Prevention of Variceal Bleeding in Candidates Awaiting Liver Transplantation

Beta blocker drugs (e.g., propranolol [Inderal]) should be the first-line treatment for prevention of variceal bleeding in patients with cirrhosis and portal hypertension, according to an article published in the September issue of Liver Transplantation.

Portal hypertension is an increase in the pressure within the portal vein (the vein that carries blood from the digestive organs to the liver).

While banding is similarly effective in reducing the incidence of such bleeding, it can have fatal complications and is more expensive compared with propranolol.

Patients with advanced liver disease may develop portal hypertension due to blockage of the blood flow through the liver. The increased blood pressure in the portal vein causes large veins, called varices, to develop across the esophagus and stomach to bypass the blockage. These varices become fragile and can bleed easily, causing frightening symptoms like vomiting blood, as well as ascites and encephalopathy.

Two ways to prevent variceal bleeding are use of beta blockers and endoscopic variceal ligation, or "banding," in which elastic bands are placed on the enlarged veins. It is unclear which approach is better for patients.

To compare the safety and efficacy of the 2 therapies in the prevention of primary variceal bleeding, researchers led by Lorenzo Norberto and Lino Polese of the University of Padova in Italy, conducted a randomized controlled trial among patients awaiting liver transplantation.

Between September 2001 and December 2005, the investigators enrolled 62 patients with Child stage B-C cirrhosis and high-risk esophageal varices. The patients were randomly assigned to received treatment with the beta blocker propranolol or variceal banding. All patients had an upper gastrointestinal endoscopy and a clinical examination every 6 months after beginning treatment.

The 31 patients who took propranolol started on a low dose and increased it until they achieved a 25% reduction of their baseline heart rate. Five patients had to suspend the treatment due to complications including bradycardia (slow heart rate), persistent hypotension (low blood pressure), and vertigo. Of the 26 who continued the treatment, 3 eventually experienced variceal bleeding, and 2 died from such bleeding. During a mean follow-up period of 7.6 months, 10 of the patients underwent liver transplantation.

Of the 31 patients treated with variceal ligation, 2 suffered a dramatic hemorrhage a few days after the first treatment and required emergency treatment. One patient recovered, the other died. The remaining patients underwent 3 ligation sessions to completely eradicate their varices. During a mean follow-up period of almost 15 months, 2 patients died of liver failure after 1 and 7 months, while 14 received a liver transplant.

Both propranolol and endoscopic banding considerably reduced the expected incidence of bleeding, normally 30% after 1 year. Propranolol lowered the risk to less than 10%, and banding to less than 7%. Although some patients in each group experienced adverse events related to their treatment, only banding was associated with a death.

"Beta blockers should remain the first choice of prophylactic therapy in candidates for liver transplantation," the authors reported, though banding should be used when beta-blockers are contraindicated.

"Both propranolol and endoscopic banding are similarly effective in reducing the incidence of variceal bleeding in cirrhotic patients with high risk varices, but ligation can be complicated by severe and fatal bleeding and is significantly more expensive," they concluded.

The mean cost for treatment with propranolol was $1425, compared to $4289 for banding.

In an accompanying editorial, Thomas Boyer of the Liver Research Institute at Arizona Health Sciences Center applauded the strides that have been made in treatment of esophageal varices. However, he wrote, "There are still areas where further studies are warranted in the prevention and management of variceal bleeding." Not all patients treated with beta-blockers benefit from the treatment and remain at high risk for bleeding.

Dr. Boyer added, "Identification of new drugs that lower portal pressure to the same or greater degree than beta-blockers with fewer side-effects are being sought and if found will further improve the management of patient with varices."

09/11/07

References

L Norberto, L Polese, U Cillo, and others. A Randomized Study Comparing Ligation with Propranolol for Primary Prophylaxis of Variceal Bleeding in Candidates for Liver Transplantation. Liver Transplantation 13(9): 1272-1278. September 2007.

T Boyer. Clinical Trials for Variceal Bleeding: And the Winner is -- The Patient (Editorial). Liver Transplantation 13(9): 1212-1213. September 2007.

Liver Transplantation is published by John Wiley & Sons. These articles are available online via Wiley Interscience at http://www.interscience.wiley.com.

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