CIRRHOSIS

The Liver
The liver is the largest organ in the body, located immediately below the diaphragm and occupying the entire upper right quadrant of the abdomen. In the healthy adult, it weighs about three pounds and is wedge shaped, with the upper part being wider than the lower. The liver is rich in blood, holding about 13% of the body's supply. It is furnished with blood from two large vessels, the portal vein and the hepatic artery. Blood that has circulated through the stomach, spleen, and intestine enters the liver through the portal vein as part of the so-called portal circulation system. The liver extracts nutrients and toxins from this blood, which is then returned through the hepatic vein to the right side of the heart.
The liver performs over 500 vital functions. It processes all of the nutrients that the body requires, including proteins, glucose, vitamins, cholesterol, and fats. It also renders harmless potentially toxic substances, including alcohol, ammonia, nicotine, drugs, and harmful by-products of digestion. The liver synthesizes blood clotting factors and albumin, the major protein in the blood. The liver also affects bilirubin, a yellow-green pigment produced from the breakdown of hemoglobin (the oxygen-carrying component in red blood cells). The liver converts bilirubin into a water-soluble form, which is then excreted into bile. Bile is a green-colored fluid that is formed in the liver and contains, in addition to bilirubin, bile salts, fatty acids, cholesterol and other substances. Bile travels from the liver to the gall bladder, where it is stored until after a meal; at that time it is secreted into the intestines to help digest fat.
These vital processes rely on well-organized liver architecture consisting of bile ducts, blood vessels, working liver tissue (called the parenchyma), and supportive (connective) tissue. The liver has two major lobes (with the right one much larger than the left), which are separated from each other by walls of tough, fibrous connective tissue. The lobes are composed of about 100,000 elegantly patterned lobules made up of liver cells and blood vessels that form microscopic columns. Bracing the corners of each lobule column are three small important structures: an artery, a vein, and a bile duct. The arteries bring oxygen-rich blood to nourish the liver cells. The blood passing through the veins supplies the liver cells with the nutrients and toxins that the liver cells process. Bile drains from tiny canals around the liver cells into the corner ducts, which eventually join to form the large common bile duct that leads from the liver to the gall bladder. A central vein runs down through each column, which collects the blood from the surrounding lobules and acts as a tributary, eventually joining with other veins to form the major hepatic veins. The hepatic veins, in turn, lead into the inferior vena cava, the large vein that conducts the worn-out blood from the liver back to the heart.
Cirrhosis
Cirrhosis is an irreversible sequel to a number of disorders that damage the liver cells and cause fibrosis (scarring). Often this process is accompanied by random clusters of regenerated liver cells that develop throughout the liver, usually forming nodules (lumps) around the scarred areas. Eventually, this damaging pattern becomes so extensive that the normal architecture of the liver is distorted. Changes in the way blood and fluid flow in and out of the liver also occur. A substance called nitric oxide is overproduced and this causes the blood vessels to relax and widen, while vessels in other parts of the body, including the kidney, narrow. The small blood vessels and bile ducts in the liver constrict (narrow), so the blood that normally passes into the liver from the intestine backs up through the portal vein and seeks other routes. Twisted swollen veins called varices form in the stomach and lower part of the esophagus. Bile builds up in the blood stream, resulting in high levels of bilirubin, which causes a yellowish cast in the skin called jaundice. Fluid build-up in the abdomen (called ascites) and swelling in the arms and legs is common. The liver enlarges in the first phases of the disease. In advanced stages, however, the liver sometimes shrinks, a condition called post necrotic cirrhosis.
Alcoholic Cirrhosis
The liver is particularly endangered by alcohol. In the body, alcohol breaks down into various chemicals, some of which are very toxic in the liver. Alcoholic cirrhosis (also sometimes referred to as portal, Laennec's, nutritional, or micro nodular cirrhosis) is the primary cause of cirrhosis. Recent data suggests that 40 grams of alcohol (1 Standard drink ie; 30 ml contains 10 grams of alcohol/ 1 bottle Beer contains 20 grams) daily for a period of 5 years is enough of cause alcoholic cirrhosis.
Over time, alcohol abuse leads to increased demands for oxygen by the liver and, at the same time, causes fat accumulation that impairs the liver's ability to absorb oxygen. The immune system over-responds by triggering an inflammatory process that damages and finally kills liver cells, a condition called alcoholic hepatitis. During the initial phase, the fat-laden liver becomes greatly enlarged, but it eventually shrinks as web-like scars and small knots of abnormal regenerated liver cells develop, the characteristics of cirrhosis.
