann R J, Bosch J, Grace N D et al.. Hemodynamic events in a prospective randomized trial of propranolol versus placebo in the prevention of a first variceal hemorrhage [see comments].  Gastroenterology. 1990;  99 1401-1407
    CrossrefPubMedGoogle Scholar
  • 13 Vorobioff J, Groszmann R J, Picabea E et al.. Prognostic value of hepatic venous pressure gradient measurements in alcoholic cirrhosis: a 10-year prospective study.  Gastroenterology. 1996;  111 701-709
    CrossrefPubMedGoogle Scholar
  • 14 North Italian Endoscopic Club . 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 [see comments].  N Engl J Med. 1988;  319 983-989
    PubMedGoogle Scholar
  • 15 Casado M, Bosch J, Garcia-Pagan J C et al.. Clinical events after transjugular intrahepatic portosystemic shunt: correlation with hemodynamic findings.  Gastroenterology. 1998;  114 1296-1303
    CrossrefPubMedGoogle Scholar
  • 16 Feu F, Garcia-Pagan J C, Bosch J et al.. Relation between portal pressure response to pharmacotherapy and risk of recurrent variceal haemorrhage in patients with cirrhosis.  Lancet. 1995;  346 1056-1059
    CrossrefPubMedGoogle Scholar
  • 17 Bosch J, Garcia-Pagan J C, Berzigotti A, Abraldes J G. Measurement of portal pressure and its role in the management of chronic liver disease.  Semin Liver Dis. 2006;  26 348-362
    Article in Thieme ConnectPubMedGoogle Scholar
  • 18 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
    CrossrefPubMedGoogle Scholar
  • 19 Moitinho E, Escorsell A, Bandi J C et al.. Prognostic value of early measurements of portal pressure in acute variceal bleeding.  Gastroenterology. 1999;  117 626-631
    CrossrefPubMedGoogle Scholar
  • 20 Ripoll C, Banares R, Rincon D 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
    CrossrefPubMedGoogle Scholar
  • 21 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
    CrossrefPubMedGoogle Scholar
  • 22 Groszmann R J, Merkel C, Iwakiri Y et al.. Prevention of the formation of varices (pre-primary prophylaxis). In: de Franchis R Proceedings of the IV Baveno International Consensus Workshop on Definitions, Methodology and Therapeutic Strategies. Oxford; Blackwell-Science 2005: 103-151
    Google Scholar
  • 23 Eisen G M, Eliakim R, Zaman A 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
    Article in Thieme ConnectPubMedGoogle Scholar
  • 24 Lapalus M G, Dumortier J, Fumex F et al.. Esophageal capsule endoscopy versus esophagogastroduodenoscopy for evaluating portal hypertension: a prospective comparative study of performance and tolerance.  Endoscopy. 2006;  38 36-41
    Article in Thieme ConnectPubMedGoogle Scholar
  • 25 Frenette C, Kuldau J G, Hillebrand D, Lane J, Pockros P J. Comparison of esophageal pill endoscopy and conventional endoscopy for variceal screening.  Hepatology. 2006;  44(suppl 1) 445A
    PubMedGoogle Scholar
  • 26 D'Amico G, Morabito A. Noninvasive markers of esophageal varices: another round, not the last.  Hepatology. 2004;  39 30-34
    CrossrefPubMedGoogle Scholar
  • 27 de Franchis R. Noninvasive diagnosis of esophageal varices: is it feasible?.  Am J Gastroenterol. 2006;  101 2520-2522
    PubMedGoogle Scholar
  • 28 Chalasani N, Imperiale T F, Ismail A et al.. Predictors of large esophageal varices in patients with cirrhosis [see comments].  Am J Gastroenterol. 1999;  94 3285-3291
    CrossrefPubMedGoogle Scholar
  • 29 Giannini E, Botta F, Borro P 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
    CrossrefPubMedGoogle Scholar
  • 30 Sanyal A J, Fontana R J, Di Bisceglie A M et al.. The prevalence and risk factors associated with esophageal varices in subjects with hepatitis C and advanced fibrosis.  Gastrointest Endosc. 2006;  64 855-864
    CrossrefPubMedGoogle Scholar
  • 31 Schepis F, Camma C, Niceforo D et al.. Which patients with cirrhosis should undergo endoscopic screening for esophageal varices detection?.  Hepatology. 2001;  33 333-338
