medigraphic.com
Órgano Oficial de la Asociación Mexicana de Hepatología

2002, Number 3

<< Back Next >>

Ann Hepatol 2002; 1 (3)

Drug treatment for portal hypertension

Mela M, Mancuso A, Burroughs HA

Language: English
References: 175
Page: 102-120
PDF size: 124.05 Kb.


Text Extraction

Pharmacological treatment of portal hypertension has played an increasing clinical role in the past 20 years. In the setting of acute variceal bleeding, drug therapy should be considered the initial treatment of choice and can be administered as soon as possible; even during the transfer of the patient to hospital. Several recent trials have reported similar efficacy to emergency sclerotherapy, therefore drug treatment should no longer be considered as a “stop gap” therapy until definitive endoscopic therapy is performed but continued for several days. Antibiotic prophylaxis is an integral part of therapy as it reduces mortality and should be instituted from admission. Non selective b-blockers are the treatment of first choice for secondary and primary prevention. If they are contraindicated or non tolerated banding ligation can be used. There is less evidence for the benefit of ligation for primary prophylaxis. The use of haemodynamic targets for reduction in hepatic venous pressure gradient response need further study, and surrogate markers of pressure response need evaluation.


REFERENCES

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

  2. The North Italian Endoscopic Group for the Study and treatment in Esophageal Varices: Prediction of the first variceal hemorraghe in patients with cirrhosis of the liver and esophageal varices: a prospective multicenter study. N Engl J Med 1988; 319: 983-989.

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

  4. Hartigan PM, Gebhard RL, Gregory BP. Sclerotherapy for active bleeding eosophageal varices on male alcoholics with cirrhosis. Gastrointest Endosc 1997; 46: 1-7.

  5. Bernard B, Cadranel JF, Valla D, Escolano S, Jarlier V, Opolon P. Prognostic significance of bacterial infections in bleeding cirrhotic patients: a prospective study. Gastroenterology 1995; 108: 1824-1834.

  6. 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.

  7. Vivas S, Rodriguez M, Palacio M, 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.

  8. Bernard B, Nguyen KE, Nguyen KE, Opolon P, Poynard T. Antibiotic prophylaxis (AbP) for the prevention of bacterial infections in cirrhotic patients with gastrointestinal bleeding (GB): A meta-analysis. Hepatology 1999; 29: 1655-1661.

  9. Soares-Weiser K, Brezis M, Tur-Kaspa R, Leibovici L. Antibiotic prophylaxis for cirrhotic patients with gastrointestinal bleeding. Cochrane Database Syst Rev 2002; (2): CD002907.

  10. Dagher L, Patch D, Burroughs A. Drug treatment for bleeding oesophageal varices. Baillieres Clin Gastroenterol 2000; 14(3): 365-390.

  11. Imperiale TF, Teran JC, McCullough AJ. A meta-analysis of somatostatin versus vasopressin in the management of acute oesophageal variceal haemorrhage. Gastroenterology 1995; 109: 1289-1294.

  12. Soderlund C, Ihre T. Endoscopic sclerotherapy versus 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.

  13. Larson AW, Cohen H, Zweiban B, Chapman D, Gourdji M, Korula J, Weiner J. Acute oesophageal variceal sclerotherapy. Results of a prospective randomized controlled trial. JAMA 1986; 255: 497-500.

  14. Westaby D, Hayes PC, Gimson AE, Polson RJ, Williams R. Controlled trial of injection sclerotherapy for active variceal bleeding. Hepatology 1989; 9: 274-277.

  15. Alexandrino P, Alves MM, Fidalgo B. Is sclerotherapy the first choice treatment for active variceal bleeding in cirrhotic patients? Final report of a randomized clinical trial. J Hepatol 1990; 11(suppl): S1.

  16. Romero G, Kravetz D, Argonz J, Bildozola M, Suarez A, Terg R. Terlipressin is more effective in decreasing variceal pressure than portal pressure in cirrhotic patients. J Hepatol 2000; 32: 419-425.

  17. Halimi C, Bonnard P, Bernard B, Mathurin P, Mofredj A, di Martin V, Demontis R, et al. Effect of terlipressin (Glypressin) on hepatorenal syndrome in cirrhotic patients: results of a multicentre pilot study. Eur J Gastroenterol Hepatol 2002; 14: 153-158.

  18. Moreau R, Durand F, Poynard D, Duhamel C, Cervoni JP, Ichai P, Abergel A, et al. Terlipressin in patients with cirrhosis and type 1 hepatorenal syndrome: a prospective multicentre study. Gastroenterology 2002; 122: 923-930.

  19. Ioannou G, Doust J, Rockey DC. Terlipressin for acute variceal haemorrhage. Cochrane Database Syst Rev 2001; (1): CD002147.

  20. Levacher S, Letoumelin O, 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.

  21. Colin R, Giuli N, Czernichow P, Ducrotte P, Lerebours E. Prospective comparison of glypressin, tamponade and their association in the treatment of bleeding esophageal varices. In: Vasopressin analogs and portal hypertension. Edited by Lebrec D, Blei AT. Paris: Libbey Eurotext; 1987: 149-153.

  22. Fort E, Sauterau D, Silvaine C, Ingrand P, Pilegrand B, Beauchant M. A randomized trial of terlipressin plus nitroglycerin vs balloon tamponade in the control of acute variceal haemorrhage. Hepatology 1990; 11: 678-681.

