Cirrhosis

Causes of Cirrhosis

Causes of cirrhosis include:

• Alcoholism
• Chronic hepatitis B and C
• Autoimmune hepatitis
• Bile duct disorders such as primary biliary cirrhosis and primary sclerosing cholangitis
• Nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH)
• Metabolic disorders such as hemachromatosis, Wilson's disease, and alpha-1 antitrypsin deficiency
• Prolonged exposure to certain types of chemicals and medications

Complications

Cirrhosis can cause many serious complications including:

• Ascites (fluid buildup in the abdomen)
• Variceal hemorrhage, severe bleeding of varices (enlarged veins in the esophagus and upper stomach)
• Spontaneous bacterial peritonitis, a severe infection of the abdominal fluid
• Hepatic encephalopathy, damage to the brain caused by buildup in the body of toxins such as ammonia
• Hepatocellular carcinoma, a type of liver cancer

Dietary and Lifestyle Changes

All patients with cirrhosis can benefit from certain types of lifestyle interventions. These include:

• Stop drinking alcohol.
• Restrict dietary salt.
• Eat a nutritious diet.
• Get vaccinations for influenza, hepatitis A and B, and pneumococcal pneumonia (if recommended by your doctor).
• Inform your doctor of all prescription and nonprescription medications, and any herbs and supplements, you take or are considering taking.

Treatment

Cirrhosis is an irreversible condition. Treatment focuses on slowing the progression of liver damage and reducing the risk of further complications. Your doctor will treat any underlying medical conditions that are the cause of your cirrhosis. If liver damage progresses to liver failure, patients may be candidates for liver transplantation. Liver donations can come from a cadaver or from a living donor. Patients with cirrhosis who have a liver transplant have very good chances for survival.

Cirrhosis is an irreversible result of various disorders that damage liver cells over time. Eventually, damage becomes so extensive that the normal structure of the liver is distorted and its function is impaired.

The disease process often takes the following path:

Scarring. The main damage in cirrhosis is triggered by scarring (fibrosis) that occurs from injuries due to alcohol, viruses, or other assaults. Normal clumps and form nodules around the scarred areas. The scar tissue and regenerated nodules act like small dams and alter the flow of blood and bile in and out of the liver.

Altered Blood and Bile Flow. The changes in blood and bile flow have significant consequences, with both the liver and other organs responding to the altered flow:

• The spleen overproduces nitric oxide, a chemical that causes blood vessels in the spleen to widen (dilate).
• The small blood vessels and bile ducts in the liver itself, however, narrow (constrict). (Blood vessels in other organs, including the kidney, also narrow.)
• Blood flow coming from the intestine into the liver is slowed by the narrow blood vessels. It backs up through the portal vein and seeks other routes.
• New, abnormally twisted and swollen veins called varices form in the stomach and lower part of the esophagus in order to compensate for the backup blood.
• Bilirubin also builds up in the bloodstream, resulting in jaundice, which causes a yellowish cast in the skin and eyes, as well as dark-colored urine.
• Fluid buildup also occurs in the abdomen (called ascites ), and swelling in the legs is common.

Functions of the Liver

The liver is the largest internal organ in the body. In the healthy adult, it weighs about 3 pounds. The liver is wedge-shaped, with the top part wider than the bottom. It is located immediately below the diaphragm and occupies the entire upper right quadrant of the abdomen.

Vital Functions. The liver performs over 500 vital functions. Damage to the liver can impair these and many other processes. Among them are the following:

Processing Healthful Nutrients. It processes all of the nutrients the body requires, including proteins, glucose, vitamins, and fats.

Bile Production. The liver produces bile, a green-colored fluid that helps the body absorb fats and fat-soluble vitamins. Bile contains bilirubin, a yellow-green pigment produced from the breakdown of hemoglobin, the oxygen-carrying component in red blood cells. Bile contains bile salts, fatty acids, cholesterol, and other substances. Bile travels from the liver to the gallbladder, where it is stored until after a meal. It is then secreted into the intestines where it helps digest fat. Because bile can also travel from the liver to the intestines, patients who have had their gallbladders removed can still absorb fat normally.

Eliminating Toxins. One of the liver's major functions is to render harmless potentially toxic substances, including alcohol, ammonia, nicotine, drugs, and harmful by-products of digestion.

Structure of the Liver

The vital processes the liver performs rely on well-organized liver architecture.

The basic building blocks of the liver are the following structures:

• Bile ducts
• Blood vessels
• Working liver tissue (called the parenchyma)
• Supportive (connective) tissue

The liver is a built on a framework of lobes:

• The lobes. The liver is divided into two major lobes, a right and a smaller left, that are separated by tough, fibrous connective tissue.
• The lobules. The liver's two major lobes contain about 100,000 smaller lobes, called lobules. Each lobule contains microscopic columns of liver cells and blood vessels. Bracing the corners of each lobule column are an artery and a vein that carry blood and a bile duct that drains bile.
• The bile ducts. The bile ducts in the column corners collect bile draining from tiny canals around the liver cells. These ducts eventually join to form the large common bile duct that leads from the liver to the gallbladder.
• The arteries and veins. The arteries bring oxygen-rich blood to nourish the liver cells. The veins supply the liver cells with blood containing the nutrients and toxins that the liver cells process. A central vein runs through each column and collects the processed blood from both sources. These veins join to form the hepatic vein.

