Nadolol in the prophylaxis of growth of
small esophageal varices
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| Beta-blocker prophylaxis of variceal bleeding in patients
with compensated cirrhosis should be started when small esophageal
varices are present, find doctors in the August issue of
Gastroenterology. |
| |
| Beta-blockers are extensively used to prevent variceal
bleeding in patients with large esophageal varices.
However, it is not clear whether beta-blockers delay the growth
of small varices.
In this study, doctors from Italy evaluated 161 patients with
cirrhosis and small esophageal varices without previous bleeding.
The team randomized 83 patients to receive nadolol (dose adjusted
to decrease resting heart rate by 25%, mean dose = 62 mg/day). The
remaining 78 patients received placebo.
The principal end point was occurrence of large esophageal
varices.
The team performed an endoscopic examination at 12, 24, 36, 48,
and 60 months of follow-up. Mean follow-up was 36 months.
 |
| The cumulative probability of variceal bleeding was lower in
the nadolol patients. |
| Gastroenterology |
The doctors found that during the study period, 9 nadolol
patients and 29 placebo patients had growth of esophageal varices.
The team calculated the cumulative risk at the end of follow-up:
20% versus 51%.
When possible confounding factors were taken into account, the
team found that treatment was a significant factor predicting growth
of varices (odds ratio, 4.0).
They determined that the cumulative probability of variceal
bleeding was lower in patients randomized to nadolol.
Survival was not different between the groups, however adverse
effects from withdrawal of the drug occurred in 9 patients in the
nadolol group and 1 patient in the placebo group.
Dr Carlo Merke and colleagues concluded, "This study
suggests that beta-blocker prophylaxis of variceal bleeding in
patients with compensated cirrhosis should be started when small
esophageal varices are present".
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Gastroenterology 2004; 127(2):
12 August 2004 |
JAMA
Vol. 292 No. 3, July 21, 2004 Featured Link
Role of Vitamin K2 in the
Development of Hepatocellular Carcinoma in Women
With Viral Cirrhosis of the Liver
Daiki Habu, MD, PhD; Susumu Shiomi, MD, PhD; Akihiro Tamori, MD, PhD;
Tadashi Takeda, MD, PhD; Takashi Tanaka, MD, PhD; Shoji Kubo, MD, PhD;
Shuhei Nishiguchi, MD, PhD
JAMA. 2004;292:358-361.
Context Previous findings indicate that vitamin K2 (menaquinone)
may play a
role in controlling cell growth.
Objective To determine whether vitamin K2has preventive effects on
the
development of hepatocellular carcinoma in women with viral cirrhosis of
the
liver.
Design, Setting, and Participants Forty women diagnosed as having
viral
liver cirrhosis were admitted to a university hospital between 1996 and
1998
and were randomly assigned to the treatment or control group. The
original
goal of the trial was to assess the long-term effects of vitamin K2 on
bone
loss in women with viral liver cirrhosis. However, study participants
also
satisfied criteria required for examination of the effects of such
treatment
on the development of hepatocellular carcinoma.
Interventions The treatment group received 45 mg/d of vitamin K2
(n = 21).
Participants in the treatment and control groups received symptomatic
therapy to treat ascites, if necessary, and dietary advice.
Main Outcome Measure Cumulative proportion of patients with
hepatocellular
carcinoma.
Results Hepatocellular carcinoma was detected in 2 of the 21 women
given
vitamin K2 and 9 of the 19 women in the control group. The cumulative
proportion of patients with hepatocellular carcinoma was smaller in the
treatment group (log-rank test, P = .02). On univariate analysis, the
risk
ratio for the development of hepatocellular carcinoma in the treatment
group
compared with the control group was 0.20 (95% confidence interval [CI],
0.04-0.91; P = .04). On multivariate analysis with adjustment for age,
alanine aminotransferase activity, serum albumin, total bilirubin,
platelet
count, -fetoprotein, and history of treatment with interferon alfa, the
risk
ratio for the development of hepatocellular carcinoma in patients given
vitamin K2 was 0.13 (95% CI, 0.02-0.99; P = .05).
Conclusion There is a possible role for vitamin K2 in the
prevention of
hepatocellular carcinoma in women with viral cirrhosis.