Cirrhosis from Chronic Hepatitis
The next leading cause of cirrhosis is chronic hepatitis, either hepatitis B or C. Chronic hepatitis C is the more dangerous form and accounts for one-third of all cirrhosis cases. Viruses or other mechanisms that cause hepatitis produce inflammation in liver cells, resulting in their 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.
Primary Biliary Cirrhosis
Primary biliary cirrhosis accounts for only 0.6% to 2% of deaths from cirrhosis. It is most likely an autoimmune disease; that is, the body's immune system attacks its own liver cells mistaking them for foreign invaders (called antigens). In the case of primary biliary cirrhosis, the cells under attack are in the bile ducts. Liver cells are destroyed as the disease progresses. Some research indicates that this autoimmune process may be triggered by a virus or an unknown intestinal microorganism. Other autoimmune diseases, such as scleroderma or Sjögren's syndrome, may also accompany this form of cirrhosis.
Uncommon Causes of Cirrhosis
Rare conditions that cause cirrhosis include hemochromatosis (iron build-up in liver cells), which is fairly common in people with diabetes, and Wilson's disease (copper build-up in liver cells). Liver damage that results in cirrhosis also may be caused by a number of inherited diseases such as cystic fibrosis, alpha-1 antitrypsin deficiency, galactosemia, and glycogen storage diseases.
Who Gets CirrhosisCirrhosis affects about three million Americans a year. The risk factors for liver injury determine an individual's chances for cirrhosis.
People with Alcoholism
The liver is particularly endangered by alcoholism. About 10% to 35% of heavy drinkers develop alcoholic hepatitis, and 10% to 20% of these individuals develop cirrhosis. In the liver, alcohol is converted to toxic chemicals, such as acetaldehyde, which trigger the production of immune factors called cytokines. In large amounts, these cytokines cause inflammation and tissue injury and are proving to be major culprits in the destructive process in the liver. Not eating when drinking and consuming a variety of alcoholic beverages are also factors that increase the risk for liver damage. People with alcoholism are also at higher risk for hepatitis B and C, potentially chronic liver diseases that can lead to cirrhosis and liver cancer. People with alcoholism should be immunized against hepatitis B; they may need a higher-than-normal dose of the vaccine for it to be effective.
People with Chronic Hepatitis
Risk Factors for Developing Cirrhosis from Hepatitis C. Between 20% and 30% of people with hepatitis C develop cirrhosis after twenty years. Men have a much higher risk than women, and the risk is greatest in older men. Other factors that put a patient at higher risk for developing cirrhosis include alcoholism or co-infection with HIV or hepatitis B. The genetic type of the virus strongly affects severity, with genotype 1 being the most serious and type 2 and 3 posing less danger. (Unfortunately, a 1999 study suggested that nearly three quarters of infected people carry genotype 1.) Men are at higher risk for a poor outlook than women. Large iron stores in the liver occur in about 25% of patients and may also increase the severity of the disease. One study suggested that hepatitis C patients who are overweight, particularly if their fat is distributed in the abdomen (an apple-shape), may be at higher risk for a fatty liver, which in turn is more apt to become scarred and cirrhotic.
Risk Factors for Developing Cirrhosis from Hepatitis B. The great majority of people with chronic persistent hepatitis B have a good long-term outlook, but between 5% and 10% become carriers of the virus and 5% to 10% of these individuals eventually develop cirrhosis. The addition of hepatitis D is a particular danger and increases the risk for cirrhosis.
Risk Factors for Primary Biliary Cirrhosis
Up to 95% of primary biliary cirrhosis cases occur in women, usually around age 50. Those with celiac sprue (an intestinal disorder associated with an allergy to wheat gluten) appear to have a higher risk. Genetic factors are involved, but the inheritance pattern is unclear. A 1999 English study suggested that the disease is on the rise, although it is unclear if this reflects an actual increase or simply a greater awareness of the disorder.
Symptoms Of Cirrhosis
General Symptoms
Fatigue and loss of energy are common early symptoms of cirrhosis, along with loss of appetite and nausea, although many people experience few symptoms at the onset of cirrhosis. Spider angiomas may develop on the skin; these are pinhead-sized red spots from which tiny blood vessels radiate. Patients in later stages develop jaundice, a yellowish cast to the skin and eyes, which is caused when the liver cannot process bilirubin for elimination from the body. The palms of the hands may be reddish and blotchy, a condition known as palmar erythema. Patients may lose body hair. In men with alcoholic cirrhosis, the testicles may atrophy and their breasts may become swollen, sometimes painfully.