  23. Blanc P, Bories J, Desprez D, Pageaux GP, David XR, Diaz D, Larrey D, et al. Balloon tamponade with Linton-Michel tube versus terlipressin in the treatment of acute oesophageal and gastric variceal bleeding (abstract). J Hepatol 1994; 21: S133.

  24. Escorsell A, Del Arbor LR, Planas R, Albillos A, Banarez R, Cales P, Pateron D, et al. Multicentre randomized controlled trial of terlipressin versus sclerotherapy in the treatment of acute variceal bleeding. The TEST study. Hepatology 2000; 32: 471-476.

  25. Reynaert H, Vaeyens F, Qin H, Hellemans K, Chatterjee N, Winand D, Quartier E, et al. Somatostatin suppresses endothelin-1-induced rat hepatic stellate cell contraction via somatostatin receptor subtype 1. Gastroenterology 2001; 121: 915-930.

  26. Huang HC, Lee FY, Chan CC, Chang FU, Wang SS, Lin HC, Hou MC, et al.. Effects of somatostatin and octreotide on portal-systemic collaterals in portal hypertensive rats. J Hepatol 2002; 36: 163-168.

  27. Eriksson LS, Law DH, Wahren J. Influence of somatostatin on splanchnic haemodynamics in patients with cirrhosis. Clin Physiol 1984; 4: 616.

  28. Merkel, Gatta A, Zuin R. Effect of somatostatin on splanchnic haemodynamics in patients with liver cirrhosis and portal hypertension. Digestion 1985; 32:92.

  29. Cirera I, Few F, Luca A, Garcia- Pagan JC, Fernandez M, Escorsell A, Basch A, et al. Effects of bolus injections and continuous infusions of somatostatin and placebo in patients with cirrhosis: A double blind haemodynamic investigation. Hepatology 1995; 22: 106-111.

  30. Averignos A, Armonis A, Rekoumis G, Manolakopoulos S, Argirakis G, Raptis S. The effect of somatostatin and octreotide on intravascular oesophageal variceal pressure in patients with cirrhosis. J Hepatol 1995; 22: 379-380.

  31. Villaneuva C, Ortiz J, Minana J, Soriano G, Sabat M, Boadas J, Balanzo J. Somatostatin treatment and risk stratification by continuous portal pressure monitoring during acute variceal bleeding. Gastroenterology 2001; 121: 110-117.

  32. Valenzuela JE, Schubert T, Fogel RM, Strong RM, Levine J, Mills PR. A multicentre, randomized, double-blind trial of SMS in the management of acute haemorrhage from esophageal varices. Hepatology 1989; 10: 958-961.

  33. Burroughs AK, McCormick PA, Hughes MD, Sprengers S, D’Heygere F, McIntyre N. Randomized, double-blind, placebo-controlled trial of SMS for variceal bleeding. Gastroenterology 1990; 99: 1388-1395.

  34. Gotzsche PC, Gjroup I, Bonnen H, Brahe N, Becker U, Burchart F. SMS vs placebo in bleeding esophageal-varices: randomised trial and meta-analysis. Br Med J 1995; 310: 1495-1498.

  35. Gotzsche PC. Somatostatin analogues for acute bleeding oesophageal varices. Cochrane Database Syst Rev 2002; (1): CD000193.

  36. Jaramillo JL, de la Mata M, Mino G, Costan G, Gomez-Camacho F. SMS versus Sengstaken tube ballon tamponade for primary haemostasis of bleeding esophageal varices: a randomised pilot study. J Hepatol 1991; 12: 100-105.

  37. Averignos A, Klonis C, Rekoumis G, Gouma P, Papadimitriou N, Raptis S. A prospective randomized trial comparing SMS, baloon tamponade and the combination of both methods in the management of acute variceal hameorrhage. J Hepatol 1991; 13: 78-83.

  38. D’Amico G, Pietrosi G, Tarantino I, Pagliaro L. Emergency sclerotherapy versus medical interventions for bleeding oesophageal varices in cirrhotic patients. Cochrane Database Syst Rev 2002; (1): CD002233.

  39. D’Amico, Pagliaro L, Bosche J. Pharmacological treatment of portal hypertension: an evidence-based approach. Semin Liver Dis 1999; 19: 475-506.

  40. Escorsell A, Bordas JM, del Arbol LR, Jaramillo JL, Planas R, Banares R, Albillos A, et al. Randomized controlled trial of sclerotherapy vs SMS infusion in the prevention of early rebleeding following variceal hemorrhage in patients with cirrhosis. J Hepatol 1998; 29: 779-788.

  41. Averignos A, Nevens F, Raptis S, Fevery J and the ABOVE study group. Early administration of SMS and efficacy of sclerotherapy in acute oesophageal variceal bleeds: the European Acute Bleeding Oesophageal Variceal Episodes (ABOVE) randomised trial. Lancet 1997; 350: 1495-1499.

  42. Signorelli S, Negrini F, Paris B, Bonelli M, Girola M. Sclerotherapy with or without SMS or octreotide in the treatment of acute variceal haemorrhage: our experience (abstract). Gastroenterology 1996; 110: 1326A.

  43. Avgerinos A, Viazis N, Vlachogiannakos J, Poulianos G, Armonis A, Manolakopoulos S, Raptis S. Two different doses and duration schedules of somatostatin-14 in the treatment of patients with bleeding oesophageal varices: a non-randomized controlled study. J Hepatol 2000; 32: 171-172.

