Die intestinale Blutung bei portaler Hypertension bei Leberzirrhose

Zusammenfassung

Die Prophylaxe und Behandlung der oberen intestinalen Blutung bei portaler Hypertension hat drei Ziele: Prophylaxe der ersten Blutung, Therapie der aktiven Blutung und Prophylaxe der Rezidivblutung. Hierfür steht eine ganze Reihe von Techniken zur Verfügung. Die Gabe eines nicht selektiven Betablockers ist bei großen Ösophagusvarizen nach wie vor die Therapie der Wahl zur Verhinderung der ersten Blutung. Alternativ kann jedoch auch ligiert werden. Die akute Blutung sollte endoskopisch (Ligatur) versorgt werden bei gleichzeitiger pharmakologischer und antibiotischer Therapie. Zur Rezidivblutungsprophylaxe muss individuell vorgegangen werden. Junge Patienten im Stadium Child A können nach wie vor durch eine offene Shuntoperation versorgt werden. Patienten mit schwer mobilisierbarem Aszites und einem Bilirubin unter 3 mg/dl sind gute Kandidaten für den Einsatz eines TIPS zur Prophylaxe der Rezidivblutung. Primär wird in Deutschland jedoch bei den meisten Patienten mit einer Ligaturbehandlung begonnen, die - zumindest nach der derzeitigen Studienlage - einer pharmakologischen Therapie nicht überlegen ist, vor allem, wenn diese unter einer hämodynamischen Kontrolle (Lebervenenverschlussdruck) vorgenommen wird. Blutungen aus extraösophagealen Quellen (hypertensive Gastropathie, Fundusvarizen) sollten individuell behandelt werden. Hier kommen die Injektionstherapie, der TIPS und auch die medikamentöse portaldrucksenkende Therapie zum Einsatz.

Abstract

There are three major goals in the prophylaxis and treatment of upper gastrointestinal bleeding in portal hypertensive patients: prophylaxis of the first bleeding episode, therapy of active bleeding and prophylaxis of recurrent bleeding. Several therapeutic options are available: non-selective beta-blockers are the treatment of choice in the primary prophylaxis of the first bleeding episode in patients with large esophageal varices. Alternatively, endoscopic band ligation therapy is an option. Acute bleeding varices should be treated by ligation pharmacological and antibiotic therapy. Prophylaxis of recurrent bleeding is patient-dependent: shunt surgery is an option in young patients in a good medical condition (Child-Pugh class A). In patients with refractory ascites and a bilirubin below 3 mg/dl, TIPS is a good option together with recurrent bleeding. At the moment, there are no trials showing that endoscopic ligation therapy is superior to prevent pharmacological therapy. Nevertheless, the first-line treatment in most patients in Germany is endoscopic band ligation. Bleeding from ectopic varices and bleeding from hypertensive gastropathy should be treated individually either by endoscopy, TIPS or drug therapy.

Obere Gastrointestinale Blutung - portale Hypertension - Ösophagusvarizen - Fundusvarizen - ektope Varizen - endoskopische Therapie - TIPS

Upper gastrointestinal bleeding - portal hypertension - esophageal varices - gastric varices - ectopic varices - endoscopic therapy - TIPS

Literatur

• 1 Cales P, Pascal J P. [Natural history of esophageal varices in cirrhosis (from origin to rupture)].  Gastroenterol Clin Biol. 1988;  12 245-254
• 2 D’Amico G, Pagliaro L, Bosch J. The treatment of portal hypertension: a meta-analytic review.  Hepatology. 1995;  22 332-354
• 3 Gines P, Quintero E, Arroyo V. et al . Compensated cirrhosis: natural history and prognostic factors.  Hepatology. 1987;  7 122-128
• 4 de Franchis R. Updating consensus in portal hypertension: report of the Baveno III Consensus Workshop on definitions, methodology and therapeutic strategies in portal hypertension.  J Hepatol. 2000;  33 846-852
• 5 The North Italian Endoscopic Club for the Study and Treatment of Esophageal Varices . Prediction of the first variceal hemorrhage in patients with cirrhosis of the liver and esophageal varices. A prospective multicenter study.  N Engl J Med. 1988;  319 983-989
• 6 Merkel C, Bolognesi M, Bellon S. et al . Prognostic usefulness of hepatic vein catheterization in patients with cirrhosis and esophageal varices.  Gastroenterology. 1992;  102 973-979