Symptoms of Complications
A swollen belly is a sign of ascites, the most common major complication of cirrhosis, which occurs when fluid accumulates in the abdomen. Fever, abdominal pain, and tenderness when the belly is pressed indicate that the fluid is infected. (Infection may occur, however, without any symptoms.) Forgetfulness, unresponsiveness, and trouble concentrating may be early symptoms of hepatic encephalopathy, which is damage to the brain caused by build-up of toxins. 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.
Symptoms Specific to Rare Cases of Cirrhosis
People with primary biliary cirrhosis are subject to severe, general itching and often develop small fatty yellow lumps called xanthomas on the eyelids, hands, and elbows. They may have an unpleasant condition called steatorrhea, in which the feces contain excessive fat, causing them to float and to be very foul smelling. In the rare disorder hemochromatosis, there is often a bronze cast to the skin, an indication of iron build-up. A thin bronze crescent bordering the cornea is called the Kayser-Fleisher ring and is a sign of copper-build up in people with Wilson's disease.
How Serious Is Cirrhosis
General Outlook for Cirrhosis
Cirrhosis is a leading cause of death. The most serious complications of cirrhosis are bleeding, infections, and encephalopathy, damage to the brain. Nearly every bodily process is affected by a damaged liver, including those of the digestive, hormonal, and circulatory systems. Less protein is produced by the liver, for example, which causes fluid build-up, bleeding problems, and susceptibility to infection. Additionally, the liver cannot detoxify harmful substances that accumulate and impair brain function. Cirrhosis is also a cause of liver cancer.
Cirrhosis is irreversible, but the rate of progression can be very slow in some patients depending on its cause and other factors. In patients with hepatitis B, for example, the five-year survival rate after a diagnosis of cirrhosis is 71%. For alcoholics with cirrhosis who abstain, a survival rate of five years or more can be as high as 85%. For those who continue drinking, the chance for living beyond five years is no higher than 60%. Often, however, it is difficult to determine prognosis at the time of diagnosis because the physician is usually unable to tell when cirrhosis first occurred.
About two-thirds of patients with primary biliary cirrhosis never develop symptoms and can have a normal life span. Once symptoms of liver damage, such as jaundice, occur, however, the average survival time declines. In one study of women diagnosed with primary biliary cirrhosis, about 36% developed symptoms over an 11-year period, and 11% either died or required liver transplantation. Unfortunately, researchers are unable to determine specific risk factors that could predict who will develop a severe condition and who won't.
Portal Hypertension and its Complications In cirrhosis, liver cell damage slows down blood flow and blood pressure therefore increases. This pressure causes a back up of blood through the portal vein, a condition called portal hypertension. The effects of portal hypertension can be widespread and serious.
Ascites.
Ascites is fluid build-up in the abdomen usually caused by portal hypertension and is such a critical event in the progression of cirrhosis that some experts refer to the phases of cirrhosis as preascitic and ascitic. Once ascites occurs, only half of patients survive after two years. Some physicians even believe that ascites signals the need for liver transplantation, particularly in patients whose cirrhosis is not due to alcohol. Swelling can also occur in the arms and legs and in the spleen. (Ascites can result from other conditions, and physicians should check for other possibly serious causes, including cancer and infections.) Ascites itself is not fatal, but it is uncomfortable and can reduce breathing function and urination. Of interest is research indicating that nitric oxide is overproduced in cirrhosis; this substance is also associated with a condition called hyperaldosteronism. Aldosterone is a steroid hormone produced in the adrenal gland that regulates sodium and potassium. High amounts (hyperaldosteronism) can result in a fluid electrolyte imbalance called hypokalemic alkalosis (low potassium levels, overly alkaline), which in turn can cause weakness, abnormal heart rhythms, a sense of paralysis, and, in severe cases, encephalopathy.
Variceal Bleeding. One of the most serious repercussions of portal hypertension is the development of varices, blood vessels that enlarge to provide an alternative pathway for blood diverted from the liver. These abnormal blood vessels are thin-walled, often twisted, and are subject to high pressure. Varices often form in the stomach and esophagus (the tube connecting the mouth and stomach). Internal bleeding from these varices occurs in 20% to 30% of all cirrhosis patients. The risk of death from a single episode can reach 70%. Recurrence is common within two weeks of the first episode, but after six weeks, the risk for recurrence is the same as for patients who have not had a bleeding event. Factors that predict bleeding include ascites, encephalopathy, large veins, and marked liver cell abnormalities. It should be noted that moderate to severe exercise may also increase the risk for variceal bleeding. (Taking beta-blockers may reduce this risk.) Some researchers believe that bacterial infection may be a primary factor in triggering a bleeding episode. There are two peak risk times for bleeding: the larger is in the evening, the smaller in the early morning.