The Liver's Blood Supply. The liver is rich in blood. It holds about a pint, or 13% of the body's supply. It is furnished with blood from two large vessels, the hepatic artery and the portal vein, and is drained of blood by the hepatic vein. (The word "hepatic" derives from the Latin word for liver.)

The hepatic artery. This artery supplies blood from the heart directly to the liver. This blood nourishes the liver.

The portal vein. The portal vein carries to the liver blood that has been circulating through the stomach, spleen, and intestine. The liver processes this blood, extracting nutrients and toxins.

The hepatic vein. This vein carries blood from the liver and connects to the inferior vena cava, a large vein that carries blood back to the heart.

Click the icon to see an image of the liver.

Several processes can lead to cirrhosis.

Alcoholism

Chronic alcoholism particularly endangers the liver by causing alcoholic liver disease (also called alcohol-induced liver disease). Alcoholic liver disease includes fatty liver (build-up of fat cells in the liver), alcoholic hepatitis (inflammation of the liver caused by chronic drinking), and alcoholic cirrhosis. Alcoholic cirrhosis is the primary type of cirrhosis in the U.S. It develops in 10 - 20% of heavy drinkers, usually after 10 - 15 years of heavy alcohol consumption. People who drink heavily and who also have hepatitis C are at particular risk of developing cirrhosis. In the liver, alcohol converts to toxic chemicals that trigger inflammation and tissue injury, which lead to cirrhosis.

Chronic Hepatitis

Chronic hepatitis, both hepatitis B and hepatitis C, is another primary cause of cirrhosis. Chronic hepatitis C is a more common cause of cirrhosis in developed countries, while hepatitis B is a more common cause of cirrhosis worldwide, especially in sub-Saharan Africa and parts of Asia. People with chronic hepatitis B who are co-infected with hepatitis D are especially at risk for cirrhosis. The longer a patient has had chronic hepatitis, the greater the risk for eventually developing cirrhosis.

The hepatitis virus can produce inflammation in liver cells, causing injury or destruction. If the condition is severe enough, the cell damage becomes progressive, building a layer of scar tissue over the liver. In advanced cases, as with alcoholic cirrhosis, the liver shrivels in size, a condition called postnecrotic or posthepatic cirrhosis.

Autoimmune Hepatitis

Autoimmune hepatitis, like other autoimmune disorders, develops when a misdirected immune system attacks the body's own cells and organs. People who have autoimmune hepatitis also often have other autoimmune conditions, including systemic lupus erythematosus, rheumatoid arthritis, Sjögren syndrome, scleroderma, inflammatory bowel disease, glomerulonephritis, and hemolytic anemia. Autoimmune hepatitis typically occurs in women ages 15 - 40.

Bile Ducts Disorders

Disorders that block or damage the bile ducts, can cause bile to back up in the liver leading to inflammation and cirrhosis. These diseases include primary biliary cirrhosis and primary sclerosing chlorangitis.

Primary Biliary Cirrhosis. Up to 95% of primary biliary cirrhosis (PBC) cases occur in women, usually around age 50. In people with PBC, the immune system attacks and destroys cells in the liver's bile ducts. Like many autoimmune disorders, the causes of PBC are unknown.

Primary Sclerosing Cholangitis. Primary sclerosing cholangitis (PSC) is a chronic disease that mostly affects men, usually around age 40. The cause is unknown, but immune system defects, genetics, and infections may play a role.

Nonalcoholic Fatty Liver Disease (NAFLD) and Nonalcoholic Steatohepatitis (NASH)

Nonalcoholic fatty liver disease (NAFLD) resembles alcoholic liver disease, but it occurs in people who do not drink a lot of alcohol. Obesity and type 2 diabetes are the two main causes of a fatty liver. Some evidence suggests that insulin resistance (the primary problem in type 2 diabetes) is a major factor in development of a fatty liver. A diet high in fatty foods may also be a risk factor, as dietary fat accumulates in the liver. Due to the recent rise in childhood obesity, NAFLD is increasingly occurring in children. In fact, NAFLD is now the most common liver disease in American children.

Nonalcoholic fatty liver disease can lead to nonalcoholic steatohepatitis (NASH). Liver inflammation and injury, as well as a fatty liver, characterize NASH. NASH occurs in about half of people with diabetes and up to 75% of obese people.