• 7 Kleber G, Sauerbruch T, Ansari H. et al . Prediction of variceal hemorrhage in cirrhosis: a prospective follow-up study.  Gastroenterology. 1991;  100 1332-1337
• 8 Sauerbruch T, Wotzka R, Kopcke W. et al . Prophylactic sclerotherapy before the first episode of variceal hemorrhage in patients with cirrhosis.  N Engl J Med. 1988;  319 8-15
• 9 D’Amico G, Luca A. Natural history. Clinical-haemodynamic correlations. Prediction of the risk of bleeding.  Baillieres Clin Gastroenterol. 1997;  11 243-256
• 10 Christensen E, Fauerholdt L, Schlichting P. et al . Aspects of the natural history of gastrointestinal bleeding in cirrhosis and the effect of prednisone.  Gastroenterology. 1981;  81 944-952
• 11 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
• 12 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
• 13 Garcia-Tsao G. Current management of the complications of cirrhosis and portal hypertension: variceal hemorrhage, ascites, and spontaneous bacterial peritonitis.  Gastroenterology. 2001;  120 726-748
• 14 Garcia-Pagan J C, Morillas R, Banares R. et al . Propranolol plus placebo versus propranolol plus isosorbide-5-mononitrate in the prevention of a first variceal bleed: a double-blind RCT.  Hepatology. 2003;  37 1260-1266
• 15 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
• 16 Abraldes J G, Tarantino I, Turnes J. et al . Hemodynamic response to pharmacological treatment of portal hypertension and long-term prognosis of cirrhosis.  Hepatology. 2003;  37 902-908
• 17 Sarin S K, Lamba G S, Kumar M. et al . Comparison of endoscopic ligation and propranolol for the primary prevention of variceal bleeding.  N Engl J Med. 1999;  340 988-993
• 18 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
• 19 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
• 20 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
• 21 Imperiale T F, Chalasani N. A meta-analysis of endoscopic variceal ligation for primary prophylaxis of esophageal variceal bleeding.  Hepatology. 2001;  33 802-807
• 22 Jalan R, Hayes P C. UK guidelines on the management of variceal haemorrhage in cirrhotic patients. British Society of Gastroenterology.  Gut. 2000;  46 (Suppl 3 - 4) III1-III15
• 23 Bernard B, Grange J D, Khac E N. et al . Antibiotic prophylaxis for the prevention of bacterial infections in cirrhotic patients with gastrointestinal bleeding: a meta-analysis.  Hepatology. 1999;  29 1655-1661
• 24 Blaise M, Pateron D, Trinchet J C. et al . Systemic antibiotic therapy prevents bacterial infection in cirrhotic patients with gastrointestinal hemorrhage.  Hepatology. 1994;  20 34-38
• 25 Soares-Weiser K, Brezis M, Tur-Kaspa R. et al . Antibiotic prophylaxis of bacterial infections in cirrhotic inpatients: a meta-analysis of randomized controlled trials.  Scand J Gastroenterol. 2003;  38 193-200
• 26 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
• 27 Conn H O, Ramsby G R, Storer E H. et al . Intraarterial vasopressin in the treatment of upper gastrointestinal hemorrhage: a prospective, controlled clinical trial.  Gastroenterology. 1975;  68 211-221
• 28 Bosch J, Groszmann R J, Garcia-Pagan J C. et al . Association of transdermal nitroglycerin to vasopressin infusion in the treatment of variceal hemorrhage: a placebo-controlled clinical trial.  Hepatology. 1989;  10 962-968
• 29 Gimson A E, Westaby D, Hegarty J. et al . A randomized trial of vasopressin and vasopressin plus nitroglycerin in the control of acute variceal hemorrhage.  Hepatology. 1986;  6 410-413
• 30 Fogel M R, Knauer C M, Andres L L. et al . Continuous intravenous vasopressin in active upper gastrointestinal bleeding.  Ann Intern Med. 1982;  96 565-569
• 31 Mallory A, Schaefer J W, Cohen J R. et al . Selective intra-arterial vasopression in fusion for upper gastrointestinal tract hemorrhage: a controlled trial.  Arch Surg. 1980;  115 30-32
• 32 Merigan T C Jr, Plotkin G R, Davidson C S. Effect of intravenously administered posterior pituitary extract on hemorrhage from bleeding esophageal varices. A controlled evaluation.  N Engl J Med. 1962;  266 134-135
