WHAT ARE THE TREATMENTS FOR ASCITES IN CIRRHOSIS?

Nearly all patients with ascites can benefit form the following measures:

Abstaining from alcohol. (Sometimes abstaining from alcohol is enough to
reverse this complication.)
Restricting salt.
Taking diuretics, usually spironolactone (Aldactone) and furosemide (Lasix).
Previously, spironolactone was usually given alone, but experts now use it by
itself only in patients with minimal fluid buildup. Patients should be monitored
carefully for excessive and too rapid fluid loss, which can set off
complications, including hypokalemia (dangerously low potassium levels), kidney
failure, or encephalopathy. Weight loss from diuretics usually should not exceed
1 or 2 pounds per day, but there is no limit for patients with massive swelling.

Physicians often recommend bed rest for patients with ascites, but many experts
believe this is not necessary and say that studies do not support its benefits.
Restricting fluid is not usually necessary unless sodium levels in the blood are
very low.
Treatment for Recurring or Refractory Ascites
Patients with recurring ascites or ascites that does not respond to standard
diuretics after a month may require procedures to reduce fluid.

Large-Volume Paracentesis. Large-volume paracentesis is the current standard
procedure and involves the following:

Large volumes of fluid are removed through a tube in the abdomen. Research
indicates that 4 to 6 liters are usually effective and safe.
Albumin (protein) may be administered intravenously. This helps prevent a
sudden drop in blood flow in the arteries. One study suggested that
terlipressin, a drug that constricts bleed vessels, may be as effective.
If the ascites does not respond to treatments, paracentesis may need to be
repeated every two weeks or more frequently, and up to 10 liters may need to be
removed.

Patients who require this are probably not complying with dietary requirements.

Transjugular Intrahepatic Portosystemic Shunt (TIPS). Studies have been mixed on
whether transjugular intrahepatic portosystemic shunt (TIPS) improves survival
without transplantation compared to large-volume paracentesis. An important 2003
study reported that although TIPS reduced the number of paracenteses, there was
no improvement in survival rates. In addition, patients who were given TIPS had
a higher risk for encephalopathy than those given large-volume paracentesis. In
general, TIPS should be a second-line option for ascites that does not respond
to diuretics. [For a description of TIPS, see How Are Portal Hypertension and
Variceal Bleeding Managed in Cirrhosis?]

Peritoneovenous Shunting. Peritoneovenous (LeVeen, Denver) shunting is an older,
more invasive procedure, involving insertion of a tube, or shunt, under the skin
that routes the fluid from the abdomen into the jugular vein. The procedure can
have serious complications, including infection, blood clots, encephalopathy,
and rupture of blood vessels in the esophagus. It is now generally reserved for
patients who are not candidates for repeat paracentesis or liver
transplantation.
Treatment of Hepatorenal Syndrome
Hepatorenal syndrome can occur in patients ascites. This is a life-threatening
condition in which kidneys fail in trying to compensate for altered blood flow
in the liver. Studies are suggesting that terlipressin may be an effective
treatment in combination with albumin for hepatorenal syndrome.
Investigative Agents
Researchers are testing certain drugs that may redress the imbalances in
circulation that lead to portal hypertension and ascites. Of particular interest
are agents called nonpeptide vasopressin antagonists, also referred to as
aquaretics. They may reverse the dilation in blood vessels that lead to salt and
fluid retention.
Liver TransplantationThe prognosis for patients with ascites is poor, even with
intensive procedures. Liver transplantation should be considered for patients
when ascites does not respond to treatments and when poor liver function or
other complications, such as peritonitis or kidney failure, are present [seeBox
Liver Transplantation].

HOW ARE PORTAL HYPERTENSION AND VARICEAL BLEEDING MANAGED IN CIRRHOSIS?

Preventing an Initial Bleeding Episode. About half of patients with mild to
moderate cirrhosis have esophageal varices (abnormal blood vessels in the
esophagus.) In such patients the risk for bleeding within two years is as high
as 35%. Bleeding is fatal in half of these patients. In general, experts now
recommend preventive drugs in such patients, even if they have not been screened
with endoscopy -- the procedure needed to actually detect varices. Beta-blockers
are the only medications to date that have some preventive effects, but others
are under investigation.

Guidelines for Treating Bleeding Episodes. The physicians should first be
certain that bleeding is caused by portal hypertension and ruptured varices and
not by other conditions. For example, cirrhosis patients are also at higher than
average risk for bleeding peptic ulcers.

Saline or Ringers solution (a fluid and electrolyte replenisher) followed by red
blood cells and plasma is administered immediately to replace lost blood.

The next step is to immediately achieve a normal blood flow (hemostasis) in
order to stop the current bleeding episode and prevent early recurrence, which
typically occurs three to five days after a bleeding episode.

In general it is a two-pronged approach using drugs and endoscopy procedures.

