Korean J Gastroenterol.  2021 Sep;78(3):152-160. 10.4166/kjg.2021.113.

Diagnosis and Management of Esophageal and Gastric Variceal Bleeding: Focused on 2019 KASL Clinical Practice Guidelines for Liver Cirrhosis

• Park MK
• Lee YB

• KMID: 2520356
• DOI: http://doi.org/10.4166/kjg.2021.113

Abstract

Varices are a frequent complication of liver cirrhosis and a major cause of mortality in patients with liver cirrhosis. Patients with decompensated cirrhosis complications have a poor prognosis and require careful management. Portal hypertension is the most common complication of liver cirrhosis, which is the key determinant for varices development. Increased intrahepatic vascular resistance to portal flow leads to the development of portal hypertension. Collateral vessels develop at the communication site between the systemic and portal circulation with the progression of portal hypertension. Varices are the representative collaterals, develop gradually with the progression of portal hypertension and may eventually rupture. Variceal bleeding is a major consequence of portal hypertension and causes the death of cirrhotic patients. The present paper reviews the latest knowledge regarding the diagnosis and management of esophageal and gastric variceal bleeding.

Keyword

sophageal and gastric varices; Liver cirrhosis; Portal hypertension; Hemorrhage; Hemostasis

Figure

• 

  Fig. 1 Esophageal varices with (A) red color sign, (B) fibrin plug and (C) active bleeding. (D) Band-ligated esophageal varices.

• 

  Fig. 2 Gastric varices. (A) Gastroesophageal varices type 1. (B) Endoscopic variceal obturation for bleeding gastric varices type 1. (C) Gastroesophageal varices type 2 with stigmata of recent bleeding before balloon-occluded retrograde transvenous obliteration (BRTO). (D) Regression of gastric varices after BRTO.

• 

  Fig. 3 Management of esophageal and gastric variceal bleeding. GOV, gastroesophageal varices; IGV, isolated gastric varices; RTO, retrograde transvenous obliteration; TIPS, transjugular intrahepatic portosystemic shunt. This algorithm was modified from 2019 KASL clinical practice guidelines for liver cirrhosis.39

Reference

1. D'Amico G, Pasta L, Morabito A, et al. 2014; Competing risks and prognostic stages of cirrhosis: a 25-year inception cohort study of 494 patients. Aliment Pharmacol Ther. 39:1180–1193. DOI: 10.1111/apt.12721. PMID: 24654740.

2. Kovalak M, Lake J, Mattek N, Eisen G, Lieberman D, Zaman A. 2007; Endoscopic screening for varices in cirrhotic patients: data from a national endoscopic database. Gastrointest Endosc. 65:82–88. DOI: 10.1016/j.gie.2006.08.023. PMID: 17185084.

3. Iwakiri Y, Groszmann RJ. 2006; The hyperdynamic circulation of chronic liver diseases: from the patient to the molecule. Hepatology. 43(2 Suppl 1):S121–S131. DOI: 10.1002/hep.20993. PMID: 16447289.

4. García-Pagán JC, Gracia-Sancho J, Bosch J. 2012; Functional aspects on the pathophysiology of portal hypertension in cirrhosis. J Hepatol. 57:458–461. DOI: 10.1016/j.jhep.2012.03.007. PMID: 22504334.

5. Abraldes JG, Iwakiri Y, Loureiro-Silva M, Haq O, Sessa WC, Groszmann RJ. 2006; Mild increases in portal pressure upregulate vascular endothelial growth factor and endothelial nitric oxide synthase in the intestinal microcirculatory bed, leading to a hyperdynamic state. Am J Physiol Gastrointest Liver Physiol. 290:G980–G987. DOI: 10.1152/ajpgi.00336.2005. PMID: 16603731.

6. Groszmann RJ, Garcia-Tsao G, Bosch J, et al. 2005; Beta-blockers to prevent gastroesophageal varices in patients with cirrhosis. N Engl J Med. 353:2254–2261. DOI: 10.1056/NEJMoa044456. PMID: 16306522.

7. Merli M, Nicolini G, Angeloni S, et al. 2003; Incidence and natural history of small esophageal varices in cirrhotic patients. J Hepatol. 38:266–272. DOI: 10.1016/S0168-8278(02)00420-8.

