Cirrhosis

Definition

Cirrhosis is a chronic degenerative disease of the liver in which normal liver cells are damaged and then replaced by scar tissue. There are different types of cirrhosis that could afflict a person.

Description

Cirrhosis changes the structure of the liver and the blood vessels that nourish it. The disease reduces the liver's ability to manufacture proteins, complex carbohydrates, fats, cholesterol , and to process hormones, nutrients, medications, and poisons. Cirrhosis worsens over time and can become potentially life threatening.

Cirrhosis is the seventh leading cause of disease-related death in the United States. It is the third most common cause of death in adults between the ages of 45 and 65. It is twice as common in men as in women. The disease occurs in more than half of all malnourished chronic alcoholics, and kills about 25,000 people a year. In Asia and Africa, however, most deaths from cirrhosis are due to chronic hepatitis B.

Types of cirrhosis

• Portal, or nutritional cirrhosis. The most common form of the disease in the United States. About 30–50% of all cases of cirrhosis are this type. Nine out of every 10 people who have nutritional cirrhosis have a history of alcoholism . Portal cirrhosis is also called Laënnec's cirrhosis.
• Biliary cirrhosis. Caused by liver bile-duct diseases that impede bile flow. Bile is formed in the liver and carried via the ducts to the intestines. Bile then helps digest fats in the intestines. Biliary cirrhosis can scar or block these ducts. It represents 15–20% of all cirrhosis.
• Postnecrotic cirrhosis. Caused by chronic infections . This form of the disease affects up to 40% of all patients who have cirrhosis.
• Pigment cirrhosis (hemochromatosis). Disorders like the inability to metabolize iron and similar disorders may cause pigment cirrhosis, which accounts for 5–10% of all instances of the disease.

Causes & symptoms

Causes and risk factors

Long-term alcoholism is the primary cause of cirrhosis in the United States. Men and women respond differently to alcohol. Although most men can safely consume two to five drinks a day, one to two drinks a day can cause liver damage in women. Individual tolerance to alcohol varies, but people who drink more and drink more often have a higher risk of developing cirrhosis. In some people, one drink a day can cause liver scarring.

Chronic liver infections, such as hepatitis B and particularly hepatitis C, are commonly linked to cirrhosis. People at high risk of contracting hepatitis B include those exposed to the virus through contact with blood and body fluids. This includes healthcare workers and intravenous (IV) drug users. In the past, people have contracted hepatitis C through blood transfusions. As of 2003, cirrhosis resulting from chronic hepatitis has emerged as a leading cause of death among HIV-positive patients; in Europe, about 30% of HIV-positive patients are coinfected with a hepatitis virus.

Liver injury, reactions to prescription medications, certain autoimmune disorders, exposure to toxic substances, and repeated episodes of heart failure with liver congestion can cause cirrhosis. A family history of diseases can genetically predispose a person to develop cirrhosis. These are:

• a lack of a specific liver enzyme (alpha₁-antitrypsin deficiency)
• the absence of a milk-digesting enzyme (galactosemia)
• an inability to convert sugars to energy (glycogen storage disease)
• an absorption deficit in which excess iron is deposited in the liver, pancreas, heart, and other organs
• a disorder characterized by accumulations of copper in the liver, brain, kidneys, and corneas (Wilson's disease)

Obesity has recently been recognized as a risk factor in nonalcoholic hepatitis and cirrhosis. Some surgeons are recommending as of 2003 that patients scheduled for weight-reduction surgery have a liver biopsy to evaluate the possibility of liver damage.

Symptoms

Symptoms of cirrhosis are usually caused by the loss of functioning liver cells or organ swelling due to scarring. The liver enlarges during the early stages of illness. Patients may experience:

• anemia
• bleeding gums
• constipation
• decreased interest in sex
• diarrhea
• dull abdominal pain
• extremely dry skin and intense itching
• fatigue
• fever
• fluid in the lungs
• hallucinations
• indigestion
• lethargy
• lightheadedness
• loss of appetite
• muscle weakness
• musty breath
• nausea
• painful nerve inflammation (neuritis)
• portal hypertension (this type of hypertension can be life threatening; it can cause veins to enlarge in the stomach and esophagus; the enlarged veins, called varices, can rupture and bleed massively)
• redness of the palms of the hands
• slurred speech
• tremors
• dark yellow or brown urine and black or bloody stools
• vomiting
• weakness
• weight loss
• yellowish whites of the eyes and skin, indicating the development of jaundice

As the disease progresses, other symptoms usually appear:

• spleen enlarges and fluid collects in the abdomen (ascites) and legs (edema)
• spider-like blood vessels appear on the chest and shoulders, and bruising becomes common
• men sometimes lose chest hair; their breasts may grow and their testicles may shrink
• women may have menstrual irregularities

If the liver loses its ability to remove toxins from the brain, the patient may have additional symptoms. The patient may become forgetful and unresponsive, neglect personal care, have trouble concentrating, and acquire new sleeping habits. These symptoms are related to ammonia intoxication and the failure of the liver to convert ammonia to urea. High protein intake in these patients can also lead to these symptoms.

Cirrhosis worsens over time and can become potentially life-threatening. This disease can cause:

• excessive bleeding (hemorrhage)
• impotence
• liver cancer
• coma due to accumulated ammonia and body wastes (liver failure)
• sepsis (blood poisoning)
• death

Diagnosis

A patient's medical history can reveal illnesses or lifestyles likely to lead to cirrhosis. Liver changes can be seen during a physical examination. A doctor who suspects cirrhosis may order blood and urine tests to measure liver function. Because only a small number of healthy cells are needed to carry out essential liver functions, test results may be normal even when cirrhosis is present.

In about 10 out of every 100 patients, the cause of cirrhosis cannot be determined. Many people who have cirrhosis do not have any symptoms (often called compensated cirrhosis). Their disease is detected during a routine physical or when tests for an unrelated medical problem are performed. This type of cirrhosis can also be detected when complications occur (decompensated cirrhosis).

Computed tomography scans (CT), ultrasound, and other imaging techniques can be used during diagnosis. They can help determine the size of the liver, indicate healthy and scarred areas of the organ, and detect gallstones . Cirrhosis is sometimes diagnosed during surgery or by examining the liver with a laparoscope. This viewing device is inserted into the patient's body through a tiny incision in the abdomen.

Liver biopsy is usually needed to confirm a diagnosis of cirrhosis. In this procedure, a tissue sample is removed from the liver and examined under a microscope in order to learn more about the organ's condition and to properly diagnose it.

A newer and less invasive test involves the measurement of hyaluronic acid in the patient's blood serum. As of 2003, however, the serum hyaluronic acid test is most useful in monitoring the progress of liver disease; it is unlikely to completely replace liver biopsy in the diagnosis of cirrhosis.

Treatment

Before starting on any alternative treatment program, patients should consult their doctor for monitoring of side effects and effectiveness of treatment. Any nutritional changes should be discussed with the primary care provider. Alternative treatments that may be of help to cirrhotic patients include nutritional and juice therapy, Western herbal therapy, traditional Chinese medicine , and homeopathy .