Bleeding Disorders
Gastrointestinal (GI) bleeding can occur from abnormal blood clotting, often caused by deficiencies in vitamin K, low levels of clotting proteins, and low counts of platelets (the blood cells that normally initiate the clotting process).
Infections
Bacterial infections are very common in advanced cirrhosis, and may even increase the risk for bleeding. Most bacterial infections, including those in the urinary, respiratory, or gastrointestinal tracts, develop when patients are in the hospital. Abdominal infections are a particular problem in cirrhosis and occur in up to 25% of patients with cirrhosis within a year of diagnosis.
Mental Impairment and 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. The development of encephalopathy is often precipitated by other problems, including gastrointestinal bleeding, constipation, excessive dietary protein, infection, surgery, or dehydration. No single toxin accounts for the mental effects of encephalopathy. A combination of conditions causes this serious complication, such as the build-up in the blood of harmful intestinal toxins, particularly ammonia, and an imbalance of amino acids that effect the central nervous system. Some people believe that alcoholics with cirrhosis are at higher risk for this complication than nonalcoholic cirrhosis patients, but a recent study indicated that the liver disease itself is responsible and alcoholics simply tend to have more severe cirrhosis.
Liver Cancer
Cirrhosis greatly increases the risk for liver cancer, regardless of the cause of cirrhosis. (Although few studies have been conducted on the risk for liver cancer in patients with primary biliary cirrhosis, one study reported an incidence of 2.3%, with the risk being highest in smokers and those also infected with hepatitis C. Another 1999 study also reported an increased risk for cancers in the liver and biliary tract.)
Osteoporosis
Primary biliary cirrhosis is associated with reduced bone growth, partly because of the liver's inability to process vitamin D and calcium and also from some of its treatments. As a result, osteoporosis occurs in 20% to 30% of these patients. Bone loss is also a complication of liver disease in alcoholics and one study indicated that it might also be a complication of cirrhosis caused by hepatitis. Treating osteoporosis in patients with cirrhosis can be complicated. One study found that calcitriol (a form of vitamin D) is especially helpful in preventing bone loss in patients with cirrhosis.
Insulin Resistance Nearly all patients with cirrhosis are insulin resistant. Insulin resistance is a primary feature in type 2 diabetes and occurs when the body is unable to use insulin, a hormone that is important for delivering blood sugar and amino acids into cells and helps determine whether these nutrients will be burned for energy or stored for future use.
Other Complications
One study reported that nearly a quarter of patients with cirrhosis had gallstones. They may also face a higher than average risk for certain abnormal heart rhythms. Peptic ulcers, sleep disorders, and respiratory problems are also more common in people with cirrhosis than in the general population.
How Is Cirrhosis Diagnosed
Physical Examination
The cirrhotic liver is often enlarged. It is also firm and may even feel rock-hard. The left side can often be felt by the physician when pressing on the abdomen. (In advanced stages, however, the liver may become small and shriveled.) If the abdomen is swollen, the physician will tap the flanks and listen for a dull thud and feel for a shifting wave of fluid in the abdomen, indications of ascites.
Biopsy
Some experts are now recommending biopsies for all chronic hepatitis C patients, regardless of severity, because of the risk for liver damage even in patients without symptoms. A liver biopsy is the only definite method for diagnosing 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 appear to have a low risk for cirrhosis. The procedure uses a needle inserted through the abdomen to obtain a tissue sample from the liver. The biopsy may also be performed during Laparoscopy, a procedure that uses a catheter and tiny camera to view the surface of the liver. Biopsies can be dangerous, so they cannot be performed on patients who have test results that indicate clotting problems, on those who have had previous liver biopsies, or who have ascites.
Blood Tests
A number of blood tests may be performed to measure liver function and to help determine the severity and cause of cirrhosis. 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 urine. In patients with hepatitis, the liver cannot process bilirubin, and blood levels of this substance rise, sometimes causing jaundice. Measurements of blood levels of certain liver enzymes are useful for diagnosing cirrhosis. To help determine outlook, experts may use a calculation called a discriminant function (DF), which uses two important measurements: serum albumin concentration and prothrombin time (PT). Serum albumin measures protein in the blood (low levels indicate poor liver function). 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).