Nonalcoholic fatty liver disease is usually benign and very slowly progressive. But, in certain patients, it can lead to cirrhosis, liver failure, or liver cancer. About 8 - 20% of people with nonalcoholic steatohepatitis go on to develop cirrhosis.

Hereditary Disorders

Hemochromatosis. Hemochromatosis is a disorder of iron metabolism. This disease interferes with the way the body normally gets rid of iron. People with hemochromatosis absorb too much more iron from the food that they eat. The iron overload accumulates in organs in the body. When excess iron deposits accumulate in the liver, they can cause cirrhosis.

Other Hereditary Disorders. Other inherited diseases that can cause cirrhosis include Wilson's disease (which causes an accumulation of copper in the body), alpha-1 antitrypsin deficiency (a genetic disorder caused by defective production of a particular enzyme), and glycogen storage diseases (a group of disorders that cause abnormal amounts of glycogen to be stored in the liver).

Other Causes

• Schistosomiasis, a disease caused by a parasite found in the Asia, Africa, and South America.
• Long-term or high-level exposure to certain chemicals and drugs, including arsenic, methotrexate, toxic doses of vitamin A, and certain types of prescription medication.

Cirrhosis is divided into stages: Compensated and decompensated.

• Compensated cirrhosis means that the body still functions fairly well despite scarring of the liver. Many people with compensated cirrhosis experience few or no symptoms.
• Decompensated cirrhosis means that the severe scarring of the liver has damaged and disrupted essential body functions. Patients with decompensated cirrhosis develop many serious and life-threatening symptoms and complications.

Early symptoms of compensated cirrhosis may include:

• Fatigue and loss of energy
• Loss of appetite and weight loss
• Nausea or abdominal pain
• Spider angiomas may develop on the skin. These are pinhead-sized red spots from which tiny blood vessels radiate.

As cirrhosis progresses to a decompensated stage, patients may develop the following symptoms:

• Fluid buildup in the legs and feet (edema) and in the abdomen (ascites). (Ascites is associated with portal hypertension, which is described in the Complications section of this report.)
• Jaundice. This yellowish cast to the skin and eyes occurs because the liver cannot process bilirubin for elimination from the body.

• Itching. Itching (pruritus) develops from buildup of bile products.
• The palms of the hands may be reddish and blotchy, a condition known as palmar erythema
• In men, swelling of breasts or shrinkage of the testicles may occur.
• Easy bruising and excessive bleeding may occur.

A damaged liver affects almost every bodily process, including the functions of the digestive, hormonal, and circulatory systems. Decompensated cirrhosis increases the risk of serious and potentially life-threatening complications. (Once decompensation occurs, mortality rates without liver transplantation can be as high as 85% within 5 years.) The most serious complications are those associated with portal hypertension (increased pressure in the portal vein that carries blood from the intestine to the liver). They include:

• Ascites (fluid buildup in the abdomen)
• Variceal hemorrhage (bleeding in the upper stomach and esophagus from ruptured blood vessels)
• Spontaneous bacterial peritonitis is a form of peritonitis (inflammation of the membrane that lines the abdomen), which is associated with ascites. Other bacterial infections are also a common complication of cirrhosis.
• Hepatic encephalopathy (damage to the brain). Impaired brain function occurs when the liver cannot detoxify harmful substances, and can lead to coma.

Liver cancer is a serious long-term risk with cirrhosis. Other complications also occur.

Ascites

Ascites is fluid buildup in the abdominal cavity. It is uncomfortable and can reduce breathing function and urination. Ascites is caused by a combination of portal hypertension (high pressure in the blood vessels of the liver) and low albumin levels. Albumin is a protein produced by the liver. Although ascites itself is not fatal, it is a marker for severe progression.

Hepatorenal syndrome occurs if the kidneys drastically reduce their own blood flow in response to the altered blood flow in the liver. It is a life-threatening complication of late-stage liver disease that occurs in patients with ascites. Symptoms include dark colored urine and a reduction in volume, yellowish skin, abdominal swelling, mental changes (such as delirium and confusion), jerking or coarse muscle movement, nausea, and vomiting.

Variceal Bleeding

One of the most serious repercussions of portal hypertension is the development of varices, veins that enlarge to provide an alternative pathway for blood diverted from the liver. In most patients, they form in the esophagus. They can also form in the upper stomach. Varices pose a high risk for rupture and bleeding because they are thin-walled, twisted, and subject to high pressure Variceal intestinal bleeding is a life-threatening event. Symptoms include vomiting blood or black and tarry stools.

Spontaneous Bacterial Peritonitis

Spontaneous bacterial peritonitis is a life-threatening bacterial infection of the ascitic fluid. The main symptoms include fever, chills, and abdominal pain.

Hepatic Encephalopathy

Mental impairment is a common event in advanced cirrhosis. In severe cases, the disease causes encephalopathy (damage to the brain), with mental symptoms that range from confusion to coma and death. Hepatic encephalopathy is caused by a buildup in the blood of harmful intestinal toxins, particularly ammonia, which then accumulate in the brain. Encephalopathy can be triggered by many different conditions including internal bleeding, infection, constipation, and dehydration.

