To the Editor:

The randomized trial by Schepke et al.,1 which showed that variceal banding ligation and propranolol were similarly effective for primary prophylaxis of variceal bleeding, is an important one. However, the study raises the issue of the effectiveness and safety of banding ligation in this setting. We feel that the safety of endoscopic ligation for primary prophylaxis is extremely important, as our own experience also raises this issue.2

Three trials have been published recently in this area.3–5 Two of these studies3, 5 did not find significant differences between banding and propranolol, but one4 suggested that propranolol-treated patients with cirrhosis with high-risk esophageal varices had a significantly higher rate of bleeding from esophageal varices and greater cumulative mortality than those who had banding.

In this study4 the selection criteria excluded the very patients who may be more at risk of first bleeding—severe coagulopathy unresponsive to blood product transfusions, severe thrombocytopenia, gastric varices, documented hepatoma, portal or hepatic thrombosis, and large-volume or tense ascites; i.e., the ones clinicians may wish to treat intensively. The impression given is that banding ligation is a totally safe procedure in terms of iatrogenic bleeding. Jutabha et al.4 suggest that this is because the operators were all very experienced in banding ligation, but this is not supported by the literature—perhaps they were just lucky!

Thus, in the trial by Schepke et al trial bleeding from ligation occurred in 5 patients (6.7%), with 1 life-threatening and 2 fatal outcomes. This reflects our recently published experience.2 A prophylactic therapy should be safe even if effective—primum non nocere.

Second, the authors should have evaluated their results in the context of others; they would have found themselves to be outliers. Indeed, the results were anomalous, as has also been felt to be the case in some previous studies.6 This is clear from a Forrest plot of a meta-analysis (Fig. 1). This should have led them to continue their study and not interrupt it early.

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Figure 1. (A) Meta-analysis plot of randomized trials of banding ligation of esophageal varices versus beta-blockers. Portal hypertensive bleeding. Data are expressed as OR (95% CI) in a log scale. (B) Meta-analysis plot of randomized trials of banding ligation of esophageal varices versus beta-blockers. Survival. Data are expressed as OR (95% CI) in a log scale. BB, beta-blockers; EBL, endoscopic band ligation.

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Moreover, it cannot be assumed that banding may be necessarily the best therapy for patients intolerant to beta-blockers.7 Although it is unlikely that varices in these patients are any different from those who tolerate beta-blockers, we experienced iatrogenic but not fatal bleeding with banding in our randomized study.2

We still need carefully conducted trials based on the population most seen in clinical practice; trials which do not have too much selection and which remember that patients may also bleed from portal hypertensive gastropathy. The published data by Schepke et al.1 and our own experience2 lead us to still consider nonselective beta-blockers as first-choice therapy for primary prophylaxis of portal hypertensive bleeding in cirrhosis, and not banding.4


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  • 1
    Schepke M, Kleber G, Nurnberg D, Willert J, Koch L, Veltzke-Schlieker W, et al. Ligation versus propranolol for the primary prophylaxis of variceal bleeding in cirrhosis. HEPATOLOGY 2004; 40: 6572.
  • 2
    Triantos C, Vlachogiannakos J, Armonis A, Saveriadis A, Kougioumtzian A, Leandro G, et al. Primary prophylaxis of variceal bleeding in cirrhotics unable to take -blockers: a randomized trial of ligation. Alimentary Pharmacology and Therapeutics 2005; 21: 14351443.
  • 3
    Drastich P, Lata J, Petryl J, Prochazka V, Vanasek T, Zdenek P, et al. Endoscopic variceal band ligation in comparison with propranolol in prophylaxis of first variceal bleeding in patients with liver cirrhosis [abstract]. J Hepatol 2005; 42( Suppl 2): 79.
  • 4
    Jutabha R, Jensen DM, Martin P, Savides T, Han SH, Gornbein J. Randomized study comparing banding and propranolol to prevent initial variceal hemorrhage in cirrhotics with high-risk esophageal varices. Gastroenterology 2005; 128: 870881.
  • 5
    Thuluvath PJ, Maheshwari A, Jagannath S, Arepally A. A randomized controlled trial of beta-blockers versus endoscopic band ligation for primary prophylaxis: a large sample size is required to show a difference in bleeding rates. Dig Dis Sci 2005; 50: 407410.
  • 6
    Burroughs AK, Patch D. Primary prevention of bleeding from esophageal varices. N Engl J Med 1999; 340: 10331035.
  • 7
    Boyer TD. Primary prophylaxis for variceal bleeding: are we there yet? Gastroenterology 2005; 128: 11201122.

Christos Triantos M.D.*, Jiannis Vlachogiannakos M.D.†, Spilios Manolakopoulos M.D.‡, Andrew Burroughs F.R.C.P.*, Alec Avgerinos M.D.†, * Liver Transplantation and Hepatobiliary Medicine, Royal Free Hospital, London, United Kingdom, † Second Department of Gastroenterology, Evangelismos General Hospital, Athens, Greece, ‡ Department of Gastroenterology, Polykliniki General Hospital, Athens, Greece.