HOW IS CIRRHOSIS TREATED?

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 antiinflammatory 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 creatinine 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.

What are the complications of cirrhosis? Edema and ascites As cirrhosis of the liver becomes severe, signals are sent to the kidneys to retain salt and water in the body. The excess salt and water first accumulates in the tissue beneath the skin of the ankles and legs because of the effect of gravity when standing or sitting. This accumulation of fluid is called edema or pitting edema. (Pitting edema refers to the fact that pressing a fingertip firmly against an ankle or leg with edema causes an indentation in the skin that persists for some time after release of the pressure. Actually, any type of pressure, such as from the elastic band of a

sock, may be enough to cause pitting.) The swelling often is worse at the end of a day after standing or sitting and may lessen overnight as a result of the loss of the effects of gravity when lying down. As cirrhosis worsens and more salt and water are retained, fluid also may accumulate in the abdominal cavity between the abdominal wall and the abdominal organs. This accumulation of fluid (called ascites ) causes swelling of the abdomen, abdominal discomfort, and increased weight. Spontaneous bacterial peritonitis (SBP) Fluid in the abdominal cavity (ascites) is the perfect place for bacteria to grow. Normally, the abdominal cavity contains a very small amount of fluid that is able to resist infection well, and bacteria that enter the abdomen (usually from the intestine) are killed or find their way into the portal vein and to the liver where they are killed. In cirrhosis, the fluid that collects in the abdomen is unable to resist infection normally. In addition, more bacteria find their way from the intestine into the ascites. Therefore, infection within the abdomen and the ascites, referred to as spontaneous bacterial peritonitis or SBP, is likely to occur. SBP is a life- threatening complication. Some patients with SBP have no symptoms, while others have fever, chills, abdominal pain and tenderness, diarrhea, and worsening ascites. Bleeding from esophageal varices In the cirrhotic liver, the scar tissue blocks the flow of blood returning to the heart from the intestines and raises the pressure in the portal vein (portal hypertension). When pressure in the portal vein becomes high enough, it causes blood to flow around the liver through veins with lower pressure to reach the heart. The most common veins through which blood bypasses the liver are the veins lining the lower part of the esophagus and the upper part of the stomach. As a result of the increased flow of blood and the resulting increase in pressure, the veins in the lower esophagus and upper stomach expand and then are referred to as esophageal and gastric varices; the higher the portal pressure, the larger the varices and the more likely a patient is to bleed from the varices into the esophagus or stomach. Bleeding from varices usually is severe and, without immediate treatment, can be fatal. Symptoms of bleeding from varices include vomiting blood (the vomitus can be red blood mixed with clots or "coffee grounds" in appearance, the latter due to the effect of acid on the blood), passing stool that is black and tarry due to changes in the blood as it passes through the intestine (melena), and orthostatic dizziness or fainting (caused by a drop in blood pressure especially when standing up from a lying position). Bleeding also may occur from varices that form elsewhere in the intestines, for example, the colon, but this is rare. For reasons yet unknown, patients hospitalized because of actively bleeding esophageal varices have a high risk of developing spontaneous bacterial peritonitis. Hepatic encephalopathy

