THE LATEST RECOMMENDATIONS IN THE PROPHYLAXIS AND TREATMENT OF BLEEDING FROM ESOPHAGOGASTRIC VARICES
Keywords:
esophageal varices, gastric varices, prophylaxis, treatment
Abstract
Esophagogastric varices develop in 50-60% of patients with liver cirrhosis, and 30% of them have one episode of variceal hemorrhage within 2 years of variceal diagnosis. Prevention of first bleeding from esophageal varices (EV) involves the use of non-selective beta blockers (NSBB) or Carvedilol, while in case of their intolerance or contraindications for their use, endoscopic band ligation (EBL) should be performed. In acute variceal bleeding, after hemodynamic stabilization of the patient, endoscopy should be performed and EBL applied, preferably within 12 hours of the presentation of the bleeding. Up to 20% of variceal hemorrhage may be refractory to standard therapy. In that case, there are several therapeutic options: repeat endoscopy and hemostasis, balloon tamponade, self-expanding metal stent (SEMS), transjugular intrahepatic portosystemic shunt (TIPS), and surgical therapy. Bleeding from gastric varices (GV) is less frequent than bleeding from EV but is significantly more severe with higher mortality and more frequent treatment failure. The therapy of choice is the application of cyanoacrylate (CYA), which can be applied under the control of endoscopic ultrasonography (EUS). In the trial is the application of coils injections with or without CYA. In the secondary prophylaxis of bleeding from EV, NSBB should be used in combination with EBL. In the case of recurrent ascites, the treatment of choice is TIPS. In the secondary prophylaxis of bleeding from cardiofundal varices, the approach is individual. The aim of the paper is to present the latest attitudes in the treatment of esophagogastric varices.
References
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9. Robic, MA, Procopet B, Métivier S, et al. Liver stiffness accurately predicts portal hypertension related complications in patients with chronic liver disease: A prospective study. J Hepatol2011; 55, 1017–1024.
10. Paternostro R, Reiberger T, Bucsics T. Elastography-based screening for esophageal varices in patients with advanced chronic liver disease. World J. Gastroenterol. 2019: 25, 308–329.
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17. Reiberger T, Ulbrich G, Ferlitsch A et al. Carvedilol for primary prophylaxis of variceal bleeding in cirrhotic patients with haemodynamic non-response to propranolol. Gut 2013; 62: 1634–1641.
18. Tian S, Li R, Guo Y, et al. Carvedilol vs endoscopic band ligation for the prevention of variceal bleeding: A meta-analysis. TherClin Risk Manag2019; 15: 191–200.
19. Hammond DA, Lam SW, Rech MA, et al. Balanced Crystalloids Versus Saline in Critically Ill Adults: A Systematic Review and Meta-analysis. Ann Pharmacother2020; 54: 5–13.
20. Veitch AM, Radaelli F, Alikhan R et al. Endoscopy in patients on antiplatelet or anticoagulant therapy: British Society of Gastroenterology (BSG) and European Society of Gastrointestinal Endoscopy (ESGE) guideline update. Gut 2021; 70: 1611–1628.
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23. Huaringa-Marcelo J, Huaman MR, Brañez-Condorena A, et al. Vasoactive Agents for the Management of Acute Variceal Bleeding: A Systematic Review and Meta-analysis. J. Gastrointestin. Liver Dis 2021, 30, 110–121.
24. Yan P, Tian X, Li J. Is additional 5-day vasoactive drug therapy necessary for acute variceal bleeding after successful endoscopic hemostasis?: A systematic review and meta-analysis. Medicine 2018, 97, e12826.
25. Lee S, Saxinger L, Ma M, et al. Bacterial infections in acute variceal hemorrhage despite antibiotics-a multicenter study of predictors and clinical impact. United EurGastroenterol2017; 5: 1090–1099.
26. Chang TS, Tsai YH, Lin YH et al. Limited effects of antibiotic prophylaxis in patients with Child-Pugh class A/B cirrhosis and upper gastrointestinal bleeding. PLoS One 2020; 15: e0229101.
27. Bai Z, Wang R, Cheng G, et al. Outcomes of early versus delayed endoscopy in cirrhotic patients with acute variceal bleeding: A systematic review with meta-analysis. Eur J GastroenterolHepatol2021; 33: 868–876.
28. Kovacs TOG, Jensen DM. Varices: Esophageal, Gastric, and Rectal. Clin Liver Dis 2019; 23: 625–642.
29. Nett A, Binmoeller KF. Endoscopic Management of Portal Hypertension-related Bleeding. GastrointEndoscClin N Am 2019; 29: 321–337.