Specific Blood Tests for Primary Biliary Cirrhosis. Very high levels of serum alkaline phosphatase, an enzyme produced in the liver, and high levels of immune factors called mitochondrial antibodies are usually present in blood tests of patients with primary biliary blood cirrhosis. Bilirubin measurements appear to be important factors in determining its severity.
Specific Blood Tests for Chronic Hepatitis. Blood tests for chronic hepatitis include measurements of aminotransferase levels, bilirubin levels, and detection of blood clotting problems. High aminotransferase levels are strong signals for the presence of cirrhosis and, in hepatitis C. High levels of a particular aminotransferase known as ALT may indicate a greater risk for progression to liver cancer among cirrhosis patients with hepatitis C. Immunoassays to detect antibodies to specific hepatitis viruses are also performed.
Imaging Tests
A number of imaging tests may be used to diagnose cirrhosis and its complications. Magnetic resonance imaging (MRI), computed tomography (CT), and ultrasound are all imaging techniques that are useful in detecting and defining the extent of cirrhosis. Such tests can reveal ascites, enlarged spleen, irregular liver surface, reversed portal vein blood flow, and liver cancer. Sometimes they can even detect abnormally large blood vessels in the liver. Sometimes liver scans are performed in which a small radioactive tracer is administered and a special camera is used to record information provided by the tracer as it passes through the liver. Arteriography uses dye injected into the hepatic arteries that then shows up on x-ray. Splenoportography uses dye injected into the spleen, which allows the physician to measure portal vein pressure; this procedure is risky.
Hepatic Vein Wedge Pressure
Hepatic vein wedge pressure involves insertion of a catheter into the hepatic veins. The blood pressure in the veins of the liver is then measured; the result is an indicator of portal vein pressure. If pressure is high, cirrhosis is likely. A low measurement is a favorable sign.
Paracentesis
If ascites is present, paracentesis is performed. This procedure involves using a thin needle to withdraw fluid from the abdomen. The fluid is tested for different factors, including protein levels, bacteria cultures, and white blood cell counts. Low levels of protein in the fluid and a low white blood cell count suggest that cirrhosis is the cause of the ascites. The appearance of the fluid is helpful in determining a cause. For example, a cloudy fluid plus a high white blood cell count means an infection is present. Bloody fluid suggests the presence of a tumor.
What Lifestyle Factors Can Help Manage Cirrhosis? A healthy lifestyle is important for everyone, and particularly for people with cirrhosis.
Dietary Factors
Enhancing Nutritional Needs. Because important antioxidant vitamins are depleted in the cirrhotic liver, in any case, any patient with cirrhosis should maintain a diet rich in fresh fruits, vegetables, and whole grains. Additional nutritional supplements may be needed, particularly for the patients with both alcoholism and cirrhosis. In one study, such patients drank Ensure every day as a supplement to their regular diet. After six months they showed significant improvement in many signs of overall health compared to those who didn't consume the beverage. High-quality dietary protein may be especially helpful for patients with ascites and for repairing muscle mass, but excessive protein loads may trigger encephalopathy. Protein solutions have been devised that provide beneficial amino acids without including those that increase this risk. There is no limit on vegetable proteins, such as those from soy.
Salt Restriction. Restricting salt consumption to less than 2,000 mg a day is particularly important for patients with ascites. The less salt the better.
Supplements. In some studies, taking zinc supplements have lowered ammonia levels in some patients who were zinc-deficient, a common problem in cirrhosis. Zinc replacement may reduce frequency and severity of muscle cramps and may even help protect against encephalopathy. Some research suggests that supplements of omega-3 fatty acids (found in fish oil and evening primrose oil) may help protect the diseased liver. Vitamin supplements are not recommended except with the advice of a physician.
Iron Restrictions. Hepatitis C is sometimes associated with abnormally high iron levels. Such patients should avoid iron-rich foods, such as red meats, liver, and iron-fortified cereals, and should avoid cooking with iron-coated cookware and utensils.
Limiting Fluids
Fluid restriction is not usually necessary, but patients with severe ascites should discuss limiting fluid with their physicians.
Exercise
Exercise increases the risk for portal pressure and variceal bleeding; a recent study reported that taking a beta-blocker might reduce this risk, although patients should discuss this with their physician.
What Are The Treatments For Conditions That Cause Cirrhosis?