Early symptoms of hepatic encephalopathy include forgetfulness, unresponsiveness, and trouble concentrating. Sudden changes in the patient's mental state, including agitation or confusion, may indicate an emergency condition. Other symptoms include bad fruity-smelling breath and tremor. Late stage symptoms of encephalopathy are stupor and eventually coma.

Liver Cancer

People with cirrhosis have an increased risk for hepatocellular carcinoma, a type of liver cancer. Hepatitis B and C, alcoholism, hemochromatosis, and primary biliary cirrhosis -- all causes of cirrhosis -- are some of the major risk factors for liver cancer. Cirrhosis due to hepatitis C is the leading cause of hepatocellular carcinoma, while cirrhosis due to hepatitis B is the leading cause of deaths related to liver cancer.

Other Complications

Kidney Failure. Portal hypertension can cause several secondary complications, including kidney failure.

Osteoporosis. Many patients with cirrhosis develop osteoporosis, a bone-thinning disease. [For more information, see In-Depth Report #18: Osteoporosis.]

Insulin Resistance and Type 2 Diabetes. Cirrhosis causes insulin resistance, a primary feature in type 2 diabetes. As insulin resistance progresses, it causes excess glucose to buildup in the blood, which leads to type 2 diabetes. Type 2 diabetes is also a risk factor for nonalcoholic fatty liver disease, one of the causes of cirrhosis. [For more information, see In-Depth Report #60: Diabetes type 2.]

Heart Problems. Cirrhosis may increase the risk for heart failure and other cardiovascular complications.

A physical examination may reveal the following in a patient with cirrhosis:

• The cirrhotic liver is firm and often enlarged in early stages of the disease. The liver may feel rock-hard. (In advanced stages of cirrhosis, the liver may become small and shriveled.)
• If the abdomen is swollen, the doctor will check for ascites by tapping the flanks and listening for a dull thud and feeling the abdomen for a shifting wave of fluid.

A patient's medical history is another indicator of cirrhosis. Patients with a history of alcoholism, hepatitis B or C, or certain other medical conditions are at risk for cirrhosis.

Other tests (blood tests, imaging tests, liver biopsy) may also be conducted. The results of these tests along with the presence of specific complications (ascites and encephalopathy) are used for calculating the Child-Pugh Classification. This is a staging system (A to C) that helps doctors determine the severity of cirrhosis and predict the development of future complications.

Blood Tests

A patient's medical history can reveal risk factors (such as alcoholism) that warrant screening for conditions such as hepatitis. Blood tests are also performed to measure liver enzymes associated with liver function. Enzymes known as aminotransferases, including aspartate (AST) and alanine (ALT), are released when the liver is damaged. Blood tests may also measure:

• Serum albumin concentration. Serum albumin measures protein in the blood (low levels indicate poor liver function).
• Prothrombin time (PT). The PT test measures in seconds the time it takes for blood clots to form (the longer it takes the greater the risk for bleeding).
• Alkaline phosphatase (ALP). High ALP levels can indicate bile duct blockage.
• Bilirubin. One of the most important factors indicative of liver damage is bilirubin, a red-yellow pigment that is normally metabolized in the liver and then excreted in the bile. In patients with hepatitis, the liver cannot process bilirubin, and blood levels of this substance rise, sometimes causing jaundice.

Imaging Tests

Magnetic resonance imaging (MRI), computed tomography (CT), and ultrasound are all imaging techniques that are useful in detecting and defining the complications of cirrhosis, such as ascites and hepatocellular carcinoma. (However, screening patients with cirrhosis or hepatitis for hepatocellular carcinoma has not yet been proven to be beneficial. The National Cancer Institute recommends against it.) These imaging tests can also provide information on the extent of liver damage.

Click the icon to see an image of an MRI scan.

Click the icon to see an image of a CT scan.

Liver Biopsy

A liver biopsy is the only definite method for confirming a diagnosis of cirrhosis. It also helps determine its cause, treatment possibilities, the extent of damage, and the long-term outlook. For example, hepatitis C patients who show no significant liver scarring when biopsied may have a low risk for cirrhosis.

The biopsy may be performed using various approaches, including:

• Percutaneous Liver Biopsy. This approach uses a needle inserted through the abdomen to obtain a tissue sample from the liver. Various forms of needles are used, including those that use suction or those that cut out the tissue. If cirrhosis is suspected, a cutting needle is the better tool. This approach should not be used in patients with bleeding problems, and it must be used with caution in patients with ascites or severe obesity.

Click the icon to see an image of liver biopsy.