Nutritional therapy

To support liver function and slow down disease progression, a naturopath may recommend the following:

• Avoid liver toxins. Cirrhotic patients must completely avoid alcohol. Alcohol accelerates liver failure and hastens death in cirrhotic patients. In addition, even over-thecounter drugs, such as acetaminophen (Tylenol), should be avoided because they can be toxic in cirrhotic patients.
• Juice therapy helps the liver detoxify toxins from the body. Patients should mix one part of pure juice with one part of water before drinking.
• Eat smaller meals. To avoid overworking the liver, five or six smaller, lighter meals per day are recommended.
• Avoid fatty foods, especially those prepared with animal fats or hydrogenated oils and processed foods. These types of foods put additional demands on the liver.
• Eat only lean proteins (containing no fats) and in limited amounts. Vegetable proteins, such as those found in legumes or tofu, and whole grains are preferred. High protein intake causes increases in ammonia levels in the blood, possibly resulting in mental confusion, and in severe cases, coma. However, do not severely limit protein intake, as this may cause protein deficiency and impair healing process.
• Increase consumption of fruits and steamed vegetables. Fruits and vegetables are easy to digest, thus less work for the liver. In addition, they are good sources of vitamins, minerals, and antioxidants that help the liver detoxify and heal.
• Practice intermittent fasting.
• Take supplements that can improve digestion and help the liver heal and prevent further injury to the liver. They include pancreatic enzymes, milk thistle (Silybum marianum ), lipotropic agents such as vitamin B₆, vitamin B₁₂, folic acid , choline, alpha lipoic acid, betaine, and methionine.

In 2001, several studies were compared to determine the effectiveness of milk thistle in treating cirrhosis and other liver diseases. The active component in milk thistle, silymarin, promotes liver protein synthesis. Studies appear to show improved survival among cirrhosis patients who use milk thistle (study subjects received 140 mg of silymarin three times a day).

Other therapies

Other types of therapies the patient may want to consider are naturopathic hydrotherapy , and ones that may improve immune function, including stress reduction, guided imagery , and massage.

Traditional Chinese medicine

Depending on a patient's specific condition, an expert Chinese herbalist may prescribe herbal remedies that may help improve liver function. Animal studies have shown that the following Chinese herbs may have protective effects on the liver:

• Propolis
• Bupleurum chinense is the most frequently used herb for a variety of liver diseases
• Phellodendron wilsonii
• Clementis chinensis
• Solanum incanum
• Ixeris chinensis
• Gardenia jasminoides

Western herbal therapy

Patients should consult an experienced herbalist for specific herbal treatments. There has also been moderate evidence regarding the use of milk thistle in helping to alter the effects of cirrhosis; however, there is no conclusive data as of 2002.

Homeopathy

For homeopathic therapy, patients should consult a homeopathic physician who will prescribe specific remedies based on knowledge of the underlying cause.

Allopathic treatment

The goal of treatment is to cure or reduce the condition causing cirrhosis, prevent or delay disease progression, and prevent or treat complications.

Salt and fluid intake is often limited, and activity is encouraged. A diet high in calories and moderately high in protein can benefit some patients. Tube feedings or vitamin supplements may be prescribed if the liver continues to deteriorate. Patients are asked not to consume alcohol.

Medication

Iron supplements, diuretics, and antibiotics may be used for anemia, fluid retention, and ammonia accumulation associated with cirrhosis. Vasoconstrictors are sometimes needed to stop internal bleeding and antiemetics may be prescribed to control nausea.

Laxatives help the body absorb toxins and accelerate their removal from the digestive tract. Beta-blockers may be prescribed to control cirrhosis-induced portal hypertension. Interferon medicines may be used by patients with chronic hepatitis B and hepatitis C to prevent post-hepatic cirrhosis.

Surgery

Medication that causes scarring can be injected directly into veins to control bleeding from varices in the stomach or esophagus. Varices may require a special surgical procedure called balloon tamponade ligation to stop the bleeding. Surgery may be required to repair disease-related throat damage. It is sometimes necessary to remove diseased portions of the spleen and other organs.

The incidence of liver cancer related to cirrhosis in the United States has increased 75% since the early 1990s. Partial surgical removal of the liver in patients with early-stage cancer of the liver appears to be as successful as transplantation, in terms of the 5-year survival rate.

Liver transplants can benefit patients with advanced cirrhosis. However, the new liver will eventually become diseased unless the underlying cause of cirrhosis (such as alcoholism) is removed.

Supportive measures

A balanced diet promotes regeneration of healthy liver cells. Eating five or six small meals throughout the day should prevent the sick or bloated feeling patients with cirrhosis often have after eating. Alcohol and caffeine , which destroy liver cells, should be avoided, as should any other foods that upset the stomach. Patients with brain disease associated with cirrhosis should avoid excessive amounts of protein in the diet.

A patient can keep a food diary that describes what was eaten, when it was eaten, and how the patient felt afterwards. This diary can be useful in identifying foods that are hard to digest and in scheduling meals to coincide with the times the patient is most hungry.

Patients who have cirrhosis should weigh themselves every day and notify their doctor of a sudden gain of 5 lb (2.3 kg) or more within a one to two week period. A doctor should also be notified if symptoms of cirrhosis appear in anyone who has not been diagnosed with the disease. A doctor should also be notified if a patient diagnosed with cirrhosis:

• vomits blood
• passes black stools
• seems confused or unresponsive
• shows signs of infection (redness, swelling, tenderness, pain)

Expected results

Cirrhosis-related liver damage cannot be reversed, but further damage can be prevented by patients who:

• eat properly
• get enough rest
• do not consume alcohol
• remain free of infection

If the underlying cause of cirrhosis cannot be corrected or removed, scarring will continue. As scarring continues, the liver will fail, and the patient will probably die within five years. Patients who stop drinking after being diagnosed with cirrhosis can increase their likelihood of living more than a few years from 40% to 60–70%.

Prevention

Eliminating alcohol abuse could prevent 75–80% of all cases of cirrhosis.

Other preventive measures include:

• maintaining a healthy diet that includes whole foods and grains, vegetable, and fruits
• obtaining counseling or other treatment for alcoholism
• taking precautions (practicing safe sex, avoiding dirty needles) to prevent hepatitis
• getting immunizations against hepatitis if a person is in a high-risk group
• receiving appropriate medical treatment quickly when diagnosed with hepatitis B or hepatitis C
• having blood drawn at regular intervals to rid the body of excess iron from hemochromatosis
• using medicines (chelating agents) to rid the body of excess copper from Wilson's disease
• wearing protective clothing and following product directions when using toxic chemicals at work, at home, or in the garden

In 2001, research scientists identified the protein segment and method in which excess tissue grows in diseases like cirrhosis. With further study, the discovery might one day result in an oral or inhalable peptide for those with cirrhosis.

Resources

BOOKS

Andrews, Marcia, and Robert B. Cooper. Everything You Need to Know About Diseases. Springhouse, PA: Springhouse Corporation, 1997.

The Burton Goldberg Group. "Cirrhosis." In Alternative Medicine: The Definitive Guide. 2nd ed. Tiburon, CA: Future Medicine Publishing, Inc., 2002.

"Cirrhosis." Section 4, Chapter 41 in The Merck Manual of Diagnosis and Therapy, edited by Mark H. Beers, MD, and Robert Berkow, MD. Whitehouse Station, NJ: Merck Research Laboratories, 2002.

Editors of Time-Life Books. The Medical Advisor: The Complete Guide to Alternative & Conventional Treatments. Alexandria, VA: Time Life Inc., 1996.

"Liver Problems." In The Hamlyn Encyclopedia of Complementary Health. London: Reed Intl. Books Ltd.

Murray, Michael T., and Joseph E. Pizzorno. "Detoxification." In Encyclopedia of Natural Medicine. Rocklin, CA: Prima Publishing, 1998.

Pelletier, Kenneth R., MD. The Best Alternative Medicine, Part II, "CAM Therapies for Specific Conditions: Alcoholism." New York: Simon & Schuster, 2002.

