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)
• death

Cirrhosis is the seventh leading cause of diseaserelated death in the United States. 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. It is the third most common cause of death in adults between the ages of 45 and 65.

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.

— Maureen Haggerty

1. A chronic disease of the liver characterized by the replacement of normal tissue with fibrous tissue and the loss of functional liver cells. It can result from alcohol abuse, nutritional deprivation, or infection especially by the hepatitis virus.
2. Chronic interstitial inflammation of any tissue or organ.

[New Latin : Greek kirros, tawny (from the color of the diseased liver) + -OSIS.]

For more information on cirrhosis, visit Britannica.com.

A liver disease characterized by a marked increase in fibrous connective tissue, resulting in a firm, nodular, distorted liver.

There are numerous causes of cirrhosis. In the United States the majority of cases are caused by excessive alcohol consumption, and the condition is referred to as alcoholic cirrhosis. Cirrhosis may occur as a result of the healing of severe fulminant hepatitis or chronic active hepatitis. Some cases are caused by obstruction of the bile duct by calculi (stones) and are referred to as secondary biliary cirrhosis. Primary biliary cirrhosis is primarily a disease of middle-aged women and is caused by an autoimmune destruction of bile ducts. Autoimmune hepatitis, sometimes referred to as lupoid hepatitis and characteristically seen in young women and associated with serum autoantibodies, may progress to cirrhosis. Relatively few cases of cirrhosis are caused by genetically determined deficiencies in certain substances. See also Alcoholism; Hepatitis.

The signs and symptoms of cirrhosis are nonspecific and frequently related to the complications. As the liver becomes fibrotic, there is obstruction of the blood flow through the liver. This results in portal hypertension, an increase in blood pressure within the portal vein and its tributaries. The obstructed hepatic blood flow also causes congestion of the spleen, leading to a markedly enlarged spleen (splenomegaly). Also, most people with cirrhosis eventually develop fluid in their abdomen (ascites) and are at an increased risk of developing a spontaneous intraabdominal infection. In addition to obstruction of blood flow, the bile ducts within the liver are distorted and frequently partially obstructed by the increased connective tissue. This results in jaundice, a yellow discoloration of all tissues and organs, including the skin. Some individuals with advanced cirrhosis develop renal failure, a condition referred to as hepatorenal syndrome. Also, there is a definite increase in liver cell cancer in cirrhotic persons. The liver may be slightly enlarged, but as the disease progresses it usually becomes smaller due to progressive loss of liver cells. See also Jaundice.

The therapy of cirrhosis is aimed primarily at preventing or reducing the complications. Bleeding esophageal varices (collateral venous channels) are a frequent serious complication of cirrhosis. Various techniques are used to control the bleeding. In some individuals with severe portal hypertension, vascular shunts are made to reduce the pressure in the portal vein by bypassing the liver. Most frequently the portal vein is surgically connected to the inferior vena cava so that some of the blood in the portal vein does not pass through the liver. See also Cardiovascular system; Liver disorders.

A chronic degenerative disease of the liver in which blood flow is restricted and metabolic and detoxification functions are impaired or destroyed. Cirrhosis is most commonly the result of chronic alcohol abuse.

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. .

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

Other

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). Cirrhosis of the Liver. April 200 [cited October 2002]. .

[Article by: Teresa G. Odle; Rebecca J. Frey, PhD]

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. 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 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.

(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.

— SAMMY SAAB; SERGIO E. ROJTER

A chronic disease of the liver, characterized by replacement of normal liver cells with a form of connective tissue. Owing to the scarring caused by this disease, irreversible damage to the liver can result.

A liver disease characterized pathologically by the loss of the normal microscopic lobular architecture and regenerative replacement of necrotic parenchymal tissue with fibrous bands of connective tissue which eventually constrict and partition the organ into irregular nodules. The term is sometimes used to refer to chronic interstitial inflammation of any organ.