30. Dai C, Liu WX, Jiang M, Sun MJ. Endoscopic variceal ligation compared with endoscopic injection sclerotherapy for treatment of esophageal variceal hemorrhage: A meta-analysis. World J Gastroenterol2015; 21; 2534–2541.
31. Karsan HA, Morton SC, Shekelle PG, et al. Combination endoscopic band ligation and sclerotherapy compared with endoscopic band ligation alone for the secondary prophylaxis of esophageal variceal hemorrhage: a meta-analysis. Dig Dis Sci 2005; 50: 399-406.
32. Djurdjević D, Janošević S, Dapčević B, et al. Combined ligation and sclerotherapy versus ligation alone for eradication of bleeding esophageal varices: a randomized and prospective trial. Endoscopy. 1999; 31(4): 286-290.
33. Singh P, Pooran N, Indaram A, Bank S. Combined ligation and sclerotherapy versus ligation alone for secondary prophylaxis of esophageal variceal bleeding: a meta-analysis. Am J Gastroenterol. 2002; 97(3): 623-629.
34. Lo GH, Lai KH, Cheng JS, et al. The additive effect of sclerotherapy to patients receiving repeated endoscopic variceal ligation: a prospective, randomized trial. Hepatology 1998; 28:391-395.
35. Hou MC, Chen WC, Lin HC, et al. A new „sandwich” method of combined endoscopic variceal ligation and sclerotherapy versus ligation alone in the treatment of esophageal variceal bleeding: a randomized trial. GastrointestEndosc 2001; 53:572-578.
36. Cheng YS, Pan S, Lien GS, et al. Adjuvant sclerotherapy after ligation for the treatment of esophageal varices: a prospective, randomized long-term study. Gastrointest Endosc.2001; 53:566-571.
37. Grgov S, Stamenković P. Does sclerotherapy of remnant little oesophageal varices after endoscopic ligation have impact on the reduction of recurrent varices? Prospective study. SrpArhCelokLek 2011; 139 (5-6): 328-332.
38. Bosch J, Berzigotti A, Garcia-Pagan JC, Abraldes JG. The management of portal hypertension: rational basis, available treatments and future options. J Hepatol 2008; 48 Suppl 1: 68-92.
39. Escorse À, Pavel O, Cárdenas A, et al. Esophageal balloon tamponade versus esophageal stent in controlling acute refractory variceal bleeding: A multicenter randomized, controlled trial. Hepatology 2016; 63: 1957–1967.
40. Shao XD, Qi XS, Guo XZ. Esophageal Stent for Refractory Variceal Bleeding: A Systemic Review and Meta-Analysis. BioMed Res Int2016, 2016, 4054513.
41. Maimone S, Saffioti F, Filomia R, et al. Predictors of Re-bleeding and Mortality Among Patients with Refractory Variceal Bleeding Undergoing Salvage Transjugular Intrahepatic Portosystemic Shunt (TIPS). Dig Dis Sci2019; 64: 1335–1345.
42. Selzner M, Tuttle-Newhall JE, Dahm F, et al. Current indication of a modified Sugiura procedure in the management of variceal bleeding. J Am Coll Surg 2001; 193 (2):166-173.
43. Deng ZC, Jiang WZ, Chen L, et al. Laparoscopic VS. Open splenectomy and oesophagogastric devascularisation for liver cirrhosis and portal hypertension: A retrospective cohort study. Int J Surg 2020; 80:79-83.
44. Luo HP, Zhang ZG, Long X, et al. Combined Laparoscopic Splenectomy and Esophagogastric Devascularization versus Open Splenectomy and Esophagogastric Devascularization for Portal Hypertension due to Liver Cirrhosis. Curr Med Sci 2020; 40 (1):117-122.
45. Rodge GA, Goenka U, Goenka M. Management of refractory variceal bleed in cirrhosis. J Clin Exp Hepatol 2022; 12: 595-602.
46. Garcia-Pagán JC, Barrufet, M, Cardenas A, Escorsell, A. Management of gastric varices. Clin. Gastroenterol. Hepatol2014; 12: 919–928.e911.
47. Gubler C, Bauerfeind, P. Safe and successful endoscopic initial treatment and long-term eradication of gastric varices by endoscopic ultrasound-guided Histoacryl (N-butyl-2-cyanoacrylate) injection. Scand J Gastroentero2014; 49: 1136–1142.
