Cirrhosis (cont.)

Treatment of cirrhosis includes 1) preventing further damage to the liver, 2) treating the complications of cirrhosis, 3) preventing liver cancer or detecting it early, and 4) liver transplantation.

Preventing further damage to the liver

• Consume a balanced diet and one multivitamin daily. Patients with PBC with impaired absorption of fat soluble vitamins may need additional vitamins D and K.

• Avoid drugs (including alcohol) that cause liver damage. All patients with cirrhosis should avoid alcohol. Most patients with alcohol induced cirrhosis experience an improvement in liver function with abstinence from alcohol. Even patients with chronic hepatitis B and C can substantially reduce liver damage and slow the progression towards cirrhosis with abstinence from alcohol.

• Avoid nonsteroidal anti-inflammatory drugs (NSAIDs, e.g., ibuprofen). Patients with cirrhosis can experience worsening of liver and kidney function with NSAIDs.

• Eradicate hepatitis B and hepatitis C virus by using anti-viral medications. Not all patients with cirrhosis due to chronic viral hepatitis are candidates for drug treatment. Some patients may experience serious deterioration in liver function and/or intolerable side effects during treatment. Thus, decisions to treat viral hepatitis have to be individualized, after consulting with doctors experienced in treating liver diseases (hepatologists).

• Remove blood from patients with hemochromatosis to reduce the levels of iron and prevent further damage to the liver. In Wilson's disease, medications can be used to increase the excretion of copper in the urine to reduce the levels of copper in the body and prevent further damage to the liver.

• Suppress the immune system with drugs such as prednisone and azathioprine (Imuran) to decrease inflammation of the liver in autoimmune hepatitis.

• Treat patients with PBC with a bile acid preparation, ursodeoxycholic acid (UDCA), also called ursodiol (Actigall). Results of an analysis that combined the results from several clinical trials showed that UDCA increased survival among PBC patients during 4 years of therapy. The development of portal hypertension also was reduced by the UDCA. It is important to note that despite producing clear benefits, UDCA treatment primarily retards progression and does not cure PBC. Other medications such as colchicine and methotrexate also may have benefit in subsets of patients with PBC.

• Immunize patients with cirrhosis against infection with hepatitis A and B to prevent a serious deterioration in liver function. There are currently no vaccines available for immunizing against hepatitis C.

Treating the complications of cirrhosis

Edema and ascites. Retention of salt and water can lead to swelling of the ankles and legs (edema) or abdomen (ascites) in patients with cirrhosis. Doctors often advise patients with cirrhosis to restrict dietary salt (sodium) and fluid to decrease edema and ascites. The amount of salt in the diet usually is restricted to 2 grams per day and fluid to 1.2 liters per day. In most patients with cirrhosis, however, salt and fluid restriction is not enough, and diuretics have to be added.

Diuretics are medications that work in the kidneys to promote the elimination of salt and water into the urine. A combination of the diuretics spironolactone (Aldactone) and furosemide can reduce or eliminate the edema and ascites in most patients. During treatment with diuretics, it is important to monitor the function of the kidneys by measuring blood levels of blood urea nitrogen (BUN) and cretonne to determine if too much diuretic is being used. Too much diuretic can lead to kidney dysfunction that is reflected in elevations of the BUN and creatinine levels in the blood.

Sometimes, when the diuretics do not work (in which case the ascites is said to be refractory), a long needle or catheter is used to draw out the ascitic fluid directly from the abdomen, a procedure called abdominal paracentesis. It is common to withdraw large amounts (liters) of fluid from the abdomen when the ascites is causing painful abdominal distension and/or difficulty breathing because it limits the movements of the diaphragms.

Another treatment for refractory ascites is a procedure called transjugular intravenous portosystemic shunting (TIPS, see below).

Bleeding from varices. If large varices develop in the esophagus or upper stomach, patients with cirrhosis are at risk for serious bleeding due to rupture of these varices. Once varices have bled, they tend to rebleed and the probability that a patient will die from each bleeding episode is high (30%-35%). Therefore, treatment is necessary to prevent the first (initial) bleeding episode as well as rebleeding. Treatments include medications and procedures to decrease the pressure in the portal vein and procedures to destroy the varices.