• Transjugular Liver Biopsy. This approach uses a catheter (a thin tube) that is inserted in the jugular vein in the neck and threaded through the hepatic vein (which leads to the liver). A needle is passed through the tube, and a suction device collects liver samples. This procedure is risky but may be used for patients with severe ascites.
• Laparoscopy. This procedure requires a small abdominal incision through which the doctor inserts a thin tube that contains small surgical instruments and a tiny camera to view the surface of the liver. This is generally reserved for staging cancer or for ascites with unknown causes.

Other Tests Used to Detect Complications of Cirrhosis

Endoscopy. Some doctors recommend endoscopy for patients newly diagnosed with mild-to-moderate cirrhosis in order to screen for esophageal varices. (These are enlarged veins in the esophagus that increase the risk for bleeding). In this test, a fiber optic tube is inserted down the throat. The tube contains tiny cameras to view the inside of the esophagus, where varices are most likely to develop.

Paracentesis. If ascites is present, paracentesis is performed to determine its cause. This procedure involves using a thin needle to withdraw fluid from the abdomen. The fluid is tested for different factors to determine the cause of ascites:

• Bacteria cultures and white blood cell counts. (These are used to determine the presence of infection.)
• Protein levels. Low levels of protein in the fluid plus a low white blood cell count suggest that cirrhosis is the cause of the ascites.

Cirrhosis is an irreversible condition. Treatment goals are to slow the progression of liver damage and reduce the risk of further complications. There are currently no drugs available to treat liver scarring, although researchers are investigating various antifibrotic drugs.

Dietary and Lifestyle Changes

All patients with cirrhosis can benefit from certain types of lifestyle interventions. These include:

• Stop drinking alcohol. It is very important for people with cirrhosis to completely abstain from alcohol.
• Restrict dietary salt. Salt can increase fluid buildup in the body.
• Eat a healthy diet. People with cirrhosis are typically malnourished and require increased calories and nutrients. A dietician may help provide you with dietary guidelines.
• Get vaccinations. Patients with cirrhosis should ask their doctors which vaccinations (such as hepatitis A, hepatitis B, influenza, pneumococcal pneumonia) they need.
• Discuss all medications with your doctor. Before you take any medications, (including nonprescription pain relievers such as acetaminophen, aspirin, naproxen, and ibuprofen), ask your doctor if they are safe for you. Liver damage affects the metabolization of drugs.
• Inform your doctor of any herbs or supplements you are considering taking. Certain types of herbal remedies (kava, chaparral, kombucha mushroom, mistletoe, pennyroyal, and some traditional Chinese herbs) can increase the risk for liver damage. Although some herbs, such as milk thistle (silymarin) have been studied for possible beneficial effects on liver disease, there is no scientific evidence to show that they can help.

Treatment of Underlying Conditions

Treatment for cirrhosis depends on the cause of cirrhosis.

Chronic Hepatitis. Many types of antiviral drugs are used to treat chronic hepatitis B, including pegylated interferon, nucleoside analogs, and nucleotide analogs. Patients with chronic hepatitis C are treated with combination therapy with pegylated interferon and ribavarin. [For more information, see In-Depth Report #59: Hepatitis.]

Autoimmune Hepatitis. Autoimmune hepatitis is treated with the corticosteroid prednisone and also sometimes immunosuppressants, such as azathioprine (Imuran).

Bile Duct Disorders. Ursodeoxycholic acid (Actigall), also known as ursodiol or UDCA, is the standard drug used for treating primary biliary cirrhosis. Several studies have reported that it slows progression and helps prevent the need for liver transplantation. However, it has no effect on symptoms, including itching and fatigue. Itching is usually controlled with cholesterol drugs such as cholestyramine (Questran) and colestipol (Colestid).

Nonalcoholic Fatty Liver Disease (NAFLD) and Nonalcoholic Steatohepatitis (NASH). Weight reduction through diet and exercise, and diabetes and cholesterol management are the primary approaches to treating these diseases. Investigators are also studying whether various drugs used to treat type 2 diabetes may help treat NAFLD and NASH.

Hemochromatosis. Hemachromatosis is treated with phlebotomy, a procedure that involves removing about a pint of blood once or twice a week until iron levels are normal.

Liver Transplantation

When cirrhosis progresses to end-stage liver disease, patients may be candidates for liver transplantation. Patients with liver cancer that has not spread beyond the liver are also candidates for transplant.

Current 5-year survival rates after liver transplantation are about 70%. Patients also report improved quality of life and mental functioning after liver transplantation. Patients should seek medical centers that perform more than 50 transplants per year and produce better-than-average results.

A scoring system called Model for End-Stage Liver Disease (MELD) is used to determine which patients are most in need of a donor liver. A MELD score predicts 3-month survival based on laboratory tests of creatinine, bilirubin, and blood-clotting time. Priority is given to patients who are most likely to die without a liver transplant.