    CrossrefPubMedGoogle Scholar
  • 32 Vanbiervliet G, Barjoan-Marine E, Anty R et al.. Serum fibrosis markers can detect large oesophageal varices with a high accuracy.  Eur J Gastroenterol Hepatol. 2005;  17 333-338
    CrossrefPubMedGoogle Scholar
  • 33 Zoli M, Iervese T, Merkel C et al.. Prognostic significance of portal hemodynamics in patients with compensated cirrhosis.  J Hepatol. 1993;  17 56-61
    CrossrefPubMedGoogle Scholar
  • 34 Bolondi L, Gandolfi L, Arienti V et al.. Ultrasonography in the diagnosis of portal hypertension: diminished response of portal vessels to respiration.  Radiology. 1982;  142 167-172
    PubMedGoogle Scholar
  • 35 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
    CrossrefPubMedGoogle Scholar
  • 36 Berzigotti A, Casadei A, Magalotti D et al.. Renovascular impedance correlates with portal pressure in patients with liver cirrhosis.  Radiology. 2006;  240 581-586
    CrossrefPubMedGoogle Scholar
  • 37 Taourel P, Blanc P, Dauzat M 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
    CrossrefPubMedGoogle Scholar
  • 38 Cho K C, Patel Y D, Wachsberg R H, Seeff J. Varices in portal hypertension: evaluation with CT.  Radiographics. 1995;  15 609-622
    PubMedGoogle Scholar
  • 39 Johnson C D, Ehman R L, Rakela J, Ilstrup D M. MR angiography in portal hypertension: detection of varices and imaging techniques.  J Comput Assist Tomogr. 1991;  15 578-584
    PubMedGoogle Scholar
  • 40 Ziol M, Handra-Luca A, Kettaneh A et al.. Noninvasive assessment of liver fibrosis by measurement of stiffness in patients with chronic hepatitis C.  Hepatology. 2005;  41 48-54
    CrossrefPubMedGoogle Scholar
  • 41 Carrion J A, 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
    CrossrefPubMedGoogle Scholar
  • 42 Lemoine M, Katsahian S, Nahon P 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
    PubMedGoogle Scholar
  • 43 Bureau C, Metivier S, Peron J M et al.. Prospective assessment of liver stiffness for the non-invasive prediction of portal hypertension.  J Hepatol. 2007;  46(suppl 1) S34
    PubMedGoogle Scholar
  • 44 Vizzutti F, Arena U, Romanelli R G et al.. Liver stiffness measurement predicts severe portal hypertension in patients with HCV-related cirrhosis.  Hepatology. 2007;  45 1290-1297
    CrossrefPubMedGoogle Scholar
  • 45 Kazemi F, Kettaneh A, N'kontchou G et al.. Liver stiffness measurement selects patients with cirrhosis at risk of bearing large oesophageal varices.  J Hepatol. 2006;  45 230-235
    CrossrefPubMedGoogle Scholar
  • 46 Bosch J. Predictions from a hard liver.  J Hepatol. 2006;  45 174-177
    CrossrefPubMedGoogle Scholar
  • 47 Bosch J, Abraldes J G, Groszmann R J. Current management of portal hypertension.  J Hepatol. 2003;  38 S54-S68
    PubMedGoogle Scholar
  • 48 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
    Article in Thieme ConnectPubMedGoogle Scholar
  • 49 Wiest R, Groszmann R J. The paradox of nitric oxide in cirrhosis and portal hypertension: too much, not enough.  Hepatology. 2002;  35 478-491
    CrossrefPubMedGoogle Scholar
  • 50 Gupta T K, Toruner M, Chung M K, Groszmann R J. Endothelial dysfunction and decreased production of nitric oxide in the intrahepatic microcirculation of cirrhotic rats.  Hepatology. 1998;  28 926-931
    CrossrefPubMedGoogle Scholar
  • 51 Rockey D C, Chung J J. Reduced nitric oxide production by endothelial cells in cirrhotic rat liver: endothelial dysfunction in portal hypertension.  Gastroenterology. 1998;  114 344-351
    PubMedGoogle Scholar
  • 52 Hernandez-Guerra M, Garcia-Pagan J C, Turnes J et al.. Ascorbic acid improves the intrahepatic endothelial dysfunction of patients with cirrhosis and portal hypertension.  Hepatology. 2006;  43 485-491
    CrossrefPubMedGoogle Scholar