PERIODICALS

Cha, C. H., L. Ruo, Y. Fong, et al. "Resection of Hepatocellular Carcinoma in Patients Otherwise Eligible for Transplantation." Annals of Surgery 238 (September 2003): 315–321.

Foreman, M. G., D. M. Mannino, and M. Moss. "Cirrhosis as a Risk Factor for Sepsis and Death: Analysis of the National Hospital Discharge Survey." Chest 124 (September 2003): 1016–1020.

Higuchi, H., and G. J. Gores. "Mechanisms of Liver Injury: An Overview." Current Molecular Medicine 3 (September 2003): 483–490.

Kamath, B. M., and D. A. Piccoli. "Heritable Disorders of the Bile Ducts." Gastroenterology Clinics of North America 32 (September 2003): 857–875.

Lin, Song-Chow, Yun-Ho Lin, Chin-Fa Chen, Chia-Yu Chung, and Shih-Hsien Hsu. "The Hepatoprotective and Therapeutic Effects of Propolis Ethanol Extract on Chronic Alcohol-induced Liver Injuries." American Journal of Chinese Medicine 25, no. 3–4 (1997): 325–332.

"Management of Alcoholic Hepatitis." Drug Therapy Bulletin 41 (July 2003): 49–52.

Moretto, M., C. Kupski, C. C. Mottin, et al. "Hepatic Steatosis in Patients Undergoing Bariatric Surgery and Its Relationship to Body Mass Index and Co-Morbidities." Obesity Surgery 13 (August 2003): 622–624.

"Peptides: Peptide Critical to Cirrhosis Development." Drug Discovery and Technology News 4, no. 11 (November 2001).

Phillips, M. G., V. R. Preedy, and R. D. Hughes. "Assessment of Prognosis in Alcoholic Liver Disease: Can Serum Hyaluronate Replace Liver Biopsy?" european Journal of Gastroenterology and Hepatology 15 (September 2003): 941–944.

Ristig, M., H. Drechsler, J. Crippin, et al. "Management of Chronic Hepatitis B in an HIV-Positive Patient with 3TC-Resistant Hepatitis B Virus." AIDS Patient Care and STDs 17 (September 2003): 439–442.

Walsh, Nancy. "Milk Thistle for Liver Disease (Alternative Medicine: An Evidence-Based Approach." Internal Medicine News (January 1, 2002): 10.

ORGANIZATIONS

American Liver Foundation. 1425 Pompton Ave., Cedar Grove, NJ 07009. (800) 465-4837. <http://www.liverfoundation.org>.

United Network for Organ Sharing. 1100 Boulders Parkway, Suite 500, P.O. Box 13770, Richmond, VA 23225-8770. (804) 330-8500. <http://www.unos.org>.

OTHER

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). Cirrhosis of the Liver. April 200 [cited October 2002]. <http://www.niddk.nih.gov/health/digest/pubs/cirrhosi/cirrhosi.htm>.

Teresa G. Odle

Rebecca J. Frey, PhD

Cirrhosis

Definition

Cirrhosis is a chronic degenerative disease in which normal liver cells are damaged and are then replaced by scar tissue.

Description

Cirrhosis changes the structure of the liver and the blood vessels that nourish it. The disease reduces the liver's ability to manufacture proteins and process hormones, nutrients, medications, and poisons.

Cirrhosis gets worse over time and can become potentially life threatening. This disease can cause:

• excessive bleeding (hemorrhage)
• impotence
• liver cancer
• coma due to accumulated ammonia and body wastes (liver failure)
• sepsis (blood poisoning)
• death

Cirrhosis is the seventh leading cause of disease-related death in the United States. It is the third most common cause of death in adults between the ages of 45 and 65. It is twice as common in men as in women. The disease occurs in more than half of all malnourished chronic alcoholics, and kills about 25,000 people a year. In Asia and Africa, however, most deaths from cirrhosis are due to chronic hepatitis B.

Types of cirrhosis

Portal or nutritional cirrhosis is the form of the disease most common in the United States. About 30-50% of all cases of cirrhosis are this type. Nine out of every 10 people who have nutritional cirrhosis have a history of alcoholism. Portal or nutritional cirrhosis is also called Laënnec's cirrhosis.

Biliary cirrhosis is caused by intrahepatic bile-duct diseases that impede bile flow. Bile is formed in the liver and is carried by ducts to the intestines. Bile then helps digest fats in the intestines. Biliary cirrhosis can scar or block these ducts. It represents 15-20% of all cirrhosis.

Various types of chronic hepatitis, especially hepatitis B and hepatitis C, can cause postnecrotic cirrhosis. This form of the disease affects up to 40% of all patients who have cirrhosis.

Disorders like the inability to metabolize iron and similar disorders may cause pigment cirrhosis (hemochromatosis ), which accounts for 5-10% of all instances of the disease.

Causes and symptoms

Long-term alcoholism is the primary cause of cirrhosis in the United States. Men and women respond differently to alcohol. Although most men can safely consume two to five drinks a day, one or two drinks a day can cause liver damage in women. Individual tolerance to alcohol varies, but people who drink more and drink more often have a higher risk of developing cirrhosis. In some people, one drink a day can cause liver scarring.

Chronic liver infections, such as hepatitis B and particularly hepatitis C, are commonly linked to cirrhosis. People at high risk of contracting hepatitis B include those exposed to the virus through contact with blood and body fluids. This includes healthcare workers and intravenous (IV) drug users. In the past, people have contracted hepatitis C through blood transfusions. As of 2003, cirrhosis resulting from chronic hepatitis has emerged as a leading cause of death among HIV-positive patients; in Europe, about 30% of HIV-positive patients are coinfected with a hepatitis virus.

Liver injury, reactions to prescription medications, exposure to toxic substances, and repeated episodes of heart failure with liver congestion can cause cirrhosis. The disorder can also be a result of diseases that run in families (inherited diseases) like:

• a lack of a specific liver enzyme (alpha₁-antitrypsin deficiency)
• the absence of a milk-digesting enzyme (galactosemia)
• an inability to convert sugars to energy (glycogen storage disease)
• an absorption deficit in which excess iron is deposited in the liver, pancreas, heart, and other organs (hemochromatosis)
• a disorder characterized by accumulations of copper in the liver, brain, kidneys, and corneas (Wilson's disease)

Obesity has recently been recognized as a risk factor in nonalcoholic hepatitis and cirrhosis. Some surgeons are recommending as of 2003 that patients scheduled for weight-reduction surgery have a liver biopsy to evaluate the possibility of liver damage.

Poor nutrition increases a person's risk of developing cirrhosis. In about 10 out of every 100 patients, the cause of cirrhosis cannot be determined. Many people who have cirrhosis do not have any symptoms (often called compensated cirrhosis). Their disease is detected during a routine physical or when tests for an unrelated medical problem are performed. This type of cirrhosis can also be detected when complications occur (decompensated cirrhosis).

Symptoms of cirrhosis are usually caused by the loss of functioning liver cells or organ swelling due to scarring. The liver enlarges during the early stages of illness. The palms of the hands turn red and patients may experience:

• constipation
• diarrhea
• dull abdominal pain
• fatigue
• indigestion
• loss of appetite
• nausea
• vomiting
• weakness
• weight loss

As the disease progresses, the spleen enlarges and fluid collects in the abdomen (ascites ) and legs (edema ). Spider-like blood vessels appear on the chest and shoulders, and bruising becomes common. Men sometimes lose chest hair. Their breasts may grow and their testicles may shrink. Women may have menstrual irregularities.