Author Affiliations: Departments of Hepatology (Drs Habu, Tamori,
Takeda,
and Nishiguchi), Nuclear Medicine (Dr Shiomi), Public Health (Dr
Tanaka),
and Surgery (Dr Kubo), Graduate School of Medicine, Osaka City
University,
Osaka, Japan.
This Week in JAMA
JAMA. 2004;292:305.
New Doppler ultrasound signs improve diagnosis of cirrhosis or
severe liver fibrosis
|
| A high proportion of patients with compensated liver disease
can be accurately diagnosed with cirrhosis using Doppler ultrasound
signs, including the new hepatic vein spectrum, reports an article
in the European Journal of Gastroenterology and Hepatology. |
| |
| Christophe Aube and colleagues have determined
whether ultrasound, and particularly, new Doppler signs, increase
the diagnostic accuracy of the most accurate, currently available
markers for the diagnosis of cirrhosis or severe fibrosis.
They studied a total of 32 clinical (n = 4), biochemical (n = 11)
and Doppler ultrasound (n = 17) variables that were recorded in 106
patients with compensated chronic liver disease.
In order to evaluate diagnostic accuracy, discriminant analysis
was used, first globally, and then using all variables by variable
analysis.
For diagnosis of cirrhosis using Doppler ultrasound, diagnostic
accuracy was 92% globally, and 89% with 3 variables (spleen length,
hepatic vein spectrum and maximum portal vein velocity).
Based upon clinical signs, diagnostic accuracy was 86% globally,
and 85% with one variable (firm liver).
When basing findings upon biochemical parameters these values
fell to 80% globally, and 81% with two variables (hyaluronate and
platelet count).
Based upon all parameters, diagnostic accuracy was 91% globally,
and 91% with four variables (firm liver, hyaluronate, platelet and
hepatic vein spectrum).
On an intention to diagnose basis, Doppler ultrasound provided a
lower independent contribution due to missing data.
In the diagnosis of severe fibrosis, diagnostic accuracy was 83%
globally, and 77% with one variable.
The researchers, who have published their study in the August
issue of the journal, conclude that cirrhosis can be correctly
diagnosed in approximately 90% of patients with compensated chronic
liver disease using a few Doppler ultrasound signs including a new
sign, the hepatic vein spectrum.
They add that Doppler ultrasound could be used for the first line
diagnosis and biochemical markers, such as hyaluronate, in patients
with missing Doppler ultrasound data.
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Eur J Gastroenterol Hepatol 2004: 16
(8): 743 - 751
19 July 2004 |
Cirrhosis is the eleventh cause of death by disease in
the U.S., and has many causes. It can result from direct injury to
liver cells, as what occurs in hepatitis, or from indirect injury by
way of inflammation or obstruction to bile ducts. Common causes of
liver cirrhosis include chronic alcoholism, chronic hepatitis
infection (types B, C and D), and autoimmune hepatitis.1
One common side effect of liver cirrhosis is fatigue.
A Common Symptom
It's a symptom that's "very common", striking "65 to 70 percent" of
cirrhotic patients, explained Douglas Dieterich, M.D., vice chair and
chief medical officer in the department of Medicine at Mount Sinai
Medical Center in New York. Dieterich and a team of researchers
released a study on the subject at Digestive Disease Week 2004, a
gastroenterology conference held in New Orleans in May.2
Fatigue in cirrhosis is a phenomenon that has had
little focus in the medical literature, Dieterich told Priority
Healthcare, in a telephone interview. In fact, this was the first
study to examine its effects in people with cirrhosis, he said.
In these patients, liver cells are damaged and can't
repair themselves. As the liver cells die, scar tissue forms, and as
it builds up, blood flow through the liver gets blocked. In turn,
blood doesn't get filtered properly, and poisons and wastes can build
up in the body. This is the condition that becomes dangerous to the
patient.3
Fatigue can crop up not only from the cirrhosis (or
the hepatitis itself), but also from the medications that are
typically prescribed, such as pegylated interferons (Pegasys, PEG-Intron)
and the anti-viral medication, ribavirin.
Managing Fatigue: Few Options
Sometimes, if side effects are too overwhelming for patients on these
medications, such as when anemia occurs, physicians may reduce their
dosage.4 Anemia is a condition in which there aren't enough
healthy red blood cells to carry oxygen to the body's tissues, which
manifests itself as fatigue.5 But doctors don’t have
therapeutic options to treat cirrhosis-related fatigue. "Well, nobody
else is using anything for it, frankly," Dieterich said. "They're just
telling the patients to rest more."
