Primary Prophylaxis of Variceal Bleeding

Variceal hemorrhage is the most serious and dreaded complication of portal hypertension, 1 of the consequences of liver cirrhosis. Esophageal varices, which are usually caused by portal hypertension, have an annual incidence rate of approximately 5–10% in patients with cirrhosis. Small varices may increase in size, developing into large varices at a rate of 5–30% per year.^1,2 Due to the risk of bleeding, primary prevention of hemorrhage is needed in patients with esophageal varices. Current options for primary prophylaxis include nonselective β-blocker (NSBB) therapy and endoscopic variceal ligation (EVL).

The patient presented by Nikoloff and colleagues exemplifies a very commonly encountered situation in daily clinical practice in hepatology units: the need for primary prophylaxis for bleeding caused by esophageal varices.³ This patient first received NSBB therapy despite having a history of asthma (which is considered to be a contraindication to NSBB therapy in many centers, although this therapy is permitted under close monitoring in some patients with asthma). However, the patient had to discontinue this treatment due to worsening breathing problems. As the patient had high-risk varices that were detected via endoscopy, EVL was used as an alternative option for the prevention of bleeding. The complication that occurred following the banding procedure is interesting but extremely rare.

The decision to use NSBBs despite a commonly considered contraindication in this patient may have been based upon the easy administration, low expense, and relatively few adverse effects of these agents, which, importantly, are usually reversible after treatment discontinuation. NSBBs are effective; in the 9 randomized trials conducted to date, NSBB therapy reduced both bleeding and mortality rates, with the latter difference being at the threshold of statistical significance.^4–12 In addition, NSBBs protect against gastric mucosal bleeding from portal hypertensive gastropathy, which causes a proportion of first bleeding episodes. It is also cheaper to use NSBBs than EVL. According to the most recent meta-analysis of 16 randomized trials comparing NSBBs with EVL, the number of patients who need to be treated with EVL to prevent 1 bleeding episode is 11. Considering that the average number of endoscopic sessions required to eradicate varices is 3, at least 33 endoscopic procedures are necessary to prevent 1 bleeding episode as compared with NSBBs. Using EVL rather than NSBBs would yield no benefit in reducing mortality and would entail much greater expense, although there is a 9% reduction in first bleeding.¹³

EVL is considered to be a relatively safe technique. As with any therapy, the risk-to-benefit ratio should be considered for different situations. In the patient treated by Nikoloff and associates, there was no therapeutic alternative to EVL.³ It should be noted that while the risk for the first bleeding episode is approximately 20% within 1–2 years, the risk of rebleeding is 70% within the same time period; thus, the risk of EVL complications must be interpreted in this light, as complications have a higher impact on primary prophylaxis when patients are asymptomatic. The most important predictors of hemorrhage are the size of the varices, the presence of red signs on the varices, and the patient's Child-Pugh class.^1,14 Although the patient treated by Nikoloff and coworkers had only Child-Pugh class A cirrhosis, the patient had grade 3 varices with red wales and cherry red spots (ie, large varices with high-risk signs).³ Therefore, the need for primary prophylaxis with EVL was clear due to the patients intolerance of NSBB therapy because of her asthma.

EVL is a relatively simple procedure: First, a diagnostic upper endoscopy is performed to identify which varices need to be treated. Elastic bands are placed on the varices from just above the gastroesophageal junction, ascending proximally in a spiral fashion in order to avoid occlusion of the lumen; while partial occlusion cannot be avoided, it is usually asymptomatic or causes only transient dysphagia. During the initial EVL session, 3–8 bands are commonly used, although there is no set limit to the number of bands that can be used. However, a randomized study showed that the use of more than 6 bands per session did not result in better outcomes; in fact, it prolonged procedural time and increased the number of misfired bands, though the number of complications did not increase.¹⁵ Endoscopic follow-up is needed to assess the eradication of varices; if they are still detected, additional bands can be applied. In the patient managed by Nikoloff and colleagues, the placement technique was followed as described above, and the patient was scheduled for a second EVL session, as she had had no problems with her first session.³ However, the time interval between the 2 banding sessions is not clear. Guidelines from the American Association for the Study of Liver Diseases recommend that EVL sessions be repeated every 1–2 weeks until variceal obliteration is achieved, with the first surveillance esophagogastroduodenoscopy performed 1–3 months after variceal obliteration and every 6–12 months thereafter to check for variceal recurrence.¹⁴