Treatment for Alcoholism
The only treatment for alcoholic cirrhosis is to stop drinking. Individuals with alcoholic cirrhosis are almost always malnourished and, therefore, require increased calories and rigorous nutritional support, which can improve survival rates. Corticosteroids may be useful for alcoholic hepatitis, an acute condition in which the liver is inflamed, but these drugs are not beneficial after cirrhosis has developed. Drugs under investigation include propylthiouracil and colchicine, which inhibit deposits of collagen, the critical protein building block in connective and scar tissue. Researchers are also investigating drugs that block factors in the immune system called thrombaxanes, which may play an important role in the inflammatory process that kills liver cells in alcoholic cirrhoses.
Treatment for Chronic Hepatitis B or C
Drug treatments for chronic hepatitis B and C are aimed at reducing or preventing liver damage and boosting or modifying the immune system to promote its attack on the viruses. Treatment outcomes are assessed by testing levels of aminotransferase to determine liver damage and using polymerase chain reaction (PCR) tests to detect the amount of virus left. After treatment, however, some patients may have low levels of virus and high indicators of liver damage while others display opposite results. It is not yet clear how to weigh these criteria in evaluating the overall health of the patient.
The important agents for treating chronic hepatitis are interferons (particularly interferon alpha) and nucleoside analogues (ribavirin, lamivudine, famciclovir, and adefovir), which act directly against the virus. They are being used as sole therapy and in combinations. These drugs are used differently depending on the specific hepatitis. Other drugs with different mechanisms are also being tested.
Treatments for Hepatitis B
Interferon alpha is the standard drug currently used for both chronic viral hepatitis B and C. It has eliminated the virus and sustained significant remission in 25% to 40% of patients with chronic hepatitis B. The drug is usually taken by injection every day for 16 weeks. (It does not appear to be effective for hepatitis D.) Unfortunately, even in hepatitis B, the virus recurs in almost all cases, although this recurring mutation may be weaker than the original strain. Administering the drug for longer periods may produce sustained remission in more patients while still being safe. Interferon beta is benefiting many children with hepatitis B who do not respond to interferon alpha.
Nucleoside analogues, such as lamivudine, are drugs that can block viral replication, and are now an important treatment for patients with hepatitis B. Lamivudine has reduced viral count in over half of hepatitis B patients who have taken it, and in such cases can significantly reduce the risk for liver damage and cirrhosis. The drug even suppresses hepatitis B viral replication in HIV-positive patients and liver transplant recipients. Some researchers fear that, although the drug may prevent cirrhosis, it might not protect against liver cancer, particularly in those who have harbored the virus since childhood. Preliminary data suggest that other nucleoside analogues, including ganciclovir, adefovir, and famciclovir, are also active against the hepatitis B virus.
Treatments for Hepatitis C
Interferon alpha, usually in combination with ribavirin is now the standard treatment for many patients with hepatitis C. In patients who respond, symptoms improve significantly. Unfortunately, only about half of patients respond to interferon alone, and only about 15% to 20% have a sustained response. In patients with hepatitis C without cirrhosis, the combination of interferon alpha and ribavirin is showing double the success rates of interferon alone, with initial response rates up to 66% for type 2 and 3 and up to 30% for the more severe genetic type 1. Sustained responses are as high as 40%. Side effects from the combination are similar to interferon alone although they occur more often, and ribavirin adds the risk for anemia. Many experts are now recommending that the combination of interferon alpha and ribavirin by the first choice for hepatitis C patients with early cirrhosis. Although studies have not found interferon alone to be of much benefit for hepatitis C, once cirrhosis develops, recent studies suggest that either long-term treatment or a new form of interferon alpha called polyethylene glycol (PEG interferon) may help to improve this condition. It is not known if interferon treatments have any effect in patients co-infected with hepatitis B or who show signs of portal hypertension.
Treatment for Primary Biliary Cirrhosis
Overall Symptom Improvement. Ursodiol or ursodeoxycholic acid appear to have properties that protect against the destructive consequences of the disease process in the bile ducts of the liver. It is the standard drug used for primary biliary cirrhosis and has only minor side effects. Methotrexate, an anti-inflammatory drug that suppresses elements of the immune system has been shown to reduce itching, improve liver enzyme levels, and even improve liver tissue health. Not all people respond to it, however, and it does not appear to be effective in low doses. Colchicine, a drug that inhibits collagen (a protein in the body the makes up scar tissue) has produced some improvement in liver function and survival, but it does not appear to be as effective as methotrexate. Both drugs can have severe side effects. Corticosteroids, such as budesonide, reduce inflammation and have been helpful in improving liver function and symptoms. Long-term use, however, can produce bone loss and other severe side effects. None of the drugs used for primary biliary cirrhosis is a cure. Experimental work with antioxidant vitamin preparations is showing promise for improving itching and fatigue.