• 33 Soderlund C, Ihre T. Endoscopic sclerotherapy v. conservative management of bleeding oesophageal varices. A 5-year prospective controlled trial of emergency and long-term treatment.  Acta Chir Scand. 1985;  151 449-456
• 34 Larson A W, Cohen H, Zweiban B. et al . Acute esophageal variceal sclerotherapy. Results of a prospective randomized controlled trial.  Jama. 1986;  255 497-500
• 35 Westaby D, Hayes P C, Gimson A E. et al . Controlled clinical trial of injection sclerotherapy for active variceal bleeding.  Hepatology. 1989;  9 274-277
• 36 Freeman J G, Cobden I, Record C O. Placebo-controlled trial of terlipressin (glypressin) in the management of acute variceal bleeding.  J Clin Gastroenterol. 1989;  11 58-60
• 37 Soderlund C, Magnusson I, Torngren S. et al . Terlipressin (triglycyl-lysine vasopressin) controls acute bleeding oesophageal varices. A double-blind, randomized, placebo-controlled trial.  Scand J Gastroenterol. 1990;  25 622-630
• 38 Levacher S, Letoumelin P, Pateron D. et al . Early administration of terlipressin plus glyceryl trinitrate to control active upper gastrointestinal bleeding in cirrhotic patients.  Lancet. 1995;  346 865-868
• 39 Chiu K W, Sheen I S, Liaw Y F. A controlled study of glypressin versus vasopressin in the control of bleeding from oesophageal varices.  J Gastroenterol Hepatol. 1990;  5 549-553
• 40 D’Amico G, Traina M, Vizzini G. et al . Terlipressin or vasopressin plus transdermal nitroglycerin in a treatment strategy for digestive bleeding in cirrhosis. A randomized clinical trial. Liver Study Group of V. Cervello Hospital.  J Hepatol. 1994;  20 206-212
• 41 Silvain C, Carpentier S, Sautereau D. et al . Terlipressin plus transdermal nitroglycerin vs. octreotide in the control of acute bleeding from esophageal varices: a multicenter randomized trial.  Hepatology. 1993;  18 61-65
• 42 Walker S, Kreichgauer H P, Bode J C. Terlipressin (glypressin) versus somatostatin in the treatment of bleeding esophageal varices - final report of a placebo-controlled, double-blind study.  Z Gastroenterol. 1996;  34 692-698
• 43 Bosch J, Kravetz D, Rodes J. Effects of somatostatin on hepatic and systemic hemodynamics in patients with cirrhosis of the liver: comparison with vasopressin.  Gastroenterology. 1981;  80 518-525
• 44 Bosch J, Kravetz D, Mastai R. et al . Effects of somatostatin in patients with portal hypertension.  Horm Res. 1988;  29 99-102
• 45 Bagarani M, Albertini V, Anza M. et al . Effect of somatostatin in controlling bleeding from esophageal varices.  Ital J Surg Sci. 1987;  17 21-26
• 46 Sung J J, Chung S C, Lai C W. et al . Octreotide infusion or emergency sclerotherapy for variceal haemorrhage.  Lancet. 1993;  342 637-641
• 47 Shields R, Jenkins S A, Baxter J N. et al . A prospective randomised controlled trial comparing the efficacy of somatostatin with injection sclerotherapy in the control of bleeding oesophageal varices.  J Hepatol. 1992;  16 128-137
• 48 Planas R, Quer J C, Boix J. et al . A prospective randomized trial comparing somatostatin and sclerotherapy in the treatment of acute variceal bleeding.  Hepatology. 1994;  20 370-375
• 49 Lin H C, Yang Y Y, Hou M C. et al . Hemodynamic effects of a combination of octreotide and terlipressin in patients with viral hepatitis related cirrhosis.  Scand J Gastroenterol. 2002;  37 482-487
• 50 Joannon G, Doust J, Rockey D C. Terlipressin for acute esophageal variceal hemorrhage. (Cochrane review).  Update Software. 2001; 
• 51 Gotzsche P C. Somatostatin or octreotide for acute bleeding oesophageal varices. (Cochrane review).  Update Software. 2001; 
• 52 Burroughs A K, Hamilton G, Phillips A. et al . A comparison of sclerotherapy with staple transection of the esophagus for the emergency control of bleeding from esophageal varices.  N Engl J Med. 1989;  321 857-862
• 53 Lo G H, Lai K H, Ng W W. et al . Injection sclerotherapy preceded by esophageal tamponade versus immediate sclerotherapy in arresting active variceal bleeding: a prospective randomized trial.  Gastrointest Endosc. 1992;  38 421-424