8. North Italian Endoscopic Club for the Study and Treatment of Esophageal Varices. 1988; Prediction of the first variceal hemorrhage in patients with cirrhosis of the liver and esophageal varices. A prospective multicenter study. N Engl J Med. 319:983–989. DOI: 10.1056/NEJM198810133191505. PMID: 3262200.

9. McCormick PA, O'Keefe C. 2001; Improving prognosis following a first variceal haemorrhage over four decades. Gut. 49:682–685. DOI: 10.1136/gut.49.5.682. PMID: 11600472. PMCID: PMC1728509.

10. Carbonell N, Pauwels A, Serfaty L, Fourdan O, Lévy VG, Poupon R. 2004; Improved survival after variceal bleeding in patients with cirrhosis over the past two decades. Hepatology. 40:652–659. DOI: 10.1002/hep.20339. PMID: 15349904.

11. Seo YS, Park SY, Kim MY, et al. 2014; Lack of difference among terlipressin, somatostatin, and octreotide in the control of acute gastroesophageal variceal hemorrhage. Hepatology. 60:954–963. DOI: 10.1002/hep.27006. PMID: 24415445.

12. Villanueva C, Piqueras M, Aracil C, et al. 2006; A randomized controlled trial comparing ligation and sclerotherapy as emergency endoscopic treatment added to somatostatin in acute variceal bleeding. J Hepatol. 45:560–567. DOI: 10.1016/j.jhep.2006.05.016. PMID: 16904224.

13. Reverter E, Tandon P, Augustin S, et al. 2014; A MELD-based model to determine risk of mortality among patients with acute variceal bleeding. Gastroenterology. 146:412–419.e3. DOI: 10.1053/j.gastro.2013.10.018. PMID: 24148622.

14. Garcia-Tsao G, Sanyal AJ, Grace ND, Carey W. Practice Guidelines Committee of the American Association for the Study of Liver Diseases. Practice Parameters Committee of the American College of Gastroenterology. 2007; Prevention and management of gastroesophageal varices and variceal hemorrhage in cirrhosis. Hepatology. 46:922–938. DOI: 10.1002/hep.21907. PMID: 17879356.

15. Lee SD, Kearney DJ. 2004; A randomized controlled trial of gastric lavage prior to endoscopy for acute upper gastrointestinal bleeding. J Clin Gastroenterol. 38:861–865. DOI: 10.1097/00004836-200411000-00005. PMID: 15492601.

16. Villanueva C, Colomo A, Bosch A, et al. 2013; Transfusion strategies for acute upper gastrointestinal bleeding. N Engl J Med. 368:11–21. DOI: 10.1056/NEJMoa1211801. PMID: 23281973.

17. Castañeda B, Morales J, Lionetti R, et al. 2001; Effects of blood volume restitution following a portal hypertensive-related bleeding in anesthetized cirrhotic rats. Hepatology. 33:821–825. DOI: 10.1053/jhep.2001.23437. PMID: 11283845.

18. Bosch J, Thabut D, Bendtsen F, et al. 2004; Recombinant factor VIIa for upper gastrointestinal bleeding in patients with cirrhosis: a randomized, double-blind trial. Gastroenterology. 127:1123–1130. DOI: 10.1053/j.gastro.2004.07.015. PMID: 15480990.

19. Bosch J, Thabut D, Albillos A, et al. 2008; Recombinant factor VIIa for variceal bleeding in patients with advanced cirrhosis: a randomized, controlled trial. Hepatology. 47:1604–1614. DOI: 10.1002/hep.22216. PMID: 18393319.

20. Bernard B, Grangé JD, Khac EN, Amiot X, Opolon P, Poynard T. 1999; Antibiotic prophylaxis for the prevention of bacterial infections in cirrhotic patients with gastrointestinal bleeding: a meta-analysis. Hepatology. 29:1655–1661. DOI: 10.1002/hep.510290608. PMID: 10347104.

21. Chavez-Tapia NC, Barrientos-Gutierrez T, Tellez-Avila F, et al. 2011; Meta-analysis: antibiotic prophylaxis for cirrhotic patients with upper gastrointestinal bleeding - an updated Cochrane review. Aliment Pharmacol Ther. 34:509–518. DOI: 10.1111/j.1365-2036.2011.04746.x. PMID: 21707680.