• cardiac c. — fibrosis or scarring of the liver resulting from the anoxia and centrilobular necrosis associated with the passive congestion of congestive heart failure.

Cirrhosis
Classification and external resources
Micrograph showing cirrhosis. Trichrome stain.
ICD-10	K70.3, K71.7, K74.
ICD-9	571
DiseasesDB	2729
eMedicine	med/3183 radio/175
MeSH	D008103

Cirrhosis (pronounced /sɪˈroʊsɪs/, si-ROH-sis) is a consequence of chronic liver disease characterized by replacement of liver tissue by fibrosis, scar tissue and regenerative nodules (lumps that occur as a result of a process in which damaged tissue is regenerated),^[1][2][3] leading to progressive loss of liver function. Cirrhosis is most commonly caused by alcoholism, hepatitis B and C, and fatty liver disease but has many other possible causes. Some cases are idiopathic, i.e., of unknown cause.

Ascites (fluid retention in the abdominal cavity) is the most common complication of cirrhosis and is associated with a poor quality of life, increased risk of infection, and a poor long-term outcome. Other potentially life-threatening complications are hepatic encephalopathy (confusion and coma) and bleeding from esophageal varices. Cirrhosis is generally irreversible once it occurs, and treatment generally focuses on preventing progression and complications. In advanced stages of cirrhosis the only option is a liver transplant.

The word "cirrhosis" derives from Greek κίρῥος, meaning tawny (the orange-yellow colour of the diseased liver). While the clinical entity was known before, it was René Laennec who gave it the name "cirrhosis" in his 1819 work in which he also describes the stethoscope.^[4]

Contents 1 Signs and symptoms 1.1 Complications 2 Causes 3 Pathophysiology 4 Diagnosis 4.1 Lab findings 4.2 Imaging 4.3 Endoscopy 4.4 Pathology 4.5 Grading 5 Management 5.1 Treating underlying causes 5.2 Preventing further liver damage 5.3 Preventing complications 5.3.1 Ascites 5.3.2 Esophageal variceal bleeding 5.3.3 Hepatic encephalopathy 5.3.4 Hepatorenal syndrome 5.3.5 Spontaneous bacterial peritonitis 5.4 Transplantation 5.5 Decompensated cirrhosis 6 Epidemiology 7 References 8 External links

Signs and symptoms

Some of the following signs and symptoms may occur in the presence of cirrhosis or as a result of the complications of cirrhosis. Many are nonspecific and may occur in other diseases and do not necessarily point to cirrhosis. Likewise, the absence of any does not rule out the possibility of cirrhosis.