  44. Moitinho E, Planas R, Banares R, Albillos A, del Arbor LR, Galvez C, Bosch J. Variceal bleed Study Group. Multicentre randomized controlled trial comparing different schedules of somatostatin in the treatment of acute variceal bleeding. J Hepatol 2001; 35: 712-718.

  45. McKee R. A study of octreotide in oesophageal varices. Digestion 1990; 45: 60-64.

  46. Jenkins SA, Baxter JN, Snowden S. The effects of SMS and SMS 201-995 on hepatic haemodynamics in patients with cirrhosis and portal hypertension. Fibrinolysis 1988; 2: 48-50.

  47. McCormick PA, Biagini MR, Dick R, Greenslade L, Chin J, Cardin F, Wagstaff D, et al. Octreotide inhibits the meal-induced increases in the portal vein pressure of cirrhotic patients with portal hypertension: a double-blind, placebo-controlled study. Hepatology 1992; 16: 1180-1186.

  48. Escorsell A, Bandi JC, Andreu V, Moitinho E, Garcia-Pagan JC, Bosch J, Rodes J. Desensitization to the effects of intravenous octreotide in cirrhotic patients with portal hypertension. Gastroenterology 2001; 120: 161-169.

  49. Moller S, Brinch K, Henriksen JH, Becker U. Efffect of octreotide on systemic, central, and splanchnic haemodynamics in cirrhosis. J Hepatol 1997; 26: 1026-1033.

  50. Lin HC, Tsai YT, Lee FY, Lee SD, Hsia HC, Lin WJ, Lo KJ. Haemodynamic evaluation of octreotide in patients with hepatitis-B related cirrhosis. Gastroenterology 1992; 103:229-234.

  51. Albillos A, Rossi I, Iborra J, Lledo JL, Calleja JL, Barrios C, Garcia P, et al. Octreotide prevents postprandial splanchnic hyperemia in patients with portal hypertension. J Hepatol 1994; 21: 88-94.

  52. Buanamico P, Sabba C, Garcia-Tsao G, Berardi E, Antonica G, Ferraioli G, Jensen JE, et al. Octreotide blunts posprandial splanchnic hyperaemia in cirrhotic patients: a double-blind randomized echo-Doppler study. Hepatology 1995; 21: 134-139.

  53. Corley D, Cello J, Adkisson W, Ko WF, Kerlikowske K. Octreotide for acute esophageal variceal bleeding: a meta-analysis. Gastroenterology 2001; 120: 946-954.

  54. Burroughs AK. International Octreotide Varices Study Group: Double blind RCT of 5-day octreotide versus placebo, associated with sclerotherapy for trial failures. Hepatology 1996; 24: 737-739.

  55. Primignani M, Andreoni B, Carpinelli L, Carpinelli L, Capria A, Rocchi G, Lorenzini I, et al. Sclerotherapy plus octreotide versus sclerotherapy alone in the prevention of early rebleeding from esophageal-varices-a randomised, double-blind, placebo-controlled, multicentre trial. Hepatology 1995; 21: 1322-1327.

  56. D’Amico G, Politi F Morabito A, D’Antoni A, Guerrera G, Giannuoli G, Traina M, et al. Octreotide compared with placebo in a treatment strategy for early rebleeding in cirrhosis: a double blind, randomized pragamatic trial. Hepatology 1998; 28: 1206-1214.

  57. Signorelli S, Negrini F, Paris B. Sclerotherapy with or without somatostatin or octreotide in the treatment of acute variceal haemorrhage: our experience. Gastroenterology 1996; 110: A1326.

  58. Freitas D, Sofia C, Pontes J, Gregorio C, Cabral JP, Andrade P, Rosa A, et al. Octreotide in acute bleeding esophageal varices: a prospective randomized study. Hepatogastroenterology 2000; 47: 1310-1314.

  59. Zuberi B, Baloch Q. Comparison of endoscopic variceal sclerotherapy alone and in combination with octreotide in controlling acute variceal haemorrhage and early rebleeding in patients with low-risk cirrhosis. Am J Gastroenterol 2000; 95: 768-771

  60. Sung JJY, Chung SS, Yung MY, Lai CW, Lau JYW, Lee YT, Leung VKS. Prospective randomized study of effect of octreotide on rebleeding from esophageal varices after endoscopic ligation. Lancet 1995; 346: 1666-1669.

  61. Cales P, Masliah C, Bernard B, Garnier PP, Silvain C, Szostak-Talbodec N, Bronowicki JP, et al. Early administration of vapreotide for variceal bleeding in patients with cirrhosis. N Engl J Med 2001; 344: 23-28.

  62. Banares R, Albillos A, Rincon D, Alonso S, Gonzalez M, Ruiz-del-Arbor L, Salcedo M, et al. Endoscopic treatment versus endoscopic plus pharmacologic treatment for acute variceal bleeding: a meta-analysis. Hepatology 2002; 35: 609-615.

  63. Kamath PS, Brenner K, Blei A, Bosch J, Carey W, Grace N, Kowdley K, et al. Lack of haemodynamic response to long-acting octreotide (sandostatin-LAR) in patients with cirrhosis. Gastroenterology 2001; 120(suppl 1): 3A.

  64. Ames RS, Sarau HM, Chambers JK, Willette RN, Aiyar NV, Romanic AM, Louden CS, et al. Urotensin II: better than somatostatin for portal hypertension? Nature 1999; 401: 282-286.