22. Fernández J, Ruiz del Arbol L, Gómez C, et al. 2006; Norfloxacin vs ceftriaxone in the prophylaxis of infections in patients with advanced cirrhosis and hemorrhage. Gastroenterology. 131:1049–1285. DOI: 10.1053/j.gastro.2006.07.010. PMID: 17030175.

23. Wells M, Chande N, Adams P, et al. 2012; Meta-analysis: vasoactive medications for the management of acute variceal bleeds. Aliment Pharmacol Ther. 35:1267–1278. DOI: 10.1111/j.1365-2036.2012.05088.x. PMID: 22486630.

24. Ioannou G, Doust J, Rockey DC. 2003; Terlipressin for acute esophageal variceal hemorrhage. Cochrane Database Syst Rev. (1):CD002147. DOI: 10.1002/14651858.CD002147. PMCID: PMC7017851.

25. Suk KT, Baik SK, Yoon JH, et al. 2012; Revision and update on clinical practice guideline for liver cirrhosis. Korean J Hepatol. 18:1–21. DOI: 10.3350/kjhep.2012.18.1.1. PMID: 22511898. PMCID: PMC3326994.

26. Solà E, Lens S, Guevara M, et al. 2010; Hyponatremia in patients treated with terlipressin for severe gastrointestinal bleeding due to portal hypertension. Hepatology. 52:1783–1790. DOI: 10.1002/hep.23893. PMID: 20931555.

27. de Franchis R. Baveno VI Faculty. 2015; Expanding consensus in portal hypertension: report of the Baveno VI consensus workshop: stratifying risk and individualizing care for portal hypertension. J Hepatol. 63:743–752. DOI: 10.1016/j.jhep.2015.05.022. PMID: 26047908.

28. Garcia-Tsao G, Abraldes JG, Berzigotti A, Bosch J. 2017; Portal hypertensive bleeding in cirrhosis: risk stratification, diagnosis, and management: 2016 practice guidance by the American Association for the study of liver diseases. Hepatology. 65:310–335. DOI: 10.1002/hep.28906. PMID: 27786365.

29. Hashizume M, Ohta M, Ueno K, Tanoue K, Kitano S, Sugimachi K. 1993; Endoscopic ligation of esophageal varices compared with injection sclerotherapy: a prospective randomized trial. Gastrointest Endosc. 39:123–126. DOI: 10.1016/S0016-5107(93)70050-4.

30. Lo GH, Lai KH, Cheng JS, et al. 1995; A prospective, randomized trial of sclerotherapy versus ligation in the management of bleeding esophageal varices. Hepatology. 22:466–471. DOI: 10.1002/hep.1840220215.

31. Laine L, Cook D. 1995; Endoscopic ligation compared with sclerotherapy for treatment of esophageal variceal bleeding. A meta-analysis. Ann Intern Med. 123:280–287. DOI: 10.7326/0003-4819-123-4-199508150-00007. PMID: 7611595.

32. Lo GH, Lai KH, Cheng JS, et al. 1997; Emergency banding ligation versus sclerotherapy for the control of active bleeding from esophageal varices. Hepatology. 25:1101–1104. DOI: 10.1002/hep.510250509. PMID: 9141424.

33. Stiegmann GV, Goff JS, Michaletz-Onody PA, et al. 1992; Endoscopic sclerotherapy as compared with endoscopic ligation for bleeding esophageal varices. N Engl J Med. 326:1527–1532. DOI: 10.1056/NEJM199206043262304. PMID: 1579136.

34. Dai C, Liu WX, Jiang M, Sun MJ. 2015; Endoscopic variceal ligation compared with endoscopic injection sclerotherapy for treatment of esophageal variceal hemorrhage: a meta-analysis. World J Gastroenterol. 21:2534–2541. DOI: 10.3748/wjg.v21.i8.2534. PMID: 25741164. PMCID: PMC4342933.

35. Monescillo A, Martínez-Lagares F, Ruiz-del-Arbol L, et al. 2004; Influence of portal hypertension and its early decompression by TIPS placement on the outcome of variceal bleeding. Hepatology. 40:793–801. DOI: 10.1002/hep.20386. PMID: 15382120.