Unfortunately, there are many more patients waiting for liver transplants than there are available organs. Patients may also want to consider living-donor liver transplantation. In living-donor transplantation, surgeons replace the patient's diseased liver with a part of the liver taken from a donor. The donor's liver regenerates to full size within a few weeks of surgery, and the recipient's liver also regrows. This procedure produces excellent results for patients, but there are some risks for the donor.

Transplantation surgery generally takes 4 - 12 hours to perform, and patients stay in the hospital for up to 3 weeks after the surgery. Most patients return to normal or near-normal activities 6 - 12 months following the transplant. For the rest of their lives, patients need to take immunosuppressive medication to prevent rejection.

Liver Transplantation in Patients with Hepatitis. One of the primary problems with many hepatitis patients is recurrence of the virus after transplantation. Recurrence typically occurs with hepatitis C. Viral recurrence can also occur with hepatitis B. In 2007, the Food and Drug Administration (FDA) approved HepaGram B, an immune globulin, to prevent recurrence of hepatitis B after transplantation. Patients need to receive HepaGram B injections on a lifelong basis.

Liver Transplantation for Patients with Primary Biliary Cirrhosis. Patients who require transplantation for primary biliary cirrhosis are those who develop major complications of portal hypertension and liver failure or who have poor quality of life and short survival without the procedure. Survival rates after transplantation are excellent.

Liver Transplantation for Patients with Autoimmune Hepatitis. The outlook is also good for patients who have autoimmune hepatitis who require a transplant. Survival rates are about 90% after 1 year, and 70 - 80% after 5 years. Rejection usually occurs in those patients whose immune systems are very compromised.

Liver Transplantation for Patients with Alcoholism. Liver transplantation is generally not recommended for patients with active alcohol or drug abuse addictions.

Click the icon to see an illustrated series detailing a liver transplant.

Treatment of Ascites

First-line treatment of patients with ascites (fluid accumulation in the abdomen) involves:

• Dietary salt restriction (no more than 1,500 mg/day of sodium)
• Drug treatment with diuretics, usually spironolactone (Aldactone) and furosemide (Lasix).
• Complete abstention from alcohol
• Fluid restriction is usually not necessary unless sodium levels in the blood are low.

Treatment for Recurring or Refractory Ascites. Patients with ascites that does not respond to standard diuretics after a month (refractory ascites) may require procedures to reduce fluid:

• Large-volume paracentesis may be used for ascites refractory to medical treatment or when complications are present. It involves removing large volumes of fluid through a tube in the abdomen.
• Transjugular intrahepatic portosystemic shunt (TIPS) uses a stent placed in veins in the middle of the liver to keep open a passage connecting the hepatic and portal veins. In the procedure, 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. The surgeon makes an incision in the hepatic vein in the liver and creates a connection to the portal vein. The stent is inserted into this connecting vein to act as a shunt and reroute blood around the scarred liver. TIPS is used for patients with refractory ascites who may require a transplant. In general, TIPS should be a second-line option for ascites that does not respond to diuretics.
• Peritoneovenous shunting is an older, more invasive, procedure involving insertion of a tube 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 paracentesis, TIPS, or liver transplantation.

Treatment of Spontaneous Bacterial Peritonitis

Patients with ascites who have high white blood cell counts should receive intravenous antibiotic therapy (usually cefotaxime). Patients who have had an episode of spontaneous bacterial peritonitis are treated with long-term antibiotic therapy of norfloxacin (Noroxin) or trimethoprim/sulfamethoxazole (such as Bactrim or Septra) to prevent further infection.

Treatment of Hepatorenal Syndrome

Hepatorenal syndrome can occur in patients with ascites. This is a life-threatening condition in which the kidneys fail in trying to compensate for altered blood flow in the liver. Patients with hepatorenal syndrome are treated with intravenous infusion of albumin. Drug therapy includes oral midodrine (ProAmatine) and octreotide (Sandostatin). Studies suggest that the vasoconstrictor drug terlipressin may be an effective treatment in combination with albumin for hepatorenal syndrome.

Treatment of Hepatic Encephalopathy

The first step in managing encephalopathy (damage to the brain) is to treat any precipitating cause, such as:

• High ammonia levels
• Bleeding
• Low oxygen
• Dehydration
• Infection
• Use of sedatives

A protein-restricted diet may be used to lower ammonia production. The laxative lactulose is given as a syrup or enema is given to empty the bowels and to help improve mental status. The antibiotic neomycin may be added for patients who do not improve with lactulose alone. Rifaximin (Xifaxan), another antibiotic, was approved in 2005 for treatment of hepatic encephalopathy.

Treatment of Variceal Bleeding

Primary Prevention. Nonselective beta-blocker drugs, which are used to treat high blood pressure, are given to reduce portal hypertension (high pressure in the portal vein) and prevent variceal bleeding in patients with cirrhosis who have small varices and risk factors for hemorrhage. Propanolol (Inderal) or nadolol (Corgard) are the standard beta-blockers used for variceal prevention.