Relief of Itching. The itching caused by primary biliary cirrhosis can be relieved by taking cholestyramine with meals. Low doses of the drug naltrexone relieved itching in one study. (High doses of this drug are toxic to the liver.) Phototherapy, which uses light, may also reduce itching.
Supplements for Fat Absorption. Because primary biliary cirrhosis affects fat absorption, patients may need high doses or injections of important fat-soluble vitamins, including K, D, A, and E. For steatorrhea, agents called medium-chain triglycerides may be helpful.
Treatment for Other Forms of Cirrhosis Secondary biliary cirrhosis caused by blockage in the bile ducts can be relieved by surgery. For hemochromatosis, weekly bleedings (phlebotomies) may be performed until iron levels are normal, then repeated as needed. If treatment is given before cirrhosis develops, life expectancy may be normal. D-penicillamine is the drug most used for Wilson's disease.
How Are The Complications Of Cirrhosis Managed And Treated?
Treating Ascites
Diuretics and Lifestyle Changes. Abstaining from alcohol, restricting sodium intake, taking diuretics, usually spironolactone (Aldactone) and furosemide (Lasix), are effective for relieving ascites in 90% of patients. Sometimes stopping drinking is enough to reverse this complication. Previously, spironolactone was usually given alone, but experts now use it by itself only in patients with minimal fluid build-up. Patients should be monitored carefully for excessive and too rapid 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 one or two pounds a day, but there is no limit for patients with massive swelling. Restricting fluid is not usually necessary unless sodium levels in the blood are very low. Physicians often recommend bed rest for patients with ascites, but many experts believe this is not necessary and say that studies do not support its benefits.
Paracentesis.
If diuretics are not successful and the ascites is very tense, patients may require large-volume paracentesis. In this procedure, albumin (protein) is administered intravenously while large volumes of fluid are removed through a tube in the abdomen. Research indicates that four to six liters are usually effective and safe. If the ascites does not respond to treatments, paracentesis may need to be repeated every two weeks or more frequently and up to 10 liters may need to be removed. Patients who require this are probably not complying with dietary requirements.
Peritoneovenous Shunting. Peritoneovenous (LeVeen, Denver) 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, and rupture of blood vessels in the esophagus. It can be beneficial for some people, but is now generally reserved for patients who are not candidates for repeat paracentesis or liver transplantation.
Liver Transplantation.
The prognosis for patients with ascites is poor. Liver transplantation should be considered for patients when ascites does not respond to treatments and when other complications, such as peritonitis or kidney failure, are present
Lowering Portal Hypertension and Treating Variceal Bleeding One of the greatest challenges in treating cirrhosis is to manage variceal bleeding. A number of drug treatments and procedures are available.
Procedures Used for Variceal Bleeding. Endoscopic sclerotherapy is the standard procedure used to treat bleeding. It involves inserting a tube through the mouth and then injecting agents called sclerosants (polidocanol and others) , which toughen the tissue around the blood vessels, into the esophagus. It may help prevent recurring bleeding from the esophagus, although not from the stomach. The treatment is repeated over a period of two or three months. Unfortunately, bleeding still occurs in up to 50% of patients, and complications of the procedure are high, about 40%. It is also an unpleasant procedure and many patients cannot tolerate it.
The transjugular intrahepatic portacaval (also called portosystemic) shunt (TIPS) is an alternative procedure that uses a thin, flexible, metal tube (a stent) threaded through a catheter in a vein that travels from the neck to the liver. The stent remains there, where it expands and forces blood vessels to reroute around the scarred liver. Blockage or closure of the shunt can develop over time. Although TIPS appears to be better than sclerotherapy in preventing re-bleeding, particularly when it is performed shortly after a bleeding episode, it poses a higher risk for encephalopathy. Studies are finding no survival advantage using TIPS over endoscopic sclerotherapy. At this time, experts do not recommend TIPS for high-risk patients and generally recommend it only for patients who cannot tolerate sclerotherapy, who are unlikely or unable to comply with the repeated procedures necessary for sclerotherapy, or who have poor blood circulation. TIPS may have some benefits for treating ascites.
