Liver Disease | Liver India | Alcoholic Liver Disease

Cirrhosis of the Liver


When the liver gets damaged uniformly by toxins, bile, drugs, alcohol, hepatitis infections or by certain genetic conditions, the normal tissue gets replaced with scars. As the disease progresses the scars coalesce to forming ‘bridging fibrosis’. Several islands of normal liver get trapped within the sea of scar and struggle to regenerate, forming nodules. This state is called cirrhosis and is the final pathway for all progressive chronic liver diseases. The liver cirrhosis is also a progressive state that leads to gradual shrinking of the size of the liver. As the volume of normal functioning liver cells reduce, a state of liver failure ensues. This is manifested as lower levels of the protein albumin and prothrombin, that can be measured by blood tests (serum albumin and prothrombin time). The shrinkage of liver also causes mechanical resistance to flow of blood in the main vein that runs through the liver (portal vein), resulting in the state of portal hypertension. This manifests in patients as fluid accumulation in the belly (ascites) and enlargement of some bypass blood channels in the food pipe (called varices). These enlarged vessels are not built to withstand high pressures and can rupture spontaneously, resulting in life threatening bleeding. Cirrhosis also predisposes the liver to cancer risk. When the liver failure advances it becomes incompatible with life and will need liver replacement. Patients with cirrhosis can be without symptoms for a long time and only suffer when the liver failure advances. Most symptomatic patients will need liver replacement within 4 years and have a death rate of 98% without liver transplant during that period. The symptoms of cirrhosis include severe itching, altered sleep wake cycle, change in hand writing, jaundice, swelling of the legs or abdomen, loss of hair from the body in men, darkening of skin, and bleeding from mouth and nose. The diagnosis is confirmed by blood tests and liver scan.


Causes

Cirrhosis has many causes. In the United States, chronic alcoholism and hepatitis C are the most common causes.


Alcoholic liver disease

To many people, cirrhosis of the liver is synonymous with chronic alcoholism, but in fact, alcoholism is only one of the causes. Alcoholic cirrhosis usually develops after more than a decade of heavy drinking. The amount of alcohol that can injure the liver varies greatly from person to person. In women, as few as two to three drinks per day have been linked with cirrhosis and in men, as few as three to four drinks per day. Alcohol seems to injure the liver by blocking the normal metabolism of protein, fats, and carbohydrates.


Chronic hepatitis C.

The hepatitis C virus ranks with alcohol as the major cause of chronic liver disease and cirrhosis in the United States. Infection with this virus causes inflammation of and low grade damage to the liver that over several decades can lead to cirrhosis.


Chronic hepatitis B and D.

The hepatitis B virus is probably the most common cause of cirrhosis worldwide, but in the United States and Western world it is less common. Hepatitis B, like hepatitis C, causes liver inflammation and injury that over several decades can lead to cirrhosis. The hepatitis D virus is another virus that infects the liver, but only in people who already have hepatitis B.


Autoimmune hepatitis.

This type of hepatitis is caused by a problem with the immune system.


Inherited diseases.

Alpha-1 antitrypsin deficiency, haemochromatosis, Wilson's disease, galactosemia, and glycogen storage diseases are among the inherited diseases that interfere with the way the liver produces, processes, and stores enzymes, proteins, metals, and other substances the body needs to function properly.


Nonalcoholic steatohepatitis (NASH).

In NASH, fat builds up in the liver and eventually causes scar tissue. This type of hepatitis appears to be associated with diabetes, protein malnutrition, obesity, coronary artery disease, and corticosteroid treatment.


Blocked bile ducts.

When the ducts that carry bile out of the liver are blocked, bile backs up and damages liver tissue. In babies, blocked bile ducts are most commonly caused by biliary atresia, a disease in which the bile ducts are absent or injured. In adults, the most common cause is primary biliary cirrhosis, a disease in which the ducts become inflamed, blocked, and scarred. Secondary biliary cirrhosis can happen after gallbladder surgery, if the ducts are inadvertently tied off or injured.


Drugs, toxins, and infections.

Severe reactions to prescription drugs, prolonged exposure to environmental toxins, the parasitic infection schistosomiasis, and repeated bouts of heart failure with liver congestion can each lead to cirrhosis.


Symptoms


As the disease progresses, complications may develop. In some people, these may be the first signs of the disease.


Complications of Cirrhosis

Loss of liver function affects the body in many ways. Following are common problems, or complications, caused by cirrhosis.


Edema and ascites.

When the liver loses its ability to make the protein albumin, water accumulates in the leg (edema) and abdomen (ascites).