• Propranolol (Inderal), a beta blocker, is effective in lowering pressure in the portal vein and is used to prevent initial bleeding and rebleeding from varices in patients with cirrhosis. Another class of oral medications that lowers portal pressure is the nitrates, for example, isosorbide dinitrate ( Isordil). Nitrates often are added to propranolol if propranolol alone does not adequately lower portal pressure or prevent bleeding.

• Octreotide (Sandostatin) also decreases portal vein pressure and has been used to treat variceal bleeding.

• During upper endoscopy (EGD), either sclerotherapy or band ligation can be performed to obliterate varices and stop active bleeding and prevent rebleeding. Sclerotherapy involves infusing small doses of sclerosing solutions into the varices. The sclerosing solutions cause inflammation and then scarring of the varices, obliterating them in the process. Band ligation involves applying rubber bands around the varices to obliterate them. (Band ligation of the varices is analogous to rubber banding of hemorrhoids.) Complications of sclerotherapy include esophageal ulcers, bleeding from the esophageal ulcers, esophageal perforation, esophageal stricture (narrowing due to scarring that can cause dysphagia), mediastinitis (inflammation in the chest that can cause chest pain), pericarditis (inflammation around the heart that can cause chest pain), and peritonitis (infection in the abdominal cavity). Studies have shown that band ligation may be slightly more effective with fewer complications than sclerotherapy.

• Transjugular intrahepatic portosystemic shunt (TIPS) is a non-surgical procedure to decrease the pressure in the portal vein. TIPS is performed by a radiologist who inserts a stent (tube) through a neck vein, down the inferior vena cava and into the hepatic vein within the liver. The stent then is placed so that one end is in the high pressure portal vein and the other end is in the low pressure hepatic vein. This tube shunts blood around the liver and by so doing lowers the pressure in the portal vein and varices and prevents bleeding from the varices. TIPS is particularly useful in patients who fail to respond to beta blockers, variceal sclerotherapy, or banding. (TIPS also is useful in treating patients with ascites that do not respond to salt and fluid restriction and diuretics.) TIPS can be used in patients with cirrhosis to prevent variceal bleeding while the patients are waiting for liver transplantation. The most common side effect of TIPS is hepatic encephalopathy. Another major problem with TIPS is the development of narrowing and occlusion of the stent, causing recurrence of portal hypertension and variceal bleeding and ascites. The estimated frequency of stent occlusion ranges from 30%-50% in 12 months. Fortunately, there are methods to open occluded stents. Other complications of TIPS include bleeding due to inadvertent puncture of the liver capsule or a bile duct, infection, heart failure, and liver failure.

• A surgical operation to create a shunt (passage) from the high-pressure portal vein to veins with lower pressure can lower blood flow and pressure in the portal vein and prevent varices from bleeding. One such surgical procedure is called distal splenorenal shunt (DSRS). It is appropriate to consider such a surgical shunt for patients with portal hypertension who have early cirrhosis. (The risks of major shunt surgery in these patients is less than in patients with advanced cirrhosis.) During DSRS, the surgeon detaches the splenic vein from the portal vein, and attaches it to the renal vein. Blood then is shunted from the spleen around the liver, lowering the pressure in the portal vein and varices and preventing bleeding from the varices.

Hepatic encephalopathy. Patients with an abnormal sleep cycle, impaired thinking, odd behavior, or other signs of hepatic encephalopathy usually should be treated with a low protein diet and oral lactulose. Dietary protein is restricted because it is a source of the toxic compounds that cause hepatic encephalopathy. Lactulose, which is a liquid, traps the toxic compounds in the colon. Consequently, they cannot be absorbed into the blood stream and cause encephalopathy. To be sure that adequate lactulose is present in the colon at all times, the patient should adjust the dose to produce 2-3 semiformed bowel movements a day. (Lactulose is a laxative, and the adequacy of treatment can be judged by loosening or increasing frequency of stools.) If symptoms of encephalopathy persist, oral antibiotics such as neomycin or metronidazole (Flagyl), can be added to the treatment regimen. Antibiotics work by blocking the production of the toxic compounds by the bacteria in the colon.

Hypersplenism. The filtration of blood by an enlarged spleen usually results in only mild reductions of red blood cells (anemia), white blood cells (leukopenia) and platelets (thrombocytopenia) that do not require treatment. Severe anemia, however, may require blood transfusions or treatment with erythropoietin or epoetin alfa (Epogen, Procrit), hormones that stimulate the production of red blood cells. If the numbers of white blood cells are severely reduced, another hormone called granulocyte-colony stimulating factor is available to increase the numbers of white blood cells. An example of one such factor is filgrastim (Neupogen).