Some of the protein in food that escapes digestion and absorption is used by bacteria that are normally present in the intestine. While using the protein for their own purposes, the bacteria make substances that they release into the intestine. These substances then can be absorbed into the body. Some of these substances, for example, ammonia, can have toxic effects on the brain. Ordinarily, these toxic substances are carried from the intestine in the portal vein to the liver where they are removed from the blood and detoxified. As previously discussed, when cirrhosis is present, liver cells cannot function normally either because they are damaged or because they have lost their normal relationship with the blood. In addition, some of the blood in the portal vein bypasses the liver through other veins. The result of these abnormalities is that toxic substances cannot be removed by the liver cells, and, instead, the toxic substances accumulate in the blood. When the toxic substances accumulate sufficiently in the blood, the function of the brain is impaired, a condition called hepatic encephalopathy. Sleeping during the day rather than at night (reversal of the normal sleep pattern) is among the earliest symptoms of hepatic encephalopathy. Other symptoms include irritability, inability to concentrate or perform calculations, loss of memory, confusion, or depressed levels of consciousness. Ultimately, severe hepatic encephalopathy causes coma and death. The toxic substances also make the brains of patients with cirrhosis very sensitive to drugs that are normally filtered and detoxified by the liver. Doses of many drugs that normally are detoxified by the liver have to be reduced to avoid a toxic buildup in cirrhosis, particularly sedatives and drugs that are used to promote sleep. Alternatively, drugs may be used that do not need to be detoxified or eliminated from the body by the liver, for example, drugs that are eliminated by the kidneys. Hepatorenal syndrome Patients with worsening cirrhosis can develop the hepatorenal syndrome. This syndrome is a serious complication in which the function of the kidneys is reduced. It is a functional problem in the kidneys, that is, there is no physical damage to the kidneys. Instead, the reduced function is due to changes in the way the blood flows through the kidneys themselves. The hepatorenal syndrome is defined as progressive failure of the kidneys to clear substances from the blood and produce adequate amounts of urine even though some other important functions of the kidney, such as retention of salt, are maintained. If liver function improves or a healthy liver is transplanted into a patient with hepatorenal syndrome, the kidneys usually begin to work normally. This suggests that the reduced function of the kidneys is the result of the accumulation of toxic substances in the blood when the liver fails. There are two types of hepatorenal syndrome. One type occurs gradually over months. The other occurs rapidly over a week or two. Hepatopulmonary syndrome Rarely, some patients with advanced cirrhosis can develop the hepatopulmonary syndrome. These patients can experience difficulty breathing because certain hormones released in advanced cirrhosis cause the lungs to function abnormally. The basic problem in the lung is that

not enough blood flows through the small blood vessels in the lungs that are in contact with the alveoli (air sacs) of the lungs. Blood flowing through the lungs is shunted around the alveoli and cannot pick up enough oxygen from the air in the alveoli. As a result the patient experiences shortness of breath, particularly with exertion. Hypersplenism The spleen normally acts as a filter to remove older red blood cells, white blood cells, and platelets (small particles that are important for the clotting of blood.). The blood that drains from the spleen joins the blood in the portal vein from the intestines. As the pressure in the portal vein rises in cirrhosis, it increasingly blocks the flow of blood from the spleen. The blood "backs-up" and accumulates in the spleen, and the spleen swells in size, a condition referred to as splenomegaly. Sometimes, the spleen is so swollen that it causes abdominal pain. As the spleen enlarges, it filters out more and more of the blood cells and platelets until their numbers in the blood are reduced. Hypersplenism is the term used to describe this condition, and it is associated with a low red blood cell count (anemia), low white blood cell count (leucopenia), and/or a low platelet count (thrombocytopenia). The anemia can cause weakness, the leucopenia can lead to infections, and the thrombocytopenia can impair the clotting of blood and result in prolonged bleeding. Liver cancer (hepatocellular carcinoma) Cirrhosis due to any cause increases the risk of primary liver cancer (hepatocellular carcinoma). Primary refers to the fact that the tumor originates in the liver. A secondary liver cancer is one that originates elsewhere in the body and spreads (metastasizes) to the liver. The most common symptoms and signs of primary liver cancer are abdominal pain and swelling, an enlarged liver, weight loss, and fever. In addition, liver cancers can produce and release a number of substances, including ones that cause an increased in red blood cell count (erythrocytosis), low blood sugar (hypoglycemia), and high blood calcium (hypercalcemia ).

Menus For Cirrhosis Of The Liver

Cirrhosis Of The Liver
Cirrhosis is a word derived from the Greek meaning yellow. It was originally intended to convey the idea of overgrowth or enlargement of this much-abused organ, but inasmuch as atrophic conditions often show yellow or tawny, there are now two kinds of cirrhosis, namely, atrophic cirrhosis, meaning a shrinkage, and hypertrophic cirrhosis, meaning enlargement of the liver. Atrophic cirrhosis is caused by alcoholism, often augmented by milder stimulants such as tea and coffee.

