I am going to have esophogeal varices banding tomorrow morning at 8 AM at Kirklin Clinic in Birmingham A. , I am confused and worried so I am looking and listening to all stories about this event, I hope I do well. I also have Hep-C...
Beta-blockers Do Not Prevent Development of Varices in Patients With Cirrhosis
Nezam H. Afdhal, MD, FRCPI
Posting Date: May 01, 2006
Associate Professor of Medicine
Harvard Medical School
Chief of Hepatology
Beth Israel Deaconess Medical Center
Boston, Massachusetts
Beta-blockers have previously been shown to reduce portal hypertension and prevent bleeding from gastroesophageal varices in patients with cirrhosis.[1] However, although beta-blockers appear effective in preventing variceal bleeding in patients with grade 2 or 3 esophageal varices, their ability to prevent the onset of varices is unproven.
Given that esophageal varices seldom occur unless portal pressure rises above 10 mm Hg, preventing a rise in portal pressure with beta-blockers might be beneficial. The working hypothesis for this study by Groszmann and colleagues,[2] therefore, was to treat patients who had cirrhosis but no varices and demonstrated minimal increases in portal pressure (≥ 6 mm Hg) in order to prevent the development of varices and bleeding over time. The nonselective beta-blocker timolol was chosen because of its high affinity for β2-adrenergic receptors. Such beta-blockade allows the unopposed alpha-vasoconstriction of the splanchnic circulation and serves as an important target for the reduction of portal pressure.
In the current trial, 213 patients were randomized to receive either timolol or placebo and were followed for a median of 54.9 months. The primary endpoint was the development of varices or variceal hemorrhage as identified through endoscopy conducted by 2 independent readers. Patients’ evaluation included annual endoscopy, portal pressure measurements, and clinical evaluation.
No significant differences were observed between the 2 groups in terms of varices or variceal hemorrhage development (39% with timolol vs 40% with placebo; P = .89) or with regard to the rates of ascites, encephalopathy, liver transplantation, or death. Moreover, serious adverse events were 3 times more likely to occur in the timolol arm than in the placebo arm (18% vs 6%; P = .006). The side effects were predominantly related to the pulmonary and cardiovascular issues which occur with beta-blockade including hypotension, bradycardia, and bronchospasm.
The current standard of care calls for use of endoscopy in patients with cirrhosis to detect varices as well as the prophylactic use of beta-blockers to prevent variceal bleeding in patients with grade 2 or 3 varices.[3] This study sought to extend use of beta-blockers for earlier prophylactic use in prevention of variceal development but found no benefit. Rather, the increased incidence of side effects argues against such prophylactic use of beta-blockers. In addition, there is no reason to suspect that propranolol or nadolol, 2 other nonselective beta-blockers widely used to treat varices, would have either a significantly different side effect profile or better efficacy.
This study confirms that these agents are most likely being used in the best possible way currently; the benefit appears to be greatest in patients with significantly elevated portal pressure and larger varices, and the data do not support the use of beta-blockers to prevent varices or for patients with very small varices. The greatest predictor of clinical outcome in this study was baseline portal pressure, which is supported by previous data indicating that beta-blockers traditionally demonstrate the greatest effects in individuals with high baseline pressure.
This finding also led to a second question about the role of portal pressure measurements in patients with cirrhosis to either subselect patients with higher pressures or to stratify for risk. Measurement of portal pressure requires the determination of the hepatic venous pressure gradient (HVPG), which is obtained by threading a catheter through either the vena cava or the femoral vein into the hepatic vein under fluoroscopic control. The HVPG is determined by subtracting free hepatic venous pressure from the wedged venous pressure generated when a balloon at the end of the catheter is expanded and the vein is blocked. Normal portal pressure is 10 mm Hg. In this study, the HVPG was measured regularly and was the best indicator for risk of clinical outcomes; however, this invasive test is primarily used in a research setting and not in regular clinical practice.
This study was well designed and adequately powered, with excellent follow-up and concrete clinical endpoints. There were only minimal drawbacks to the study: The authors noted that they enrolled patients who had undergone only a minimal washout period for use of alcohol, whereas most studies require a minimum of 6 months of prior abstinence. The bias from including patients with recent alcohol use would have been manifested by earlier events on the Kaplan-Meier analysis, but such an outcome was not observed. The importance of this negative study is clearly apparent and illustrated by its publication in a premier clinical journal.
Mike
I will tell you my story because it demonstrates the bad treatment that we can get.