Bruising and bleeding

When the liver slows or stops production of the proteins needed for blood clotting, a person will bruise or bleed easily.


Jaundice.

Jaundice is a yellowing of the skin and eyes that occurs when the diseased liver does not absorb enough bilirubin.


Itching.

Bile products deposited in the skin may cause intense itching.


Gallstones.

If cirrhosis prevents bile from reaching the gallbladder, a person may develop gallstones.


Toxins in the blood or brain.

A damaged liver cannot remove toxins from the blood, causing them to accumulate in the blood and eventually the brain. There, toxins can dull mental functioning and cause personality changes, coma, and even death. Signs of the buildup of toxins in the brain include neglect of personal appearance, unresponsiveness, forgetfulness, trouble concentrating, or changes in sleep habits.


Sensitivity to medication.

Cirrhosis slows the liver's ability to filter medications from the blood. Because the liver does not remove drugs from the blood at the usual rate, they act longer than expected and build up in the body. This causes a person to be more sensitive to medications and their side effects.


Portal hypertension

Normally, blood from the intestines and spleen is carried to the liver through the portal vein. But cirrhosis slows the normal flow of blood through the portal vein, which increases the pressure inside it. This condition is called portal hypertension.


Varices

When blood flow through the portal vein slows, blood from the intestines and spleen backs up into blood vessels in the stomach and esophagus. These blood vessels may become enlarged because they are not meant to carry this much blood. The enlarged blood vessels, called varices, have thin walls and carry high pressure, and thus are more likely to burst. If they do burst, the result is a serious bleeding problem in the upper stomach or esophagus that requires immediate medical attention.


Problems in other organs

Cirrhosis can cause immune system dysfunction, leading to infection. Ascites (fluid) in the abdomen may become infected with bacteria normally present in the intestines, and cirrhosis can also lead to kidney dysfunction and failure.


Diagnosis

The doctor may diagnose cirrhosis on the basis of symptoms, laboratory tests, the patient's medical history, and a physical examination. For example, during a physical examination, the doctor may notice that the liver feels harder or larger than usual and order blood tests that can show whether liver disease is present.


If looking at the liver is necessary to check for signs of disease, the doctor might order a computerized axial tomography (CAT) scan, ultrasound, or a scan of the liver using a radioisotope (a harmless radioactive substance that highlights the liver). Or the doctor might look at the liver using a laparoscope, an instrument inserted through the abdomen that relays pictures back to a computer screen.


A liver biopsy will confirm the diagnosis. For a biopsy, the doctor uses a needle to take a small sample of tissue from the liver, then examines it for scarring or other signs of disease.


Treatment

Liver damage from cirrhosis cannot be reversed, but treatment can stop or delay further progression and reduce complications. Treatment depends on the cause of cirrhosis and any complications a person is experiencing. For example, cirrhosis caused by alcohol abuse is treated by abstaining from alcohol. Treatment for hepatitis-related cirrhosis involves medications used to treat the different types of hepatitis, such as interferon for viral hepatitis and corticosteroids for autoimmune hepatitis. Cirrhosis caused by Wilson's disease, in which copper builds up in organs, is treated with medications to remove the copper. These are just a few examples--treatment for cirrhosis resulting from other diseases will depend on the underlying cause. In all cases, regardless of the cause, following a healthy diet and avoiding alcohol are essential because the body needs all the nutrients it can get, and alcohol will only lead to more liver damage.


Treatment will also include remedies for complications. For example, for ascites and edema, the doctor may recommend a low-sodium diet or the use of diuretics, which are drugs that remove fluid from the body. Antibiotics will be prescribed for infections, and various medications can help with itching. Protein causes toxins to form in the digestive tract, so eating less protein will help decrease the buildup of toxins in the blood and brain. The doctor may also prescribe laxatives to help absorb the toxins and remove them from the intestines.


For portal hypertension, the doctor may prescribe blood pressure medication such as a beta-blocker. If varices bleed, the doctor may either inject them with a clotting agent or perform a rubber-band ligation, which uses a special device to compress the varices and stop the bleeding.


When complications cannot be controlled or when the liver becomes so damaged from scarring that it completely stops functioning, a liver transplant is necessary. In liver transplantation surgery, a diseased liver is removed and replaced with a healthy one from an organ donor. About 80 to 90 percent of people survive liver transplantation. Survival rates have improved over the past several years because of drugs such as cyclosporine and tacrolimus, which suppress the immune system and keep it from attacking and damaging the new liver.


What is the Impact of Cirrhosis?