Cirrhosis can cause extremely dry skin and intense itching. The whites of the eyes and the skin may turn yellow (jaundice ), and urine may be dark yellow or brown. Stools may be black or bloody. Sometimes the patient develops persistent high blood pressure due to the scarring (portal hypertension ). This type of hypertension can be life threatening. It can cause veins to enlarge in the stomach and in the tube leading from the mouth to the stomach (esophagus). These enlarged veins are called varices, and they can rupture and bleed massively.

Other symptoms of cirrhosis include:

• anemia
• bleeding gums
• decreased interest in sex
• fever
• fluid in the lungs
• hallucinations
• lethargy
• lightheadedness
• muscle weakness
• musty breath
• painful nerve inflammation (neuritis)
• slurred speech
• tremors

If the liver loses its ability to remove toxins from the brain, the patient may have additional symptoms. The patient may become forgetful and unresponsive, neglect personal care, have trouble concentrating, and acquire new sleeping habits. These symptoms are related to ammonia intoxication and the failure of the liver to convert ammonia to urea. High protein intake in these patients can also lead to these symptoms.

Diagnosis

A patient's medical history can reveal illnesses or lifestyles likely to lead to cirrhosis. Liver changes can be seen during a physical examination. A doctor who suspects cirrhosis may order blood and urine tests to measure liver function. Because only a small number of healthy cells are needed to carry out essential liver functions, test results may be normal even when cirrhosis is present.

Computed tomography scans (CT), ultrasound, and other imaging techniques can be used during diagnosis. They can help determine the size of the liver, indicate healthy and scarred areas of the organ, and detect gallstones. Cirrhosis is sometimes diagnosed during surgery or by examining the liver with a laparoscope. This viewing device is inserted into the patient's body through a tiny incision in the abdomen.

Liver biopsy is usually needed to confirm a diagnosis of cirrhosis. In this procedure, a tissue sample is removed from the liver and is examined under a microscope in order to learn more about the organ.

A newer and less invasive test involves the measurement of hyaluronic acid in the patient's blood serum. As of 2003, however, the serum hyaluronic acid test is most useful in monitoring the progress of liver disease ; it is unlikely to completely replace liver biopsy in the diagnosis of cirrhosis.

Treatment

The goal of treatment is to cure or reduce the condition causing cirrhosis, prevent or delay disease progression, and prevent or treat complications.

Salt and fluid intake are often limited, and activity is encouraged. A diet high in calories and moderately high in protein can benefit some patients. Tube feedings or vitamin supplements may be prescribed if the liver continues to deteriorate. Patients are asked not to consume alcohol.

Medication

Iron supplements, diuretics, and antibiotics may be used for anemia, fluid retention, and ammonia accumulation associated with cirrhosis. Vasoconstrictors are sometimes needed to stop internal bleeding and antiemetics may be prescribed to control nausea.

Laxatives help the body absorb toxins and accelerate their removal from the digestive tract. Beta blockers may be prescribed to control cirrhosis-induced portal hypertension. Because the diseased liver can no longer efficiently neutralize harmful substances, medications must be given with caution. Interferon medicines may be used by patients with chronic hepatitis B and hepatitis C to prevent post-hepatic cirrhosis.

Surgery

Medication that causes scarring can be injected directly into veins to control bleeding from varices in the stomach or esophagus. Varices may require a special surgical procedure called balloon tamponade ligation to stop the bleeding. Surgery may be required to repair disease-related throat damage. It is sometimes necessary to remove diseased portions of the spleen and other organs.

Liver transplants can benefit patients with advanced cirrhosis. However, the new liver will eventually become diseased unless the underlying cause of cirrhosis is removed. Patients with alcoholic cirrhosis must demonstrate a willingness to stop drinking before being considered suitable transplant candidates.

The incidence of liver cancer related to cirrhosis in the United States has increased 75% since the early 1990s. Partial surgical removal of the liver in patients with early-stage cancer of the liver appears to be as successful as transplantation, in terms of the 5-year survival rate.

Supportive measures

A balanced diet promotes regeneration of healthy liver cells. Eating five or six small meals throughout the day should prevent the sick or bloated feeling patients with cirrhosis often have after eating. Alcohol and caffeine, which destroy liver cells, should be avoided. So should any foods that upset the stomach. Patients with brain disease associated with cirrhosis should avoid excessive amounts of protein in the diet.

A patient can keep a food diary that describes what was eaten, when it was eaten, and how the patient felt afterwards. This diary can be useful in identifying foods that are hard to digest and in scheduling meals to coincide with the times the patient is most hungry.

Patients who have cirrhosis should weigh themselves every day and notify their doctor of a sudden gain of five pounds or more. A doctor should also be notified if symptoms of cirrhosis appear in anyone who has not been diagnosed with the disease. A doctor should also be notified if a patient diagnosed with cirrhosis:

• vomits blood
• passes black stools
• seems confused or unresponsive
• shows signs of infection (redness, swelling, tenderness, pain)

Alternative treatment

Alternative treatments for cirrhosis are aimed at promoting the function of healthy liver cells and relieving the symptoms associated with the disease. Several herbal remedies may be helpful to cirrhosis patients. Dandelion (Taraxacum officinale ) and rock-poppy (Chelidonium majus ) may help improve the efficiency of liver cells. Milk thistle extract (Silybum marianum ) may slow disease progression and significantly improve survival rates in alcoholics and other cirrhosis patients. Practitioners of homeopathy and traditional Chinese medicine can also prescribe treatments that support healthy liver function.

Prognosis

Cirrhosis-related liver damage cannot be reversed, but further damage can be prevented by patients who:

• eat properly
• get enough rest
• do not consume alcohol
• remain free of infection

If the underlying cause of cirrhosis cannot be corrected or removed, scarring will continue. The liver will fail, and the patient will probably die within five years. Patients who stop drinking after being diagnosed with cirrhosis can increase their likelihood of living more than a few years from 40% to 60-70%.

Prevention

Eliminating alcohol abuse could prevent 75-80% of all cases of cirrhosis.

Other preventive measures include:

• obtaining counseling or other treatment for alcoholism
• taking precautions (practicing safe sex, avoiding dirty needles) to prevent hepatitis
• getting immunizations against hepatitis if a person is in a high-risk group
• receiving appropriate medical treatment quickly when diagnosed with hepatitis B or hepatitis C
• having blood drawn at regular intervals to rid the body of excess iron from hemochromatosis

• using medicines (chelating agents) to rid the body of excess copper from Wilson's disease
• wearing protective clothing and following product directions when using toxic chemicals at work, at home, or in the garden

In 2001, research scientists identified the protein segment and method in which excess tissue grows in diseases like cirrhosis. With further study, the discovery might one day result in an oral or inhalable peptide for those with cirrhosis.

Resources

BOOKS

Beers, Mark H., MD, and Robert Berkow, MD. editors. "Cirrhosis." Section 4, Chapter 41 In The Merck Manual of Diagnosis and Therapy. Whitehouse Station, NJ: Merck Research Laboratories, 2004.

Pelletier, Kenneth R., MD. The Best Alternative Medicine, Part II, "CAM Therapies for Specific Conditions: Alcoholism." New York: Simon & Schuster, 2002.

PERIODICALS

Cha, C. H., L. Ruo, Y. Fong, et al. "Resection of Hepatocellular Carcinoma in Patients Otherwise Eligible for Transplantation." Annals of Surgery 238 (September 2003): 315-321.