48. Bick BL, Al-Haddad M, Liangpunsakul S, et al. EUS-guided fine needle injection is superior to direct endoscopic injection of 2-octyl cyanoacrylate for the treatment of gastric variceal bleeding. SurgEndosc2019; 33: 1837–1845.
49. Bhat YM, Weilert F, Fredrick RT, et al. EUS-guided treatment of gastric fundal varices with combined injection of coils and cyanoacrylate glue: a large U.S. experience over 6 years. Gastrointest Endosc 2016; 83(6):1164-1172.
50. Orloff MJ, Hye RJ, Wheeler HO, et al. Randomized trials of endoscopic therapy and transjugular intrahepatic portosystemic shunt versus portacaval shunt for emergency and elective treatment of bleeding gastric varices in cirrhosis. Surgery 2015; 157: 1028–1045.
51. Cheung J, Zeman M, van Zanten SV, et al. Systematic review: secondary prevention with band ligation, pharmacotherapy or combination therapy after bleeding from oesophageal varices. Aliment PharmacolTher 2009; 30: 577–588.
52. Thiele M, Krag A, Rohde U, et al. Meta-analysis: banding ligation and medical interventions for the prevention of rebleeding from oesophageal varices. Aliment PharmacolTher 2012; 36: 1155–1165.
53. Puente A, Hernández-Gea V, Graupera I, et al. Drugs plus ligation to prevent rebleeding in cirrhosis: an updated systematic review. Liver Int 2014; 34: 823–833.
2. Nusrat S, Khan, MS, Fazili J, et al. Cirrhosis and its complications: Evidence based treatment. World J. Gastroenterol2014; 20: 5442–5460.
3. Garcia-Tsao G, Abraldes JG, Berzigotti A, et al. Portal hypertensive bleeding in cirrhosis: Risk stratification, diagnosis, and management: 2016 practice guidance by the American Association for the study of liver diseases. Hepatology 2017; 65: 310–335.
4. Yue X, Wang Z, Li J, et al. Esophageal variceal ligation plus sclerotherapy vs. ligation alone for the treatment of esophageal varices. Front Surg 2022; 9: 928873.doi: 10.3389/fsurg.2022.928873.
5. Sarin SK, Lahoti D, Saxena SP, 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.
6. Mishra SR, Sharma BC, Kumar A, et al. Primary prophylaxis of gastric variceal bleeding comparing cyanoacrylate injection and beta blockers: A radnomized controlled trial. J Hepatol 2011; 54: 1161-1167.
7. Biecker E. Portal hypertension and gastrointestinal bleeding: diagnosis, prevention and management. World J Gastroenterol 2013; 19: 5035-5050.
8. Ding NS, Nguyen T, Iser, DM, et al. Liver stiffness plus platelet count can be used to exclude high-risk oesophageal varices. Liver Int2016; 36: 240–245.
9. Robic, MA, Procopet B, Métivier S, et al. Liver stiffness accurately predicts portal hypertension related complications in patients with chronic liver disease: A prospective study. J Hepatol2011; 55, 1017–1024.
10. Paternostro R, Reiberger T, Bucsics T. Elastography-based screening for esophageal varices in patients with advanced chronic liver disease. World J. Gastroenterol. 2019: 25, 308–329.
11. De Franchis R, Bosch J, Garcia-Tsao G, et al. Baveno VII – renewing consensus in portal hypertension. J Hepatol 2022; 76 (4): 959-974.
12. Gralnek IM, Duboc MC, Garcia-Pagan JC, et al. Endoscopic diagnosis and management of esophagogastric varciceal hemorrhage: European Society of Gastrointestinal Endoscopy (ESGE) Guideline. Endoscopy 2022; 54: 1094-1120.
13. De Franchis R. Baveno VI Faculty. Expanding consensus in portal hypertension Report of the Baveno VI consensus workshop: stratifying risk and individualizing care for portal hypertension. J Hepatol 2015; 63: 743-752.
14. Sharma M, Singh S, Desai V et al. Comparison of therapies for primary prevention of esophageal variceal bleeding: a systematic review and network meta-analysis. Hepatology 2019; 69: 1657–1675
15. Villanueva C, Sapena V, Lo GH et al. Stratified efficacy of first-line therapy to prevent first variceal bleeding according to previous decompensation of cirrhosis. A competing-risk meta-analyses of individual participant data. J Hepatol 2022; 77: (S1): 625-626.