Cirrhosis is the eleventh leading cause of death by disease in the United States. Almost one-half of these are alcohol related. About 25,000 people die from cirrhosis each year. There also is a great toll in terms of human suffering, hospital costs, and the loss of work by people with cirrhosis.


What are the Major Causes of Cirrhosis?

Cirrhosis has many causes. It can result from direct injury to the liver cells (i.e., hepatitis) or from indirect injury via inflammation or obstruction to bile ducts which drain the liver cells of bile. Common causes of direct liver injury include chronic alcoholism (most common cause in the United States), chronic viral hepatitis (types B, C, and D) and auto immune hepatitis. Common causes of indirect injury by way of bile duct damage include primary biliary cirrhosis, primary sclerosing cholangitis and biliary atresia (common cause of cirrhosis in infants).


Less common causes of cirrhosis include direct liver injury from inherited disease such as cystic fibrosis, alpha-1-antitrypsin deficiency, haemochromatosis, Wilson’s disease, galactosemia, and glycogen storage disease.


Two inherited disorders result in the abnormal storage of metals in the liver leading to tissue damage and cirrhosis. People with Wilson’s disease store too much copper in their liver, brain, kidneys, and in the corneas of their eyes.


In another disorder, known as haemochromatosis, too much iron is absorbed, and the excess iron is deposited in the liver and in other organs, such as the pancreas, skin, intestinal lining, heart and endocrine glands.


If a person’s bile duct becomes blocked, this also may cause cirrhosis. The bile ducts carry bile formed in the liver to the intestines, where the bile helps in the digestion of fat.


In babies, the most common cause of cirrhosis due to blocked bile ducts is a disease called biliary atresia. In this case, the bile ducts are absent or injured, causing the bile to back up in the liver. These babies are jaundiced (their skin is yellowed) after their first month of life. Sometimes they can be helped by surgery in which a new duct is formed to allow bile to drain again from the liver.


In adults, the bile ducts may become inflamed, blocked, and scarred due to another liver disease, primary biliary cirrhosis. Another type of biliary cirrhosis also may occur after a patient has gallbladder surgery in which the bile ducts are injured or tied off.


Very rare causes of cirrhosis include: reactions to drugs (e.g., vitamin A, methotrexate, amiodarone) exposure to environmental toxins, and repeated bouts of heart failure with liver congestion.


f after full evaluation of a patient with cirrhosis, the etiology still is not clear, the disease is called "cystogenic cirrhosis." As much as 10 percent of cirrhosis falls into this category.


What are the symptoms of Cirrhosis?

People with cirrhosis often have few symptoms at first. The two major problems that eventually cause symptoms are loss of functioning liver cells and distortion of the liver caused by scarring. The person may experience fatigue, weakness, and exhaustion. Loss of appetite is usual, often with nausea and weight loss. Some patients present with menstrual abnormalities (amenorrhea), impotence, loss of sexual drive or painfully enlarged breasts (in men).


As liver function declines, less protein is made by the organ. For example, less of the protein albumin is made, which results in water accumulating in the legs (edema) or abdomen (ascites). A decrease in proteins needed for blood clotting makes it easy for the person to bruise or to bleed.


In the later stages of cirrhosis, jaundice (yellow skin) may occur, caused by the buildup of bile pigment that is normally passed by the liver into the intestines. Some people with cirrhosis experience intense itching due to bile products that are deposited in the skin. Gallstones often form in persons with cirrhosis because not enough bile reaches the gallbladder.


The liver of a person with cirrhosis also has trouble removing toxins, which may build up in the blood. These toxins can dull mental function and lead to personality changes and even coma (encephalopathy). Early signs of toxin accumulation in the brain may include neglect of personal appearance, unresponsiveness, forgetfulness, trouble concentrating, or changes in sleeping habits.


Drugs taken usually are filtered out by the liver, and this cleansing process is also slowed down by cirrhosis. The liver does not remove the drugs from the blood at the usual rate, so the drugs act longer than expected, building up in the body. People with cirrhosis are often very sensitive to medications and their side effects.


A serious problem for people with cirrhosis is pressure on blood vessels that flow through the liver. Normally, blood from the intestines and spleen is pumped to the liver through the portal vein. But in cirrhosis, this normal flow of blood is slowed, building pressure in the portal vein (portal hypertension). This blocks the normal flow of blood, causing the spleen to enlarge. So blood from the intestines tries to find a way around the liver through new vessels.


Some of these new blood vessels become quite large and are called "varices." These vessels may form in the stomach and esophagus (the tube that connects the mouth with the stomach). They have thin walls and carry high pressure. There is great danger that they may break, causing a serious bleeding problem in the upper stomach or esophagus. If this happens, the patientХs life is in danger, and the doctor must act quickly to stop the bleeding.