Foreman, M. G., D. M. Mannino, and M. Moss. "Cirrhosis as a Risk Factor for Sepsis and Death: Analysis of the National Hospital Discharge Survey." Chest 124 (September 2003): 1016-1020.

Higuchi, H., and G. J. Gores. "Mechanisms of Liver Injury: An Overview." Current Molecular Medicine 3 (September 2003): 483-490.

Kamath, B. M., and D. A. Piccoli. "Heritable Disorders of the Bile Ducts." Gastroenterology Clinics of North America 32 (September 2003): 857-875.

"Management of Alcoholic Hepatitis." Drug Therapy Bulletin 41 (July 2003): 49-52.

Moretto, M., C. Kupski, C. C. Mottin, et al. "Hepatic Steatosis in Patients Undergoing Bariatric Surgery and Its Relationship to Body Mass Index and Co-Morbidities." Obesity Surgery 13 (August 2003): 622-624.

"Peptides: Peptide Critical to Cirrhosis Development." Drug Discovery and Technology News 4, no. 11 (November 2001).

Phillips, M. G., V. R. Preedy, and R. D. Hughes. "Assessment of Prognosis in Alcoholic Liver Disease: Can Serum Hyaluronate Replace Liver Biopsy?" European Journal of Gastroenterology and Hepatology 15 (September 2003): 941-944.

Ristig, M., H. Drechsler, J. Crippin, et al. "Management of Chronic Hepatitis B in an HIV-Positive Patient with 3TC-Resistant Hepatitis B Virus." AIDS Patient Care and STDs 17 (September 2003): 439-442.

ORGANIZATIONS

American Liver Foundation. 1425 Pompton Ave., Cedar Grove, NJ 07009. (800) 223-0179. 〈http://www.liverfoundation.org〉.

United Network for Organ Sharing. 1100 Boulders Parkway, Suite 500, P.O. Box 13770, Richmond, VA 23225-8770. (804) 330-8500. 〈http://www.unos.org〉.

OTHER

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). Cirrhosis of the Liver. April 200 [cited October 2002]. 〈http://www.niddk.nih.gov/health/digest/pubs/cirrhosi/cirrhosi.htm〉.

CIRRHOSIS

The term "cirrhosis" was first used by René Laënnec (1781–1826) to describe the abnormal liver color of individuals with alcohol-induced liver disease. The word cirrhosis comes from the Greek word kirrhos, the name for a yellowish-brown color.

The human liver is the largest single organ in the body and consists of parenchymal cells, which metabolize, detoxify, synthesize, and store nutrients. Normal functioning of these cells depends on their proper organization. Cirrhosis, the final common pathway for a variety of liver diseases, occurs when excessive fibrosis results in the conversion of normal liver architecture into structurally abnormal nodules. Cirrhosis is irreversible and can be life threatening—it is a public health concern because of its associated mortality and morbidity. The only available and definitive treatment is liver transplantation. Cirrhosis is, however, preventable in most cases.

PREVALENCE

The exact prevalence of cirrhosis is unknown, but it has been estimated, through autopsies, to be between 5 and 10 percent. Incidence of cirrhosis varies by country and region, and reflects relative contributions from different risk factors. In countries where alcohol consumption is common, alcoholic cirrhosis is the major contributor to the overall prevalence of cirrhosis. In countries with low alcohol consumption, hepatotropic viruses (hepatitis B and C) are the major contributors.

An estimated 25,000 individuals in the United States died from liver disease in 1998, making liver disease the tenth leading cause of death. For individuals between 45 and 64 years of age, chronic liver disease had an associated mortality rate of 19.6 per 100,000 persons and was the seventh leading cause of death. The mortality rate for

Table 1

white men between 45 and 64 years of age was 28.2 per 100,000 persons, and cirrhosis was the fourth leading cause of death (in 1998).

CAUSES OF LIVER DISEASES

Ethanol. Ethanol (alcohol) is the most common cause of cirrhosis in the United States (see Table1). Over three-quarters of Americans drink ethanol. The amount necessary to cause cirrhosis differs based on gender and nutritional status, and the relative risk of alcoholic cirrhosis increases with greater amounts of alcohol consumption. It has been estimated that alcoholic cirrhosis develops in women drinking at least 20 grams of alcohol a day for 5 to 10 years, and in men drinking at least 40 grams per day for the same period. A 12-ounce can of beer, 5-ounce a glass of wine, and a 1.5 ounce shot of hard liquor all contain between 10 and 20 grams of ethanol. Malnutrition and infection with hepatotropic viruses may also increase the risk of cirrhosis.

Compelling epidemiological data indicate a strong association between alcohol consumption and cirrhosis mortality. Between 1906 and 1934, per capita alcohol consumption in the United States dropped from 9.8 liters of absolute alcohol to 3.7 liters. Liver cirrhosis mortality fell from approximately 16 deaths per 100,000 prior to the Prohibition era, to 8 deaths per 100,000 during the Prohibition era and for several decades after Prohibition laws were repealed (see Figure 1). Between 1950 and 1973, however, mortality due to cirrhosis rose from 8.5 deaths per 100,000 to 14.9 deaths per 100,000. This increase followed and paralleled an increase in total alcohol consumption. Between 1970 and 1990, although total alcohol consumption remained stable, the mortality rate from cirrhosis decreased. Plausible reasons

Figure 1

for this discrepancy include lowering the greater than previously recognized nonalcohol contribution to the overall mortality rate due to cirrhosis and improved behavior regarding alcohol.

Hepatotropic Viruses. Hepatotropic viruses represent the second major category of the causes of cirrhosis. Hepatotropic viruses account for most orthotopic liver transplantations in the United States.

Approximately 4 million people in the United States are believed to be infected by hepatitis C. Prevalence varies considerably by country, e.g., from 0.1 to 2 percent in Europe and North America to 5 to 20 percent in Egypt (see Table 2). Hepatitis C infection results in chronic hepatitis in 85 percent of infected individuals, and in cirrhosis in 20 percent. The mean time progression to hepatic cirrhosis following viral infection is twenty years. Factors associated with progression of hepatitis C-related liver disease include chronic alcoholism and viral coinfection with hepatitis B.

Blood transfusion was the single major risk factor for hepatitis C infection until the early 1990s; today it accounts for a minority of hepatitis C cases because of blood screening for hepatitis C. Illegal drug use now accounts for more than half of the cases of hepatitis C infection, and this proportion is likely to increase in the near future when many individuals infected with hepatitis C in the 1960s and 1970s, largely as a result of sharing needles, seek medical attention.

Public health efforts are best directed at preventing viral hepatitis infection. Once patients are

Table 2

infected, antiviral therapy may eliminate the virus from the blood and prevent the progression to hepatic cirrhosis.

Approximately 1 to 1.25 million Americans are infected with the hepatitis B virus. Worldwide, an estimated 1 to 2 million people die of hepatitis B-associated liver disease annually (see Table 3). The worldwide prevalence varies greatly among countries, from 0.1 to 2 percent in Europe and North America, and from 5 to 20 percent in Southeast Asia and Eastern Europe. It is estimated that 12 to 20 percent of patients with chronic hepatitis B progress to cirrhosis within five years. The risk of hepatitis B infection from a blood transfusion was once up to 50 percent, but it is now exceedingly uncommon, largely as a result of blood screening. The implementation of hepatitis B immunization programs in infants has also contributed to the decreasing number of new cases of hepatitis B infection.

Although the major risk factor for hepatitis B transmission is sexual, the rate has also fallen significantly in recent years because of changes in high-risk sexual behavior. Like hepatitis C, progression to cirrhosis can be halted with antiviral therapy.