As I told you, I bled out one night (lost 4 units of blood) and went to the hospital the next day - I was pretty stupid too. A GI sclerosed my vessels which stopped the bleeding. He diagnosed me as an alcoholic despite my protestation that I wasn't. I stayed in the hospital 3 or 4 days and was released. I got no instructions other than not to drink. 2 or 3 months later I bled out again and this time I was smarter and went right to the hospital. A different GI sclerosed the vessels. I didn't have any idea that another bleed would occur so I asked the GI what was wrong with me. He said hepatitis c. I asked when I got it and he said he didn't know. I asked how he knew I had HCV and he said it was on my blood work from the time of my previous bleed. When I asked him what he would suggest he said he wanted me to have 5 or 6 sclerosing treatments to obliterate the varices. I naively told him I already had one a couple of months ago and he looked a bit bemused and replied "that one doesn't count". Well, I knew that the first GI was guilty of malpractice that second. I would have sued him but I had enough on my plate so I let him slide. Anyway, the point of this too long story is - make sure you are schedules to be monitored with endoscopies and if your doctor says that is unnecessary ask the hard questions - could I re-bleed? - how will you know if my vessels are becoming distended? - and anything else you can think of. And read everything you can find about varices. I should have something ...I found it. I'll post it below. Mike
How did they stop the bleeding - banding or injection of sclerosing agent? Mike
Guys thanks for all of your help. Mike I let my wife read your post about your first bleed in 1995 and everything you have gone through and she was very relieved. The death sentence the Dr. gave us at the hospital scared her badly and you really helped her. I guess part of that is the fact that I appear to be very healthy and have had no complications from the disease, so this is still a shock to us. I would very much be interested in an opinion of a DR in my area. I live in Dayton, Ohio
Thanks agin for everything
What Mike said about doctors is spot on. Don't think twice about changing doctors if you don't have full confidence where you are -- and don't even be shy about getting a second opinion, even when you do have confidence. If you want to share about where you live, maybe someone here has a name or two.
-- Jim
I saw this post after I posted above. Glad you two got together.
I had my first bleed in 1995 and my vessels were sclerosed rather than banded. I had an idiot for a doctor and had another bleed 2 or 3 months later. This time I got a good doctor and he sclerosed my vessels to stop the bleeding and then followed up with 5 or 6 more sclerosing treatments spaced 1 week to 10 days apart and obliterated the vessels - that was the goal of the treatments. I didn't bleed again and in 2000 I was transplanted because during a routine scan a lesion was seen on my liver and cancer was suspected. I didn't have cancer as it turned out. After the sclerosing treatment I was put on a beta blocker to reduce portal hypertension. From what I have read this drug is still prescribed for varices but I have never seen any really convincing evidence that it is an effective approach. After my vessels were obliterated I had periodic endoscopies to monitor my esophageal vessels and there was no vessel distension seen for 5 years. I think that banding of the vessels is a better approach than sclerosing but sclerosing worked for me so I really don't know for certain which approach is better.
I am always suspicious when I hear a doctor predicting lifespan in the context of cirrhosis because I have seen people live a lot longer and a lot shorter than predicted. I know how devastating this type of news can be but try not to become too depressed. Just aggressively pursue the course of getting answers to the tough questions and try and take it one day at a time. I trust you have confidence in your physician but if you don't get another opinion and don't be shy about it. That was a mistake I made but I won't ever make that mistake again. This can be an intimidating event but be strong and be aggressive because you can prevail and you can get well. Good luck. Mike
Mike
Thanks for your response. I have an appointment with a hepatologist on Thursday the 11th. I had my first liver biopsy in June 2005 and my spleen appreared normal at that time and the Dr quoted in his notes.... (that the Liver may be prominant in size espicially the right Lobe, but there does not appear to be any degree of hepatocellular dysfunction since there has been no shift of the radiotracer to the spleen and only faint activity is seen in the bone marrow. The spleen is unremarkable. There are no focal abnormalities associated with either the liver or the spleen)
Then last week I have the Esophageal Varices episode and the attending Dr. at the hospital tells my
wife and I that this is a cause of Cirossis of the Liver and that after the onset of Cirossis I have 10 years to live. I am 52 and I drank Alcohol occaisionally (wine maybe twice a week, a beer maybe twice a month, and a coctail maybe twice a month) I obviously don't do that now. I just find it hard to believe that this can happen so fast. When did you have your Varices and did you have a recurrence? It's a little scary to wait a week before I talk to the Dr. I do not know the results of the Liver Spleen Scan that I had yesterday as of yet. Thanks for listening
Esophageal varices are associated with cirrhosis as is an enlarged spleen. You can feel relatively good and still be cirrhotic. I had no idea that I was sick with anything when my varices ruptured. It is not unusual for patients with esophageal bleeds to be evaluated for liver transplantation because it is suggestive of advanced liver deterioration. There are blood markers that are also suggestive such as a low platelet count, an elevated GGT and an elevated bilirubin. You should definitely follow up with a hepatologist soon. Don't assume your PCP will address this in the manner in which it should be addressed - get to a good hepatologist if you haven't already. Mike