• 54 Moreto M, Zaballa M, Bernal A. et al . A randomized trial of tamponade or sclerotherapy as immediate treatment for bleeding esophageal varices.  Surg Gynecol Obstet. 1988;  167 331-334
• 55 Paquet K J, Feussner H. Endoscopic sclerosis and esophageal balloon tamponade in acute hemorrhage from esophagogastric varices: a prospective controlled randomized trial.  Hepatology. 1985;  5 580-583
• 56 Sclerotherapy after first variceal hemorrhage in cirrhosis. A randomized multicenter trial. The Copenhagen Esophageal Varices Sclerotherapy Project.  N Engl J Med. 1984;  311 1594-1600
• 57 Van Stiegmann G, Goff J S. Endoscopic esophageal varix ligation: preliminary clinical experience.  Gastrointest Endosc. 1988;  34 113-117
• 58 Laine L, el-Newihi H M, Migikovsky B. et al . Endoscopic ligation compared with sclerotherapy for the treatment of bleeding esophageal varices.  Ann Intern Med. 1993;  119 1-7
• 59 Stiegmann G V, Goff J S, Michaletz-Onody P A. et al . Endoscopic sclerotherapy as compared with endoscopic ligation for bleeding esophageal varices.  N Engl J Med. 1992;  326 1527-1532
• 60 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
• 61 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
• 62 Panes J, Teres J, Bosch J. et al . Efficacy of balloon tamponade in treatment of bleeding gastric and esophageal varices. Results in 151 consecutive episodes.  Dig Dis Sci. 1988;  33 454-459
• 63 Cook D, Laine L. Indications, technique, and complications of balloon tamponade for variceal gastrointestinal bleeding.  J Intensive Care Med. 1992;  7 212-218
• 64 McCormick P A, Dick R, Chin J. et al . Transjugular intrahepatic portosystemic stent-shunt.  Br J Hosp Med. 1993;  49 791-793, 796 - 797
• 65 Jalan R, John T G, Redhead D N. et al . A comparative study of emergency transjugular intrahepatic portosystemic stent-shunt and esophageal transection in the management of uncontrolled variceal hemorrhage.  Am J Gastroenterol. 1995;  90 1932-1937
• 66 Sanyal A J, Freedman A M, Luketic V A. et al . Transjugular intrahepatic portosystemic shunts for patients with active variceal hemorrhage unresponsive to sclerotherapy.  Gastroenterology. 1996;  111 138-146
• 67 Jalan R, Forrest E H, Stanley A J. et al . A randomized trial comparing transjugular intrahepatic portosystemic stent-shunt with variceal band ligation in the prevention of rebleeding from esophageal varices.  Hepatology. 1997;  26 1115-1122
• 68 Rossle M, Deibert P, Haag K. et al . Randomised trial of transjugular-intrahepatic-portosystemic shunt versus endoscopy plus propranolol for prevention of variceal rebleeding.  Lancet. 1997;  349 1043-1049
• 69 Sanyal A J, Freedman A M, Luketic V A. et al . The natural history of portal hypertension after transjugular intrahepatic portosystemic shunts.  Gastroenterology. 1997;  112 889-898
• 70 Jalan R, Elton R A, Redhead D N. et al . Analysis of prognostic variables in the prediction of mortality, shunt failure, variceal rebleeding and encephalopathy following the transjugular intrahepatic portosystemic stent-shunt for variceal haemorrhage.  J Hepatol. 1995;  23 123-128
• 71 Jabbour N, Zajko A B, Orons P D. et al . Transjugular intrahepatic portosystemic shunt in patients with end-stage liver disease: results in 85 patients.  Liver Transpl Surg. 1996;  2 139-147
• 72 Freedman A M, Sanyal A J, Tisnado J. et al . Complications of transjugular intrahepatic portosystemic shunt: a comprehensive review.  Radiographics. 1993;  13 1185-1210
• 73 Sanyal A J, Freedman A M, Purdum P P 3rd. TIPS-associated hemolysis and encephalopathy.  Ann Intern Med. 1992;  117 443-444
• 74 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
• 75 Rosemurgy A S, Goode S E, Zwiebel B R. et al . A prospective trial of transjugular intrahepatic portasystemic stent shunts versus small-diameter prosthetic H-graft portacaval shunts in the treatment of bleeding varices.  Ann Surg. 1996;  224 378-384; discussion 384 - 386