  • 53 Vorobioff J, Bredfeldt J, Groszmann R J. Hyperdynamic circulation in a portal hypertensive rat model: a primary factor for maintenance of chronic portal hypertension.  Am J Physiol. 1983;  244 G52-G56
    PubMedGoogle Scholar
  • 54 Pizcueta M P, Piqué J M, Bosch J, Whittle B J, Moncada S. Effects of inhibiting nitric oxide biosynthesis on the systemic and splanchnic circulation of rats with portal hypertension.  Br J Pharmacol. 1992;  105 184-190
    PubMedGoogle Scholar
  • 55 Pizcueta P, Piqué J M, Fernández M et al.. Modulation of the hyperdynamic circulation of cirrhotic rats by nitric oxide inhibition.  Gastroenterology. 1992;  103 1909-1915
    PubMedGoogle Scholar
  • 56 Garcia-Pagan J C, Salmeron J M, Feu F et al.. Effects of low-sodium diet and spironolactone on portal pressure in patients with compensated cirrhosis.  Hepatology. 1994;  19 1095-1099
    PubMedGoogle Scholar
  • 57 Bosch J, Thabut D, Bendtsen F et al.. Recombinant factor VIIa for upper gastrointestinal bleeding in patients with cirrhosis: a randomized, double-blind trial.  Gastroenterology. 2004;  127 1123-1130
    CrossrefPubMedGoogle Scholar
  • 58 Bosch J, Thabut D, Albillos A 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) S295
    PubMedGoogle Scholar
  • 59 D'Amico G, de Franchis R. Upper digestive bleeding in cirrhosis: post-therapeutic outcome and prognostic indicators.  Hepatology. 2003;  38 599-612
    PubMedGoogle Scholar
  • 60 D'Amico G, Pagliaro L, Bosch J. Pharmacological treatment of portal hypertension: an evidence-based approach.  Semin Liver Dis. 1999;  19 475-505
    PubMedGoogle Scholar
  • 61 Graham D Y, Smith J L. The course of patients after variceal hemorrhage.  Gastroenterology. 1981;  80 800-809
    CrossrefPubMedGoogle Scholar
  • 62 Bernard B, Cadranel J F, 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
    PubMedGoogle Scholar
  • 63 Goulis J, Armonis A, Patch D, Sabin C, Greenslade L, Burroughs A K. Bacterial infection is independently associated with failure to control bleeding in cirrhotic patients with gastrointestinal hemorrhage.  Hepatology. 1998;  27 1207-1212
    CrossrefPubMedGoogle Scholar
  • 64 Abraldes J G, Aracil C, Catalina M V et al.. Value of HVPG predicting 5-day treatment failure in acute variceal bleeding: comparison with clinical variables.  J Hepatol. 2006;  44(suppl 2) 12A
    PubMedGoogle Scholar
  • 65 Monescillo A, Martinez-Lagares F, Ruiz-del-Arbol L et al.. Influence of portal hypertension and its early decompression by TIPS placement on the outcome of variceal bleeding.  Hepatology. 2004;  40 793-801
    CrossrefPubMedGoogle Scholar
  • 66 Carbonell N, Pauwels A, Serfaty L, Fourdan O, Levy V G, Poupon R. Improved survival after variceal bleeding in patients with cirrhosis over the past two decades.  Hepatology. 2004;  40 652-659
    CrossrefPubMedGoogle Scholar
  • 67 Chalasani N, Kahi C, Francois F et al.. Improved patient survival after acute variceal bleeding: a multicenter, cohort study.  Am J Gastroenterol. 2003;  98 653-659
    PubMedGoogle Scholar
  • 68 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
    CrossrefPubMedGoogle Scholar
  • 69 Nidegger D, Ragot S, Berthelemy P et al.. Cirrhosis and bleeding: the need for very early management.  J Hepatol. 2003;  39 509-514
    CrossrefPubMedGoogle Scholar
  • 70 Cardenas A, Ginès P, Uriz J et al.. Renal failure after upper gastrointestinal bleeding in cirrhosis: incidence, clinical course, predictive factors, and short-term prognosis.  Hepatology. 2001;  34(4 Pt 1) 671-676
    CrossrefPubMedGoogle Scholar
  • 71 McCormick P A, Jenkins S A, McIntyre N, Burroughs A K. Why portal hypertensive varices bleed and bleed: a hypothesis.  Gut. 1995;  36 100-103
    CrossrefPubMedGoogle Scholar
