Saudi Journal of Gastroenterology

ARTICLES
Year
: 1997  |  Volume : 3  |  Issue : 2  |  Page : 70--73

Primary prophylaxis for bleeding from esophageal varices


Indrajit Tiwari 
 Department of Internal Medicine, Armed Forces Hospital, Southern Region, P.O. Box 101, Khamis Mushayt, Saudi Arabia

Correspondence Address:
Indrajit Tiwari
361 Chelsea Cloisters, Sloane Avenue, London SW 3 3DW, United Kingdom

Abstract

Esophageal varices develop in 30-70% of patients with liver cirrhosis. One-third of these varices will eventually bleed and first episode could be fatal in 40-50% of patients. Because of this, primary prophylaxis can be justified if patients at high risk of bleeding can be identified. Many endoscopic findings can identify the patients likely to bleed in near future. The results of primary prophylaxis with portacaval shunts and endoscopic sclerotherapy have been disappointing. Nonselective betablockers have been found effective in preventing bleeding from varices and their use is justified for this purpose.



How to cite this article:
Tiwari I. Primary prophylaxis for bleeding from esophageal varices.Saudi J Gastroenterol 1997;3:70-73


How to cite this URL:
Tiwari I. Primary prophylaxis for bleeding from esophageal varices. Saudi J Gastroenterol [serial online] 1997 [cited 2022 Oct 4 ];3:70-73
Available from: https://www.saudijgastro.com/text.asp?1997/3/2/70/33928


Full Text

Esophageal varices result from portal hypertension which may be due to different causes. Schistosomiasis is probably the most common cause of portal hypertension worldwide. This has better prognosis with proper treatment as compared to other causes, like alcoholic cirrhosis. About 30-70% of patients with liver cirrhosis develop esophageal varices and one-third of these will eventually bleed [1],[2] . The first episode of bleeding from esophageal varices could be fatal in the first year [3],[4] . Bleeding due to portal hypertension is a leading cause of death in patients with cirrhosis of the liver [5] .

 Why do varices bleed ?



Bleeding often occurs from the varices in the lower 5 cm of the esophagus [6] . The elevation of the portal pressure above threshold of 12 mm Hg appears to be necessary for the varices to form and subsequently bleed [7] . Bleeding is thought to result from internal disruption or explosion of varices because of increased pressure of thinning of the overlying structures rather than from the erosion of esophageal lumen by acid pepsin digestion or trauma of swallowing solid foods [6],[7],[8] .

A wall stress formula based on Laplace's law has been proposed, that includes the size of the varix, the thickness of the wall and the transmural pressure [7] . But the predictive value of these is limited in individual patients and there is not a good technique to measure the thickness of variceal wall accurately.

The prophylactic therapy could be applied at two different stages-primary prophylaxis for the varices which have never bled and secondary prophylaxis after an episode of bleeding from the varices. This article discusses the role of primary prophylaxis.

 Primary prophylaxis



One-third of patients with cirrhosis and varices are likely to bleed and half of these may die due to bleeding [9],[10] . Thus, if prophylactic treatment is used in all the patients with varices, two thirds will be treated unnecessarily. On the other hand, it may be justified to use it because of high mortality after first episode of bleeding from varices. It is very important that the prophylactic therapy should have minimal complications, be free of side effects and if possible non-invasive.

Prophylactic therapy can be justified only if the patient at high risk of bleeding from varices can be identified. Endoscopic markers of high risk of bleeding from varices have been described. Large varices have been shown to bleed more often than small varices [7],[11] . Other signs to identify the high risk groups have been described by various workers in Germany, Japan and India [12],[13],[14] . These include large varices, cherry red spots, red wale markings, blue varices, hematocystic spots over varices and high intra variceal pressure.

