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Cirrhosis of the Liver
(See also Overview of Fibrosis and Cirrhosis of the Liver.)
Cirrhosis is the widespread distortion of the liver's internal structure that occurs when a large amount of normal liver tissue is permanently replaced with nonfunctioning scar tissue. The scar tissue develops when the liver is damaged repeatedly or continuously.
Symptoms, when they occur, include poor appetite, weight loss, fatigue, and a general feeling of illness.
The diagnosis is based on symptoms and results of a physical examination and sometimes a biopsy.
Doctors treat complications, but the damage due to cirrhosis is permanent.
People who have cirrhosis are at risk of liver cancer, so ultrasonography and, if needed, magnetic resonance imaging (MRI) or computed tomography (CT) are done regularly to check for cancer.
Cirrhosis is a common cause of death worldwide. In the United States, about 35,000 people die of complications of cirrhosis each year.
Various disorders, drugs, or toxins can repeatedly or continuously damage the liver. When the liver is damaged, it attempts to repair itself by forming scar tissue (fibrosis). When fibrosis is widespread and severe, the scar tissue forms bands throughout the liver, destroying the liver’s internal structure and impairing the liver’s ability to regenerate itself and to function. Such severe scarring is called cirrhosis.
Because liver function is impaired, the liver is less able to
The liver processes many drugs, toxins, and body waste products. It breaks them down into substances that are less harmful and/or easier to remove from the body. The liver removes the substances by excreting them in bile, a brown or greenish yellow digestive fluid produced by cells in the liver. When the liver is less able to process these substances, they accumulate in the bloodstream. As a result, the effects of many drugs and toxins, including sometimes serious side effects, are increased. Such side effects may develop even when people are taking a dose that they previously took with no ill effects. Bilirubin is an important body waste product that the liver processes and removes. If the liver cannot process bilirubin quickly enough, it builds up in the blood and is deposited in the skin. The result is jaundice (a yellow coloring of the eyes and skin).
Within the liver, the bile moves into small channels (bile ducts) that join to form larger and larger ducts. These large ducts eventually leave the liver and connect to the gallbladder (which stores bile) or to the small intestine. Bile helps make fats easier to absorb in the intestine and carries toxins and waste products into the intestine so that they can be excreted in stool. When scar tissue blocks bile flow through the bile ducts, fats, including fat-soluble vitamins (A, D, E, and K), are not absorbed as well. In addition, fewer toxins and waste products are eliminated from the body.
Normally, a large part of bile (bile salts) is reabsorbed into the bloodstream from the intestine and circulated back to the liver. The liver extracts the bile salts and reuses them. However, in cirrhosis, the liver cannot extract bile salts normally. As a result, the liver cannot produce as much bile, further interfering with digestion and elimination of toxins and waste products.
In addition to interfering with liver function, scar tissue also can block blood flow into the liver from the portal vein (which carries blood from the intestine to the liver). The blockage results in high blood pressure in the portal vein (portal hypertension). Portal hypertension leads to high blood pressure in the veins connected to the portal vein, including veins in the stomach, esophagus, and rectum.
As scarring progresses, the liver shrinks.
In the United States and other developed countries, the most common causes of cirrhosis are
One way that chronic alcohol abuse damages the liver is by causing fat to accumulate (fatty liver). Fatty liver that is not caused by alcohol (called nonalcoholic fatty liver) usually occurs in people who are overweight and/or have diabetes.
Any disorder, drug, or toxin that causes fibrosis (see Table: Some Conditions and Drugs That Can Cause Fibrosis of the Liver) can cause cirrhosis. Some specific causes include certain hereditary metabolic disorders, such as iron overload (hemochromatosis) and alpha-1 antitrypsin deficiency, and disorders that damage the bile ducts, such as primary biliary cirrhosis and primary sclerosing cholangitis.
In many parts of Asia and Africa, cirrhosis often results from
Many people with cirrhosis have no symptoms and appear to be well for years. About one third never develop symptoms.
Others feel tired and generally unwell, lose their appetite, and lose weight:
Their fingertips may enlarge (called clubbing).
Jaundice can develop, making the skin and whites of the eyes look yellow and the urine look dark like cola.
When fats and fat-soluble vitamins are poorly absorbed, stools may be light-colored, soft, bulky, oily-looking, and unusually foul-smelling (called steatorrhea).