  65. 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.

  66. Grace ND, Groszmann RJ, Garcia-Tsao G, Burroughs AK , Pagliaro L, Makuch RW, BoschJ, et al. Portal hypertension and variceal bleeding: An AASLD single topic symposium. Hepatology 1998; 28: 868-880.

  67. Groszmann RJ, Bosch J, Grace ND, Conn HO, Garcia-Tsao G, Navasa M, Alberts J, et al. Hemodynamic events in a prospective randomized trial of propranol versus placebo in the prevention of the 1st variceal hemorrhage. Gastroenterology 1990; 99: 1401-1407.

  68. Feu F, Garcia-Pagan JC, Bosch J, Luca A, Teres J, Escorsell A, Rodes J. Relation between portal pressure response to pharmacotherapy and risk of recurrent variceal hemorrhage in patients with cirrhosis. Lancet 1995; 346: 1056-1059.

  69. Garcia-Pagan JC, Escorsell A, Moitinho E, Bosch J. Influence of pharmacological agents on portal haemodynamics: Basis for its use in the treatment of portal hypertension. Semin Liver Dis 1999; 19: 427-438.

  70. 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.

  71. Dawson J, Gertsch P, Mosimann F, West R, Elias E. Endoscopic variceal pressure measurements: response to isosorbide dinitrate. Gut 1985; 26: 843-847.

  72. Navasa M, Chesta J, Bosch J, Rodes J. Reduction of portal pressure by isosorbide-5-mononitrate in patients with cirrhosis. Effects upon splanchnic and systemic haemodynamics and liver function. Gastroenterology 1989; 96: 1110-1118.

  73. Moreau R, Lebrec D. Nitrovasodilators and portal hypertension. J Hepatol 1990; 10: 263-267.

  74. Gronzmann RJ. B-Adrenergic blockers and nitrovasodilators for the treatment of portal hypertension: the good, the bad, the ugly. Gastroenterology 1997; 113: 1794-1797.

  75. Gournay J, Masliah C, Martin T, Perrin D, Galmiche JP, et al. Isosorbide mononitrate and propranolol compared with propranolol alone for the prevention of variceal rebleeding. Hepatology 2000; 31: 1239-1245.

  76. Patti R, D’Amico G, Pasta L, Vizzini G, Traina M, Madonia S, Licata A, et al. Isosorbide mononitrate (IMN) with nadolol compared to nadolol alone for prevention of recurrent bleeding in cirrhosis. A double-blind placebo-controlled randomised trial. J Hepatol 1999; 30 (suppl): 81

  77. Jensen LS, Kraup N. Propranolol in prevention of rebleeding from esophageal-varices during the course of endoscopic sclerotherapy. Scand J Gastroenterol 1989; 24: 339-345.

  78. Benedeto-Stojanov D, Tasic T, Bjelakovic G, Nagorni A. Prevention of recurrent upper gastrointestinal bleeding with propranolol in patients with cirrhosis undergoing endoscopic sclerotherapy. J Hepatol 2000; 32(suppl 2): 72.

  79. Jenkins SA, Baxter JN, Critchley M, Kingsnorth AN, Makin CA, Ellenbogen S, Grime JS, et al. Randomised trial of octreotide for long term management of cirrhosis after variceal haemorrhage. Br Med J 1997; 315: 1338-1341.

  80. Minyana J, Gallego A, Sola V, Dedeu JM, Ortiz J, Sabat M, Boadas J, et al. Endoscopic ligation versus nadolol plus isosorbide-5-mononitrate for the prevention of variceal rebleeding. A prospective and randomised trial. Hepatology 1999; 30: 214A.

  81. Agrawal SR, Gupta R, Murthy NS, Sarin S. comparable efficacy of propranolol plus isosorbide mononitrate and endoscopic variceal ligation in prevention of variceal rebleed. J Hepatol 2002; 36: 631A.

  82. Lo GH. Nadolol plus isosorbide mononitrate compared with band ligation for the prevention of rebleeding from oesophageal varices. Endoscopy 2001; 33(suppl): 1118A.

  83. Villanueva C, Minana J, Ortiz J, Gallego A, Soriano G, Torras X, Sainz S, 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.

  84. Patch D, Goulis J, Gerunda G, Merkel C, Greenslade L, Burroughs AK. A randomized controlled trial comparing wedge pressure guided medical therapy (MT) against variceal banding (VB) in the secondary prevention of variceal haemorrhage. Gastroenterology 2002 [in press].

  85. Lo GH, Lai KH, Cheng JS, Chen MH, Huang HC, Hsu PI, Lin CK. Endoscopic variceal ligation plus nadolol and sucralfate compared with ligation alone for the prevention of variceal rebleeding: a prospective randomised trial. Hepatology 2000; 32: 461-465.

  86. Escorsell A, Banares R, Garcia-Pagan JC, Gilabert R, Moitinho E, Piqueras B, Bru C, et al. TIPS versus drug therapy in preventing variceal rebleeding in advanced cirrhosis: a randomised controlled trial. Hepatology 2002; 35: 385-392.

  87. Luca A, D’Amico G, La Galla R, Midiri M, Morabito A, Pagliaro L. TIPS for prevention of recurrent bleeding in patients with cirrhosis: meta-analysis of randomized controlled trials. Radiology 1999; 212: 411-421.