Cirrhosis is a major public health concern. The major causes of cirrhosis are mostly related to

Table 3

lifestyle behaviors such as alcohol consumption, injectable drug use, and unprotected sex. Public health efforts should focus on programs that address these activities.

Sammy Saab

Sergio E. Rojter

(see also: Alcohol Use and Abuse; Hepatitis A Vaccine; Hepatitis B Vaccine )

Bibliography

Alter, M. J. (1997). "The Epidemiology of Acute and Chronic Hepatitis C." Clinical Liver Disease 1:559–568.

Garcia, G.; Petrovic, L. M.; and Vierling, J. M. (2000). "Overview of Hepatitis B and Transplantation in the Hepatitis B Patient." Semin Liver Dis 20 (Supp. 1): 3–6.

Giarelli, L.; Melato, M.; Laurino, L.; Peruzzo, P.; Musse, M. M.; and Delendi, M. (1991). "Occurrence of Liver Cirrhosis among Autopsies in Trieste." Internal Agency for Research on Cancer Science Publications 112:37–43.

Graudal, N.; Leth, P.; Marbjerg, L.; and Galloe, A. M. (1991). "Characteristics of Cirrhosis Undiagnosed During Life: A Comparative Analysis of 73 Undiagnosed Cases and 149 Diagnosed Cases of Cirrhosis, Detected in 4929 Consecutive Autopsies." Journal of Internal Medicine 230:165–171.

McCullough, A. J. (1999). "Alcoholic Liver Disease." In Schiff's Diseases of the Liver, 8th edition, eds. E. R. Schiff, M. F. Sorrell, and W. C. Maddrey. Philadelphia, PA: Lippincott-Raven.

Roizen, R.; Kerr, W. C.; and Fillmore, K. M. (1999). "Cirrhosis Mortality and Per Capita Consumption of Distilled Spirits, United States, 1949–94: Trend Analysis." British Medical Journal 319:666–670.

Rothenberg, R. B., and Koplan, J. P. (1990). "Chronic Disease in the 1990s." Annual Review of Public Health 11:267–296.

Cirrhosis

Definition

Cirrhosis is a chronic degenerative disease in which normal liver cells are damaged and are then replaced by scar tissue.

Description

Cirrhosis changes the structure of the liver and the blood vessels that nourish it. The disease reduces the liver's ability to manufacture proteins and process hormones, nutrients, medications, and poisons.

Cirrhosis gets worse over time and can become potentially life threatening. This disease can cause:

• excessive bleeding (hemorrhage)
• impotence
• liver cancer
• coma due to accumulated ammonia and body wastes (liver failure)
• sepsis (blood poisoning)
• death

Cirrhosis is the seventh leading cause of disease-related death in the United States. It is the third most common cause of death in adults between the ages of 45 and 65. It is twice as common in men as in women. The disease occurs in more than half of all malnourished chronic alcoholics, and kills about 25,000 people

a year. In Asia and Africa, however, most deaths from cirrhosis are due to chronic hepatitis B.

Types of cirrhosis

Portal or nutritional cirrhosis is the form of the disease most common in the United States. About 30–50% of all cases of cirrhosis are this type. Nine out of every 10 people who have nutritional cirrhosis have a history of alcoholism. Portal or nutritional cirrhosis is also called Laënnec's cirrhosis.

Biliary cirrhosis is caused by intrahepatic bileduct diseases that impede bile flow. Bile is formed in the liver and is carried by ducts to the intestines. Bile then helps digest fats in the intestines. Biliary cirrhosis can scar or block these ducts. It represents 15–20% of all cirrhosis.

Various types of chronic hepatitis, especially hepatitis B and hepatitis C, can cause postnecrotic cirrhosis. This form of the disease affects up to 40% of all patients who have cirrhosis.

Disorders like the inability to metabolize iron and similar disorders may cause pigment cirrhosis (hemochromatosis ), which accounts for 5–10% of all instances of the disease.

Causes and symptoms

Long-term alcoholism is the primary cause of cirrhosis in the United States. Men and women respond differently to alcohol. Although most men can safely consume two to five drinks a day, one or two drinks a day can cause liver damage in women. Individual tolerance to alcohol varies, but people who drink more and drink more often have a higher risk of developing cirrhosis. In some people, one drink a day can cause liver scarring.

Chronic liver infections, such as hepatitis B and particularly hepatitis C, are commonly linked to cirrhosis. People at high risk of contracting hepatitis B include those exposed to the virus through contact with blood and body fluids. This includes healthcare workers and intravenous (IV) drug users. In the past, people have contracted hepatitis C through blood transfusions. As of 2003, cirrhosis resulting from chronic hepatitis has emerged as a leading cause of death among HIV-positive patients; in Europe, about 30% of HIV-positive patients are coinfected with a hepatitis virus.

Liver injury, reactions to prescription medications, exposure to toxic substances, and repeated episodes of heart failure with liver congestion can

cause cirrhosis. The disorder can also be a result of diseases that run in families (inherited diseases) like:

• a lack of a specific liver enzyme (alpha₁-antitrypsin deficiency)
• the absence of a milk-digesting enzyme (galactosemia)
• an inability to convert sugars to energy (glycogen storage disease)
• an absorption deficit in which excess iron is deposited in the liver, pancreas, heart, and other organs (hemochromatosis)
• a disorder characterized by accumulations of copper in the liver, brain, kidneys, and corneas (Wilson's disease)

Obesity has recently been recognized as a risk factor in nonalcoholic hepatitis and cirrhosis. Some surgeons are recommending as of 2003 that patients scheduled for weight-reduction surgery have a liver biopsy to evaluate the possibility of liver damage.

Poor nutrition increases a person's risk of developing cirrhosis. In about 10 out of every 100 patients, the cause of cirrhosis cannot be determined. Many people who have cirrhosis do not have any symptoms (often called compensated cirrhosis). Their disease is detected during a routine physical or when tests for an unrelated medical problem are performed. This type of cirrhosis can also be detected when complications occur (decompensated cirrhosis).

Symptoms of cirrhosis are usually caused by the loss of functioning liver cells or organ swelling due to scarring. The liver enlarges during the early stages of illness. The palms of the hands turn red and patients may experience:

• constipation
• diarrhea
• dull abdominal pain
• fatigue
• indigestion
• loss of appetite
• nausea
• vomiting
• weakness
• weight loss

As the disease progresses, the spleen enlarges and fluid collects in the abdomen (ascites) and legs (edema ). Spider-like blood vessels appear on the chest

and shoulders, and bruising becomes common. Men sometimes lose chest hair. Their breasts may grow and their testicles may shrink. Women may have menstrual irregularities.

Cirrhosis can cause extremely dry skin and intense itching . The whites of the eyes and the skin may turn yellow (jaundice), and urine may be dark yellow or brown. Stools may be black or bloody. Sometimes the patient develops persistent high blood pressure due to the scarring (portal hypertension ). This type of hypertension can be life threatening. It can cause veins to enlarge in the stomach and in the tube leading from the mouth to the stomach (esophagus). These enlarged veins are called varices, and they can rupture and bleed massively.

Other symptoms of cirrhosis include:

• anemia
• bleeding gums
• decreased interest in sex
• fever
• fluid in the lungs
• hallucinations
• lethargy
• lightheadedness
• muscle weakness
• musty breath
• painful nerve inflammation (neuritis)
• slurred speech
• tremors

If the liver loses its ability to remove toxins from the brain, the patient may have additional symptoms.

