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Cirrhosis and Liver Disease

The liver is the largest organ in the body, weighing up to 2.5 percent of total lean body mass. Located in the upper right quadrant of the abdomen, the liver varies in size and shape, depending on each person’s anatomy. Its main function is to metabolize substances in the blood in preparation for excretion, although it has many other important functions, including synthesis of most essential proteins, production of bile, and regulation of nutrients such as glucose, cholesterol, and amino acids.

The main kind of liver cell is called a hepatocyte. These cells comprise about two thirds of the liver’s mass. The liver’s blood supply comes from the hepatic artery, which supplies oxygen-rich blood. The liver also receives blood from the portal vein, which filters blood from the stomach, intestines, pancreas, and spleen.

The most common liver function tests are enzyme, bilirubin, albumin, and prothrombin time tests. The liver contains thousands of enzymes, only a few of which are routinely measured as indicators of liver function. These enzymes include the following:

  • Alkaline phosphatase. Abnormal levels may indicate bile obstruction, liver injury, or some forms of cancer.
  • Alanine transaminase. Abnormal levels may indicate hepatitis or other liver cell injury.
  • Aspartate transaminase. Abnormal levels may indicate injury to liver, heart, muscle, or brain.
  • Gamma-glutamyl transpeptidase. Abnormal levels may indicate organ damage, drug toxicity, alcohol abuse, or pancreatic disease.
  • Lactic dehydrogenase. Abnormal levels may indicate damage to liver, heart, or lung, and excessive breakdown of red blood cells.
  • 5'-nucleotidase. Abnormal levels may indicate impaired bile flow.

The other major liver tests include the serum bilirubin test, which measures bile excretion, and the albumin test, which can indicate liver damage. Finally, the prothrombin time test measures the time needed for blood to clot. Because most blood clotting factors are produced in the liver, and they have rapid turnover, this test can help measure the liver’s ability to synthesize cells. Prothrombin may be elevated in hepatitis and cirrhosis as well as in disorders related to vitamin K deficiency.

Taken together, these tests provide physicians with a relatively complete picture of liver function and can help diagnose liver disease.

Forms of Liver Disease

The many possible liver diseases can be grouped loosely into three categories: hepatocellular diseases, cholestatic diseases, and mixed forms. In hepatocellular diseases, the liver is typically inflamed and shows signs of injury. Over time, liver cells may begin to die. Causes of hepatocellular liver disease include alcoholic cirrhosis and viral hepatitis, both of which attack liver cells directly. In cholestatic diseases, the flow of fluid through the liver is blocked by such things as gall stones, liver cancer, or biliary cirrhosis. In mixed forms of liver disease, both conditions are present.

The pattern and onset of symptoms can help physicians determine what kind of liver disease is present. Symptoms of liver disease include jaundice, fatigue, itching, pain in the upper abdomen, distention of the abdomen, and intestinal bleeding. However, many forms of liver disease have no symptoms and are diagnosed only during routine blood tests that detect abnormalities in the markers of liver function.

Cirrhosis is an end-stage liver disease. It is characterized by chronic injury to the liver cells, fibrosis (scarring) within the liver, and the formation of regenerative nodules. The causes of cirrhosis include the following:

Alcohol consumption. Excess alcohol consumption is a primary cause of cirrhosis. However, only 10 percent to 20 percent of alcoholics develop cirrhosis (Beers MH et al 2004–2005).

Alcohol lowers the liver’s levels of antioxidants, including vitamin E (Kawase T et al 1989; Leo MA et al 1993) and S-adenosyl-L-methionine (SAMe) (Lieber CS 1997), making the liver vulnerable. In addition, alcohol lowers glutathione, an important internal antioxidant (Speisky H et al 1985; Hirano T et al 1992).

Because heavy drinkers consume a substantial number of calories as alcohol, they consume less vitamin- and mineral-rich food than they otherwise might, exacerbating alcohol-induced nutritional deficiencies. Virtually all individuals with alcoholic hepatitis suffer from malnutrition to a degree more or less proportional to the severity of their disease (Mendenhall CL et al 1984).