16. Funakoshi N, Duny Y, Valats JC et al. Meta-analysis: beta-blockers versus banding ligation for primary prophylaxis of esophageal variceal bleeding. Ann Hepatol 2012; 11: 369–383.
17. Reiberger T, Ulbrich G, Ferlitsch A et al. Carvedilol for primary prophylaxis of variceal bleeding in cirrhotic patients with haemodynamic non-response to propranolol. Gut 2013; 62: 1634–1641.
18. Tian S, Li R, Guo Y, et al. Carvedilol vs endoscopic band ligation for the prevention of variceal bleeding: A meta-analysis. TherClin Risk Manag2019; 15: 191–200.
19. Hammond DA, Lam SW, Rech MA, et al. Balanced Crystalloids Versus Saline in Critically Ill Adults: A Systematic Review and Meta-analysis. Ann Pharmacother2020; 54: 5–13.
20. Veitch AM, Radaelli F, Alikhan R et al. Endoscopy in patients on antiplatelet or anticoagulant therapy: British Society of Gastroenterology (BSG) and European Society of Gastrointestinal Endoscopy (ESGE) guideline update. Gut 2021; 70: 1611–1628.
21. Dasa O, Pepine CJ, Pearson TA. Aspirin in primary prevention: what changed? A critical appraisal of current evidence Am J Cardiol 2021; 141: 38–48.
22. Eisenberg MJ, Richard PR, Libersan D, et al. Safety of short-term discontinuation of antiplatelet therapy in patients with drug-eluting stents. Circulation 2009; 119: 1634–1642.
23. Huaringa-Marcelo J, Huaman MR, Brañez-Condorena A, et al. Vasoactive Agents for the Management of Acute Variceal Bleeding: A Systematic Review and Meta-analysis. J. Gastrointestin. Liver Dis 2021, 30, 110–121.
24. Yan P, Tian X, Li J. Is additional 5-day vasoactive drug therapy necessary for acute variceal bleeding after successful endoscopic hemostasis?: A systematic review and meta-analysis. Medicine 2018, 97, e12826.
25. Lee S, Saxinger L, Ma M, et al. Bacterial infections in acute variceal hemorrhage despite antibiotics-a multicenter study of predictors and clinical impact. United EurGastroenterol2017; 5: 1090–1099.
26. Chang TS, Tsai YH, Lin YH et al. Limited effects of antibiotic prophylaxis in patients with Child-Pugh class A/B cirrhosis and upper gastrointestinal bleeding. PLoS One 2020; 15: e0229101.
27. Bai Z, Wang R, Cheng G, et al. Outcomes of early versus delayed endoscopy in cirrhotic patients with acute variceal bleeding: A systematic review with meta-analysis. Eur J GastroenterolHepatol2021; 33: 868–876.
28. Kovacs TOG, Jensen DM. Varices: Esophageal, Gastric, and Rectal. Clin Liver Dis 2019; 23: 625–642.
29. Nett A, Binmoeller KF. Endoscopic Management of Portal Hypertension-related Bleeding. GastrointEndoscClin N Am 2019; 29: 321–337.
30. Dai C, Liu WX, Jiang M, Sun MJ. Endoscopic variceal ligation compared with endoscopic injection sclerotherapy for treatment of esophageal variceal hemorrhage: A meta-analysis. World J Gastroenterol2015; 21; 2534–2541.
31. Karsan HA, Morton SC, Shekelle PG, et al. Combination endoscopic band ligation and sclerotherapy compared with endoscopic band ligation alone for the secondary prophylaxis of esophageal variceal hemorrhage: a meta-analysis. Dig Dis Sci 2005; 50: 399-406.
32. Djurdjević D, Janošević S, Dapčević B, et al. Combined ligation and sclerotherapy versus ligation alone for eradication of bleeding esophageal varices: a randomized and prospective trial. Endoscopy. 1999; 31(4): 286-290.
33. Singh P, Pooran N, Indaram A, Bank S. Combined ligation and sclerotherapy versus ligation alone for secondary prophylaxis of esophageal variceal bleeding: a meta-analysis. Am J Gastroenterol. 2002; 97(3): 623-629.
34. Lo GH, Lai KH, Cheng JS, et al. The additive effect of sclerotherapy to patients receiving repeated endoscopic variceal ligation: a prospective, randomized trial. Hepatology 1998; 28:391-395.
35. Hou MC, Chen WC, Lin HC, et al. A new „sandwich” method of combined endoscopic variceal ligation and sclerotherapy versus ligation alone in the treatment of esophageal variceal bleeding: a randomized trial. GastrointestEndosc 2001; 53:572-578.