• Spider angiomata or spider nevi. Vascular lesions consisting of a central arteriole surrounded by many smaller vessels due to an increase in estradiol. These occur in about 1/3 of cases.^[5]
• Palmar erythema. Exaggerations of normal speckled mottling of the palm, due to altered sex hormone metabolism.
• Nail changes.
  • Muehrcke's nails - paired horizontal bands separated by normal color due to hypoalbuminemia (inadequate production of albumin).
  • Terry's nails - proximal two thirds of the nail plate appears white with distal one-third red, also due to hypoalbuminemia
  • Clubbing - angle between the nail plate and proximal nail fold > 180 degrees
• Hypertrophic osteoarthropathy. Chronic proliferative periostitis of the long bones that can cause considerable pain.
• Dupuytren's contracture. Thickening and shortening of palmar fascia that leads to flexion deformities of the fingers. Thought to be due to fibroblastic proliferation and disorderly collagen deposition. It is relatively common (33% of patients).
• Gynecomastia. Benign proliferation of glandular tissue of male breasts presenting with a rubbery or firm mass extending concentrically from the nipples. This is due to increased estradiol and can occur in up to 66% of patients.
• Hypogonadism. Manifested as impotence, infertility, loss of sexual drive, and testicular atrophy due to primary gonadal injury or suppression of hypothalamic or pituitary function.
• Liver size. Can be enlarged, normal, or shrunken.
• Splenomegaly (increase in size of the spleen). Due to congestion of the red pulp as a result of portal hypertension.
• Ascites. Accumulation of fluid in the peritoneal cavity giving rise to flank dullness (needs about 1500 mL to detect flank dullness). It may be associated with hydrocele and penile flomation (swelling of the penile shaft)^{[citation needed]} in men.
• Caput medusa. In portal hypertension, the umbilical vein may open. Blood from the portal venous system may be shunted through the periumbilical veins into the umbilical vein and ultimately to the abdominal wall veins, manifesting as caput medusa.
• Cruveilhier-Baumgarten murmur. Venous hum heard in epigastric region (on examination by stethoscope) due to collateral connections between portal system and the remnant of the umbilical vein in portal hypertension.
• Fetor hepaticus. Musty odor in breath due to increased dimethyl sulfide.
• Jaundice. Yellow discoloring of the skin, eye, and mucus membranes due to increased bilirubin (at least 2–3 mg/dL or 30 mmol/L). Urine may also appear dark.
• Asterixis. Bilateral asynchronous flapping of outstretched, dorsiflexed hands seen in patients with hepatic encephalopathy.
• Other. Weakness, fatigue, anorexia, weight loss.

Complications

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

• Bruising and bleeding due to decreased production of coagulation factors.
• Jaundice due to decreased processing of bilirubin.
• Itching (pruritus) due to bile salts products deposited in the skin.
• Hepatic encephalopathy - the liver does not clear ammonia and related nitrogenous substances from the blood, which are carried to the brain, affecting cerebral functioning: neglect of personal appearance, unresponsiveness, forgetfulness, trouble concentrating, or changes in sleep habits.
• Sensitivity to medication due to decreased metabolism of the active compounds.
• Hepatocellular carcinoma is primary liver cancer, a frequent complication of cirrhosis. It has a high mortality rate.
• Portal hypertension - blood normally carried from the intestines and spleen through the hepatic portal vein flows more slowly and the pressure increases; this leads to the following complications:
  • Ascites - fluid leaks through the vasculature into the abdominal cavity.
  • Esophageal varices - collateral portal blood flow through vessels in the stomach and esophagus. These blood vessels may become enlarged and are more likely to burst.
• Problems in other organs.
  • Cirrhosis can cause immune system dysfunction, leading to infection. Signs and symptoms of infection may be aspecific are more difficult to recognize (e.g. worsening encephalopathy but no fever).
  • Fluid in the abdomen (ascites) may become infected with bacteria normally present in the intestines (spontaneous bacterial peritonitis).
  • Hepatorenal syndrome - insufficient blood supply to the kidneys, causing acute renal failure. This complication has a very high mortality (over 50%).
  • Hepatopulmonary syndrome - blood bypassing the normal lung circulation (shunting), leading to cyanosis and dyspnea (shortness of breath), characteristically worse on sitting up.^[6]
  • Portopulmonary hypertension - increased blood pressure over the lungs as a consequence of portal hypertension.^[6]

Causes

Cirrhosis has many possible causes; sometimes more than one cause is present in the same patient. In the Western World, chronic alcoholism and hepatitis C are the most common causes.

