Prevention of primary variceal bleeding

Sep 10 2007

Beta blockers should be the first line of prevention against variceal bleeding in patients with cirrhosis and portal hypertension. While banding is similarly effective in reducing the incidence of such bleeding, it can have fatal complications and is more expensive.

These findings are published in the September issue of Liver Transplantation, a journal by John Wiley & Sons. The article is also available online via Wiley Interscience at http://www.interscience.wiley.com/journal/livertransplantion

Patients with liver disease often develop portal hypertension from a blockage in 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 beta blockers and endoscopic variceal ligation, however it is unclear which is better for patients.

To compare the safety and efficacy of the two 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, they enrolled sixty-two patients with Child-B-C cirrhosis and high-risk esophagal varices into their study. The patients were randomly divided between treatment with the beta blocker, propranolol, or variceal banding. All patients had an EGD and a clinical examination every 6 months after beginning treatment.

The 31 patients who took beta blockers started on a low dose and increased it until they achieved a 25 percent reduction of their baseline heart rate. Five patients had to suspend the treatment due to complications including bradycardia, persistent hypotension and vertigo. Of the 26 who continued the treatment, three eventually bled from esophageal varices and two died of such bleeding. During the mean follow-up of 7.6 months, ten of the patients underwent liver transplantation.

Of the 31 patients treated with ligation, two 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 three ligation sessions to completely eradicate their varices. During the mean follow up of almost 15 months, two patients died of liver failure after 1 and 7 months respectively, while 14 of the patients received a liver transplant.

Both propranolol and endoscopic banding considerably reduced the expected incidence of bleeding, normally 30 percent after one year. The beta blocker lowered the risk to less than 10 percent, the banding to less than 7 percent. 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 report, 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 conclude. 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 applauds the strides that have been made however, he says, “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.

“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 the patient with varices,” he says.