  • 72 Castaneda B, Debernardi-Venon W, Bandi J C et al.. The role of portal pressure in the severity of bleeding in portal hypertensive rats.  Hepatology. 2000;  31 581-586
    CrossrefPubMedGoogle Scholar
  • 73 Villanueva C, Ortiz J, Miñana J et al.. Somatostatin treatment and risk stratification by continuous portal pressure monitoring during acute variceal bleeding.  Gastroenterology. 2001;  121 110-117
    CrossrefPubMedGoogle Scholar
  • 74 Morales J, Moitinho E, Abraldes J G, 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
    PubMedGoogle Scholar
  • 75 Ejlersen E, Melsen T, Ingerslev J, Andreasen R B, 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
    CrossrefPubMedGoogle Scholar
  • 76 Hou M C, Lin H C, Liu T T et al.. Antibiotic prophylaxis after endoscopic therapy prevents rebleeding in acute variceal hemorrhage: a randomized trial.  Hepatology. 2004;  39 746-753
    CrossrefPubMedGoogle Scholar
  • 77 Bernard B, Grange J D, Khac E N, 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
    CrossrefPubMedGoogle Scholar
  • 78 Rimola A, Garcia-Tsao G, Navasa M et al.. Diagnosis, treatment and prophylaxis of spontaneous bacterial peritonitis: a consensus document. International Ascites Club.  J Hepatol. 2000;  32 142-153
    PubMedGoogle Scholar
  • 79 Fernandez J, Ruiz-del-Arbol L, Gomez C, Durandez R et al.. Norfloxacin vs ceftriaxone in the prophylaxis of infections in patients with advanced cirrhosis and hemorrhage.  Gastroenterology. 2006;  131 1049-1056
    CrossrefPubMedGoogle Scholar
  • 80 Levacher S, Letoumelin P, Pateron D, Blaise M, Lapandry C, Pourriat J L. Early administration of terlipressin plus glyceryl trinitrate to control active upper gastrointestinal bleeding in cirrhotic patients.  Lancet. 1995;  346 865-868
    CrossrefPubMedGoogle Scholar
  • 81 Abraldes J G, Bosch J. Somatostatin and analogues in portal hypertension.  Hepatology. 2002;  35 1305-1312
    CrossrefPubMedGoogle Scholar
  • 82 Escorsell A, Ruiz-del-Arbol L, Planas R, Albillos A 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
    CrossrefPubMedGoogle Scholar
  • 83 Ioannou G N, Doust J, Rockey D C. Systematic review: terlipressin in acute oesophageal variceal haemorrhage.  Aliment Pharmacol Ther. 2003;  17 53-64
    PubMedGoogle Scholar
  • 84 Uriz J, Ginès P, Cardenas A et al.. Terlipressin plus albumin infusion: an effective and safe therapy of hepatorenal syndrome.  J Hepatol. 2000;  33 43-48
    PubMedGoogle Scholar
  • 85 Escorsell A, Bordas J M, del Arbol L 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
    CrossrefPubMedGoogle Scholar
  • 86 Moitinho E, Planas R, Bañares R et al.. Multicenter randomized controlled trial comparing different schedules of somatostatin in the treatment of acute variceal bleeding.  J Hepatol. 2001;  35 712-718
    CrossrefPubMedGoogle Scholar
  • 87 Villanueva C, Ortiz J, Sabat M 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
    CrossrefPubMedGoogle Scholar
  • 88 Escorsell A, Bandi J C, Andreu V et al.. Desensitization to the effects of intravenous octreotide in cirrhotic patients with portal hypertension.  Gastroenterology. 2001;  120 161-169
    CrossrefPubMedGoogle Scholar
  • 89 Burroughs A K. International Octreotide Varices Study Group . Double blind RCT of 5 day octreotide versus placebo, associated with sclerotherapy for trial failures.  Hepatology. 1996;  24 352A
    CrossrefPubMedGoogle Scholar
  • 90 Corley D A, Cello J P, Adkisson W, Ko W F, Kerlikowske K. Octreotide for acute esophageal variceal bleeding: a meta-analysis.  Gastroenterology. 2001;  120 946-954
    CrossrefPubMedGoogle Scholar
  • 91 Lo G H, Lai K H, Cheng J S et al.. Emergency banding ligation versus sclerotherapy for the control of active bleeding from esophageal varices.  Hepatology. 1997;  25 1101-1104
    CrossrefPubMedGoogle Scholar
  • 92 Villanueva C, Piqueras M, Aracil C 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