  88. Escorsell A, Bordas JM, Castaneda B, Llach J, Garcia-Pagan JC, Rodes J, Bosch J, et al. Predictive value of the variceal pressure response to continued pharmacological therapy in patients with cirrhosis and portal hypertension. Hepatology 2000; 31: 1061-1067.

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

  90. McCormick A, Patch D, Greenslade L, Chin J, McIntyre N, Burroughs AK. Clinical versus haemodynamic response to drugs in portal hypertension. J Hepatol 1998; 28: 1015-1019.

  91. Valla D, Jiron MI, Poynard T, Braillon A, Lebrec D. Failure of haemodynamic measurement to predict recurrent gastrointestinal bleeding in cirrhotic patients receiving propranolol. J Hepatol 1987; 5: 144-148.

  92. Perez-Ayuso RM, Pique JM, Bosch J, Panes J, Gonzalez A, Perez R, Rigau J, et al. Propranolol in prevention of recurrent bleeding from severe portal hypertensive gastropathy in cirrhosis. Lancet 1991; 337: 1431-1434.

  93. Hayes PC, Davis JM, Lewis JA, Bouchier IA. Meta-analysis of the value of propranolol in the prevention of variceal bleeding. Lancet 1990; 336: 153-156.

  94. Poynard T, Cales P, Pasta L, Ideo G, Pascal JP, Pagliaro L, Lebrec D. Beta-adrenergic-antagonist drugs in the prevention of gastrointestinal bleeding in patients with cirrhosis and esophageal varices-an analysis of data and prognostic factors in 589 patients from four randomized clinical trials. N Engl J Med 1991; 324: 1532-1538.

  95. Garcia-Pagan J, Villanueva C, Vila M, Albillos A, Genesca J, Ruiz-del-Arbor L, Planas R, et al. Isosorbide mononitrate in the prevention of first variceal bleed in patients who cannot receive b-blockers. Gastroenterology 2001; 121: 908-914.

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

  97. Angelico M, Carli L, Piat C, Gentile S, Capocaccia L. Effects of Isosorbide-5-mononitrate compared with propranolol on first bleeding and long term survival in cirrhosis. Gastroenterology 1997; 113: 1632-1639.

  98. Borroni G, Salermo F, Cazzaniga M, Bissoli F, Lorenzano E, Maggi A, Visentin S, et al. Nadolol is superior to isosorbide mononitrate for the prevention of the first variceal bleeding in cirrhotic patients with ascites. J Hepatol 2002; 37: 315-321.

  99. Merkel C, Marin R, Enzo E, Donada C, Cavallarin G, Torboli P, Amodio P, et al. Randomized 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.

  100. Merkel C, Marin R, Sacerdoti D, Donata C, Cavallarin G, Torboli P, Amodio 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.

  101. Andreani T, Poupon RE, Balkau BJ, Trinchet JC, Grange JD, Peigney M, Beaugrand M, et al. Preventive therapy of 1st gastrointestinal bleeding in patients with cirrhosis-results of controlled trial comparing propranolol, endoscopic sclerotherapy and placebo. Hepatology 1990; 12: 1413-1419.

  102. The PROVA Study Group: Prophylaxis of first haemorrhage from oesophageal varices by sclerotherapy, propranolol or both in cirrhotic patients. A randomized multicentre trial. Hepatology 1991; 14: 1016-1024.

  103. Avgerinos A, Armonis A, Manolakopoulos S, Rekoumis G, Argirakis G, Viazis N, Vlachogiannakos J, et al. Endoscopic sclerotherapy plus propranolol versus propranolol alone in the primary prevention of bleeding in high risk cirrhotic patients with eosophageal varices: a prospective multicentre randomized trial. Gastrointest Endosc 2000; 51: 652-658.

  104. Imperiale T, Chalasani N. A meta-analysis of endoscopic variceal ligation for primary prophylaxis of oesophageal variceal bleeding. Hepatology 2001; 33:802-807.

  105. Aoki N, Kajiyama T, Beck R, Cone RW, Soma K, Fukui T. Decision analysis of prophylactic treatment for patients with high-risk oesophageal varices. Gastrointest Endosc 2000; 52: 707-714.

  106. Agrawal SR, Singh J, Sharma S, Sarin SK. Combination of endoscopic variceal ligation and propranolol with endoscopic variceal ligation alone in the prevention of first variceal bleed: an interim analysis. J Hepatol 2002; 36: 697A.

  107. Merkel C, Bolognesi M, Sacerdoti D, Bombonato G, Bellini B, Bighin R, Gatta A, et al. The haemodynamic 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.

  108. De BK, Sen S, Biswas PK, Sengupta D, Biswas J, Santra A, Hazra B, et al. Propranolol in primary and secondary prophylaxis of variceal bleeding among cirrhotics in India; A haemodynamic evaluation. Am J Gastroenterol 2000; 95: 2023-2028.

  109. Cales P, Oberti F, Payen JL, Naveau S, Guyander D, Blanc P, Abergel A, et al. Lack of effect of propranolol in the prevention of large oesophageal varices in patients with cirrhosis; a randomized trial. Eur J Gastroenterol Hepatol 1999; 11: 741-745.

  110. Plevris JN, Elliot R, Mills PR, Hislop WS, Davies JM, Bouchier JA, Hayes PC. Effect of propranolol on prevention of first variceal bleed and survival in patients with chronic liver disease. Aliment Pharmacol Ther 1994; 8: 63-70.