Indeed, survival in alcoholics with moderate or severe hepatitis is directly proportional to how much food they consume. Mortality drops to zero in those consuming 3000 or more calories during treatment (Mendenhall C et al 1995). Similar results were seen with alcoholic cirrhosis patients, except for the most severely malnourished, who may have been too compromised to recover (Hirsch S et al 1993,1999; Gopalan S et al 2000).

In addition to antioxidant depletion, alcoholics tend to have a number of other nutritional deficiencies. These include low levels of vitamin C, riboflavin, zinc, pyridoxine (vitamin B6), and vitamin A (Gruchow HW et al 1985; Rosenthal WS et al 1973; Ijuin H 1998; Fonda ML et al 1989; Lumeng LJ 1978; Lieber CS 2000).

Hepatitis. Hepatitis, another common cause of liver cirrhosis, is caused by infection with the hepatitis B or C virus. Because the symptoms of infection are mild and flulike, viral hepatitis often goes undiagnosed. Blood donors sometimes find out they are infected when their donated blood undergoes routine screening. Viral hepatitis causes chronic liver inflammation, which results in cirrhosis in the majority of those infected.

Nonalcoholic fatty liver disease. The most common cause of fatty liver disease is alcohol consumption, but it can also be caused by a number of other conditions, including obesity, diabetes, and elevated triglyceride levels. If the condition is associated with obesity, it is sometimes called nonalcoholic fatty liver disease, or NAFLD. Up to one-third of patients with NAFLD also have type 2 diabetes, high cholesterol levels, or both. NAFLD is closely associated with metabolic syndrome, which is a related cluster of conditions, including obesity, diabetes, elevated triglycerides, and high blood pressure, that is considered a major risk factor for heart attack. Fatty liver disease is exacerbated by inflammation within the liver, which may hasten its progression to cirrhosis.

Biliary cirrhosis. Biliary cirrhosis results from prolonged obstruction of or injury to the biliary system. One of the liver’s functions is to secrete bile, which is used in the gut in the normal breakdown and absorption of fats from the diet, among other things. Primary biliary cirrhosis, which has no known cause, is characterized by inflammation of the liver and the destruction of the liver bile ducts by scar tissue. It is associated with various autoimmune diseases, such as Raynaud’s phenomenon.

Cardiac cirrhosis. Cardiac cirrhosis occurs when prolonged, severe right-sided congestive heart failure leads to chronic liver injury and inflammation and the formation of scar tissue in the liver (fibrosis). A heart in this condition cannot handle the venous circulation, causing blood to back up in the body’s major veins. Eventually, the liver becomes engorged and swollen.

Inherited disorders. Various inherited disorders can cause cirrhosis.

Whatever the cause of cirrhosis, it is a difficult disease to manage in its advanced stages, in part because of the complications that it causes. For example, people suffering from cirrhosis also frequently suffer from portal hypertension, or elevated blood pressure in the vein that drains into the liver. This, in turn, can cause complications in the stomach and esophagus, such as ascites (see below). Portal hypertension occurs in about 60 percent of cases of cirrhosis in the United States (Kasper DL et al 2005). The treatment of portal hypertension often focuses on relieving the underlying liver disease. In serious cases, drugs such a diuretics might be prescribed to reduce blood pressure.

Cirrhosis may entail other complications:

  • Esophageal varices. Portal hypertension can cause varicose veins in the esophagus. They can rupture, requiring emergency surgery.
  • Ascites. The pressure created by portal hypertension can also cause the liver and intestines to exude fluid into the abdominal cavity, which can become swollen and distended, a condition known as ascites.
  • Hepatoma. Not surprisingly, a compromised liver is more susceptible to cancer. Hepatocellular carcinoma occurs in about 10 percent to 20 percent of cirrhotic patients (Wolf DC 2001). Liver cancer is relatively asymptomatic. It is usually not detected until it has progressed significantly. Consequently, the patient’s prognosis is usually poor.
  • Hepatic encephalopathy. This is a complex condition characterized by psychological and personality disturbances. Its specific cause is unknown; in serious cases, it can result in coma or death.