36. García-Pagán JC, Caca K, Bureau C, et al. 2010; Early use of TIPS in patients with cirrhosis and variceal bleeding. N Engl J Med. 362:2370–2379. DOI: 10.1056/NEJMoa0910102. PMID: 20573925.

37. Rudler M, Cluzel P, Corvec TL, et al. 2014; Early-TIPSS placement prevents rebleeding in high-risk patients with variceal bleeding, without improving survival. Aliment Pharmacol Ther. 40:1074–1080. DOI: 10.1111/apt.12934. PMID: 25230051.

38. Shaheen NJ, Stuart E, Schmitz SM, et al. 2005; Pantoprazole reduces the size of postbanding ulcers after variceal band ligation: a randomized, controlled trial. Hepatology. 41:588–594. DOI: 10.1002/hep.20593. PMID: 15726658.

39. Korean Association for the Study of the Liver (KASL). 2020; KASL clinical practice guidelines for liver cirrhosis: varices, hepatic encephalopathy, and related complications. Clin Mol Hepatol. 26:83–127. DOI: 10.3350/cmh.2019.0010n. PMID: 31918536. PMCID: PMC7160350.

40. Labenz C, Beul L, Toenges G, et al. 2019; Validation of the simplified Animal Naming Test as primary screening tool for the diagnosis of covert hepatic encephalopathy. Eur J Intern Med. 60:96–100. DOI: 10.1016/j.ejim.2018.08.008. PMID: 30131209.

41. de Franchis R. Baveno V Faculty. 2010; Revising consensus in portal hypertension: report of the Baveno V consensus workshop on methodology of diagnosis and therapy in portal hypertension. J Hepatol. 53:762–768. DOI: 10.1016/j.jhep.2010.06.004. PMID: 20638742.

42. Azoulay D, Castaing D, Majno P, et al. 2001; Salvage transjugular intrahepatic portosystemic shunt for uncontrolled variceal bleeding in patients with decompensated cirrhosis. J Hepatol. 35:590–597. DOI: 10.1016/S0168-8278(01)00185-4.

43. Panés J, Terés J, Bosch J, Rodés J. 1988; Efficacy of balloon tamponade in treatment of bleeding gastric and esophageal varices. Results in 151 consecutive episodes. Dig Dis Sci. 33:454–459. DOI: 10.1007/BF01536031. PMID: 3280273.

44. Terés J, Cecilia A, Bordas JM, Rimola A, Bru C, Rodés J. 1978; Esophageal tamponade for bleeding varices. Controlled trial between the Sengstaken-Blakemore tube and the Linton-Nachlas tube. Gastroenterology. 75:566–569. DOI: 10.1016/S0016-5085(19)31660-9.

45. Haq I, Tripathi D. 2017; Recent advances in the management of variceal bleeding. Gastroenterol Rep (Oxf). 5:113–126. DOI: 10.1093/gastro/gox007. PMID: 28533909. PMCID: PMC5421505.

46. Sarin SK, Lahoti D, Saxena SP, Murthy NS, Makwana UK. 1992; Prevalence, classification and natural history of gastric varices: a long-term follow-up study in 568 portal hypertension patients. Hepatology. 16:1343–1349. DOI: 10.1002/hep.1840160607. PMID: 1446890.

47. de Franchis R, Primignani M. 2001; Natural history of portal hypertension in patients with cirrhosis. Clin Liver Dis. 5:645–663. DOI: 10.1016/S1089-3261(05)70186-0.

48. Sarin SK. 1997; Long-term follow-up of gastric variceal sclerotherapy: an eleven-year experience. Gastrointest Endosc. 46:8–14. DOI: 10.1016/S0016-5107(97)70202-5.

49. Chavez-Tapia NC, Barrientos-Gutierrez T, Tellez-Avila FI, Soares-Weiser K, Uribe M. 2010; Antibiotic prophylaxis for cirrhotic patients with upper gastrointestinal bleeding. Cochrane Database Syst Rev. 2010:CD002907. DOI: 10.1002/14651858.CD002907.pub2. PMID: 20824832. PMCID: PMC7138054.