  111. Escorsell A, Ferayorni L, Bosch J, Garcia-Pagan JC, Garcia-Tsao G, Grace ND, Rodes J, et al. The portal pressure response to b-blockade is greater in cirrhotic patients without varices than in those with varices. Gastroenterology 1997; 112: 2012-2016.

  112. Rockey D. The cellular pathogenesis of Portal Hypertension: stellate cell contractility, endothelin and nitric oxide. Hepatology 1997; 25: 2-5.

  113. Shah V, Garcia-Cardena G, Sessa W, Groszmann. The hepatic circulation in health and disease: Report of a single-topic symposium. Hepatology 1998; 27: 279-288.

  114. Sogni P, Moreau R, Gomola A, Gadano A, Cailmail S, Calmus Y, Clozel M, et al. Beneficial hemodynamic effects of bosentan, a mixed ETa and ETb receptor antagonist, in portal hypertensive rats. Hepatology 1998; 28: 655-659.

  115. Mittal MK, Gupta TK, Lee FY, Sieber CC, Gronzmann RJ. Nitric oxide modulates hepatic vascular tone in normal at liver. Am J Physiol (Gastrointest Liver Physiol) 1994; 267: G416-422.

  116. Gupta TK, Chung MK, Toruner M, Groszmann RJ. Endothelial dysfunction in the intrahepatic microcirculation of the cirrhotic rat. Hepatology 1998; 28: 926-931.

  117. Fevery J, Roskams T, Van de Casteele M, Omasta A, Janssens S, Desmet V, et al. NO synthase in the liver; prospects of in vivo gene transfer. Digestion 1998; 59: S2: 58-59.

  118. Bataller R, Gines P, Nicolas J, Gorbig MN, Garcia-Ramallo E, Gasull X, Bosch J, et al. Angiotensin II induces contraction and proliferation of human hepatic stellate cells. Gastroenterology 2000; 118: 1149-1156.

  119. Yoo KH, Thornhill BA, Wolstenholme JT, Chevalier RL. Tissue specific regulation of growth factors and clusterin by angiotensin II. Am J Hypertens 1998; 11: 715-722.

  120. Jonsson J, Clouston A, Ando Y, Kelemen L, Horn M, Adamson M, Purdie DM, et al. Angiotensin-converting enzyme inhibition attenuates the progression of rat hepatic fibrosis. Gastroenterology 2001; 121: 148-155.

  121. Cho JJ, Hocher B, Herbst H, Jia JD, Ruehl M, Eckhart GH, Riecken EO, et al. An oral endothelin-A receptor antagonist blocks collagen synthesis and deposition in advanced rat liver fibrosis. Gastroenterology 2000; 118: 1169-1178.

  122. Rockey DC, Chung JJ. Endothelin antagonism in experimental hepatic fibrosis. Implications for endothelin in the pathogenesis of wound healing. J Clin Invest 1996; 98: 1381-1388.

  123. Poo JL, Jimenez W, Munoz RM, Bosch-Marce M, Bordas N, Morales-Ruiz M, Perez M, et al. Chronic blockade of endothelin receptors in cirrhotic rats; hepatic and haemodynamic effects. Gastroenterology 1999; 116: 161-167.

  124. Rockey DC. Vasoactive agents in intrahepatic portal hypertension and fibrogenesis; implications for therapy. Gastroenterology 2000; 118: 1261-1265.

  125. Pariente AE, Bataille C, Bercoff E, Lebrec D. Acute effects of captopril on systemic and renal hemodynamic and on renal function in cirrhotic patients with ascites. Gastroenterology 1985; 88: 1255-1259.

  126. Ibarra FR, Afione C, Garzon D, Barotini M, Santos JC, Arrizurieta E. Portal pressure, renal function and hormonal profile after acute and chronic captopril treatment in cirrhosis. Eur J Clin Pharmacol 1992; 43: 477-482.

  127. Gentilini P, Romanelli RG, La Villa G, Maggiore Q, Pesciullesi E, Capelli G, Casini Raggi V, et al. Effects of low dose captopril on renal haemodynamics and function in patients with cirrhosis of the liver. Gastroenterology 1993; 104: 588-594.

  128. Atlas SA, Case DB, Yu ZY, Laragh JH. Hormonal and metabolic effects of angiotensin converting enzyme inhibitors. Possible differences between enalapril and captopril. Am J Med 1984; 77: 13-17.

  129. Chiang HT, Cheng JS, Lin M, Tseng WS, Chang JM, Lai KH. Hemodynamic effects of enalaprilat on portal hypertension in patients with HBsAg-positive cirrhosis. J Gastroenterol Hepatol 1995; 10: 256-260.

  130. Svoboda P, Ochmann J, Kantrova I. Effect of enalapril treatment and sclerotherapy of esophageal varices on hepatic hemodynamics in portal hypertension. Hepatogastroenterology 1992; 39: 549-552.

  131. Nasr AA, el Hak NG, Settein ME, Khafegy MA, Tadros MT. Effects of angiotensin converting enzyme inhibitors and sclerotherapy on portal haemodynamics in patients with portal hypertension. Hepatogastroenterology 2000; 47: 795-806.