In some cases, experts have suggested that fatigue
in patients with hepatitis C (HCV) may be related to the severity of
their depression, rather than the hepatitis itself, and recommend
prescribing anti-depressant medications in these cases.6
But fatigue can still be a side effect in patients
in which there is no available treatment, and medical experts are just
beginning to understand its impact.7,8
Medications Under Scrutiny
One medication is getting some attention, however. In some
cases, doctors prescribe recombinant erythropoietin, a drug that helps
the body boost its production of red blood cells, and thus, alleviate
fatigue. Erythropoietin is marketed under such brand names as Procrit
(Ortho Biotech) and Epogen (Amgen).
In a previous clinical trial published in May,
Dieterich teamed up with doctors at Harvard University to test the
effects of epoietin alfa—a manmade version of erythropoietin—as a
treatment for anemia in cirrhotic patients with fatigue.9
In 185 patients, the investigators found that the medication
significantly improved hemoglobin levels, and helped more patients
maintain their dosage of ribavirin.
Measuring the Impact of
Fatigue
In the new study, Dieterich and his associates recruited 100 patients
with cirrhosis being treated at a liver transplant clinic. Each
patient underwent a comprehensive examination for liver disease
severity, anemia, and the presence of cardiopulmonary disease—a common
contributing factor to fatigue in such patients.
The doctors then measured levels of fatigue using a
special Fatigue Severity Scale and asking patients to walk as far as
they could for 6 minutes—a standard exercise test.
The researchers assessed each patient's related
quality of life using a special questionnaire. The additional
influence of anemia was then tested, as well.
What the Investigators Found
"Fatigue was a common complaint," the study authors wrote. Patients
scored relatively high on fatigue measurements, and the average
distance walked in 6 minutes was 266 meters (291 yards). Those who had
higher levels of severity were less likely to travel farther in the
walking test, and "correlated with poor quality of life."
Normal hemoglobin levels in the average adult range
from 12 to 18 grams per deciliter (g/dL).(9) In this study, average
hemoglobin levels stood at 12.4 g/dL, with the lowest level at 7.3 g/dL,
the investigators found. Thirty-four of the patients were considered
anemic.
After taking each patient's age into account—older people generally
have lower hemoglobin levels—the researchers discovered that ascites
(a condition characterized by high abdominal fluid levels), higher
weight, severity of liver disease, difficulty absorbing oxygen, and
anemia tended to negatively affect a patient's ability to travel
farther in the walking test.
"Severe fatigue … is common in cirrhotic patients, and high fatigue
scores are associated with poor quality of life," the study
researchers concluded.
They added that if certain medications prescribed for anemia are also
effective for patients with cirrhosis, the findings will be
significant for patients. "Demonstration that human recombinant
erythropoietin therapy improves the anemia of cirrhotic patients will
have important therapeutic implications," the research team wrote.
1. American Gastroenterological Association.
2. Anemia is a major determinant of fatigue in patients with
cirrhosis. Digestive Disease Week 2004. 2004 May 15-20. New Orleans,
LA.
3. American Academy of Family Physicians.
4. Fried MW. Side effects of therapy of hepatitis C and their
management. Hepatology 2002 Nov;36(5 Suppl 1):S2370-44.
5. Mayo Foundation for Medical Education and Research.
6. Dwight MM et al. Depression, fatigue, and functional disability in
patients with chronic hepatitis C. J Psychosom Res. 2000
Nov;49(5):311-7.
7. van Mens-Verhulst J, van Dijkum C et al. Dealing with fatigue: The
importance of health-related action pattierns. Patient Educ Couns
1999 Jan;36(1):65-74.
8. Glacken M, Coates V et al. The experience of fatigue for people
living with hepatitis C. J Clin Nurs 2003 Mar;12(2):244-52.
9. Afdhal NH, Dieterich DT, Pockros PJ et al. Epoetin alfa maintains
ribavirin dose in HCV-infected patients: A prospective, double-blind,
randomized controlled study. Gastroenterology 2004
May;126(5):1302-11.