• 76 Teres J, Baroni R, Bordas J M. et al . Randomized trial of portacaval shunt, stapling transection and endoscopic sclerotherapy in uncontrolled variceal bleeding.  J Hepatol. 1987;  4 159-167
• 77 Lebrec D, Poynard T, Bernuau J. et al . A randomized controlled study of propranolol for prevention of recurrent gastrointestinal bleeding in patients with cirrhosis: a final report.  Hepatology. 1984;  4 355-358
• 78 Burroughs A K, Jenkins W J, Sherlock S. et al . Controlled trial of propranolol for the prevention of recurrent variceal hemorrhage in patients with cirrhosis.  N Engl J Med. 1983;  309 1539-1542
• 79 Villeneuve J P, Pomier-Layrargues G, Infante-Rivard C. et al . Propranolol for the prevention of recurrent variceal hemorrhage: a controlled trial.  Hepatology. 1986;  6 1239-1243
• 80 Colombo M, de Franchis R, Tommasini M. et al . Beta-blockade prevents recurrent gastrointestinal bleeding in well-compensated patients with alcoholic cirrhosis: a multicenter randomized controlled trial.  Hepatology. 1989;  9 433-438
• 81 Garden O J, Motyl H, Gilmour W H. et al . Prediction of outcome following acute variceal haemorrhage.  Br J Surg. 1985;  72 91-95
• 82 Gatta A, Merkel C, Sacerdoti D. et al . Nadolol for prevention of variceal rebleeding in cirrhosis: a controlled clinical trial.  Digestion. 1987;  37 22-28
• 83 Queuniet A M, Czernichow P, Lerebours E. et al . [Controlled study of propranolol in the prevention of recurrent hemorrhage in cirrhotic patients].  Gastroenterol Clin Biol. 1987;  11 41-47
• 84 Sheen I S, Chen T Y, Liaw Y F. Randomized controlled study of propranolol for prevention of recurrent esophageal varices bleeding in patients with cirrhosis.  Liver. 1989;  9 1-5
• 85 Rossi V, Cales P, Burtin P. et al . Prevention of recurrent variceal bleeding in alcoholic cirrhotic patients: prospective controlled trial of propranolol and sclerotherapy.  J Hepatol. 1991;  12 283-289
• 86 Garcia-Pagan J C, Feu F, Bosch J. et al . Propranolol compared with propranolol plus isosorbide-5-mononitrate for portal hypertension in cirrhosis. A randomized controlled study.  Ann Intern Med. 1991;  114 869-873
• 87 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
• 88 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
• 89 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
• 90 Thalheimer U, Mela M, Patch D. et al . Monitoring target reduction in hepatic venous pressure gradient during pharmacological therapy of portal hypertension: a close look at the evidence.  Gut. 2004;  53 143-148
• 91 Terblanche J, Bornman P C, Kahn D. et al . Failure of repeated injection sclerotherapy to improve long-term survival after oesophageal variceal bleeding. A five-year prospective controlled clinical trial.  Lancet. 1983;  2 1328-1332
• 92 Westaby D, Macdougall B R, Williams R. Improved survival following injection sclerotherapy for esophageal varices: final analysis of a controlled trial.  Hepatology. 1985;  5 827-830
• 93 Korula J, Balart L A, Radvan G. et al . A prospective, randomized controlled trial of chronic esophageal variceal sclerotherapy.  Hepatology. 1985;  5 584-589
• 94 Dasarathy S, Dwivedi M, Bhargava D K. et al . A prospective randomized trial comparing repeated endoscopic sclerotherapy and propranolol in decompensated (Child class B and C) cirrhotic patients.  Hepatology. 1992;  16 89-94
• 95 Westaby D, Polson R J, Gimson A E. et al . A controlled trial of oral propranolol compared with injection sclerotherapy for the long-term management of variceal bleeding.  Hepatology. 1990;  11 353-359
• 96 Dollet J M, Champigneulle B, Patris A. et al . Endoscopic sclerotherapy versus propranolol after hemorrhage caused by rupture of esophageal varices in patients with cirrhosis. Results of a 4-year randomized study.  Gastroenterol Clin Biol. 1988;  12 234-239
• 97 Martin T, Taupignon A, Lavignolle A. et al . Prevention of recurrent hemorrhage in patients with cirrhosis. Results of a controlled trial of propranolol versus endoscopic sclerotherapy.  Gastroenterol Clin Biol. 1991;  15 833-837
• 98 Teres J, Bosch J, Bordas J M. et al . Propranolol versus sclerotherapy in preventing variceal rebleeding: a randomized controlled trial.  Gastroenterology. 1993;  105 1508-1514