Endoscopic band ligation (EVL) simply involves wrapping latex bands around the bleeding varices, shutting off the blood supply. There are few complications. In some studies it requires fewer sessions than sclerotherapy and may even be more effective in preventing re-bleeding. One study even found the procedure to be more protective than beta-blockers, the standard drugs used to prevent bleeding episodes, although other studies have not confirmed this. More research is needed, and studies on combinations of the procedure and drug therapy may be particularly useful.
Balloon tamponade employs 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. A recurrence of bleeding following this procedure is common.
Drug Therapies for Lowering Portal Hypertension and Preventing Variceal Bleeding. Beta-blockers, including propranolol and nadolol, used alone or with sclerotherapy, reduce the heart rate and can lower portal vein pressure, thereby reducing bleeding. (Carvedilol, a newer agent, called a nonselective beta-blocker, may be even more effective, but more research is needed to confirm this.) Beta-blockers are also used as a primary approach for prevention of recurrence. It is not yet clear if these drugs are more effective against bleeding than sclerotherapy, but they are inexpensive and safe. Studies are indicating that a combination of a nitrate, such as isosorbide mononitrate, with a beta-blocker is less expensive and may, in some cases, be even more effective than sclerotherapy. Nitrates alone are not as effective as beta-blockers, but may be useful in certain people. Lifetime therapy may be necessary.
Vasopressin (Pitressin) with nitroglycerine is often used. Vasopressin poses some risk to the heart, however, and it is not clear whether it is actually helpful.
Somatostatin is a hormone that constricts (narrows) blood vessels and helps help prevent variceal bleeding from portal hypertension. In one 2000 study, it controlled bleeding in 87% of patients. Taking the drug within 12 hours of bleeding and continuing it for about five days may also improve the success of subsequent sclerotherapies. Octreotide (Sandostatin), a drug that resembles somatostatin, has been tested with mixed results; some have shown no benefits in survival rates, although one indicated that it might improve survival rates compared to sclerotherapy after taking the drug for a year. It may reduce the risk of early re-bleeding in patients treated with either beta-blockers, sclerotherapy, or both.
Drugs known as angiotensin II receptor antagonists, including losartan, are being studied for lowering portal pressure.
Treating and Preventing Abdominal Infection (Peritonitis)
Antibiotics are administered when ascites fluid examination and tests indicate the presence of infection. For a first episode, the antibiotic cefotaxime is typically administered intravenously, requiring hospitalization. Treatment usually lasts 10 days but research indicates that five days may be sufficient for certain patients. One study indicated that adding intravenous albumin (a protein) to this regimen reduced the risk of kidney damage and early death. Some research indicates that the oral antibiotic ofloxacin may be as effective and is without complications, allowing patients to be treated at home.
Preventing and Treating Encephalopathy
The first step in managing encephalopathy is to treat any precipitating cause, if known, such as bleeding, high ammonia levels, low oxygen, infection, dehydration, or use of sedatives. 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 and lactitol, known as disaccharides, help lower blood ammonia levels. 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. Adding non-ammonia producing bacteria, including L. acidophilus and E. faecium, to the intestine is showing promise as a safe and effective treatment.
Treatment for Gastrointestinal Bleeding
Gastrointestinal (GI) bleeding is often first treated with medications to reduce stomach acid. Reduced clotting factors or platelets are common causes of GI bleeding in people with alcoholic cirrhosis. Some will respond to three days of injected vitamin K. People with alcoholism also often require folic acid. Transfusions of replacement clotting factors or platelets may be needed.
Liver Transplantation
Liver transplantation is indicated in patients who have developed life-threatening cirrhosis and who have a life expectancy of more than 12 years. Patients with liver cancer that has not spread beyond the liver may also be candidates. Current five-year survival rates after liver transplantation are now about 75%. Unfortunately, in about half of hepatitis patients, the viruses recur in the transplanted organ. (One study of patients with hepatitis C reported five-year risks for viral recurrence of 80% and for cirrhosis of 10%. The success rate is higher in those who have hepatitis D.) Experiments using monthly infusions of hepatitis B immune globulin (HBIg) after transplantation show great promise in preventing recurrence in these patients. These may need to be administered life long. Lamivudine may also be helpful in preventing recurrence of hepatitis B after liver transplantation. Autoimmune hepatitis may also recur after liver transplantation, but only after several years. Patients with primary biliary cirrhosis may be at higher risk for early rejection of the transplanted organ than patients with other forms of cirrhosis. There is considerable controversy over whether liver transplantation should be performed in alcoholics with cirrhosis who are unlikely to abstain. Patients should seek medical centers that have performed more than 50 transplants per year, which produces better than average results




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