No approved medication is available yet to increase the number of platelets. As a necessary precaution, patients with low platelets should not use aspirin or other nonsteroidal antiinflammatory drugs (NSAIDS) since these drugs can hinder the function of platelets. If a low number of platelets is associated with significant bleeding, transfusions of platelets usually should be given. Surgical removal of the spleen (called splenectomy) should be avoided, if possible, because of the risk of excessive bleeding during the operation and the risk of anesthesia in advanced liver disease.

Spontaneous bacterial peritonitis (SBP). Patients suspected of having spontaneous bacterial peritonitis usually will undergo paracentesis. Fluid that is removed is examined for white blood cells and cultured for bacteria. Culturing involves inoculating a sample of the ascites into a bottle of nutrient-rich fluid that encourages the growth of bacteria, thus facilitating the identification of even small numbers of bacteria. Blood and urine samples often are obtained as well for culturing because many patients with spontaneous bacterial peritonitis also will have infection in their blood and urine. In fact, many doctors believe that infection may have begun in the blood and the urine and spread to the ascitic fluid to cause spontaneous bacterial peritonitis. Most patients with spontaneous bacterial peritonitis are hospitalized and treated with intravenous antibiotics such as ampicillin, gentamycin, and one of the newer generation cephalosporin. Patients usually treated with antibiotics include:

• Patients with blood, urine, and/or ascites fluid cultures that contain bacteria.
• Patients without bacteria in their blood, urine, and ascitic fluid but who have elevated numbers of white blood cells (neutrophils) in the asciticfluid(>250 neutrophils/cc). Elevated neutrophil numbers in ascitic fluid often means that there is bacterial infection. Doctors believe that the lack of bacteria with culturing in some patients with increased neutrophils is due either to a very small number of bacteria or ineffective culturing techniques.

Spontaneous bacterial peritonitis is a serious infection. It often occurs in patients with advanced cirrhosis whose immune systems are weak, but with modern antibiotics and early detection and treatment, the prognosis of recovering from an episode of spontaneous bacterial peritonitis is good.

In some patients oral antibiotics (such as Cipro or Septra) can be prescribed to prevent spontaneous bacterial peritonitis. Not all patients with cirrhosis and ascites should be treated with antibiotics to prevent spontaneous bacterial peritonitis, but some patients are at high risk for developing spontaneous bacterial peritonitis and warrant preventive treatment:

• Patients with cirrhosis who are hospitalized for bleeding varices have a high risk of developing spontaneous bacterial peritonitis and should be started on antibiotics early during the hospitalization to prevent spontaneous bacterial peritonitis
• Patients with recurring episodes of spontaneous bacterial peritonitis
• Patients with low protein levels in the ascitic fluid (Ascitic fluid with low levels of protein is more likely to become infected.)

Prevention and early detection of liver cancer

Several types of liver disease that cause cirrhosis are associated with a particularly high incidence of liver cancer, for example, hepatitis B and C, and it would be useful to screen for liver cancer since early surgical treatment or transplantation of the liver can cure the patient of cancer. The difficulty is that the methods available for screening are only partially effective, identifying at best only 50% of patients at a curable stage of their cancer. Despite the partial effectiveness of screening, most patients with cirrhosis, particularly hepatitis B and C, are screened yearly or every six months with ultrasound examination of the liver and measurements of cancer-produced proteins in the blood, e.g. alpha fetoprotein.

Liver transplantation

Cirrhosis is irreversible. Many patients' liver function will gradually worsen despite treatment and complications of cirrhosis will increase and become difficult to treat. Therefore, when cirrhosis is far advanced, liver transplantation often is the only option for treatment. Recent advances in surgical transplantation and medications to prevent infection and rejection of the transplanted liver have greatly improved survival after transplantation. On average, more than 80% of patients who receive transplants are alive after five years. Not everyone with cirrhosis is a candidate for transplantation. Furthermore, there is a shortage of livers to transplant, and there usually is a long (months to years) wait before a liver for transplanting becomes available. Therefore, measures to retard the progression of liver disease and treat and prevent complications of cirrhosis are vitally important.

Source: MedicineNet.com
http://www.medicinenet.com/cirrhosis/article.htm