Cirrhosis

Description

Alternative Names

Bleeding Episodes

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.
• 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. 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. Rebleeding 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 tubes 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.