• 99 Lo G H, Lai K H, Cheng J S. et al . A prospective, randomized trial of sclerotherapy versus ligation in the management of bleeding esophageal varices.  Hepatology. 1995;  22 466-471
• 100 Gimson A E, Ramage J K, Panos M Z. et al . Randomised trial of variceal banding ligation versus injection sclerotherapy for bleeding oesophageal varices.  Lancet. 1993;  342 391-394
• 101 Hou M C, Lin H C, Kuo B I. et al . Comparison of endoscopic variceal injection sclerotherapy and ligation for the treatment of esophageal variceal hemorrhage: a prospective randomized trial.  Hepatology. 1995;  21 1517-1522
• 102 Hashizume M, Ohta M, Ueno K. et al . Endoscopic ligation of esophageal varices compared with injection sclerotherapy: a prospective randomized trial.  Gastrointest Endosc. 1993;  39 123-126
• 103 Laine L, Cook D. Endoscopic ligation compared with sclerotherapy for treatment of esophageal variceal bleeding. A meta-analysis.  Ann Intern Med. 1995;  123 280-287
• 104 Villanueva C, Minana 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
• 105 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
• 106 Sauer P, Theilmann L, Stremmel W. et al . Transjugular intrahepatic portosystemic stent shunt versus sclerotherapy plus propranolol for variceal rebleeding.  Gastroenterology. 1997;  113 1623-1631
• 107 Merli M, Salerno F, Riggio O. et al . Transjugular intrahepatic portosystemic shunt versus endoscopic sclerotherapy for the prevention of variceal bleeding in cirrhosis: a randomized multicenter trial. Gruppo Italiano Studio TIPS (G.I.S.T.).  Hepatology. 1998;  27 48-53
• 108 Garcia-Villarreal L, Martinez-Lagares F, Sierra A. et al . Transjugular intrahepatic portosystemic shunt versus endoscopic sclerotherapy for the prevention of variceal rebleeding after recent variceal hemorrhage.  Hepatology. 1999;  29 27-32
• 109 Cello J P, Ring E J, Olcott E W. et al . Endoscopic sclerotherapy compared with percutaneous transjugular intrahepatic portosystemic shunt after initial sclerotherapy in patients with acute variceal hemorrhage. A randomized, controlled trial.  Ann Intern Med. 1997;  126 858-865
• 110 Cabrera J, Maynar M, Granados R. et al . Transjugular intrahepatic portosystemic shunt versus sclerotherapy in the elective treatment of variceal hemorrhage.  Gastroenterology. 1996;  110 832-839
• 111 Sanyal A J, Freedman A M, Luketic V A. et al . Transjugular intrahepatic portosystemic shunts compared with endoscopic sclerotherapy for the prevention of recurrent variceal hemorrhage. A randomized, controlled trial.  Ann Intern Med. 1997;  126 849-857
• 112 Gulberg V, Schepke M, Geigenberger G. et al . Transjugular intrahepatic portosystemic shunting is not superior to endoscopic variceal band ligation for prevention of variceal rebleeding in cirrhotic patients: a randomized, controlled trial.  Scand J Gastroenterol. 2002;  37 338-343
• 113 Papatheodoridis G V, Goulis J, Leandro G. et al . Transjugular intrahepatic portosystemic shunt compared with endoscopic treatment for prevention of variceal rebleeding: A meta-analysis.  Hepatology. 1999;  30 612-622
• 114 Luca A, D’Amico G, La Galla R. et al . TIPS for prevention of recurrent bleeding in patients with cirrhosis: meta-analysis of randomized clinical trials.  Radiology. 1999;  212 411-421
• 115 Resnick R H, Iber F L, Ishihara A M. et al . A controlled study of the therapeutic portacaval shunt.  Gastroenterology. 1974;  67 843-857
• 116 Rueff B, Prandi D, Degos F. et al . A controlled study of therapeutic portacaval shunt in alcoholic cirrhosis.  Lancet. 1976;  1 655-659
• 117 Reichle F A, Fahmy W F, Golsorkhi M. Prospective comparative clinical trial with distal splenorenal and mesocaval shunts.  Am J Surg. 1979;  137 13-21
• 118 Reynolds T B, Donovan A J, Mikkelsen W P. et al . Results of a 12-year randomized trial of portacaval shunt in patients with alcoholic liver disease and bleeding varices.  Gastroenterology. 1981;  80 1005-1011