How is Cirrhosis Diagnosed?

The doctor often can diagnose cirrhosis from the patient’s symptoms and from laboratory tests. During a physical exam, for instance, the doctor could notice a change in how your liver feels or how large it is. If the doctor suspects cirrhosis, you will be given blood tests. The purpose of these tests is to find out if liver disease is present. In some cases, other tests that take pictures of the liver are performed such as the computerized axial tomography (CAT) scan, ultrasound, and the radioisotope liver/spleen scan.


The doctor may decide to confirm the diagnosis by putting a needle through the skin (biopsy) to take a sample of tissue from the liver. In some cases, cirrhosis is diagnosed during surgery when the doctor is able to see the entire liver. The liver also can be inspected through a laparoscope, a viewing device that is inserted through a tiny incision in the abdomen.


What are the Treatments for Cirrhosis?

Treatment of cirrhosis is aimed to stop the development of scar tissue in the liver and prevent complications. When cirrhosis is due to an identifiable cause, treatment programs may be specific, such as for management of hepatitis B and C, or steroids and immunosuppressive agents for auto-immune chronic active hepatitis.


No matter what the cause of cirrhosis, every patient must avoid all substances, habits, and drugs that may further damage the liver, precipitate complications, or speed the progression to liver failure. Alcohol, in addition to causing cirrhosis, may accelerate the progression of liver scarring due to other causes, such as hepatitis C. All patients with liver disease should not drink alcoholic beverages. Even some non-prescription drugs and vitamins, acetaminophen, in relatively small doses (more than five doses a day) and Vitamin A (more than 25,000 IU/day) may precipitate liver failure. Non-steroidal anti-inflammatory drugs, such as ibuprofen, may precipitate severe bleeding and/or kidney failure.


The cirrhotic patient is at increased risk of contracting other infections that may be more severe than in healthy patients. Immunizations for hepatitis A, B, influenza, and pneumococcal pneumonia are available and should be administered. Raw seafood may contain bacteria that can cause life-threatening infections and therefore should be avoided.


How are the Complications of Cirrhosis Treated?

The abnormal accumulation of fluid may cause swelling of the ankles (edema) and abdomen (ascites). Therefore, patients should reduce the amount of fluid and salt in their diet or use drugs called "diuretics" that mobilize and excrete the excess fluid through the kidneys. Occasionally, the ascites may become infected, a condition known as Spontaneous Bacterial Peritonitis, and require treatment with antibiotics.


When the liver does not efficiently function to cleanse the body of toxins and drugs, the mental state of patients may change dramatically and lead to coma, called Hepatic Encephalopathy. Treatment is directed at reducing the protein in the diet, avoiding sedatives and pain medications, and using laxatives and/or antibiotics to decrease the absorption of toxins from the intestines.


Sometimes, bleeding from the esophagus or stomach caused by abnormal veins (varices) may occur and is a life-threatening emergency requiring hospitalization. Variceal bleeding can usually be controlled with the use of a flexible tube (endoscope) that is inserted through the mouth into the esophagus and stomach and used to inject clotting agents into the veins or to rubberband ligate the varices.


Liver failure refers to the end stage of liver disease and cirrhosis when the liver stops working and cannot support life. Liver failure is difficult to treat and survival is limited. Therefore, patients with any complication of cirrhosis are considered to be at risk of developing liver failure.


When complications develop, it may be possible to manage them. When it is likely that liver failure will develop, some patients with cirrhosis are able to undergo liver transplantation. The treating gastroenterologist may recommend liver transplantation when complications of cirrhosis develop in an attempt to avoid liver failure.


Additional Reading:


Biliary Atresia..

This fact sheet presents information on biliary atresia and cirrhosis, including discussions of diagnosis, treatment, and complications. Available from the American Liver Foundation. 1428 Pompton Avenue, Cedar Grove, NJ 07009. (201) 256-2550 or (800) 223-0179.


Cirrhosis: Many Causes..

This fact sheet presents general information on cirrhosis of the liver, research, and the work of the American Liver Foundation. Available from the foundation.


Clayman, CB, ed. The American Medical Association Encyclopedia of Medicine..

New York: Random House, 1989. Authoritative reference guide for patients, with sections on cirrhosis, hepatitis, and other disorders affecting the liver. Widely available in libraries and bookstores.


Primary Biliary Cirrhosis..

This fact sheet presents information on PBC and cirrhosis, including discussions of diagnosis, treatment, and liver transplantation.

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