Drugs. The patient should be given drugs to reduce portal pressure and blood
flow, typically octreotide or vasopressin. [See below.]
Endoscopy. Endoscopy employs an insertion of a thin tube containing a tiny
camera and surgical instruments in order to make repairs. Endoscopic
sclerotherapy is the most common procedure. [See below.] Emergency sclerotherapy
is often used as first-line therapy for variceal bleeding, but a major 2002
analysis of the existing evidence suggests that it is no more effective than
agents used to stop bleeding and it has potentially serious adverse effects.

A combination of drugs and endoscopy is the best approach for stopping bleeding
compared to endoscopy alone. It is not clear if there is any difference in
long-term survival however.

Prevent Bleeding Recurrence. Re-bleeding is common after an episode.
Investigation is ongoing concerning the most cost-efficient ways for preventing
recurrence. At this time, beta blockers are the best treatments available,
although they are not effective in many patients. Drug combinations and
endoscopic procedures are under investigation to determine if they offer any
additional benefits.

Preventing Complications. The patients who is experiencing a bleeding episode is
at high risk for other complications including pneumonia, bacterial infections,
and hepatic encephalopathy. Bacterial infections can also impair blood clotting.
Preventive oral antibiotics are often problematic in these patients. One study
suggested that intravenous ciprofloxacin may be helpful.
Drugs Used for Prevention of Bleeding
Beta Blockers. Beta-blockers, typically propranolol (Inderal) or nadolol
(Corgard), reduce the heart rate and can lower portal vein pressure in many
patients and so reduce variceal bleeding. Carvedilol (Coreg), a newer agent may
be even more effective, but more research is needed. Beta-blockers are also used
as a primary approach for prevention of recurring bleeding. Nevertheless they
fail to reduce portal pressure in nearly 40% of patients with cirrhosis. They
may not be appropriate for patients with type 1 diabetes, asthma, emphysema, and
chronic bronchitis. They must be taken for at least two years and most likely
longer to sustain a survival advantage.

Other Agents. Other agents are being used or investigated, mostly in combination
with beta blockers, to reduce recurrence rates.

Isosorbide mononitrate is a nitrate, a type of drug commonly used for angina.
Combinations with beta-blockers suggest appear to prevent rebleeding more
effectively than beta-blockers alone. It is not clear if the combination
improves any other aspects of the disease. (One study suggested that taking a
low dose of before a meal might help reduce a rise in portal pressure that
typically occurs after eating.) The nitrate has also been given as the
alternative agent for patients who cannot tolerate beta-blockers. Studies have
failed to show any survival advantage with isosorbide mononitrate when used
alone, however.
The diuretic spironolactone may be helpful in combination with a beta blocker
for reducing both ascites and rebleeding after an initial episode.
Angiotensin II receptor antagonists, including losartan (Cozaar), are being
studied for lowering portal pressure.
Drugs Used to Treat Bleeding Episodes
Somatostatin and Similar Agents. Somatostatin is a natural hormone that
constricts blood vessels. This agent or synthetic derivatives (octreotide and
vapreotide) may be more effective than the common procedure, endoscopic
sclerotherapy, for controlling bleeding. No single agent is more effective than
another. Their benefits for improving overall survival, however, are still
uncertain, and a major 2002 analysis of current studies found no effects on
survival rates with either octreotide or somatostatin.

Somatostatin, the natural hormone, controlled variceal bleeding in 87% of
patients in one 2000 study, but it is short acting.
Octreotide (Sandostatin) is a derivative of somatostatin and is longer
acting. It has largely replaced the older agent. It is very safe, even for heart
patients, and has few serious side effects.
Vapreotide (Octastatin) also resembles somatostatin. A 2001 study concluded
that a combination of vapreotide and endoscopic treatment is more effective than
endoscopic treatment alone for controlling bleeding, but the combination therapy
did not improve mortality rates at 42 days. The study suggested that these drugs
should be taken for five days.

Vasoconstrictors. Vasoconstrictors narrow the blood vessels and reduce flow in
the spleen. They are particularly effective when used with nitroglycerin.

Vasopressin (Pitressin) is the most commonly used vasoconstrictor. It poses a
risk to the heart, however, and it is not clear whether it is actually helpful.
Terlipressin is a synthetic version of vasopressin that is proving to be as
effective as sclerotherapy in controlling bleeding. It also lacks vasopressin's
side effects and may prove to prolong survival and serve as bridge for patients
waiting for liver transplantation.
Endoscopic Procedures Used to Stop Bleeding and Prevent Recurrence
Endoscopic procedures employ a tube inserted down through the esophagus that
contains microcameras and tiny instruments. Endoscopy is used both to diagnose
the disease and stop bleeding. The two standard procedures are band ligation and
sclerotherapy. In general, a combination of drug therapies and an endoscopic
procedure is the usual approach for preventing a bleeding recurrence.