Many people are undernourished and lose weight because they have lost their appetite and because fats and vitamins are poorly absorbed. People may have a reddish purple rash of tiny dots or larger splotches, caused by bleeding from small blood vessels in the skin.
If the liver function has been impaired for a long time, people may itch all over, and small yellow bumps of fat can be deposited in the skin or eyelids.
Other symptoms may develop if cirrhosis is caused by chronic alcohol abuse or if people have a chronic liver disorder:
Muscles waste away (atrophy).
The palms become red (called palmar erythema).
The tendons of the hand shrink, causing the fingers to curl up (called Dupuytren contracture).
Small spiderlike blood vessels (spider angiomas) appear in the skin.
Salivary glands in the cheeks enlarge.
The nerves outside the brain and spinal cord (peripheral nerves) malfunction (called peripheral neuropathy).
Men may have enlarged breasts (gynecomastia) and shrunken testes (testicular atrophy) because the damaged liver cannot break down estrogens (female hormones) as it usually does. Hair in the armpits decreases.
Advanced cirrhosis causes additional problems.
Portal hypertension (high blood pressure in the portal vein) is the most serious complication. When it causes blood to back up in the veins connected to it, these veins may enlarge and twist (called varicose veins). Varicose veins may develop at the lower end of the esophagus (esophageal varices—see Portal Hypertension), in the stomach (gastric varices), or in the rectum (rectal varices). Varicose veins are fragile and prone to bleeding. People may vomit large amounts of blood if esophageal or gastric varices bleed (see Gastrointestinal Bleeding). If bleeding is slow and continues for a long time, it may cause anemia. If bleeding is rapid and more severe, it may result in shock and death.
Portal hypertension plus impaired liver function may lead to accumulation of fluid within the abdomen (ascites). As a result, the abdomen swells and may feel tight. Also, the fluid in the abdomen may become infected (called spontaneous bacterial peritonitis).
Over time, poor absorption of fats, particularly fat-soluble vitamins, can lead to several problems. When vitamin D is poorly absorbed, osteoporosis can develop. When vitamin K (which helps blood clot) is poorly absorbed, people may bleed more easily.
Cirrhosis causes other problems that can interfere with how blood clots (cause disordered blood clotting). Some problems make people more likely to bleed. For example, the spleen may enlarge. The enlarged spleen may trap blood cells and platelets. Thus, fewer platelets (which help blood clot) are in the bloodstream. Also, the damaged liver is less able to produce the proteins that help blood clot (clotting factors).
However, some liver problems make blood more likely to clot. For example, the damaged liver is less able to produce the substances that prevent blood from clotting too much. Thus, blood clots may form in blood vessels (such as veins of the legs).
Liver failure can also cause brain function to deteriorate (called hepatic encephalopathy) because the damaged liver can no longer remove toxic substances from the blood. These toxic substances then travel through the bloodstream and build up in the brain.
Liver cancer (hepatocellular carcinoma, or hepatoma) can develop, particularly when cirrhosis is due to chronic hepatitis B or hepatitis C, chronic alcohol abuse, hemochromatosis, alpha-1 antitrypsin deficiency, or glycogen storage diseases.
Complications of Cirrhosis
Cirrhosis is usually strongly suspected based on symptoms, results of the physical examination, and a history of risk factors for cirrhosis such as chronic alcohol abuse. Often during the physical examination, a doctor notices problems that typically result from cirrhosis, such as an enlarged spleen, a swollen abdomen (indicating ascites), jaundice, or a rash indicating bleeding in the skin. Doctors typically then do tests to look for other disorders that can cause similar symptoms.
Blood tests to evaluate the liver are done. Results are often normal because these tests are relatively insensitive and the liver can function for a long time despite damage. The liver can carry out essential functions even when its function is reduced by 80%. A complete blood count (CBC) is done to check for anemia and other blood abnormalities. Blood tests are done to check for hepatitis and often other possible causes.
Imaging tests cannot accurately identify cirrhosis but can sometimes show some of its complications:
If the diagnosis is still uncertain, a liver biopsy (removal of a tissue sample for examination under a microscope) is usually done to confirm it. Biopsy and sometimes blood tests can also help doctors determine the cause of cirrhosis.