John Martin is a long-time health journalist and an
editor for Priority Healthcare. His credits include coverage of health
news for the website of Fox Television's The Health Network, and
articles for the New York Post and other consumer and trade
publications.
http://www.hepatitisneighborhood.com/content/in_the_news/archive_1947.aspx
Introduction
A 47 year-old business executive came to me with
fatigue and swelling in her legs. She said that for the past 6 months
she had felt more tired than usual, but attributed it to putting in
longer hours at work. She became more concerned when she developed
swelling in her legs and her doctor told her she had an enlarged spleen.
Her doctor thought she may have a liver problem and she wanted to know
what she should do.
Cirrhosis is irreversible end-stage liver disease,
and is the eleventh leading cause of death in the United States. In a
cirrhotic liver, the normal liver cells transform into nonfunctioning
cells, and the architecture of the liver is altered, leaving it bumpy
and scarred. My patients are often surprised to learn that excessive
alcohol consumption is not the only cause of cirrhosis. Other potential
causes of cirrhosis include viral hepatitis,
some metabolic disorders (such as
hemochromatosis) and
autoimmune diseases. Sometimes a cause
of cirrhosis is not even found.
Diagnosing Cirrhosis
There are different degrees of cirrhosis ranging from
mild to severe, and they can be graded using the
Child-Turcotte-Pugh scoring system. You
can determine the degree of cirrhosis by blood tests that measure
proteins and bilirubin, which are
manufactured and processed by the liver. There are a number of
diagnostic approaches to this disease, including liver biopsy, careful
attention to patient history and symptoms, blood tests, and x-rays.
Liver Biopsy
The ‘gold-standard’, or the most certain method of
diagnosing cirrhosis is with liver biopsy. This involves extracting
cells from the liver itself for testing. However, in some patients liver
biopsy may not be necessary or safe and the diagnosis of cirrhosis can
be made by other means. In some cases the combination of the patient’s
history, physical exam, blood work, and ultrasound or
computerized tomography,
or CT scan (an exam that uses x-rays to take detailed pictures of
body in cross-section) support the diagnosis of cirrhosis.
Patient History and Symptoms
Clues provided by the patient can be a helpful first
step in the diagnosis, but a cirrhosis diagnosis can be a wily one
indeed. There are individuals with the disease who have no symptoms and
no obvious clues in their medical histories that might point to
cirrhosis.
However, there are clues doctors can look for
as they approach a diagnosis. Heavy alcoholic drinking and chronic
hepatitis are both states that can result in liver damage, and so may
support a diagnosis of cirrhosis.
Patients may complain of fluid in their legs (edema)
or swelling (distension) of the
abdomen. Some patients may have disabling symptoms such as fatigue,
fluid retention, or confusion. But again, they may have no symptoms at
all. Sometimes the only findings suggestive of cirrhosis are in the
blood work.
Blood work
Laboratory tests that may be abnormal in individuals
with cirrhosis include those tests measuring proteins manufactured by
the liver, red blood cells and platelets.
The liver makes proteins that are important in normal clot formation.
When the liver is damaged, as in cirrhosis, there is decreased
production in the formation of a clotting protein called
prothrombin and another protein called
albumin. Cirrhosis is also
associated with an enlarged spleen. Platelets, the blood cells involved
in clotting, may become trapped in an enlarged spleen, resulting in a
low platelet count. It is also not uncommon for people with cirrhosis
to have a low red blood cell count, or anemia.
X-rays
In addition to laboratory blood work, x-ray studies can
help in forming a diagnosis. Ultrasound
(an exam that uses ultrasound waves to look at structures in the body)
or computerized tomography
(CT scan) can be used to take pictures of
the liver. In cases where there is liver damage, these pictures may
reveal a shrunken liver with a nodular or bumpy surface.
These findings on ultrasound or CT scan, along with
the information provided by laboratory blood work, the history, and the
physical exam can be used to make the diagnosis of cirrhosis. In unclear
cases, a liver biopsy can be performed to confirm clinical suspicion.
Cirrhosis Complications
Imagine that the normal liver is a brand new sponge
that grows soft and pliable after it is wet with water. Now imagine an
old used sponge that is hard, and crumbles when squeezed. Water easily
flows through the new sponge, but has a harder time passing through the
old sponge. A cirrhotic liver is like an old sponge. Elevated pressure
in the liver prevents blood from passing through it freely and normally.
Complications from cirrhosis result from the high pressures in the liver
and abnormal flow of blood.
Bleeding
Bleeding may occur from the stomach or esophagus. The
low production of clotting proteins and the low platelet count render
patients with cirrhosis particularly susceptible to bleeding.