• 119 Langer B, Taylor B R, Mackenzie D R. et al . Further report of a prospective randomized trial comparing distal splenorenal shunt with end-to-side portacaval shunt. An analysis of encephalopathy, survival, and quality of life.  Gastroenterology. 1985;  88 424-429
• 120 Millikan W J Jr, Warren W D, Henderson J M. et al . The Emory prospective randomized trial: selective versus nonselective shunt to control variceal bleeding. Ten year follow-up.  Ann Surg. 1985;  201 712-722
• 121 Harley H A, Morgan T, Redeker A G. et al . Results of a randomized trial of end-to-side portacaval shunt and distal splenorenal shunt in alcoholic liver disease and variceal bleeding.  Gastroenterology. 1986;  91 802-809
• 122 Grace N D, Conn H O, Resnick R H. et al . Distal splenorenal vs. portal-systemic shunts after hemorrhage from varices: a randomized controlled trial.  Hepatology. 1988;  8 1475-1481
• 123 Rikkers L F, Burnett D A, Volentine G D. et al . Shunt surgery versus endoscopic sclerotherapy for long-term treatment of variceal bleeding. Early results of a randomized trial.  Ann Surg. 1987;  206 261-271
• 124 Henderson J M, Kutner M H, Millikan W J Jr. et al . Endoscopic variceal sclerosis compared with distal splenorenal shunt to prevent recurrent variceal bleeding in cirrhosis. A prospective, randomized trial.  Ann Intern Med. 1990;  112 262-269
• 125 Spina G P, Santambrogio R, Opocher E. et al . Distal splenorenal shunt versus endoscopic sclerotherapy in the prevention of variceal rebleeding. First stage of a randomized, controlled trial.  Ann Surg. 1990;  211 178-186
• 126 Planas R, Boix J, Broggi M. et al . Portacaval shunt versus endoscopic sclerotherapy in the elective treatment of variceal hemorrhage.  Gastroenterology. 1991;  100 1078-1086
• 127 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
• 128 Sauerbruch T, Schepke M. Variceal hemorrhage: primary and secondary prophylaxis.  Dtsch Med Wochenschr. 2004;  129 (Suppl 2) S68-S70
• 129 Sarin S K, Lahoti D, Saxena S P. et al . Prevalence, classification and natural history of gastric varices: a long-term follow-up study in 568 portal hypertension patients.  Hepatology. 1992;  16 1343-1349
• 130 Bosch J, Abraldes J G, Groszmann R. Current management of portal hypertension.  J Hepatol. 2003;  38 (Suppl 1) S54-S68
• 131 Tajiri T, Onda M, Yoshida H. et al . The natural history of gastric varices.  Hepatogastroenterology. 2002;  49 1180-1182
• 132 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
• 133 Lee Y T, Chan F K, Ng E K. et al . EUS-guided injection of cyanoacrylate for bleeding gastric varices.  Gastrointest Endosc. 2000;  52 168-174
• 134 Lo G H, Lai K H, Cheng J S. et al . A prospective, randomized trial of butyl cyanoacrylate injection versus band ligation in the management of bleeding gastric varices.  Hepatology. 2001;  33 1060-1064
• 135 Sarin S K, Jain A K, Jain M. et al . A randomized controlled trial of cyanoacrylate versus alcohol injection in patients with isolated fundic varices.  Am J Gastroenterol. 2002;  97 1010-1015
• 136 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
• 137 Chau T N, Patch D, Chan Y W. et al . „Salvage” transjugular intrahepatic portosystemic shunts: gastric fundal compared with esophageal variceal bleeding.  Gastroenterology. 1998;  114 981-987
• 138 Wu C Y, Yeh H Z, Chen G H. Pharmacologic efficacy in gastric variceal rebleeding and survival: including multivariate analysis.  J Clin Gastroenterol. 2002;  35 127-132
• 139 Sarin S K, Sreenivas D V, Lahoti D. et al . Factors influencing development of portal hypertensive gastropathy in patients with portal hypertension.  Gastroenterology. 1992;  102 994-999
• 140 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
• 141 Zhou Y, Qiao L, Wu J. et al . Comparison of the efficacy of octreotide, vasopressin, and omeprazole in the control of acute bleeding in patients with portal hypertensive gastropathy: a controlled study.  J Gastroenterol Hepatol. 2002;  17 973-979
• 142 Orloff M J, Orloff M S, Orloff S L. et al . Treatment of bleeding from portal hypertensive gastropathy by portacaval shunt.  Hepatology. 1995;  21 1011-1017