    CrossrefPubMedGoogle Scholar
  • 93 Avgerinos A, Armonis A, Stefanidis G et al.. Sustained rise of portal pressure after sclerotherapy, but not band ligation, in acute variceal bleeding in cirrhosis.  Hepatology. 2004;  39 1623-1630
    CrossrefPubMedGoogle Scholar
  • 94 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
    CrossrefPubMedGoogle Scholar
  • 95 Cales P, Masliah C, Bernard B 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
    CrossrefPubMedGoogle Scholar
  • 96 Bañares R, Albillos A, Rincón D et al.. Endoscopic treatment versus endoscopic plus pharmacologic treatment for acute variceal bleeding: a meta-analysis.  Hepatology. 2002;  35 609-615
    CrossrefPubMedGoogle Scholar
  • 97 Hubmann R, Bodlaj G, Czompo M et al.. The use of self-expanding metal stents to treat acute esophageal variceal bleeding.  Endoscopy. 2006;  38 896-901
    Article in Thieme ConnectPubMedGoogle Scholar
  • 98 Bosch J. Salvage transjugular intrahepatic portosystemic shunt: is it really life-saving?.  J Hepatol. 2001;  35 658-660
    CrossrefPubMedGoogle Scholar
  • 99 Patch D, Nikolopoulou V, McCormick A 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
    CrossrefPubMedGoogle Scholar
  • 100 Sarin S K, Lahoti D, Saxena S P, Murthy N S, Makwana U K. Prevalence, classification and natural history of gastric varices: a long-term follow-up study in 568 portal hypertension patients.  Hepatology. 1992;  16 1343-1349
    CrossrefPubMedGoogle Scholar
  • 101 Terés J, Cecilia A, Bordas J M, Rimola A, Bru C, Rodés J. Esophageal tamponade for bleeding varices: controlled trial between the Sengstaken-Blakemore tube and the Linton-Nachlas tube.  Gastroenterology. 1978;  75 566-569
    PubMedGoogle Scholar
  • 102 Panés J, Terés J, Bosch J, Rodés 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
    CrossrefPubMedGoogle Scholar
  • 103 Sarin S K, Agarwal S R. Gastric varices and portal hypertensive gastropathy.  Clin Liver Dis. 2001;  5 727-767
    CrossrefPubMedGoogle Scholar
  • 104 Huang Y H, Yeh H Z, Chen G H 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
    CrossrefPubMedGoogle Scholar
  • 105 Lo G H, Lai K H, Cheng J S, Chen M H, Chiang H T. A prospective, randomized trial of butyl cyanoacrylate injection versus band ligation in the management of bleeding gastric varices.  Hepatology. 2001;  33 1060-1064
    CrossrefPubMedGoogle Scholar
  • 106 Tan P C, Hou M C, Lin H C 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
    CrossrefPubMedGoogle Scholar
  • 107 Sarin S K, Jain A K, 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
    CrossrefPubMedGoogle Scholar
  • 108 Chau T N, Patch D, Chan Y W, Nagral A, Dick R, Burroughs A K. “Salvage” transjugular intrahepatic portosystemic shunts: gastric fundal compared with esophageal variceal bleeding.  Gastroenterology. 1998;  114 981-987
    PubMedGoogle Scholar
  • 109 Barange K, Peron J M, Imani K et al.. Transjugular intrahepatic portosystemic shunt in the treatment of refractory bleeding from ruptured gastric varices.  Hepatology. 1999;  30 1139-1143
    CrossrefPubMedGoogle Scholar
  • 110 Primignani M, Carpinelli L, Preatoni P 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
    CrossrefPubMedGoogle Scholar
  • 111 Panés J, Bordas J M, Piqué J M et al.. Effects of propranolol on gastric mucosal perfusion in cirrhotic patients with portal hypertensive gastropathy.  Hepatology. 1993;  17 213-218
    PubMedGoogle Scholar
  • 112 Panés J, Piqué J M, Bordas J M et al.. Reduction of gastric hyperemia by glypressin and vasopressin administration in cirrhotic patients with portal hypertensive gastropathy.  Hepatology. 1994;  19 55-60
    CrossrefPubMedGoogle Scholar
  • 113 Panés J, Piqué J M, Bordas J M 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
    PubMedGoogle Scholar