  132. Arroyo V, Bosch J, Mauri M, Ribera F, Navarro-Lopez F, Rodes J. Effect of angiotensin II blockade on systemic and hepatic haemodynamics and on renin-angiotensin-aldosterone system in cirrhosis with ascites. Eur J Clin Invest 1981; 11: 221-229.

  133. Schneider AW, Kalk FJ, Klein CP. Effect of Losartan, an Angiotensin II receptor antagonist on portal pressure in Cirrhosis. Hepatology 1999; 29: 334-339.

  134. Gonzalez-Abraldes J, Albillos A, Banares B, del Arbol LR, Moitinho E, Rodriguez C, Gonzalez M, et al. Randomized comparison of long term losartan versus propranolol in lowering portal pressure in cirrhosis. Gastroenterology 2001; 121: 382-388.

  135. Klein CG, Kalk JF, May B, Klein CP. Efficiency of irbesartan, an angiotensin II receptor antagonist on portal pressure and intrahepatic resistance in cirrhosis of the liver. Hepatology 2000; 32: 523A.

  136. Schepke M, Werner E, Bieker E, Schiedermaier P, Heller J, Neef M, Stoffel-Wagner B, et al. Haemodynamic effects of the angiotensin II receptor antagonist irbesartan in patients with cirrhosis and portal hypertension. Gastroenterology 2001; 121: 389-395.

  137. Debernardi-Venon D, Barletti C, Marzano A, Alessandria C, Marzano A, Baronio M, Todros L, et al. Efficacy of Irbestartan, a receptor selective antagonist an angiotensin II, in reducing portal hypertension. Dig Dis Sci 2002; 47: 401-404.

  138. Mills PR, Rae AP, Farah DA, Russel RI, Lorimer AR, Carter DC. Comparison of three adrenoreceptor blocking agents in patients with cirrhosis and portal hypertension. Gut 1984; 25: 73-78.

  139. Albillos A, Lledo JL, Rossi I, Perez-Paramo M, Tabuenca MJ, Iborra J, Garrido A, et al. Continuous prazosin administration in cirrhotic patients: effects on portal haemodynamics and on liver and renal function. Gastroenterology 1995; 109: 1257-1265.

  140. Albillos A, Garcia-Pagan JC, Iborra J, Bandi JC, Cacho G, Perez-Paramo M, Escorsell A, et al. Propranolol plus prazosin compared to propranolol plus isosorbide-5-mononitrate in the chronic treatment of portal hypertension. Gastroenterology 1998; 115: 116-123.

  141. Frishman WH. Drug therapy: carvedilol. N Engl J Med 1998; 339: 1759-1765.

  142. Forrest EH, Bouchier IA, Hayes PC. Acute haemodynamic changes after oral carvedilol, a vasodilating bet-blocker, in patients with cirrhosis. J Hepatol 1996; 25: 909-915.

  143. Banares R, Moitinho E, Piqueras B, Casado M, Garcia-Pagan JC, De Diego A, Bosch J. Carvedilol, a N non-selective beta-blocker with intrinsic anti-alpha1 adrenergergic activity, has a greater portal hypotensive effects than propranolol in patients with cirrhosis. Hepatology 1999; 30: 79-83

  144. Banares R, Moitinho E, Matilla A. Carvedilol (Carv) vs Propranolol (Prop) in the long term treatment of portal hypertension. J Hepatol 2000; 32(suppl 2): 62A.

  145. Stanley AJ, Therapondos G, Helmy A, Hayes PC. Acute and chronic haemodynamic and renal effects of carvedilol in patients with cirrhosis. J Hepatol 1999; 30: 479-484.

  146. Tripathi D, Therapondos H, Lui HF, Stanley AJ, Hayes PC. Haemodynamic effects of acute and chronic administration of low-dose carvedilol, a vasodilating b-blocker, in patients with cirrhosis and portal hypertension. Aliment Pharmacol Ther 2002; 16: 373-380.

  147. Albillos A, Banares R, Barrios G, Clemente G, Rossi I, Escartin P, Bosch J. Oral administration of clonidine in patients with alcoholic cirrhosis. Hemodynamic and liver function effects. Gastroenterology 1992; 102: 248-254.

  148. Roulot D, Moreau R, Gaudin C, Bacq Y, Braillon A, Hadengue A, Frohly P, et al. Long-term sympathetic and hemodynamic responses to clonidine in patients with cirrhosis and ascites. Gastroenterology 1992; 102: 1309-1318.

  149. Tincani E, Gioni G, D’Alimonte P, Cristani A, Turrini F, Romagnoli R, Ventura E. Effects of propranolol compared with clonidine on portal haemodynamics; a double-blind cross-over study using duplex-Doppler ultrasonography. Eur J Gastroenterol Hepatol 1995; 7: 893-897.

  150. Atkinsons M. The effects of diuretics on portal venous pressure. Lancet 1959; 2: 819-823.

  151. Cereda JM, Roulot D, Braillon A, Moreau R, Koshy A, Lebrec D. Reduction in portal pressure by acute administration of furosemide in patients with alcoholic cirrhosis. J Hepatol 1989; 9: 246-251.

  152. Okumura H, Aramaki T, Katsuta Y, Satomura K, Akaike M, Sekiyama T, Terada H, et al. Reduction in hepatic vein pressure gradient as a consequence of volume contraction due to chronic administration of spironolactone in patients with cirrhosis and no ascites. Am J Gastroenterol 1991; 86: 46-52.

