CC BY-NC-ND 4.0 · Endosc Int Open 2019; 07(11): E1503-E1514
DOI: 10.1055/a-0901-7146
Review
Owner and Copyright © Georg Thieme Verlag KG 2019

Efficacy of endoscopic treatments for acute esophageal variceal bleeding in cirrhotic patients: systematic review and meta-analysis

Fernanda de Quadros Onofrio
1   Department of Gastroenterology and Hepatology, Santa Casa Hospital, Federal University of Health Sciences of Porto Alegre (UFCSPA), Porto Alegre, Brazil
,
Julio Carlos Pereira-Lima
1   Department of Gastroenterology and Hepatology, Santa Casa Hospital, Federal University of Health Sciences of Porto Alegre (UFCSPA), Porto Alegre, Brazil
,
Felipe Marquezi Valença
1   Department of Gastroenterology and Hepatology, Santa Casa Hospital, Federal University of Health Sciences of Porto Alegre (UFCSPA), Porto Alegre, Brazil
,
André Luis Ferreira Azeredo-da-Silva
2   Department of Internal Medicine, Santa Casa Hospital/Federal University of Health Sciences of Porto Alegre (UFCSPA), Porto Alegre, Brazil
,
Airton Tetelbom Stein
3   Department of Public Health, Federal University of Health Sciences of Porto Alegre (UFCSPA), Porto Alegre, Brazil
› Author Affiliations
Further Information

Publication History

submitted 18 December 2018

accepted after revision 04 April 2019

Publication Date:
23 October 2019 (online)

Abstract

Background and aim Guidelines recommend use of ligation and vasoactive drugs as first-line therapy and as grade A evidence for acute variceal bleeding (AVB), although Western studies about this issue are lacking.

Methods We performed a systematic review and meta-analysis of randomized controlled trials (RCT) to evaluate the efficacy of endoscopic treatments for AVB in patients with cirrhosis. Trials that included patients with hepatocellular carcinoma, use of portocaval shunts or esophageal resection, balloon tamponade as first bleeding control measure, or that received placebo or elective treatment in one study arm were excluded.

Results A total of 8382 publications were searched, of which 36 RCTs with 3593 patients were included. Ligation was associated with a significant improvement in bleeding control (relative risk [RR] 1.08; 95 % confidence interval [CI] 1.02 – 1.15) when compared to sclerotherapy. Sclerotherapy combined with vasoactive drugs showed higher efficacy in active bleeding control compared to sclerotherapy alone (RR 1.17; 95 % CI 1.10 – 1.25). The combination of ligation and vasoactive drugs was not superior to ligation alone in terms of overall rebleeding (RR 2.21; 95 %CI 0.55 – 8.92) and in-hospital mortality (RR 1.97; 95 %CI 0.78 – 4.97). Other treatments did not generate meta-analysis.

Conclusions This study showed that ligation is superior to sclerotherapy, although with moderate heterogeneity. The combination of sclerotherapy and vasoactive drugs was more effective than sclerotherapy alone. Although current guidelines recommend combined use of ligation with vasoactive drugs in treatment of esophageal variceal bleeding, this study failed to demonstrate the superiority of this combined treatment.