North Italian Endoscopic Club (NIEC) index includes Pugh's grade (as an index of liver - function), variceal size and the presence of red wale (wheal) markings and can reliably identify one year probability of bleeding [15] The endoscopic measurement of variceal pressure and size could be used to estimate variceal wall tension and could be a better guide to predict variceal hemorrhage [16] . Various prophylactic methods tried are discussed below:

 Portacaval shunts



The concept of prophylaxis is not new. Portal systemic shunting was popular three decades ago. Prophylactic shunt surgery prevented bleeding in over 90% of patients, but worsened the survival [17] . It has ultimately been abandoned after the control trials demonstrated decreased survival in the patients who had received shunts [18],[19],[20] . At present there is no role of prophylactic portacaval shunt in primary prevention of bleeding from esophageal varices.

 Endoscopic sclerotherapy



The first study of primary prevention sclerotherapy for large varices showed promising results but similar results have not been reproduced [12] . Witzel et al showed reduction in mortality in sclerotherapy group, but their study was criticized because of very high mortality in control group, who were thought not to have received proper treatment at the time of bleeding [9],[21],[22] . Although Italian study also came in favor of prophylactic sclerotherapy, it is not without risk [23] .

Both fatal and non-fatal complications like esophageal perforation, mediastinitis, stricture formation, dysphagia and bleeding from ulceration after sclerotherapy have been reported [24] . Veterans administration cooperative group study reported excessive mortality in patients who reeived sclerotherapy [25] .

Another American study reported more episodes of bleeding and death in the group which received sclerotherapy than in the control group [26],[27] . Two other studies showed no significant difference in bleeding episodes between control and sclerotherapy group [28],[29] . Thus prophylactic sclerotherapy of the varices which have not bled is useful only in limited circumstances and may not be beneficial in many patients [24],[30] . It should, therefore, not be used in routine clinical practice. Endoscopic band ligation heralds the hope that prophylactic eradication, before the first life threatening hemorrhage, can be achieved safely, but its role for primary prophylaxis is not established yet [30] .

 Beta blockers



Drug therapy with Betablocker fulfils the criteria for optimal prophylactic treatment. These drugs have a long safety record, are easy to adminsiter and have few side effects. In 1980, Lebrec demonstrated that propranolol could reduce portal pressure in portal hypertension [31] .There have been several trials since then on primary and secondary prevention of bleeding from esophageal varices with propranolol.

In the Italian multicenter trial it did not significantly reduce bleeding or increased survival [32] . However, in non-ascitic cirrhotics, bleeding was reduced by propranolol. In another trial, nadalol reduced the bleeding, but there was no significant difference in survival [33] . The French multicenter group reported both decrease in the incidence of first bleeding and death in patients receiving propanolol [34] . The meta-analysis of all seven trials published until early 1990 for primary prevention of bleeding from esophageal varices shows a reduction in the incidence of bleeding by 47%, in death due to bleeding by 45% and in total mortality of 22% [35] .

One of the selection criteria in almost all of those trials has been large varices. Since no other therapy is effective in the primary prevention of variceal hemorrhage, betablockade is indicated at least for those with large varices [35],[36],[37] . The starting dose should be 20 mg twice daily and gradually increased to decrease the heart rate by 20 to 25 percent or to a maximum dose of 320 mg daily [34] .

Propranalol will not effectively reduce the portal pressure in all patients and addition of isorbide mononitrate to propanolol may convert many nonresponders to responders [38] . At present, prophylaxis with betablockade seems to offer the best therapeutic option, but the future may lie in the development of new interventional techniques such as transjugular intrahepatic portosystemic shunting (TIPS) or variceal banding and ultimately with hepatic transplantation [39] .

Currently, TIPS is not indicated for primary prophylaxis of variceal hemorrhage, and its role in routine management of variceal hemorrhage is not justified [40],[41] .

 Conclusion



As careful endoscopic examination can help predict reliably the varices which are likely to bleed in near future, there is a place for prophylactic therapy in these patients. Prophylactic portacaval shunting was abandoned more than three decades ago, as it diminished patient survival in spite of the fact that it prevented bleeding. Prophylactic sclerotherapy has not stood to its earlier promise and this could lead to more harm than good in many patients. Its use cannot be justified in patients who have never bled. Propranolol on the other hand is a cheap and safe drug and most of the trials have shown favorable results.