Hypertrophic cirrhosis is caused by overeating, especially of meat, sweets, and starchy foods. The causes of the former should be removed by ceasing the use of tea, coffee, and all alcoholic stimulants, and of the latter by omitting sweets, and limiting the diet in quantity to, or in severe cases below, the actual needs of the body. The following menus are laid out for the treatment of severe cases. They are designed both as a counteractive and as a remedial measure. In mild cases, or as the patient recovers, the diet may be increased in quantity, but it should be confined very rigidly to the articles named in the list below, and in the menus which follow. Foods to be used in the treatment of cirrhosis of the liver: Proteids Egg whites Fish Fowl - white meat Nuts Sour milk Carbohydrates Bananas Corn bread ' Flaked rye Wheat bran Whole wheat Fats Butter Nut butter Nuts Vegetables Asparagus Beets Beans Brussels sprouts Cauliflower

Cabbage Carrots Celery Onions Potatoes Spinach Squash Turnip-greens Turnips Fruits Apples Apricots Cantaloup Cherries Grapes Melons Oranges Peaches Pears Plums Prunes Raisins Tomatoes.

Spring Menu. Cirrhosis Of The Liver

Breakfast
Soaked apricots; neither sugar nor cream Very ripe bananas Nuts Note: If bananas are not "dead ripe" they should be baked.

Luncheon
1 Peas in the pod Bran meal gems Buttermilk

Dinner
Peas or asparagus Lettuce, spinach, or turnip-greens Carrots or turnips A potato.

Summer Menu. Cirrhosis Of The Liver

Breakfast
Peaches, cherries, apricots, or cantaloup Three or four egg whites whipped with a spoonful of cream Flaked rye, well cooked

Luncheon
Beans, Brussels sprouts, or cauliflower Lettuce and tomato A potato

A glass of buttermilk

Dinner
Vegetable soup - very little fat Any fresh vegetable in above list Fish or chicken - very little A potato or tender corn

Fall Menu. Cirrhosis Of The Liver

Breakfast
Grapes, peaches, or plums Two baked bananas Whole wheat

Luncheon
Boiled onions Squash Lima beans or bran gems

Dinner
Celery or spinach Any fresh vegetable in above list A potato or corn bread Two tablespoonfuls of wheat bran

Winter Menu. Cirrhosis Of The Liver

Breakfast
A baked banana or a baked apple A baked potato - eat skins and all

Luncheon
Celery soup Corn bread Winter squash

Dinner
Parsnips or turnips A potato or baked beans Celery, with nuts Fish or buttermilk

If the breakfast is late, and the labor is light, the noon meal should be omitted.

Spring Menu. Cirrhosis Of The Liver

Breakfast
Baked apples or very ripe berries without sugar A very ripe banana with cream Flaked wheat, thoroughly cooked with one-half bran

Luncheon
Peas in the pod - en casserole A baked potato

Dinner
Peas, asparagus, or onions A baked potato Nuts with cream Cheese with water-cracker From one to three glasses of water should be drunk at each of these meals. Mastication should be very thorough. For cooking "en casserole," see p. 671.

Summer Menu. Cirrhosis Of The Liver

Breakfast
Cantaloup, peaches, plums, or berries Two tablespoonfuls of plain boiled wheat A pint of rich milk; buttermilk preferred

Luncheon
Young onions, lettuce, romaine, or any fresh salad with either nuts or oil Carrots, squash, or tender corn A baked potato - sweet or white

Dinner
Vegetable soup A Spanish onion, en casserole Squash, carrots, parsnips, okra, cauliflower - any two of these A baked potato Tender corn or lima beans Cheese, with nuts and raisins

Fall Menu. Cirrhosis Of The Liver

Breakfast
Cantaloup, peaches, or grapes One egg, prepared choice Bran meal gems or a potato A glass of milk

Luncheon
Squash Okra, or an onion, en casserole A corn muffin or a baked potato Celery, or lettuce, with nuts

Dinner
Vegetable or cream soup Celery, or slaw, with nuts - no vinegar Winter squash, stewed pumpkin, or a baked sweet potato Bran meal gems A morsel of cheese, with either raisins or nuts

Winter Menu. Cirrhosis Of The Liver Breakfast

A baked apple or soaked prunes A pint of milk Plain boiled wheat or corn hominy. (If hominy is chosen, a heaping tablespoonful of wheat bran should be taken)

Luncheon
Two or three glasses o buttermilk Two tablespoonfuls of wheat bran

Dinner
Cream of tomato soup Turnips, cabbage, carrots, cauliflower - any two of these A potato or a bran meal gem (A small portion of tender fish may be added if much desired) If there is a tendency toward constipation, two or three tablespoonfuls of wheat bran should be taken, and an abundance of water drunk both at meals and between meals.