Patients with medium-to-large varices that have not bled but have a high risk for hemorrhage may be treated with either these beta-blocker drugs, or with a surgical procedure called endoscopic variceal ligation (EVL). EVL is also called band ligation. Endoscopic procedures use a tube inserted down through the esophagus, which contains microcameras and tiny instruments. In EVL, latex bands are wrapped around the bleeding varices, which shut off the blood supply.

EVL as preventive therapy may also be considered for patients who are not appropriate candidates for beta-blocker therapy. The American College of Gastroenterology and the American Association for the Study of Liver Diseases does not recommend other types of therapy such as nitrate drugs, shunts, or sclerotherapy as primary prevention of variceal bleeding.

Treatment. Variceal hemorrhage is an emergency situation. The first step is to immediately achieve normal blood clotting (hemostasis) in order to stop the current bleeding episode. Patients almost always need blood transfusions.

The primary treatment for variceal hemorrhage is drug therapy with ocreotide (Sandostatin). This drug is given for 3 - 5 days after a diagnosis is made, as this time period poses the greatest risk for rebleeding. Drug therapy is combined with endoscopic therapy. Endoscopic variceal ligation (band ligation) is usually the preferred method. An alternative procedure is endoscopic sclerotherapy. In endoscopic sclerotherapy, the endoscopic tube is inserted through the mouth and a sclerosant (a solution that toughens the tissue around the variceal blood vessels) is injected to stop the bleeding.

If these treatments do not successfully control variceal bleeding, or bleeding recurs, a transjugular intrahepatic portosystemic shunt (TIPS) procedure is performed. (For more information on TIPS, see Treatment of Ascites above.) TIPS is not useful as the first choice for stopping an initial bleeding episode or for preventing rebleeding since it poses a high risk for encephalopathy.

Another procedure, called balloon tamponade, may be used to temporarily control bleeding prior to the TIPS procedure. Balloon tamponade has been available for years, but it is now used only for bleeding that cannot be controlled by drugs or endoscopy. It uses 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. Balloon tamponade poses a risk for serious and potentially lethal complications, the most dangerous being rupture of the esophagus. For this reason, balloon tamponade is used only for patients with uncontrollable bleeding.

Secondary Prevention. Patients who survive an episode of variceal bleeding need to be treated with drugs to prevent bleeding recurrence. Patients are prescribed either a combination of a nitrate drug [such as isosorbide (Ismo), which is used to treat angina] and a nonselective beta-blocker (propanolol or nadolol) or a beta-blocker alone. Patients are also given several sessions of endoscopic variceal ligation over the course of several months. The TIPS procedure may be recommended for patients who experience recurrent bleeding despite drug and endoscopic therapy.

• www2.niddk.nih.gov -- National Institute of Diabetes and Digestive and Kidney Diseases
• www.aasld.org -- American Association for the Study of Liver Diseases
• www.liverfoundation.org -- American Liver Foundation
• www.gastro.org -- American Gastrointestinal Association
• www.cdc.gov/ncidod/diseases/hepatitis -- Centers for Disease Control and Prevention, Hepatitis
• www.hepfi.org -- Hepatitis Foundation International
• www.organdonor.org -- National Transplant Society
• www.unos.org -- United Network for Organ Sharing
• www.organdonor.gov -- US government organ donor site

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The first step in managing encephalopathy (damage to the brain) is to treat any precipitating cause, such as:

• High ammonia levels
• Bleeding
• Low oxygen
• Dehydration
• Infection
• Use of sedatives

Some studies indicate that manganese poisoning may be partially responsible for encephalopathy in cirrhosis. Studies are needed to determine if drugs that remove manganese improve this complication.

Eliminating Ammonia

Ammonia is the leading toxin in causing encephalopathy related to cirrhosis. Mild encephalopathy is managed by directing therapy toward eliminating ammonia in the intestine:

• The first step is to restrict animal protein, substituting meats and dairy products with vegetable protein, such as soy, and amino acid supplements.
• Enemas, which clean out the intestine, may be effective.
• Lactulose (Cephulac, Chronulac, Constulose, Duphalac, Enulose) and lactitol, known as disaccharides, help lower blood ammonia levels and have been shown to be effective in improving cognitive function and quality of life in people with mild encephalopathy.
• Antibiotics, such as metronidazole, rifamycin, or neomycin, are effective in reducing levels of ammonia-producing bacteria in the intestine, although long-term use of these drugs can cause toxic side effects. Rifaximin (Xifaxan), another antibiotic, was approved in 2005 for treatment of hepatic encephalopathy.
• L. acidophilus is the probiotic found in live culture yogurt. Researchers are studying whether L. acidophilus food or supplements can aid in improving liver and cognitive functions.
• Researchers are investigating whether exercise can help remove ammonia from the body and improve encephalopathy.