Thus oral propranolol can be recommended for primary prophylaxis in the patients identified to have high risk of variceal bleeding. Future placebo controlled trials may provide definite answers. Trials combining betablockers and isosarbide mononitrate are in progress and their results may provide more information.

References

1Conn HO, Groszmann RJ. The Pathophysiology of Portal Hypertension. In: Arias I, Popper H, Schachter D, Shafritz DA eds. The Liver Biology and Pathobiology. New York, Raven 1982:821-48.
2Sauerbruch T, Kleber G, Gerbes A, et al. Prophylaxis of first Variceal Hemorrhage in patients with liver cirrhosis. Clinical Progress. Klin Wochenschr 1986;64:1267-75.
3Graham DY, Smith JL. The course of Patients after Variceal Hemorrhage. Gastroenterol 1981;80:800-9.
4Soederlund C. Variceal Hemorrhage. Gastroenterol 1981;81:635.
5Schilchting P, Christensen E, Fauerholdt L, et al. Main causes of death in cirrhosis. Scand J Gastroenterol 1983;18:881-8.
6Reynolds TB. Why do varices bleed ? In: Westaby D, MacDougall BRD, Williams R, eds. Variceal Bleeding. London: Pitman 1982:3-12.
7Gracia - Tsao G, Groszmann RJ, Fisher RL, Conn HO, Atterbury CE, Glickmann M. Portal Pressure, presence of gastroesophageal varices and variceal bleeding. Hepatology 1985;5:419-24.
8Reding P, Urbain D, Grivegnee A, Frere D. Portal Venous­esophageal luminal pressure gradient in cirrhosis. Hepatology 1986;6:98-100.
9Terbelanche J. Sclerotherapy for prophylaxis of variceal bleeding. Lancet 1986;1:961-3.
10Burroughs AK, D'Heygere F, McIntyre N. Pitfals in studies of prophylactic therapy for variceal bleeding in cirrhosis. Hepatology 1986;6:1407-13.
11Lebrec D, Fluery PD, Rueft B, Nahum H, Benhamou JP. Portal pressure, size of esophageal varices, and risk of gastrointestinal bleeding in alcoholic cirrhosis. Gastroenterol 1980;79:113-44.
12Paquet KJ. Prophylactic endoscopic scelerosing treatment of the esophageal wall in varices - 9 prospective controlled trial. Endoscopy 1982;14:4-5.
13Beppu K, Inokuchi K, Koyanagi N, et al. Prediction of variceal hemorrhage by esophageal endoscopy. Gastrointest Enclose 1981;27:213-8.
14Sarin SK, Sundaram KR, Ahuja RK. Prediction of variceal bleeding: an analysis of clinical, endoscopic, and hemodynamic variables, with special reference to intravariceal pressure. Gut 1989;30:1757-64,
15North Italian Endoscopic Club for the study and treatment of esophageal varices. Prediction of the first variceal hemorrhage in patients with cirrhosis of the liver and esophageal varices: a prospective multicenter study. N Eng J Med 1988;319:983-9.
16Rigan J, Bosch J, Bordas JM, et al. Endoscopic measurement of variceal pressure in cirrhosis: correlation with portal pressure and variceal hemorrhage. Gastroenterol 1989;96:873-80.
17Burroughs AK. The management of bleeding due to portal hypertension. Part 2, Prevention of variceal rebleeding and prevention of the first bleeding episode in patients with portal hypertension. Quart J Med 1988;255:507-16.
18Jackson FC, Perrin ED, Smith AG, Dagradi AE, Nadal HM. A clinical investigation of the portacaval shunt. II. Survival analysis of the prophylactic operation. Am J Surg 1968;115:22-42.
19Resnick RH, Chalmers TC, Ishihara AM, et al. A controlled study of the prophylactic portacaval shunt: a final report. Ann Intern Med 1969;70:675-88.