While cirrhosis is irreversible, it is usually the result of a chronic condition and thus takes a long time to develop. In fact, many people with developing liver disease (e.g., fibrotic livers) have no symptoms, and their condition is detected only by routine blood tests. If the condition is detected early enough, the patient may have an opportunity to arrest the cirrhotic process before it goes too far.

As is the case with many other diseases, cirrhosis is characterized by inflammation (hepatitis literally means “inflammation of the liver”). This liver inflammation is often caused by a rise in free radicals within the liver. Under normal circumstances, the liver maintains a supply of internal antioxidants to neutralize the free radicals generated by the toxins processed in the liver. However, when the liver antioxidants are low, or when the liver is overwhelmed by continued toxic insults (e.g., alcohol or chronic drug use), damage from free radicals increases, resulting in inflammation and the formation of scar tissue (fibrosis). Thus, it is important to maintain a healthy supply of antioxidants and to make positive lifestyle changes, such as abstaining from all alcohol and avoiding environmental toxins whenever possible, to reduce the strain on the liver.

If cirrhosis is allowed to progress and the liver’s function is compromised beyond repair, the only solution is a liver transplant. This is a complicated medical procedure with a significant risk of organ rejection, and even in successful cases, lifelong follow-up therapy with immunosuppressant drugs will be necessary.

Diagnosis of Liver Disease and Cirrhosis

The symptoms of cirrhosis may be insidious, or there may be no symptoms at all for many years. If symptoms are present, they can include jaundice (yellowing of the eyes and skin), lethargy, bleeding from varices, and spidery veins under the skin.

While it can be difficult to diagnose liver disease by its symptoms alone, early liver damage is often apparent from blood test results. Standard blood tests of liver enzymes or bilirubin may show a suspicious elevation and alert the clinician to the possibility of liver dysfunction.

The deposition of fat in the liver (such as in fatty liver disease) can also be detected by diagnostic imaging techniques, such as computed tomography scanning, ultrasound, and magnetic resonance imaging.

Treatment of Liver Disease

The goal of medicine with regard to the liver is to prevent liver disease and, if it is diagnosed, to stop its progression toward cirrhosis. Cirrhosis is an end-stage disease with a poor prognosis and can require a liver transplant if liver failure occurs. Thus, lifestyle changes that support liver health, especially abstention from alcohol, are the cornerstone of treatment for liver disease. No matter the cause of cirrhosis, alcohol aggravates the condition and should be avoided.

In addition, physicians will attempt to treat the complications of cirrhosis, including portal hypertension and ascites, with various medications. In general, however, the use of medications must be approached with caution in people with liver disease because the liver metabolizes many of these substances. For example, aspirin should be avoided in patients with cirrhosis because of its effects on coagulation and the gastric mucosa (Kasper DL et al 2005). The following conventional medicines are often prescribed to treat cirrhosis or fibrotic liver disease:

  • Corticosteroids. These drugs have been shown to reduce the inflammation that characterizes liver disease. While they may be helpful to patients with alcoholic hepatitis and encephalopathy, they are less helpful to patients with alcoholic cirrhosis (Kasper DL et al 2005; Glanze WD 1996; Mathurin P et al 2002).
  • Ursodiol. Among people with biliary cirrhosis, this drug replaces lost biliary acids. Side effects are rare. This drug may not halt progression of the disease (Kasper DL et al 2005).

What You Have Learned So Far

  • The liver is the largest internal organ. It filters the blood from the digestive system, metabolizing toxins and monitoring nutrients such as glucose and cholesterol.
  • Liver disease often develops over years, without obvious symptoms. Many people are diagnosed with liver disease after abnormalities are detected during routine blood tests.
  • Cirrhosis occurs when the liver is inflamed and scar tissue forms. It is irreversible; thus prevention of liver disease is the ideal. Cirrhosis can be caused by alcohol consumption, hepatitis, right-sided heart failure, and other conditions.
  • Antioxidants, which neutralize the toxins processed by the liver, are an important element in liver health.
  • Treatment of liver disease is limited because many drugs are metabolized by the liver; thus only a few drugs, including corticosteroids, which have significant side effects, are used routinely to treat liver disease.




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