• Alcoholic liver disease (ALD). Alcoholic cirrhosis develops for between 10% and 20% of individuals who drink heavily for a decade or more.^[7] There is great variability in the amount of alcohol needed to cause cirrhosis (as little as 3-4 drinks a day in some men and 2-3 in some women^{[citation needed]}). Alcohol seems to injure the liver by blocking the normal metabolism of protein, fats, and carbohydrates. Patients may also have concurrent alcoholic hepatitis with fever, hepatomegaly, jaundice, and anorexia. AST and ALT are both elevated but less than 300 IU/L with a AST:ALT ratio > 2.0, a value rarely seen in other liver diseases. Liver biopsy may show hepatocyte necrosis, Mallory bodies, neutrophilic infiltration with perivenular inflammation.
• Chronic hepatitis C. Infection with the hepatitis C virus causes inflammation of the liver and a variable grade of damage to the organ that over several decades can lead to cirrhosis. Cirrhosis caused by hepatitis C is the most common reason for liver transplant. Can be diagnosed with serologic assays that detect hepatitis C antibody or viral RNA. The enzyme immunoassay, EIA-2, is the most commonly used screening test in the US.
• Chronic hepatitis B. The hepatitis B virus causes liver inflammation and injury that over several decades can lead to cirrhosis. Hepatitis D is dependent on the presence of hepatitis B, but accelerates cirrhosis in co-infection. Chronic hepatitis B can be diagnosed with detection of HBsAG > 6 months after initial infection. HBeAG and HBV DNA are determined to assess whether patient will need antiviral therapy.
• Non-alcoholic steatohepatitis (NASH). In NASH, fat builds up in the liver and eventually causes scar tissue. This type of hepatitis appears to be associated with diabetes, protein malnutrition, obesity, coronary artery disease, and treatment with corticosteroid medications. This disorder is similar to that of alcoholic liver disease but patient does not have an alcohol history. Biopsy is needed for diagnosis.
• Primary biliary cirrhosis. May be asymptomatic or complain of fatigue, pruritus, and non-jaundice skin hyperpigmentation with hepatomegaly. There is prominent alkaline phosphatase elevation as well as elevations in cholesterol and bilirubin. Gold standard diagnosis is antimitochondrial antibodies with liver biopsy as confirmation if showing florid bile duct lesions. It is more common in women.
• Primary sclerosing cholangitis. PSC is a progressive cholestatic disorder presenting with pruritus, steatorrhea, fat soluble vitamin deficiencies, and metabolic bone disease. There is a strong association with inflammatory bowel disease (IBD), especially ulcerative colitis. Diagnosis is best with contrast cholangiography showing diffuse, multifocal strictures and focal dilation of bile ducts, leading to a beaded appearance. Non-specific serum immunoglobulins may also be elevated.
• Autoimmune hepatitis. This disease is caused by the immunologic damage to the liver causing inflammation and eventually scarring and cirrhosis. Findings include elevations in serum globulins, especially gamma globulins. Therapy with prednisone +/- azathioprine is beneficial. Cirrhosis due to autoimmune hepatitis still has 10-year survival of 90%+. There is no specific tool to diagnose autoimmune but it can be beneficial to initiate a trial of corticosteroids.
• Hereditary hemochromatosis. Usually presents with family history of cirrhosis, skin hyperpigmentation, diabetes mellitus, pseudogout, and/or cardiomyopathy, all due to signs of iron overload. Labs will show fasting transferrin saturation of > 60% and ferritin > 300 ng/mL. Genetic testing may be used to identify HFE mutations. If these are present, biopsy may not need to be performed. Treatment is with phlebotomy to lower total body iron levels.
• Wilson's disease. Autosomal recessive disorder characterized by low serum ceruloplasmin and increased hepatic copper content on liver biopsy. May also have Kayser-Fleischer rings in the cornea and altered mental status.
• Alpha 1-antitrypsin deficiency (AAT). Autosomal recessive disorder. Patients may also have COPD, especially if they have a history of tobacco smoking. Serum AAT levels are low. Recombinant AAT is used to prevent lung disease due to AAT deficiency.
• Cardiac cirrhosis. Due to chronic right sided heart failure which leads to liver congestion.
• Galactosemia
• Glycogen storage disease type IV
• Cystic fibrosis
• Hepatotoxic drugs or toxins
• Certain parasitic infections (such as schistosomiasis)

Pathophysiology

The liver plays a vital role in synthesis of proteins (e.g. albumin, clotting factors and complement), detoxification and storage (e.g. vitamin A). In addition, it participates in the metabolism of lipids and carbohydrates.