  153. Garcia-Pagan JC, Salmeron JM, Feu F, Luca A, Gines P, Pizcueta P, Clarice J, et al. Effects of low sodium diet and spironolactone on portal pressure in patients with compensated cirrhosis. Hepatology 1994; 19: 1095-1099.

  154. Nevens F, Lijnen P, VanBilloen H, Fevery J. The effect of long-term treatment with spironolactone on variceal pressure in patients with portal hypertension without ascites. Hepatology 1996; 23: 1047-1052.

  155. Sugano S, Susuki T, Nishio M, Makino H, Okajima T. Chronic splanchnic haemodynamic effects of low dose transdermal nitroglycerin versus low-dose transdermal nitroglycerin plus spironolactone in patients with cirrhosis (abstract). Dig Dis Sci 1997; 42: 529-535

  156. Hadengue A, Lee SS, Moreau R, Braillon A, Lebrec D. Beneficial hemodynamic effects of ketanserin in patients with cirrhosis: possible role of serotonergic mechanism in portal hypertension. Hepatology 1987; 7: 644-647.

  157. Vorobioff J, Garcia-Tsao G, Groszmann RJ, Aceves G, Picabea E, Villavicencio R, Hernandez-Ortiz J. Long term haemodynamic effects of ketanserin, a 5-hydroxytryptamine blocker in portal hypertensive patients. Hepatology 1989; 6: 88-91.

  158. Ladero Quesada JM, Diez Ordonez S, Gallego Beuter JJ, Hernandez Lezana A, Herraiz Serrana ML, Diaz-Rubio Garcia M. Addition of ritanserin to the treatment with propranolol in cirrhotic patients; effects on portal pressure. Ann Med Interna 1994; 11: 162-166.

  159. Hadengue A, Moreau R, Cerini R, Koshy A, Lee SS Lebrec D. Combination of ketanserin and verapamil or propranolol in patients with alcoholic cirrhosis; search for an additive effect. Hepatology 1989; 9; 83-87.

  160. Goulis J, Patch D, Burroughs AK. Bacterial infection in the pathogenesis of variceal bleeding. Lancet 1999; 353: 139-142.

  161. Guarner C, Soriano G, Tomas A, Bulbena O, Novella MT, Balanzo J, Vilardell F, et al. Increased serum nitrite and nitrate levels in patients with cirrhosis: relationship to endotoxaemia. Hepatology 1993; 18: 1139-1143.

  162. Ziegler EJ, McCutchan JA, Fierer J, Clauser MP, Sadoff JC, Douglas H, Braude AI. Treatment of gram-negative bacteraemia and shock with human antiserum to a mutant Escherichia Coli. N Engl J Med 1982; 307: 1225-1230.

  163. Rockey DC, Wesiger 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.

  164. Yamamoto S, Burman HP, O’Donnell CP, Cahill PA, Robotham JL. Endothelin causes portal and pulmonary hypertension in porcine endotoxemic shock. Am J Physiol 1997; 27: H1 239-249.

  165. Radomski MW, Palmer RMJ, Moncada S. Endogenous nitric oxide inhibits human platelet adhesion to vascular endothelium. Lancet 1987; ii; 1057-1058.

  166. Mastai R, Grande L, Bosch J, Bruix J, Rigau J, Kravetz D, Navasa M, et al. Effects of metoclopramide and domperidone on azygos venous blood flow in patients with cirrhosis and portal hypertension. Hepatology 1986; 6: 1244-1247.

  167. Kleber G, Fisher G, Geinberger G, Paumgartner G, Sauerbruch T. Metoclopramide lowers intraoesophageal variceal pressure in patients with portal hypertension. J Hepatol 1989; 9(S1): S50.

  168. Feu F, Mas A, Bosch J, Salmeron JM, Garcia-Pagan JP, Teres J. Domperidone or metoclopramide vs placebo in the prevention of early variceal rebleeding in cirrhosis. A prospective randomized trial. J Hepatol 1988; 7(suppl 1): S31.

  169. Hoskins SW, Doss W, El-Zeiny H, Robinson P, Barsoum MS, Johnson AG. Pharmacological constriction of the lower oesophageal sphincter; a simple method of arresting variceal haemorrhage. Gut 1988; 29: 1098-1102.

  170. Bernstein DE, Jeffers L, Erhardsten E, Reddy KR, Glazer S, Squiban P, Hedner U, et al. Recombinant factor VIIa corrects prothrombin time in cirrhotic patients: a preliminary study. Gastroenterology 1997; 113: 1390-1397.

  171. Pauwels A, Fourdan O, Carbonel N. La mortalité des heamorragies digestives des cirrhoses a étè reduite de plus des moitié en 15 ans. Gastroenterol Clin Biol 1998; 22 (suppl 2): 27A.

  172. El-Serag HB, Everhart JE. Improved survival after variceal haemorrhage over a 11-year period in the department of veterans affairs. Am J Gastroenterol 2002; 95: 3566-3573.

  173. McCormick PA, O’Keefe C. Improving prognosis following a first variceal haemorrhage over four decades. Gut 2001; 49: 682-685.

  174. Berck PD, Sacks HS. Assessing the quality of randomized controlled trials: quality of design is not only the relevant variable. Hepatology 1999; 30: 1332-1334.

  175. Kjaergard LL, Nikilova D, Gluud C. Randomised clinical trails in Hepatology: predictors of quality. Hepatology 1999; 30: 1134-1138.




2020     |     www.medigraphic.com