Endoscopic Band Ligation. In endoscopic band ligation, latex bands are wrapped
around the bleeding varices, shutting off the blood supply. It is the method of
choice to control of bleeding and, in weekly sessions, to prevent rebleeding,
because it has a lower risk for complications than sclerotherapy. Recurrence
rates are higher with band ligation, however. Studies are mixed on whether
weekly treatments with band ligation any more effective in preventing rebleeding
than beta-blockers plus isosorbide mononitrate. A combination of medications
plus band ligation is under investigation.

Investigators are studying argon plasma coagulation (APC) after band ligation to
prevent variceal recurrence and rebleeding. This procedure employs argon gas to
deliver electric currents that coagulate and stop bleeding. In one small study,
no recurrence of varices or bleeding occurred after APC, while recurrence
occurred in 42% and bleeding in 7.2% of patients without the argon procedure.
More work is warranted.

Endoscopic Sclerotherapy. Endoscopic sclerotherapy is only effective against
bleeding in the esophagus. The endoscopic tube is inserted through the mouth.
Agents are injected through what are called sclerosants (polidocanol and
others). They toughen the tissue around the variceal blood vessels. The
procedure is repeated over a period of two or three months. Repeat treatments
appear to reduce rebleeding and death. Minor complications (usually ulcers in
the mucus membranes) are common and serious complications can occur (narrowing
or perforation of the esophagus and leakage at the injection site.)
Balloon Tamponade for Uncontrolled Bleeding
Balloon tamponade has been available for years but is now used only for bleeding
not controlled by drugs or endoscopy. It employs a tube inserted through the
nose and down through the esophagus until it reaches the upper part of the
stomach. A balloon at the tube's end is inflated and positioned tightly against
the esophageal wall. It is usually deflated in about 24 hours. Serious
complications can occur, the most dangerous being rupture of the esophagus.
Recurrence of bleeding is common.
Shunt Procedures for Uncontrolled Bleeding
Shunts are used for patients who are still bleeding in the esophagus after
endoscopic sclerotherapy or who are bleeding in the stomach. Choices include the
following:

Transjugular intrahepatic portosystemic shunt (TIPS).
A surgical shunt.

Shunt operations usually eliminate variceal bleeding, but encephalopathy and
shunt failure are frequent complications. Experts do not recommend shunts as
elective surgery for high-risk patients who are candidates for liver
transplantation, since shunts makes this operation more difficult.

Transjugular Intrahepatic Portosystemic Shunt (TIPS). A transjugular
intrahepatic portosystemic (or portal-systemic) shunt involves the following:

The patient only requires a local anesthetic and a sedative.
A long needle is inserted into the jugular vein in the neck and passed down
through the vena cava, a large vein that conducts blood back to the heart. This
serves to widen the vein.
The surgeon makes an incision in the hepatic vein in the liver and creates a
connection to the portal vein.
A cylindrical wire-mesh stent is inserted into this connecting vein.
The stent now acts as a shunt, which reroutes blood around the scarred liver.

TIPS is a good choice for bleeding that is not controlled by endoscopy,
particularly when it is performed shortly after a bleeding episode. It also
reduces ascites.

It is not useful as the first choice for stopping an initial bleeding episode or
for preventing rebleeding, however, since it poses a high risk for
encephalopathy. This complication outweighs its benefits compared to endoscopy
for initial treatment and to beta blockers for preventing recurrence. Blockage
or closure of the shunt can develop over time.

TIPS is generally recommended only for the following patients:

Cannot tolerate sclerotherapy.
Are unlikely or unable to comply with the repeated procedures necessary for
sclerotherapy.
Have poor blood circulation.

Surgical Shunts. There are two types of surgical shunts:

A portal shunt, or portal systemic shunt. It was introduced in 1945 and was
the first significant treatment for bleeding varices. It relieves pressure in
the portal vein by surgically joining it to the inferior vena cava, a large vein
that conducts blood back to the heart. It poses a high risk for encephalopathy
and does not appear to improve survival, so is not used often.
A variation called the H-graft portacaval shunt is a partial shunt that is
proving to be effective for treating bleeding. It controls bleeding in 90% of
patients and has a lower encephalopathy rate than the complete portal shunt or
TIPS. In fact, early studies report that it may have lower rates for
transplantation and death than TIPS.
A distal splenorenal shunt (DSRS) preserves blood flow through the portal
vein while relieving pressure on the varices by joining the left kidney vein to
the splenic vein. (The splenic vein returns blood from the spleen and is one of
two veins that form the portal vein.) Studies show that DSRS has similar
mortality rates compared to the portal shunt but lower rates of encephalopathy
afterwards. Patients with alcoholic cirrhosis fare worse with DSRS than
nonalcoholic patients. It is probably best used as an elective operation in
patients with good liver function who continue to bleed in spite of endoscopy.




Sandra Tara Balduf (Ane)

Frontline Hepatitis Awareness

Support for patients and educational materials

http://frontline-hepatitis-awareness.com

1-866-Hep-GoGo 866-437-4646




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