The patient may become forgetful and unresponsive, neglect personal care, have trouble concentrating, and acquire new sleeping habits. These symptoms are related to ammonia intoxication and the failure of the liver to convert ammonia to urea. High protein intake in these patients can also lead to these symptoms.

Diagnosis

A patient's medical history can reveal illnesses or lifestyles likely to lead to cirrhosis. Liver changes can be seen during a physical examination. A doctor who suspects cirrhosis may order blood and urine tests to measure liver function. Because only a small number of healthy cells are needed to carry out essential liver functions, test results may be normal even when cirrhosis is present.

Computed tomography scans (CT), ultrasound, and other imaging techniques can be used during diagnosis. They can help determine the size of the liver, indicate healthy and scarred areas of the organ, and detect gallstones. Cirrhosis is sometimes diagnosed during surgery or by examining the liver with a laparoscope. This viewing device is inserted into the patient's body through a tiny incision in the abdomen.

Liver biopsy is usually needed to confirm a diagnosis of cirrhosis. In this procedure, a tissue sample is removed from the liver and is examined under a microscope in order to learn more about the organ.

A newer and less invasive test involves the measurement of hyaluronic acid in the patient's blood serum. However, the serum hyaluronic acid test is most useful in monitoring the progress of liver disease; it is unlikely to completely replace liver biopsy in the diagnosis of cirrhosis.

Treatment

The goal of treatment is to cure or reduce the condition causing cirrhosis, prevent or delay disease progression, and prevent or treat complications.

Salt and fluid intake are often limited, and activity is encouraged. A diet high in calories and moderately high in protein can benefit some patients.

Tube feedings or vitamin supplements may be prescribed if the liver continues to deteriorate. Patients are asked not to consume alcohol.

Medication

Iron supplements, diuretics , and antibiotics may be used for anemia , fluid retention, and ammonia ac-cumulation associated with cirrhosis. Vasoconstrictors are sometimes needed to stop internal bleeding and antiemetics may be prescribed to control nausea.

Laxatives help the body absorb toxins and accelerate their removal from the digestive tract. Beta blockers may be prescribed to control cirrhosis-induced portal hypertension. Because the diseased liver can no longer efficiently neutralize harmful substances, medications must be given with caution. Interferon medicines may be used by patients with chronic hepatitis B and hepatitis C to prevent post-hepatic cirrhosis.

Surgery

Medication that causes scarring can be injected directly into veins to control bleeding from varices in the stomach or esophagus. Varices may require a special surgical procedure called balloon tamponade ligation to stop the bleeding. Surgery may be required to repair disease-related throat damage. It is sometimes necessary to remove diseased portions of the spleen and other organs.

Liver transplants can benefit patients with advanced cirrhosis. However, the new liver will eventually become diseased unless the underlying cause of cirrhosis is removed. Patients with alcoholic cirrhosis must demonstrate a willingness to stop drinking before being considered suitable transplant candidates.

The incidence of liver cancer related to cirrhosis in the United States has increased 75% since the early 1990s. Partial surgical removal of the liver in patients with early-stage cancer of the liver appears to be as successful as transplantation, in terms of the 5-year survival rate.

Supportive measures

A balanced diet promotes regeneration of healthy liver cells. Eating five or six small meals throughout the day should prevent the sick or bloated feeling patients with cirrhosis often have after eating. Alcohol and caffeine , which destroy liver cells, should be avoided. So should any foods that upset the stomach. Patients with brain disease associated with cirrhosis should avoid excessive amounts of protein in the diet.

A patient can keep a food diary that describes what was eaten, when it was eaten, and how the patient felt afterwards. This diary can be useful in identifying foods that are hard to digest and in scheduling meals to coincide with the times the patient is most hungry.

Patients who have cirrhosis should weigh them-selves every day and notify their doctor of a sudden gain of five pounds or more. A doctor should also be notified if symptoms of cirrhosis appear in anyone who has not been diagnosed with the disease. A doctor should also be notified if a patient diagnosed with cirrhosis:

• vomits blood
• passes black stools
• seems confused or unresponsive
• shows signs of infection (redness, swelling, tenderness, pain)

Alternative treatment

Alternative treatments for cirrhosis are aimed at promoting the function of healthy liver cells and relieving the symptoms associated with the disease. Several herbal remedies may be helpful to cirrhosis patients. Dandelion (Taraxacum officinale) and rock-poppy (Chelidonium majus) may help improve the efficiency of liver cells. Milk thistle extract (Silybum marianum) may slow disease progression and significantly improve survival rates in alcoholics and other cirrhosis patients. Practitioners of homeopathy and traditional Chinese medicine can also prescribe treatments that support healthy liver function.

Prognosis

Cirrhosis-related liver damage cannot be reversed, but further damage can be prevented by patients who:

• eat properly
• get enough rest
• do not consume alcohol
• remain free of infection

If the underlying cause of cirrhosis cannot be corrected or removed, scarring will continue. The liver will fail, and the patient will probably die within five years. Patients who stop drinking after being diagnosed with cirrhosis can increase their likelihood of living more than a few years from 40% to 60–70%.

Prevention

Eliminating alcohol abuse could prevent 75–80% of all cases of cirrhosis.

Other preventive measures include:

• obtaining counseling or other treatment for alcoholism
• taking precautions (practicing safe sex, avoiding dirty needles) to prevent hepatitis
• getting immunizations against hepatitis if a person is in a high-risk group
• receiving appropriate medical treatment quickly when diagnosed with hepatitis B or hepatitis C
• having blood drawn at regular intervals to rid the body of excess iron from hemochromatosis
• using medicines (chelating agents) to rid the body of excess copper from Wilson's disease
• wearing protective clothing and following product directions when using toxic chemicals at work, at home, or in the garden

In 2001, research scientists identified the protein segment and method in which excess tissue grows in diseases like cirrhosis. With further study, the discovery might one day result in an oral or inhalable peptide for those with cirrhosis.

Resources

BOOKS

Beers, Mark H., MD, and Robert Berkow, MD, editors. “Cirrhosis.” Section 4, Chapter 41 In The Merck Manual of Diagnosis and Therapy. Whitehouse Station, NJ: Merck Research Laboratories, 2004.

Pelletier, Kenneth R., MD. The Best Alternative Medicine, Part II, “CAM Therapies for Specific Conditions: Alcoholism.” New York: Simon & Schuster, 2002.

PERIODICALS

Cha, C. H., L. Ruo, Y. Fong, et al. “Resection of Hepatocellular Carcinoma in Patients Otherwise Eligible for Transplantation.” Annals of Surgery 238 (September 2003): 315–321.

Foreman, M. G., D. M. Mannino, and M. Moss. “Cirrhosis as a Risk Factor for Sepsis and Death: Analysis of the National Hospital Discharge Survey.” Chest 124 (September 2003): 1016–1020.

Higuchi, H., and G. J. Gores. “Mechanisms of Liver Injury: An Overview.” Current Molecular Medicine 3 (September 2003): 483–490.

Kamath, B. M., and D. A. Piccoli. “Heritable Disorders of the Bile Ducts.” Gastroenterology Clinics of North America 32 (September 2003): 857–875.

“Management of Alcoholic Hepatitis.” Drug Therapy Bulletin 41 (July 2003): 49–52.

Moretto, M., C. Kupski, C. C. Mottin, et al. “Hepatic Steatosis in Patients Undergoing Bariatric Surgery and Its Relationship to Body Mass Index and Co-Morbidities.” Obesity Surgery 13 (August 2003): 622–624.

“Peptides: Peptide Critical to Cirrhosis Development.” Drug Discovery and Technology News 4, no. 11 (November 2001).