• 143 Urata J, Yamashita Y, Tsuchigame T. et al . The effects of transjugular intrahepatic portosystemic shunt on portal hypertensive gastropathy.  J Gastroenterol Hepatol. 1998;  13 1061-1067
• 144 Shimizu T, Onda M, Tajiri T. et al . Bleeding portal-hypertensive gastropathy managed successfully by partial splenic embolization.  Hepatogastroenterology. 2002;  49 947-949
• 145 Perez-Ayuso R M, Pique J M, Bosch J. et al . Propranolol in prevention of recurrent bleeding from severe portal hypertensive gastropathy in cirrhosis.  Lancet. 1991;  337 1431-1434
• 146 Burak K W, Lee S S, Beck P L. Portal hypertensive gastropathy and gastric antral vascular ectasia (GAVE) syndrome.  Gut. 2001;  49 866-872
• 147 Kamath P S, Lacerda M, Ahlquist D A. et al . Gastric mucosal responses to intrahepatic portosystemic shunting in patients with cirrhosis.  Gastroenterology. 2000;  118 905-911
• 148 Sebastian S, McLoughlin R, Qasim A. et al . Endoscopic argon plasma coagulation for the treatment of gastric antral vascular ectasia (watermelon stomach): long-term results.  Dig Liver Dis. 2004;  36 212-217
• 149 Yusoff I, Brennan F, Ormonde D. et al . Argon plasma coagulation for treatment of watermelon stomach.  Endoscopy. 2002;  34 407-410
• 150 Kinkhabwala M, Mousavi A, Iyer S. et al . Bleeding ileal varicosity demonstrated by transhepatic portography.  AJR Am J Roentgenol. 1977;  129 514-516
• 151 Tsuji H, Okano H, Fujino H. et al . A case of endoscopic injection sclerotherapy for a bleeding duodenal varix.  Gastroenterol Jpn. 1989;  24 60-64
• 152 Kirkpatrick J R, Shoenut J P, Micflikier A B. Successful injection sclerotherapy for bleeding duodenal varix in intrahepatic portal obstruction.  Gastrointest Endosc. 1985;  31 259-260
• 153 Gertsch P, Blumgart L H. Cure of a bleeding duodenal varix by sclerotherapy.  Br J Surg. 1988;  75 717
• 154 Sauerbruch T, Weinzierl M, Dietrich H P. et al . Sclerotherapy of a bleeding duodenal varix.  Endoscopy. 1982;  14 187-189
• 155 Bhasin D K, Sharma B C, Sriram P V. et al . Endoscopic management of bleeding ectopic varices with histoacryl.  HPB Surg. 1999;  11 171-173
• 156 Chen W C, Hou M C, Lin H C. et al . An endoscopic injection with N-butyl-2-cyanoacrylate used for colonic variceal bleeding: a case report and review of the literature.  Am J Gastroenterol. 2000;  95 540-542
• 157 Norton I D, Andrews J C, Kamath P S. Management of ectopic varices.  Hepatology. 1998;  28 1154-1158
• 158 Rikkers L F, Jin G, Burnett D A. et al . Shunt surgery versus endoscopic sclerotherapy for variceal hemorrhage: late results of a randomized trial.  Am J Surg. 1993;  165 27-32; discussion 32 - 33
• 159 Rahmani O, Wolpert L M, Drezner A D. Distal inferior mesenteric veins to renal vein shunt for treatment of bleeding anorectal varices: case report and review of literature.  J Vasc Surg. 2002;  36 1264-1266
• 160 Wang C S, Jeng L B, Chen M F. Duodenal variceal bleeding - successfully treated by mesocaval shunt after failure of sclerotherapy.  Hepatogastroenterology. 1995;  42 59-61
• 161 Wong R C, Berg C L. Portal hypertensive stomapathy: a newly described entity and its successful treatment by placement of a transjugular intrahepatic portosystemic shunt.  Am J Gastroenterol. 1997;  92 1056-1057
• 162 McChesney L, Jensen D, Matalon T. et al . Duodenal varices: a case report and review of the literature.  HPB Surg. 1995;  9 31-35
• 163 Johnson P A, Laurin J. Transjugular portosystemic shunt for treatment of bleeding stomal varices.  Dig Dis Sci. 1997;  42 440-442
• 164 Bernstein D I, Bernstein C K, Deng C. et al . Evaluation of the clinical efficacy and safety of grapeseed extract in the treatment of fall seasonal allergic rhinitis: a pilot study.  Ann Allergy Asthma Immunol. 2002;  88 272-278
• 165 Shibata D, Brophy D P, Gordon F D. et al . Transjugular intrahepatic portosystemic shunt for treatment of bleeding ectopic varices with portal hypertension.  Dis Colon Rectum. 1999;  42 1581-1585
• 166 Born P, Huber W, Neuhaus H. et al . [Hemorrhage caused by duodenal varices].  Dtsch Med Wochenschr. 1995;  120 1241-1247