Fluid retention
Fluid retention may occur in the abdomen or legs. Fluid
retention in the abdomen is called ascites.
Encephalopathy
One of the jobs of a normal liver is to clear toxins
from the blood. In a cirrhotic liver this is not possible and toxins may
build up in the body. These toxins may pass to the brain and cause
confusion. This confusion, called encephalopathy, may be very mild and
unnoticeable or it may be so severe that it results in coma.
Individuals with cirrhosis may experience none or all
of these symptoms, but when they develop any one of these complications
then they are said to have decompensated
cirrhosis.
Treatment of Complications
Patients often say to me, “I’ve heard that liver
cells can regenerate. If the liver can regenerate then why can’t it
recover from cirrhosis?” The normal liver can regenerate, but a
liver with cirrhosis does not contain normal liver cells.
Once cirrhosis has occurred therapy is
supportive, meaning the damage to the
liver has been done and only the complications resulting from the damage
can be treated. This includes diet and fluid pills (diuretics)
for patients with fluid retention. Individuals with bleeding may be
treated with oral medication or endoscopy
(a procedure where a long tube with a camera is inserted through mouth
and into the stomach; bleeding areas can be stopped by burning them or
by injecting a substance that causes the blood vessels to close). The
encephalopathy associated with cirrhosis can be treated with a
lactulose (a liquid medication that
causes a diarrhea which lowers the level of harmful toxins in the body).
In severe cases patients with cirrhosis may require liver
transplantation.
My patient with the fatigue and swelling in her
legs did in fact have cirrhosis. Her records showed she had a low
platelet count and an ultrasound showed an enlarged spleen and fluid in
her abdomen (ascites). On further
evaluation her blood work demonstrated that she might have autoimmune
hepatitis, a disease in which the body attacks the liver and causes
scarring. I performed a liver biopsy to confirm the diagnosis of
autoimmune hepatitis so she could start on the appropriate treatment.
She was very surprised that she had cirrhosis. She
thought cirrhosis was only from heavy alcohol drinking and she rarely
drank. Also, she could not understand how she could feel so well with
cirrhosis. I explained that alcohol abuse is not the only cause of
cirrhosis and there are many other causes. We also discussed the wide
spectrum of symptoms that go along with cirrhosis from having no
symptoms at all to feeling very ill.
Commonly Asked Questions
Even if I have cirrhosis, doesn’t
the liver grow back and replace the damaged portion?
A normal liver can grow back or regenerate, but a liver
with cirrhosis is not normal and does not regenerate. This is why it is
important to stop any ongoing injury to your liver once you find out you
have cirrhosis, such as stopping alcohol intake. The earlier you stop
whatever is causing the injury to your liver the better the chances are
the liver will recover.
I’ve been diagnosed with cirrhosis
and my doctor did not even do a liver biopsy. Is this possible?
Yes. There may be certain findings on your history and
physical exam that suggest cirrhosis and that are supported by the blood
work. In some settings it is unsafe to perform a liver biopsy and
unnecessary as well. If you have: a history of heavy alcohol use, an
enlarged spleen on physical exam, a low platelet count on your blood
work, and a small nodular liver on ultrasound, then a liver biopsy is
probably not necessary. A biopsy may
be unsafe if there is a low platelet count because of the risk of
excessive bleeding.
If, however, there is doubt about the cause of the
cirrhosis or the diagnosis itself, a liver biopsy is very useful.
Is there any special diet I should
be on?
I recommend to my patients with cirrhosis to stop all
alcohol or to drink infrequently only on special occasions. I also tell
them not to take iron pills unless needed for other medical conditions.
Iron in excessive amounts may be harmful to the liver in certain
settings. Otherwise, eating a balanced healthy diet is the best
approach.
Conclusion
The liver is an important organ involved in many
critical functions. It is fairly forgiving and can repair itself after
injury, but will succumb to repeated insult and negligence. Therefore,
it is important to stop any ongoing injury to the liver before this
critical organ sustains damage that is irreparable. The take home
message is: Take care of yourself and love your liver!
|
(6 MU 3 times weekly), and the reported risk reduction can mostly
be attributed to the unusually low number of hepatocellular
carcinoma cases in the control group. The retrospective studies
cited by Dr. Stark are prone to inflated estimates of benefit
because of selection bias favoring better outcomes among treated
patients 
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