20Conn HO, Lindenmuth WW, May CJ, Ramsby GR, Prophylactic portacaval anastomosis: a tale of two studies. Medicine (Baltimore) 1972;51:27-40.
21Witzel L, Wolbergs E, Merki H. Prophylactic endoscopic sclerotherapy of esophageal varices: a prospective controlled study. Lancet 1985;1:773-5.
22Burroughs AK, Hamilton G, Prophylactic endoscopic variceal sclerotherapy of esophageal varices. Lancet 1985;1:1105-6.
23Piai G, Cipolletta L, Claar M, et al. Prophylactic sclerotherapy of high risk esophageal varices: multicenter prospective controlled trial. Hepatology 1988;8:1495-500.
24Bullimore DW, Foster P. Prophylactic sclerotherapy for varices. Br Med J 1988;297:370-1.
25Gregory P, Hartigan P, Amodio D, et al. Prophylactic sclerotherapy for esophageal varices in alcoholic liver disease: Results of a VA cooperative randomized trial. Gastoenterol 1987;92:1414 (abstract).
26Veterans affair cooperative variceal sclerotherapy group, prophylactic scletotherapy for esophageal varices in men with alcoholic liver disease. A randomized, single blind multicenter clinical trial. N Eng J Med 1991;324:1779-84.
27Santangelo WC, Dueno MI, Estes BL, Krejs GJ. Prophylactic sclerotherapy of large esophageal varices. N Engl J Med 1988;318:814-8.
28Sanerbruch T, Wotzka R, Kopche W, et al. Prophylactic sclerotherapy before the first episode of variceal hemorrhage in patients with cirrhosis. N EngI J Med 1988;319:8-15.
29Potzi R, Bauer P, Reichel W, Kerstan E, Renner F, Gangl A. Prophylactic Endoscopic Sclerotherapy of esophageal varices in liver cirrhosis. A multicenter prospective controlled randomized trial in Vienna. Gut 1989;30:873-9.
30Wong RC, Carr-Locke DL. Endoscopic band ligation of esophageal varices. Gastroenterol 1993;1:177-84.
31Lebrec D, Corbic M, Morel O, Benhaman P. Propranalol-a medical treatment for portal hypertension. Lancet 1980;11:180-2.
32Italian multicenter project for propranalol for prophylaxis of bleeding in cirrhosis patients with large varices: a multicenter randomized clinical trial. Hepatology 1988;8:1­5.
33Ideo G, Billati G, Fesce E, Grimoldi D. Nadolol can prevent the first gastrointestinal bleeding in cirrhosis: a prospective, randomized study. Hepatology 1988;8:6-9.
34Pascal JP, Cales P. Multicenter study group. Propranalol in the prevention of first upper gastrointestinal hemorrhage in patients with cirrhosis and esophageal varices. N Eng J Med 1987;317:856-61.
35Hayes PC, Davis JM, Lweis JA, Bouchier IAD. Metaanalysis of value of propranalol in prevention of variceal hemorrhage. Lancet 1990;336:153-6.
36Korula J. Variceal bleeding, can it be prevented ? Post Grad Med 1995;98:131-4.
37Kleber G, Ansari H, Sauerbruch T. Prophylaxis of first variceal bleeding. Baillieres Clinic Gastroenterol 1992;6:563-80.
38Burroughs AK, Panagou E. Pharmacological therapy for portal hypertension: rationale and results, Semin. Gastrointest Dis 1995;6:148-64.
39Greig JD, Garden OJ, Carter DC. Prophylactic treatment of patients with esophageal varices: is it ever indicated ? World J Surg 1994;18:176-84.
40Sanyal AJ, Shiffman ML. Transjugular intrahepatic portosysternic shunt: a medical perspective. Dig Dis 1995;13:153-62.
41Gimson A. Beware of TIPPSters. Gut 1996;39:493-4.