36. Cheng YS, Pan S, Lien GS, et al. Adjuvant sclerotherapy after ligation for the treatment of esophageal varices: a prospective, randomized long-term study. Gastrointest Endosc.2001; 53:566-571.
37. Grgov S, Stamenković P. Does sclerotherapy of remnant little oesophageal varices after endoscopic ligation have impact on the reduction of recurrent varices? Prospective study. SrpArhCelokLek 2011; 139 (5-6): 328-332.
38. Bosch J, Berzigotti A, Garcia-Pagan JC, Abraldes JG. The management of portal hypertension: rational basis, available treatments and future options. J Hepatol 2008; 48 Suppl 1: 68-92.
39. Escorse À, Pavel O, Cárdenas A, et al. Esophageal balloon tamponade versus esophageal stent in controlling acute refractory variceal bleeding: A multicenter randomized, controlled trial. Hepatology 2016; 63: 1957–1967.
40. Shao XD, Qi XS, Guo XZ. Esophageal Stent for Refractory Variceal Bleeding: A Systemic Review and Meta-Analysis. BioMed Res Int2016, 2016, 4054513.
41. Maimone S, Saffioti F, Filomia R, et al. Predictors of Re-bleeding and Mortality Among Patients with Refractory Variceal Bleeding Undergoing Salvage Transjugular Intrahepatic Portosystemic Shunt (TIPS). Dig Dis Sci2019; 64: 1335–1345.
42. Selzner M, Tuttle-Newhall JE, Dahm F, et al. Current indication of a modified Sugiura procedure in the management of variceal bleeding. J Am Coll Surg 2001; 193 (2):166-173.
43. Deng ZC, Jiang WZ, Chen L, et al. Laparoscopic VS. Open splenectomy and oesophagogastric devascularisation for liver cirrhosis and portal hypertension: A retrospective cohort study. Int J Surg 2020; 80:79-83.
44. Luo HP, Zhang ZG, Long X, et al. Combined Laparoscopic Splenectomy and Esophagogastric Devascularization versus Open Splenectomy and Esophagogastric Devascularization for Portal Hypertension due to Liver Cirrhosis. Curr Med Sci 2020; 40 (1):117-122.
45. Rodge GA, Goenka U, Goenka M. Management of refractory variceal bleed in cirrhosis. J Clin Exp Hepatol 2022; 12: 595-602.
46. Garcia-Pagán JC, Barrufet, M, Cardenas A, Escorsell, A. Management of gastric varices. Clin. Gastroenterol. Hepatol2014; 12: 919–928.e911.
47. Gubler C, Bauerfeind, P. Safe and successful endoscopic initial treatment and long-term eradication of gastric varices by endoscopic ultrasound-guided Histoacryl (N-butyl-2-cyanoacrylate) injection. Scand J Gastroentero2014; 49: 1136–1142.
48. Bick BL, Al-Haddad M, Liangpunsakul S, et al. EUS-guided fine needle injection is superior to direct endoscopic injection of 2-octyl cyanoacrylate for the treatment of gastric variceal bleeding. SurgEndosc2019; 33: 1837–1845.
49. Bhat YM, Weilert F, Fredrick RT, et al. EUS-guided treatment of gastric fundal varices with combined injection of coils and cyanoacrylate glue: a large U.S. experience over 6 years. Gastrointest Endosc 2016; 83(6):1164-1172.
50. Orloff MJ, Hye RJ, Wheeler HO, et al. Randomized trials of endoscopic therapy and transjugular intrahepatic portosystemic shunt versus portacaval shunt for emergency and elective treatment of bleeding gastric varices in cirrhosis. Surgery 2015; 157: 1028–1045.
51. Cheung J, Zeman M, van Zanten SV, et al. Systematic review: secondary prevention with band ligation, pharmacotherapy or combination therapy after bleeding from oesophageal varices. Aliment PharmacolTher 2009; 30: 577–588.
52. Thiele M, Krag A, Rohde U, et al. Meta-analysis: banding ligation and medical interventions for the prevention of rebleeding from oesophageal varices. Aliment PharmacolTher 2012; 36: 1155–1165.
53. Puente A, Hernández-Gea V, Graupera I, et al. Drugs plus ligation to prevent rebleeding in cirrhosis: an updated systematic review. Liver Int 2014; 34: 823–833.
Published
2025/11/19
Section
Originalni rad / Original article