  • 114 Panés J, Casadevall M, Fernández M et al.. Gastric microcirculatory changes of portal-hypertensive rats can be attenuated by long-term estrogen-progestagen treatment.  Hepatology. 1994;  20 1261-1270
    CrossrefPubMedGoogle Scholar
  • 115 Kouroumalis E A, Koutroubakis I E, Manousos O N. Somatostatin for acute severe bleeding from portal hypertensive gastropathy.  Eur J Gastroenterol Hepatol. 1998;  10 509-512
    CrossrefPubMedGoogle Scholar
  • 116 Sarin S K, Groszmann R J, Mosca P G 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
    PubMedGoogle Scholar
  • 117 Fernandez M, Vizzutti F, Garcia-Pagan J C, 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
    CrossrefPubMedGoogle Scholar
  • 118 Fernandez M, Mejias M, Angermayr B, Garcia-Pagan J C, Rodés 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
    CrossrefPubMedGoogle Scholar
  • 119 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
    CrossrefPubMedGoogle Scholar
  • 120 Spiegel B M, Targownik L, Dulai G S, Karsan H A, Gralnek I M. Endoscopic screening for esophageal varices in cirrhosis: is it ever cost-effective?.  Hepatology. 2003;  37 366-377
    CrossrefPubMedGoogle Scholar
  • 121 Arguedas M R, Heudebert G R, Eloubeidi M A, Abrams G A, Fallon M B. Cost-effectiveness of screening, surveillance, and primary prophylaxis strategies for esophageal varices.  Am J Gastroenterol. 2002;  97 2441-2452
    CrossrefPubMedGoogle Scholar
  • 122 Imperiale T F, Chalasani N. A meta-analysis of endoscopic variceal ligation for primary prophylaxis of esophageal variceal bleeding.  Hepatology. 2001;  33 802-807
    CrossrefPubMedGoogle Scholar
  • 123 Lo G H, Chen W C, Chen M H et al.. Endoscopic ligation vs. nadolol in the prevention of first variceal bleeding in patients with cirrhosis.  Gastrointest Endosc. 2004;  59 333-338
    CrossrefPubMedGoogle Scholar
  • 124 Chen C Y, Sheu M Z, Tsai T L, Lin Y L. Endoscopic variceal ligation with multiple band ligator for prophylaxis of first hemorrage esophageal varices.  Endoscopy. 1999;  31(suppl 1) 35A
    PubMedGoogle Scholar
  • 125 Schepke M, Kleber G, Nurnberg D et al.. Ligation versus propranolol for the primary prophylaxis of variceal bleeding in cirrhosis.  Hepatology. 2004;  40 65-72
    CrossrefPubMedGoogle Scholar
  • 126 Song H, Shin J W, Kim H I 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(suppl 2) 41A
    PubMedGoogle Scholar
  • 127 Sarin S K, Lamba G S, Kumar M, Misra A, Murthy N S. Comparison of endoscopic ligation and propranolol for the primary prevention of variceal bleeding [see comments].  N Engl J Med. 1999;  340 988-993
    CrossrefPubMedGoogle Scholar
  • 128 de la Mora G, Farca-Belsaguy A A, 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
    PubMedGoogle Scholar
  • 129 Lui H F, Stanley A J, Forrest E H et al.. Primary prophylaxis of variceal hemorrhage: a randomized controlled trial comparing band ligation, propranolol, and isosorbide mononitrate.  Gastroenterology. 2002;  123 735-744
    CrossrefPubMedGoogle Scholar
  • 130 Jutabha R, Jensen D M, Martin P, Savides T, Han S H, 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
    CrossrefPubMedGoogle Scholar
  • 131 Thuluvath P J, 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
    CrossrefPubMedGoogle Scholar
  • 132 De B K, Ghoshal U C, Das T, Santra A, Biswas P K. Endoscopic variceal ligation for primary prophylaxis of oesophageal variceal bleed: preliminary report of a randomized controlled trial.  J Gastroenterol Hepatol. 1999;  14 220-224
    CrossrefPubMedGoogle Scholar
  • 133 Drastich P, Lata J, Petrtyl J 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
    PubMedGoogle Scholar
  • 134 Lay C S, Tsai Y T, Lee F Y et al.. Endoscopic variceal ligation versus propranolol in prophylaxis of first variceal bleeding in patients with cirrhosis.  J Gastroenterol Hepatol. 2006;  21 413-419