A universal complication of EVL is mucosal ulceration at the ligation sites due to tissue necrosis produced by the band. This is usually asymptomatic, although it sometimes causes bleeding. The ulcers usually heal within 14 days.

Because the ulcers are superficial, the development of strictures after EVL is rare, occurring at arate of 0–1%.^16,17 In an isolated case, a stricture was reported following inadvertent binding of 2 varices with a single band at the same level in opposite walls.¹⁸ Local necrosis and fatal perforation of the esophagus can occur, particularly in patients taking corticosteroids.¹⁹ Although pain is uncommon, some patients experience pain immediately after the bands are placed, and dysphagia and odynophagia may occur. Esophageal spasm may be responsible for these symptoms. Transient bacteriemia may occur, although this condition is thought to be of no clinical significance; therefore, routine antibiotic prophylaxis is not needed.²⁰ Pulmonary infections are uncommon.^21,22 Unusual complications—such as esophageal obstruction, paraplegia, mesenteric vein thrombosis, banding of laryngeal mucosa, or pyogenic meningitis—have also been reported in the literature, usually in single case reports.^23–28

Esophageal obstruction, which was documented in the case reported by Nikoloff and associates, is an extremely rare complication, and the authors identified 1 other such case in the literature.³ We have identified an additional case in the literature: a 65-year-old woman with cirrhosis who had EVL for secondary prophylaxis of variceal bleeding and developed total esophageal obstruction 1 day after EVL.²⁸ Her previous EVL session had been 2 weeks earlier. The obstruction was caused by a necrotic and obstructing mass involving 3 bands. The patient received conservative treatment, and after 2 weeks, the obstruction completely resolved. Nikoloff and colleagues suggest that the obstruction in their patient occurred as a result of luminal compromise secondary to tissue edema and necrosis at the banding site.³ They recommend spiral application of the bands—which is the recommended technique, particularly in patients who need multiple sessions—so as to avoid developing a “transverse” that could potentially cause luminal obstruction.

As only 3 cases of esophageal obstruction after EVL have been published in the literature and the complication is so dramatic, it can be assumed that esophageal obstruction must be extremely rare. It is also reasonable to assume that placing a band close to mucosa that is already damaged with edema, inflammation, and/or necrosis from previous endoscopic procedures may cause further injury and edema. Nikoloff and coworkers also postulate that a previously unnoticed esophageal abnormality, such as a Schatzki ring, could have acted as a trigger in their patient.³

Regardless of the reason for the obstruction, it would be sensible to ensure that bands are applied in a spiral fashion, as is commonly recommended. It is clear from these 3 cases that treatment for obstruction following EVL should be conservative, as this type of therapy was successful in each case. It is reasonable to expect that further endoscopic interventions could result in complications such as bleeding or perforation.

Summary

The first choice for primary prophylaxis of esophageal variceal bleeding is an NSBB, such as propranolol, as these agents are cheaper than EVL and easy to administer. Carvedilol could be an alternative option.²⁹ NSBBs are effective for controlling variceal hemorrhage and bleeding from gastric mucosa, as well as providing potential benefits related to the reduction of bacterial translocation and infections.³⁰ EVL should be offered to patients who are unable to use NSBBs, as in the case presented by Nikoloff and coworkers, or patients in whom drug therapy has failed.^3,31 Patient preference should also be taken into account whenever possible. EVL is a relatively safe technique for primary prophylaxis of esophageal varices, with a low rate of complications (although serious complications may occur, as in the reported case).