Phillips, M. G., V. R. Preedy, and R. D. Hughes. “Assessment of Prognosis in Alcoholic Liver Disease: Can Serum Hyaluronate Replace Liver Biopsy?” European Journal of Gastroenterology and Hepatology 15 (September 2003): 941–944.

Ristig, M., H. Drechsler, J. Crippin, et al. “Management of Chronic Hepatitis B in an HIV-Positive Patient with 3TC-Resistant Hepatitis B Virus.” AIDS Patient Care and STDs 17 (September 2003): 439–442.

ORGANIZATIONS

American Liver Foundation. 1425 Pompton Ave., Cedar Grove, NJ 07009. (800) 223-0179. http://www.liverfoundation.org.

United Network for Organ Sharing. 1100 Boulders Parkway, Suite 500, P.O. Box 13770, Richmond, VA 23225-8770. (804) 330-8500. http://www.unos.org.

Maureen Haggerty

Rebecca J. Frey Ph.D.

Cirrhosis

Causes of cirrhosis

Progression of cirrhosis

Cirrhosis is a degenerative liver disease in which the lobes of the liver become infiltrated with fat and fibrous tissue. (Fibrous tissue is a type of connective tissue composed of protein fibers called collagen.) The word cirrhosis is derived from the Greek words kirrhos, meaning yellowish orange and osis, meaning condition, and aptly describes the appearance of the liver of a patient with cirrhosis.

The infiltration of these substances within the liver disrupts liver functions, including the conversion of the storage carbohydrate glycogen into glucose; detoxification of drugs and other substances; vitamin absorption; gastrointestinal functions; and hormone metabolism. Because the blood vessels of the liver are affected by fibrous tissue formation, blood flow through the liver is impaired, leading to increased blood pressure within the liver. Impaired blood flow in the liver also causes a condition called esophageal varices, in which blood vessels in the esophagus bleed due to their increased internal pressure. In addition, patients with cirrhosis are often weakened by hypoglycemia, or low blood sugar.

Complications of cirrhosis include coma, gastrointestinal hemorrhage, and kidney failure. No definitive treatment for cirrhosis is available besides management of symptoms and complications. The mortality rate of cirrhosis ranges from 40–63%, and it is the ninth leading cause of death in the United States.

Causes of cirrhosis

Cirrhosis is most often caused by excessive ingestion of alcohol. In the United States, 90% of all cases of cirrhosis are related to alcohol overconsumption. Although researchers still do not have a clear understanding of how alcohol damages the liver, evidence suggests that consuming more than 1 pint of alcohol (86 proof) daily for 10 years increases the risk of cirrhosis by 10%. The risk of cirrhosis increases to 50% if this consumption lasts 25 years. Women may be more susceptible to alcoholic cirrhosis than men. Women have lower levels of the enzyme alcohol dehydrogenase, which breaks down alcohol in the stomach. Lower levels of this enzyme lead to higher blood alcohol levels.

Researchers believe that the main cause of alcohol-induced cirrhosis is acetaldehyde, the first product created when alcohol is broken down in the stomach. Acetaldehyde combines with proteins in the body and damages the liver cells, leading to fat accumulation and fibrous tissue formation. Further damage to liver cells may be caused by a secondary effect of alcohol on the liver: the acetaldehyde may make the liver cells vulnerable to the potentially damaging effects of substances such as acetaminophen (a common over-the-counter pain reliever), industrial solvents, and certain anesthetics on the liver cells.

Although excessive alcohol intake is considered the leading cause of cirrhosis, there are numerous other causes of the disease. These include several types of viral hepatitis, nutritional factors, genetic conditions, and others. In addition, these are often contributing factors in alcoholic cirrhosis. Chronic infection with hepatitis B virus (HBV) can lead to cirrhosis and is also related to liver cancer.

Progression of cirrhosis

Cirrhosis is a progressive disease; in other words, the symptoms become more severe and more numerous over time. In cases of alcoholic cirrhosis, it begins with a condition called alcoholic fatty liver. In this condition, fat accumulates in the liver. The liver enlarges, sometimes to as much as 10 lb (5000 g), and appears yellow and greasy. Patients with this condition often have no symptoms beyond low blood sugar or some digestive upset. Some patients have more severe symptoms, such as jaundice (a condition caused by the accumulation of a yellowish bile pigment in the blood; patients with jaundice have yellow-tinged skin) and weight loss. Complete recovery is possible at this stage of liver disease if the patient abstains from alcohol.

The next stage in the progression of cirrhosis is often a condition called hepatitis. Hepatitis is a general term meaning inflammation of the liver. Hepatitis may be caused by alcohol, several different types of virus, or other factors. In acute alcoholic hepatitis, the inflammation is caused by alcohol. Fibrous tissue is deposited in the liver, the liver cells degenerate, and a type of connective tissue called hyaline infiltrates the liver cells. Regardless of the cause, patients with hepatitis have serious symptoms, which include general debilitation, loss of muscle mass, jaundice, fever, and abdominal pain. The liver is firm, tender, and enlarged. Vascular “spiders,” or varicose veins of the liver, are present. Again, no definitive treatment is available, although some patients respond well to corticosteroids. General treatment for this condition includes treatment of symptoms and complications.

Acute alcoholic hepatitis often progresses to cirrhosis. In cirrhosis, the fibrous tissue and fat

Key Terms

Acute alcoholic hepatitis —Inflammation of the liver caused by excessive alcohol consumption.

Collagen— A type of protein that comprises connective tissue; infiltrates the liver in cirrhosis.

Fatty liver— A condition in which the liver accumulates fat due to excessive alcohol consumption.

Fibrous tissue— Connective tissue composed primarily of collagen.

Hepatitis— General inflammation of the liver; may be caused by viral infection or by excessive alcohol consumption.

Jaundice— condition in which a yellowish bile pigment increases in the blood; patients with jaundice have a characteristic yellow tinge to their skin.

accumulation is prominent. Collagen is deposited around the veins of the liver, leading to impairment of blood flow. The liver cells degenerate further and die, leading to formation of nodules in the liver, and the liver shrinks (atrophy). Symptoms of cirrhosis include nausea, weight loss, jaundice, and esophageal varices. Gastrointestinal symptoms, such as diarrhea and gastric distention, are also features of cirrhosis. The mortality rate of cirrhosis is high. Studies have established that the five-year survival of patients with cirrhosis is only about 65% for patients who stop drinking, and around 40% for patients who continue to drink. Death results from kidney failure, coma, malnutrition, and cardiac arrest.

Treatment of cirrhosis depends on the type and cause. For patients with alcoholic cirrhosis, it includes general support, treatment of complications, a nutritious diet, and abstention from alcohol consumption. In selected patients, liver transplant may be indicated. Although the liver has a remarkable ability to regenerate, the damage that cirrhosis inflicts on the liver may be so severe that recovery is not possible. In cirrhosis caused by viral hepatitis, the use of experimental drugs has had some success. Research continues into blocking the effects of the various hepatitis viruses, or preventing their replication in the liver cells.

Resources

BOOKS

Chen, T.M. New Developments in Liver Cirrhosis Research. Hauppage NY: Nova Biomedical Books, 2006.

Dickerson, James L. and Fredric Regenstein. The First Year: Cirrhosis: An Essential Guide for the Newly Diagnosed. Washington: Marlowe & Company, 2006.

Parker, James N. and Philip M. Parker. The Official Patient’s Sourcebook on Primary Biliary Cirrhosis. San Diego: Icon Health Publications, 2002.

Kathleen Scogna