    CrossrefPubMedGoogle Scholar
  • 135 Psilopoulos D, Galanis P, Goulas S 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
    CrossrefPubMedGoogle Scholar
  • 136 Abdelfattah M H, Rashed M A, Elfakhry A A, Soliman M A, Shiha G H. Endoscopic variceal ligation versus pharmacological treatment for primary prophylaxis of variceal bleeding: a randomized study.  J Hepatol. 2006;  44(suppl 2) 83A
    PubMedGoogle Scholar
  • 137 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(suppl 1) 38A
    PubMedGoogle Scholar
  • 138 Norberto L, Polese L, Cillo U 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
    CrossrefPubMedGoogle Scholar
  • 139 Khuroo M S, Khuroo N S, Farahat K L, Khuroo Y S, Sofi A A, Dahab S T. Meta-analysis: endoscopic variceal ligation for primary prophylaxis of oesophageal variceal bleeding.  Aliment Pharmacol Ther. 2005;  21 347-361
    CrossrefPubMedGoogle Scholar
  • 140 Garcia-Pagan J C, Bosch J. Endoscopic band ligation in the treatment of portal hypertension.  Nat Clin Pract Gastroenterol Hepatol. 2005;  2 526-535
    PubMedGoogle Scholar
  • 141 Abraczinskas D R, Ookubo R, Grace N D et al.. Propranolol for the prevention of first esophageal variceal hemorrhage: a lifetime commitment?.  Hepatology. 2001;  34 1096-1102
    CrossrefPubMedGoogle Scholar
  • 142 Turnes J, Garcia-Pagan J C, Abraldes J G, 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
    CrossrefPubMedGoogle Scholar
  • 143 Imperiale T F, Klein R W, Chalasani N. Cost-effectiveness analysis of variceal ligation vs. beta-blockers for primary prevention of variceal bleeding.  Hepatology. 2007;  45 870-878
    CrossrefPubMedGoogle Scholar
  • 144 Triantos C, Vlachogiannakos J, Armonis A et al.. Primary prophylaxis of variceal bleeding in cirrhotics unable to take beta-blockers: a randomized trial of ligation.  Aliment Pharmacol Ther. 2005;  21 1435-1443
    CrossrefPubMedGoogle Scholar
  • 145 Sarin S K, Wadhawan M, Agarwal S R, Tyagi P, Sharma B C. Endoscopic variceal ligation plus propranolol versus endoscopic variceal ligation alone in primary prophylaxis of variceal bleeding.  Am J Gastroenterol. 2005;  100 797-804
    CrossrefPubMedGoogle Scholar
  • 146 Imperiale T F, Chalasani N, Klein R W. Measuring the hemodynamic response to primary pharmacoprophylaxis of variceal bleeding: a cost-effectiveness analysis.  Am J Gastroenterol. 2003;  98 2742-2750
    CrossrefPubMedGoogle Scholar
  • 147 Hicken B L, Sharara A I, Abrams G A, Eloubeidi M, Fallon M B, Arguedas M R. 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
    PubMedGoogle Scholar
  • 148 Bureau C, Peron J M, Alric L 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
    CrossrefPubMedGoogle Scholar
  • 149 Garcia-Pagan J C, 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
    PubMedGoogle Scholar
  • 150 Merkel C, Marin R, Enzo E 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) [see comments].  Lancet. 1996;  348 1677-1681
    CrossrefPubMedGoogle Scholar
  • 151 Merkel C, Marin R, Sacerdoti D 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
    CrossrefPubMedGoogle Scholar
  • 152 Garcia-Pagan J, Morillas R, Bañares R 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
    CrossrefPubMedGoogle Scholar
  • 153 Yoshida H, Mamada Y, Taniai N 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
    CrossrefPubMedGoogle Scholar
  • 154 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
    PubMedGoogle Scholar
  • 155 Gournay J, Masliah C, Martin T, Perrin D, Galmiche J P. Isosorbide mononitrate and propranolol compared with propranolol alone for the prevention of variceal rebleeding.  Hepatology. 2000;  31 1239-1245
    CrossrefPubMedGoogle Scholar