Supplementary Material

 
  • References

  • 1 Ferguson JW, Tripathi D, Hayes PC. Review article: the management of acute variceal bleeding. Aliment Pharmacol Ther 2003; 18: 253-262
  • 2 Marot A, Trepo E, Doerig C. et al. P Systematic review with meta-analysis: self-expanding metalstents in patients with cirrhosis and severe or refractory oesophageal variceal bleeding. Aliment Pharmacol Ther 2015; 42: 1250-260
  • 3 Gross M, Schiemann U, Muhlhfer A. et al. Meta-analysis: efficacy of therapeutic regimens in ongoing variceal bleeding. Endoscopy 2001; 33: 737-746
  • 4 Copenhagen Esophageal Varices Sclerotherapy Project. Sclerotherapy after first variceal hemorrhage in cirrhosis. N Engl J Med 1984; 311: 1594-1600
  • 5 Bendtsen F, Krag E, Moller S. Treatment of acute variceal bleeding. Dig Liver Dis 2008; 40: 328-336
  • 6 Deltenre P, Trepo E, Rudler M. et al. Early transjugular intrahepatic portosystemic shunt in cirrhotic patients with acute variceal bleeding: a systematic review and meta-analysis of controlled trials. Eur J Gastroenterol Hepatol 2015; 27: e1-9
  • 7 Guyatt G, Oxman AD, Akl EA. et al. GRADE guidelines: 1 Introduction-GRADE evidence profiles and summary of findings tables. J Clin Epidemiol 2011; 64: 383-394
  • 8 Guyatt GH, Oxman AD, Vist GE. et al. GRADE: an emerging consensus on rating quality of evidence and strength of recommendations. BMJ 2008; 336: 924-926
  • 9 Higgins JP, Thompson SG, Deeks JJ. et al. Measuring inconsistency in meta-analyses. BMJ 2003; 327: 557-560
  • 10 Riley RD, Higgins JPT, Deeks JJ. Research Methods & Reporting: Interpretation of random effects meta-analyses. Br Med J 2011; 342: d549
  • 11 Westaby D, Hayes PC, Gimson AE. et al. Controlled clinical trial of injection sclerotherapy for active variceal bleeding. Hepatology 1989; 9: 274-277
  • 12 Shields R, Jenkins SA, Baxter JN. 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
  • 13 Stiegmann GV, Goff JS, Michaletz-Onody PA. et al. Endoscopic sclerotherapy as compared with endoscopic ligation for bleeding esophageal varices. N Engl J Med 1992; 326: 1527-1532
  • 14 Laine L, el-Newihi HM, Migikovsky B. et al. Endoscopic ligation compared with sclerotherapy for the treatment of bleeding esophageal varices. Ann Intern Med 1993; 119: 1-7
  • 15 Gimson AE, Ramage JK, Panos MZ. et al. Randomised trial of variceal banding ligation versus injection sclerotherapy for bleeding oesophageal varices. Lancet 1993; 342: 391-394
  • 16 Sung JJ, Chung SC, Lai CW. et al. Octreotide infusion or emergency sclerotherapy for variceal haemorrhage. Lancet 1993; 342: 637-641
  • 17 Planas R, Quer JC, Boix J. et al. A prospective randomized trial comparing somatostatin and sclerotherapy in the treatment of acute variceal bleeding. Hepatology 1994; 20: 370-375
  • 18 Besson I, Ingrand P, Person B. et al. Sclerotherapy with or without octreotide for acute variceal bleeding. N Engl J Med 1995; 333: 555-560
  • 19 Lo GH, Lai KH, Cheng JS. et al. A prospective, randomized trial of sclerotherapy versus ligation in the management of bleeding esophageal varices. Hepatology 1995; 22: 466-471
  • 20 Sung JJ, Chung SC, Yung MY. et al. Prospective randomized study of effect of octreotide on rebleeding from oesophageal varices after endoscopic ligation. Lancet 1995; 346: 1666-1669
  • 21 Hou MC, Lin HC, Kuo BI. 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
  • 22 Laine L, Stein C, Sharma V. Randomized comparison of ligation versus ligation plus sclerotherapy in patients with bleeding esophageal varices. Gastroenterol 1996; 110: 529-533
  • 23 Shiha G, Hamid M, El-Said SS. et al. Octreotide infusion plus emergency sclerotherapy versus sclerotherapy alone for the control of bleeding oesophageal varices: A prospective randomized clinical trial. Mans Med J 1996; 26: 109-121
  • 24 Lo GH, Lai KH, Cheng JS. et al. Emergency banding ligation versus sclerotherapy for the control of active bleeding from esophageal varices. Hepatology 1997; 25: 1101-1104
  • 25 Avgerinos A, Nevens F, Raptis S. et al. Early administration of somatostatin and efficacy of sclerotherapy in acute oesophageal variceal bleeds: the European Acute Bleeding Oesophageal Variceal Episodes (ABOVE) randomised trial. Lancet 1997; 350: 1495-1499
  • 26 Saeed ZA, Stiegmann GV, Ramirez FC. et al. Endoscopic variceal ligation is superior to combined ligation and sclerotherapy for esophageal varices: a multicenter prospective randomized trial. Hepatology 1997; 25: 71-74
  • 27 Shafqat F, Khan AA, Alam A. et al. Band ligation vs endoscopic sclerotherapy in esophageal varices: a prospective randomized comparison. J Pak Med Assoc 1998; 48: 192-196