50. Besson I, Ingrand P, Person B, et al. 1995; Sclerotherapy with or without octreotide for acute variceal bleeding. N Engl J Med. 333:555–560. DOI: 10.1056/NEJM199508313330904. PMID: 7623904.

51. Calès P, Masliah C, Bernard B, et al. 2001; Early administration of vapreotide for variceal bleeding in patients with cirrhosis. N Engl J Med. 344:23–28. DOI: 10.1056/NEJM200101043440104. PMID: 11136956.

52. Zuberi BF, Baloch Q. 2000; Comparison of endoscopic variceal sclerotherapy alone and in combination with octreotide in controlling acute variceal hemorrhage and early rebleeding in patients with low-risk cirrhosis. Am J Gastroenterol. 95:768–771. DOI: 10.1111/j.1572-0241.2000.01858.x. PMID: 10710072.

53. Seewald S, Ang TL, Imazu H, et al. 2008; A standardized injection technique and regimen ensures success and safety of N-butyl-2-cyanoacrylate injection for the treatment of gastric fundal varices (with videos). Gastrointest Endosc. 68:447–454. DOI: 10.1016/j.gie.2008.02.050. PMID: 18760173.

54. Bhasin DK, Sharma BC, Prasad H, Singh K. 2000; Endoscopic removal of sclerotherapy needle from gastric varix after N-butyl-2-cyanoacrylate injection. Gastrointest Endosc. 51:497–498. DOI: 10.1016/S0016-5107(00)70459-7.

55. Henry Z, Patel K, Patton H, Saad W. 2021; AGA clinical practice update on management of bleeding gastric varices: expert review. Clin Gastroenterol Hepatol. 19:1098–1107.e1. DOI: 10.1016/j.cgh.2021.01.027. PMID: 33493693.

56. Park SW, Seo YS, Lee HA, et al. 2016; Changes in cardiac varices and their clinical significance after eradication of esophageal varices by band ligation. Can J Gastroenterol Hepatol. 2016:2198163. DOI: 10.1155/2016/2198163. PMID: 28116285. PMCID: PMC5220445.

57. Tan PC, Hou MC, Lin HC, et al. 2006; A randomized trial of endoscopic treatment of acute gastric variceal hemorrhage: N-butyl-2-cyanoacrylate injection versus band ligation. Hepatology. 43:690–697. DOI: 10.1002/hep.21145. PMID: 16557539.

58. Seo YS. 2018; Prevention and management of gastroesophageal varices. Clin Mol Hepatol. 24:20–42. DOI: 10.3350/cmh.2017.0064. PMID: 29249128. PMCID: PMC5875194.

59. El Amin H, Abdel Baky L, Sayed Z, et al. 2010; A randomized trial of endoscopic variceal ligation versus cyanoacrylate injection for treatment of bleeding junctional varices. Trop Gastroenterol. 31:279–284.

60. Lo GH, Lin CW, Perng DS, et al. 2013; A retrospective comparative study of histoacryl injection and banding ligation in the treatment of acute type 1 gastric variceal hemorrhage. Scand J Gastroenterol. 48:1198–1204. DOI: 10.3109/00365521.2013.832792. PMID: 24047398.

61. Park SJ, Kim YK, Seo YS, et al. 2016; Cyanoacrylate injection versus band ligation for bleeding from cardiac varices along the lesser curvature of the stomach. Clin Mol Hepatol. 22:487–494. DOI: 10.3350/cmh.2016.0050. PMID: 28081588. PMCID: PMC5266343.

62. Watanabe K, Kimura K, Matsutani S, Ohto M, Okuda K. 1988; Portal hemodynamics in patients with gastric varices. A study in 230 patients with esophageal and/or gastric varices using portal vein catheterization. Gastroenterology. 95:434–440. DOI: 10.1016/0016-5085(88)90501-X.

63. Saad WE. 2013; Vascular anatomy and the morphologic and hemodynamic classifications of gastric varices and spontaneous portosystemic shunts relevant to the BRTO procedure. Tech Vasc Interv Radiol. 16:60–100. DOI: 10.1053/j.tvir.2013.02.002. PMID: 23830670.