Investigational Drugs. Certain drugs, such as rifaximin (Xifaxan) and flumazenil (Mazicon, Romazicon), are under investigation for treating encephalopathy. Flumazenil is typically administered to counteract the effects of sedatives.

Nearly all patients with ascites (fluid accumulation in the abdomen) can benefit from the following measures:

• Abstaining from alcohol. (Sometimes abstaining from alcohol is enough to improve 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-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 - 2 pounds per day, but there is no limit for patients with massive swelling.

Doctors often recommend bed rest for patients with ascites, but 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 (refractory ascites), 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 - 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 blood vessels, may be as effective.
• If the ascites does not respond to treatments, the patient may need paracentesis every 2 weeks or more frequently, and up to 10 liters may need to be removed.

Patients who need this procedure are probably not complying with dietary requirements.

Transjugular Intrahepatic Portosystemic Shunt. 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.

Peritoneovenous Shunting. Peritoneovenous 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 with ascites. This is a life-threatening condition in which the kidneys fail in trying to compensate for altered blood flow in the liver. Studies suggest that terlipressin may be an effective treatment in combination with albumin for hepatorenal syndrome.

Investigational Drugs

Researchers are testing certain drugs that may correct the imbalances in circulation that lead to portal hypertension and ascites. Of particular interest are drugs 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 Transplantation

The 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.

Preventing an Initial Bleeding Episode. About half of patients with mild-to-moderate cirrhosis have esophageal varices (enlarged veins in the esophagus). In such patients, the risk for bleeding within 2 years is as high as 35%. Bleeding is fatal in half of these patients. In general, experts recommend preventive drugs for 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 doctor should first be certain that bleeding is caused by portal hypertension and ruptured varices and not by other conditions. For example, patients with cirrhosis 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 normal blood clotting (hemostasis) in order to stop the current bleeding episode and prevent early recurrence, which typically occurs 3 - 5 days after a bleeding episode.

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

• Drugs. Either octreotide or vasopressin are typically used to reduce portal pressure and blood flow.
• Endoscopy. Endoscopy involves insertion of a thin tube containing a tiny camera followed by surgery 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 suggested that it is no more effective than drugs for stopping 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. Beta-blocker drugs are typically used, although they are not effective for many patients.

Preventing Complications. The patient 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 drug, 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 2 years and most likely longer to sustain a survival advantage.

Other Drugs. Other drugs 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 appear to prevent rebleeding more effectively than beta-blockers alone. It is not clear if the combination improves any other aspects of the disease. The nitrate may also be an alternative drug for patients who cannot tolerate beta-blockers. Studies have failed to show any survival advantage, however, when isosorbide mononitrate is used alone.
• 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 Drugs. Somatostatin is a natural hormone that constricts blood vessels. This drug or synthetic derivatives (octreotide and vapreotide) may be more effective than the common procedure, endoscopic sclerotherapy, for controlling bleeding. No single drug is more effective than another. Their benefits for improving overall survival, however, are still uncertain, and a major 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 study, but it is short acting.
• Octreotide (Sandostatin) is a derivative of somatostatin and is longer acting. It has largely replaced the older drug. It is very safe, even for heart patients, and has few serious side effects.
• Vapreotide (Octastatin) also resembles somatostatin. One 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 5 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 a bridge for patients waiting for liver transplantation.

Endoscopic Procedures Used to Stop Bleeding and Prevent Recurrence

Endoscopic procedures use a tube inserted down through the esophagus, containing 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 are 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 uses argon gas to deliver electric currents that coagulate and stop bleeding.

Endoscopic Sclerotherapy. Endoscopic sclerotherapy is only effective against bleeding in the esophagus. The endoscopic tube is inserted through the mouth. A sclerosant (a solution that toughens the tissue around the variceal blood vessels) is injected to stop the bleeding. The procedure is repeated over a period of 2 - 3 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 it is now used only for bleeding that cannot be controlled by drugs or endoscopy. It uses 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. Doctors do not recommend shunts as elective surgery for high-risk patients who are candidates for liver transplantation, since shunts make this operation more difficult.

Transjugular Intrahepatic Portosystemic Shunt.A transjugular intrahepatic portosystemic (or portal-systemic) shunt (TIPS) 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 for only patients who:

• 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.

• www2.niddk.nih.gov -- National Institute of Diabetes and Digestive and Kidney Diseases
• www.aasld.org -- American Association for the Study of Liver Diseases
• www.liverfoundation.org -- American Liver Foundation
• www.gastro.org -- American Gastrointestinal Association
• www.cdc.gov/ncidod/diseases/hepatitis -- Centers for Disease Control and Prevention, Hepatitis
• www.hepfi.org -- Hepatitis Foundation International
• www.pbcers.org -- Primary Biliary Cirrhosis Organization
• www.organdonor.org -- National Transplant Society
• www.unos.org -- United Network for Organ Sharing
• www.organdonor.gov -- US government organ donor site

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