  • 156 Rosalia P, Pasta L, D'Amico G et al.. Isosorbide mononitrate with nadolol compared to nadolol alone for prevention of recurrent bleeding in cirrhosis: a double blind placebo controlled randomized trial-final report.  J Hepatol. 2001;  34(suppl 1) 63A
    PubMedGoogle Scholar
  • 157 Villanueva C, Balanzo J, Novella M T et al.. Nadolol plus isosorbide mononitrate compared with sclerotherapy for the prevention of variceal rebleeding.  N Engl J Med. 1996;  334 1624-1629
    CrossrefPubMedGoogle Scholar
  • 158 Villanueva C, Miñana J, Ortiz J 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
    CrossrefPubMedGoogle Scholar
  • 159 Patch D, Sabin C A, Goulis J 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
    CrossrefPubMedGoogle Scholar
  • 160 Lo G H, Chen W C, Chen M H et al.. Banding ligation versus nadolol and isosorbide mononitrate for the prevention of esophageal variceal rebleeding.  Gastroenterology. 2002;  123 728-734
    CrossrefPubMedGoogle Scholar
  • 161 Romero G, Kravetz D, Argonz J 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
    CrossrefPubMedGoogle Scholar
  • 162 Escorsell A, Banares R, Garcia-Pagan J C et al.. TIPS versus drug therapy in preventing variceal rebleeding in advanced cirrhosis: a randomized controlled trial.  Hepatology. 2002;  35 385-392
    CrossrefPubMedGoogle Scholar
  • 163 Lo G H, Lai K H, Cheng J S 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
    CrossrefPubMedGoogle Scholar
  • 164 de la Pena J, Brullet E, Sanchez-Hernandez E, Rivero M et al.. Variceal ligation plus nadolol compared with ligation for prophylaxis of variceal rebleeding: a multicenter trial.  Hepatology. 2005;  41 572-578
    CrossrefPubMedGoogle Scholar
  • 165 Spanish Cooperative Variceal Rebleeding Study Group . 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
    PubMedGoogle Scholar
  • 166 Rosemurgy A S, Serafini F M, Zweibel B R 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
    CrossrefPubMedGoogle Scholar
  • 167 Henderson J M, Boyer T D, Kutner M H et al.. Distal splenorenal shunt versus transjugular intrahepatic portal systematic shunt for variceal bleeding: a randomized trial.  Gastroenterology. 2006;  130 1643-1651
    CrossrefPubMedGoogle Scholar
  • 168 Bureau C, Garcia-Pagan J C, Otal P et al.. Improved clinical outcome using polytetrafluoroethylene-coated stents for tips: results of a randomized study.  Gastroenterology. 2004;  126 469-475
    CrossrefPubMedGoogle Scholar
  • 169 D'Amico G, Garcia-Pagan J C, Luca A, Bosch J. Hepatic vein pressure gradient reduction and prevention of variceal bleeding in cirrhosis: a systematic review.  Gastroenterology. 2006;  131 1611-1624
    CrossrefPubMedGoogle Scholar
  • 170 Bosch J, Garcia-Pagan J. Prevention of variceal rebleeding.  Lancet. 2003;  361 952-954
    CrossrefPubMedGoogle Scholar
  • 171 Targownik L E, Spiegel B M, Dulai G S, Karsan H A, Gralnek I M. The cost-effectiveness of hepatic venous pressure gradient monitoring in the prevention of recurrent variceal hemorrhage.  Am J Gastroenterol. 2004;  99 1306-1315
    CrossrefPubMedGoogle Scholar
  • 172 Gonzalez A, Augustin S, Perez M et al.. Hemodynamic response-guided therapy for prevention of variceal rebleeding: an uncontrolled pilot study.  Hepatology. 2006;  44 806-812
    CrossrefPubMedGoogle Scholar
  • 173 Perez-Ayuso R M, Piqué J M, Bosch J et al.. Propranolol in prevention of recurrent bleeding from severe portal hypertensive gastropathy in cirrhosis.  Lancet. 1991;  337 1431-1434
    CrossrefPubMedGoogle Scholar
  • 174 Escorsell A, Bosch J. Pathophysiology of variceal bleeding. In: Groszmann RJ, Bosch J Portal Hypertension in the 21st Century. Dordrecht/Boston/London; Kluwer Academic Publishers 2004: 155-166
    Google Scholar

Professor Jaime BoschM.D. Ph.D. 

Hepatic Hemodynamic Laboratory, Liver Unit, Hospital Clínic, Villarroel 170

08036 Barcelona, Spain

Email: jbosch@clinic.ub.es

      >