64. Maruyama H, Okugawa H, Yoshizumi H, Kobayashi S, Yokosuka O. 2008; Hemodynamic features of gastrorenal shunt: a Doppler study in cirrhotic patients with gastric fundal varices. Acad Radiol. 15:1148–1154. DOI: 10.1016/j.acra.2008.03.008. PMID: 18692756.

65. Kim MY, Um SH, Baik SK, et al. 2013; Clinical features and outcomes of gastric variceal bleeding: retrospective Korean multicenter data. Clin Mol Hepatol. 19:36–44. DOI: 10.3350/cmh.2013.19.1.36. PMID: 23593608. PMCID: PMC3622854.

66. Qiao W, Ren Y, Bai Y, Liu S, Zhang Q, Zhi F. 2015; Cyanoacrylate injection versus band ligation in the endoscopic management of acute gastric variceal bleeding: meta-analysis of randomized, controlled studies based on the PRISMA statement. Medicine (Baltimore). 94:e1725. DOI: 10.1097/MD.0000000000001725. PMID: 26469912. PMCID: PMC4616775.

67. Mahadeva S, Bellamy MC, Kessel D, Davies MH, Millson CE. 2003; Cost-effectiveness of N-butyl-2-cyanoacrylate (histoacryl) glue injections versus transjugular intrahepatic portosystemic shunt in the management of acute gastric variceal bleeding. Am J Gastroenterol. 98:2688–2693. DOI: 10.1111/j.1572-0241.2003.08769.x. PMID: 14687818.

68. Procaccini NJ, Al-Osaimi AM, Northup P, Argo C, Caldwell SH. 2009; Endoscopic cyanoacrylate versus transjugular intrahepatic portosystemic shunt for gastric variceal bleeding: a single-center U.S. analysis. Gastrointest Endosc. 70:881–887. DOI: 10.1016/j.gie.2009.03.1169. PMID: 19559425.

69. Sanyal AJ, Freedman AM, Luketic VA, et al. 1996; Transjugular intrahepatic portosystemic shunts for patients with active variceal hemorrhage unresponsive to sclerotherapy. Gastroenterology. 111:138–146. DOI: 10.1053/gast.1996.v111.pm8698192. PMID: 8698192.

70. Chau TN, Patch D, Chan YW, Nagral A, Dick R, Burroughs AK. 1998; "Salvage" transjugular intrahepatic portosystemic shunts: gastric fundal compared with esophageal variceal bleeding. Gastroenterology. 114:981–987. DOI: 10.1016/S0016-5085(98)00640-4.

71. Barange K, Péron JM, Imani K, et al. 1999; Transjugular intrahepatic portosystemic shunt in the treatment of refractory bleeding from ruptured gastric varices. Hepatology. 30:1139–1143. DOI: 10.1002/hep.510300523. PMID: 10534333.

72. Choi YH, Yoon CJ, Park JH, Chung JW, Kwon JW, Choi GM. 2003; Balloon-occluded retrograde transvenous obliteration for gastric variceal bleeding: its feasibility compared with transjugular intrahepatic portosystemic shunt. Korean J Radiol. 4:109–116. DOI: 10.3348/kjr.2003.4.2.109. PMID: 12845306. PMCID: PMC2698068.

73. Sabri SS, Abi-Jaoudeh N, Swee W, et al. 2014; Short-term rebleeding rates for isolated gastric varices managed by transjugular intrahepatic portosystemic shunt versus balloon-occluded retrograde transvenous obliteration. J Vasc Interv Radiol. 25:355–361. DOI: 10.1016/j.jvir.2013.12.001. PMID: 24468043.

74. Terrault NA, Bzowej NH, Chang KM, et al. 2016; AASLD guidelines for treatment of chronic hepatitis B. Hepatology. 63:261–283. DOI: 10.1002/hep.28156. PMID: 26566064. PMCID: PMC5987259.

75. Gimm G, Chang Y, Kim HC, et al. 2018; Balloon-occluded retrograde transvenous obliteration versus transjugular intrahepatic portosystemic shunt for the management of gastric variceal bleeding. Gut Liver. 12:704–713. DOI: 10.5009/gnl17515. PMID: 29938456. PMCID: PMC6254622.