If cirrhosis is confirmed, ultrasonography is done every 6 months to check for liver cancer. If ultrasonography detects abnormalities that suggest cancer, doctors do magnetic resonance imaging (MRI) or CT after a dye that can be seen on x-rays (contrast agent) is injected.
When cirrhosis is confirmed, endoscopy of the upper digestive tract (inserting a flexible viewing tube) is done to check for varices. This test is repeated every two to three years. It is done more often if varices are detected.
Cirrhosis is permanent and usually progressive, but how quickly it will progress is often hard to predict. The outlook for people with cirrhosis depends on the cause, severity, presence of other symptoms and disorders, and effectiveness of treatment.
Stopping all consumption of alcohol prevents further scarring in the liver but cannot reverse damage already done. If people continue to drink alcohol—even small amounts—cirrhosis progresses, causing serious complications.
Once a major complication (such as vomiting of blood, accumulation of fluid within the abdomen, or deterioration in brain function) occurs, the outlook is grim.
There is no cure for cirrhosis. The liver is damaged permanently and will never be normal again.
The best approach is to stop cirrhosis in its earliest stages by correcting or treating the cause. Treating the cause usually prevents any further damage and sometimes causes the person's condition to improve.
People are given the hepatitis A and B vaccines if they have not had them before.
To prevent cirrhosis from progressing, people should stop drinking alcohol completely (see Alcohol : Treatment). Withdrawal symptoms, if they occur, are treated.
People must inform their doctor of all the drugs they are taking, including over-the-counter drugs, herbal products, and dietary supplements, because the damaged liver may not be able to process (metabolize) them. If people need to take drugs that are metabolized by the liver, much smaller doses are used to avoid further damage to the liver. Also, people may be taking a drug that can damage the liver and thus contribute to cirrhosis. Such drugs are stopped whenever possible, and another drug is substituted if needed.
For hemochromatosis, bloodletting is the best treatment.
Chronic hepatitis is treated with drugs, such as antiviral drugs or corticosteroids, and sometimes liver transplantation.
For complications, treatment includes
For accumulation of fluid within the abdomen (when cirrhosis is advanced): Restriction of sodium in the diet because excess sodium can contribute to fluid accumulation
For vitamin deficiencies: Supplemental vitamins
For bleeding from the digestive tract varices: Beta-blockers to lower blood pressure in the liver's blood vessels and/or application of elastic bands to tie off the bleeding blood vessels (called endoscopic banding, or ligation)
To place the bands, doctors use a viewing tube (endoscope) inserted through the mouth. If beta-blockers or band ligation cannot be used or is unsuccessful, doctors may use one of the following procedures:
Endoscopic cyanoacrylate injection: Doctors pass an endoscope through the mouth and into the digestive tract. Working through the endoscope, they inject cyanoacrylate into the bleeding vein. The cyanoacrylate closes the blood vessel, and bleeding stops.
Balloon-occluded retrograde transvenous obliteration: After injecting a local anesthetic, doctors make a small incision in the skin over a large vein, typically in the neck or groin. Then they insert a thin, flexible tube (catheter) with a deflated balloon at its tip into the vein and thread the tube to the site of the bleeding. The balloon is inflated to block blood flow. Then a substance that causes scar tissue to form is injected in or near the vein to block it and stop the bleeding.
Transjugular intrahepatic portosystemic shunting (TIPS): Doctors insert a catheter into a vein in the neck and, using x-rays to guide them, thread the catheter to veins in the liver. The catheter is used to create a passage (shunt) that connects the portal vein (or one of its branches) directly with one of the hepatic veins, which carry blood from the liver to the body's largest vein, which returns blood to the heart. Thus, most of the blood that normally goes to the liver is rerouted to bypass the liver. This procedure lowers blood pressure in the portal vein because pressure is lower in the hepatic veins. By reducing this pressure, TIPS helps reduce bleeding from the veins in the digestive tract and accumulation of fluid within the abdomen.
For suitable candidates, liver transplantation may be done. If transplantation is successful, the transplanted liver typically functions normally, and the symptoms of cirrhosis and liver failure should disappear. Liver transplantation can be lifesaving for people with advanced cirrhosis or liver cancer. Liver transplantation is usually done based on how likely people are to die if they do not receive a liver transplant.
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