  • 28 Al Traif I, Fachartz FS, Al Jumah A. et al. Randomized trial of ligation versus combined ligation and sclerotherapy for bleeding esophageal varices. Gastrointest Endosc 1999; 50: 1-6
  • 29 de la Pena J, Rivero M, Sanchez E. et al. Variceal ligation compared with endoscopic sclerotherapy for variceal hemorrhage: prospective randomized trial. Gastrointest Endosc 1999; 49: 417-423
  • 30 Djurdjevic D, Janosevic S, Dapcevic B. et al. Combined ligation and sclerotherapy versus ligation alone for eradication of bleeding esophageal varices: a randomized and prospective trial. Endoscopy 1999; 31: 286-290
  • 31 Sivri B, Oksuzoglu G, Bayraktar Y. et al. A prospective randomized trial from Turkey comparing octreotide versus injection sclerotherapy in acute variceal bleeding. Hepatogastroenterol 2000; 47: 168-173
  • 32 Farooqi JI, Farooqi RJ, Haq N. et al. Treatment and outcome of variceal bleeding - A comparison of two methods. J Coll Phys Surg Pakistan 2000; 10: 131-133
  • 33 Bildozola M, Kravetz D, Argonz J. et al. Efficacy of octreotide and sclerotherapy in the treatment of acute variceal bleeding in cirrhotic patients. A prospective, multicentric, and randomized clinical trial. Scand J Gastroenterol 2000; 35: 419-425
  • 34 Escorsell A, Ruiz del Arbol L, Planas R. et al. Multicenter randomized controlled trial of terlipressin versus sclerotherapy in the treatment of acute variceal bleeding: The TEST Study. Hepatology 2000; 32: 471-476
  • 35 Zuberi BF, Baloch K. 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 2000; 95: 768-771
  • 36 Patsanas T, Kousopoulou N, Kapetanos D. et al. A randomized controlled trial comparing octreotide vs octreotide plus sclerotherapy in the control of bleeding and early mortality from esophageal varices. Ann Gastroenterol 2002; 153-157
  • 37 Shah HA, Muntaz K, Jafri W. et al. Sclerotherapy plus octreotide versus sclerotherapy alone in the management of gastro-oesophageal variceal hemorrhage. J Ayub Med Coll Abbottabad 2005; 17: 10-14
  • 38 Chen WC, Lo Gh, Tsai Wl. et al. Emergency endoscopic variceal ligation versus somatostatin for acute esophageal variceal bleeding. J Chin Med Assoc 2006; 69: 60-67
  • 39 Morales GF, Pereira Lima JC, Homos AP. et al. Octreotide for esophageal variceal bleeding treated with endoscopic sclerotherapy: a randomized, placebo-controlled trial. Hepatogastroenterol 2007; 54: 195-200
  • 40 Sarin SK, Kumar A, Jha SK. et al. Combination of somatostatin plus endoscopic variceal ligation (EVL) is similar to EVL alone in control of acute variceal bleeding: a randomized controlled trial. Hepatology (Baltimore, Md.) 2008; 628a
  • 41 Liu JS, Liu J. Comparison of emergency endoscopic variceal ligation plus octride or octride alone for acute esophageal variceal bleeding. Chin Med J (Engl) 2009; 122: 3003-3006
  • 42 Ljubicic N, Biscanin A, Nikolic M. et al. A randomized-controlled trial of endoscopic treatment of acute esophageal variceal hemorrhage: N-butyl-2-cyanoacrylate injection vs. variceal ligation. Hepatogastroentero 2011; 58: 438-443
  • 43 Luz GO, Maluf-Filho F, Matuguma SE. et al. Comparison between endoscopic sclerotherapy and band ligation for hemostasis of acute variceal bleeding. World J Gastrointest Endosc 2011; 3: 95-100
  • 44 Ximing W. Treatment experience of esophageal varices ligation in control of acute variceal bleeding. J Gastroenterol Hepatol 2013; 28: 774
  • 45 Sahu P, Kar P, Kumar KS. Endoscopic ligation compared with sclerotherapy for treatment of bleeding esophageal varices in decompensated cirrhotics. Indian J Gastroenterol 2014; 33: A53-54
  • 46 Mansour L, El-Kalla F, El-Bassat H. et al. Randomized controlled trial of scleroligation versus band ligation alone for eradication of gastroesophageal varices. Gastrointest Endosc 2017; 86: 307-315
  • 47 Wells M, Chande N, Adams P. et al. Meta-analysis: vasoactive medications for the managementof acute variceal bleeds. Aliment Pharmacol Ther 2012; 35: 1267-1278
  • 48 D’Amico G, Pagliaro L, Pietrosi G. et al. Emergency sclerotherapy versus vasoactive drugs for bleeding oesophageal varices in cirrhotic patients. Cochrane Database Syst Rev 2010; 17: CD002233
  • 49 de Franchis R. Baveno V 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
  • 50 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
  • 51 American Society for Gastrointestinal Endoscopy. The role of endoscopy in the management of variceal hemorrhage. Gastrointest Endosc 2014; 80: 221-227
  • 52 Garcia-Pagan JC, Caca K, Bureau C. et al. Early use of TIPS in patients with cirrhosis and variceal bleeding. N Engl J Med 2010; 362: 2370-2379