Cirrhosis is often preceded by hepatitis and fatty liver (steatosis), independent of the cause. If the cause is removed at this stage, the changes are still fully reversible.

The pathological hallmark of cirrhosis is the development of scar tissue that replaces normal parenchyma, blocking the portal flow of blood through the organ and disturbing normal function. Recent research shows the pivotal role of stellate cell, a cell type that normally stores vitamin A, in the development of cirrhosis. Damage to the hepatic parenchyma leads to activation of the stellate cell, which becomes contractile (called myofibroblast) and obstructs blood flow in the circulation. In addition, it secretes TGF-β₁, which leads to a fibrotic response and proliferation of connective tissue. Furthermore, it disturbs the balance between matrix metalloproteinases and the naturally occurring inhibitors (TIMP 1 and 2), leading to matrix breakdown and replacement by connective tissue-secreted matrix.^[8]

The fibrous tissue bands (septa) separate hepatocyte nodules, which eventually replace the entire liver architecture, leading to decreased blood flow throughout. The spleen becomes congested, which leads to hypersplenism and increased sequestration of platelets. Portal hypertension is responsible for most severe complications of cirrhosis.

Diagnosis

The gold standard for diagnosis of cirrhosis is a liver biopsy, through a percutaneous, transjugular, laparoscopic, or fine-needle approach. Histologically cirrhosis can be classified as micronodular, macronodular, or mixed, but this classification has been abandoned since it is non-specific to the aetiology, it may change as the disease progresses, and serological markers are much more specific^{[citation needed]}. However, a biopsy is not necessary if the clinical, laboratory, and radiologic data suggests cirrhosis. Furthermore, there is a small but significant risk to liver biopsy, and cirrhosis itself predisposes for complications due to liver biopsy.^[9]

Lab findings

The following findings are typical in cirrhosis:

• Aminotransferases - AST and ALT are moderately elevated, with AST > ALT. However, normal aminotransferases do not preclude cirrhosis.
• Alkaline phosphatase - usually slightly elevated.
• GGT – correlates with AP levels. Typically much higher in chronic liver disease from alcohol.
• Bilirubin - may elevate as cirrhosis progresses.
• Albumin - levels fall as the synthetic function of the liver declines with worsening cirrhosis since albumin is exclusively synthesized in the liver
• Prothrombin time - increases since the liver synthesizes clotting factors.
• Globulins - increased due to shunting of bacterial antigens away from the liver to lymphoid tissue.
• Serum sodium - hyponatremia due to inability to excrete free water resulting from high levels of ADH and aldosterone.
• Thrombocytopenia - due to both congestive splenomegaly as well as decreased thrombopoietin from the liver. However, this rarely results in platelet count < 50,000/mL.
• Leukopenia and neutropenia - due to splenomegaly with splenic margination.
• Coagulation defects - the liver produces most of the coagulation factors and thus coagulopathy correlates with worsening liver disease.

There is now a validated and patented combination of 6 of these markers as non-invasive biomarker of fibrosis (and so of cirrhosis) : FibroTest ^[10].

Other laboratory studies performed in newly diagnosed cirrhosis may include:

• Serology for hepatitis viruses, autoantibodies (ANA, anti-smooth muscle, anti-mitochondria, anti-LKM)
• Ferritin and transferrin saturation (markers of iron overload), copper and ceruloplasmin (markers of copper overload)
• Immunoglobulin levels (IgG, IgM, IgA) - these are non-specific but may assist in distinguishing various causes
• Cholesterol and glucose
• Alpha 1-antitrypsin

Imaging

Liver cirrhosis as seen on an axial CT of the abdomen.

Ultrasound is routinely used in the evaluation of cirrhosis, where it may show a small and nodular liver in advanced cirrhosis along with increased echogenicity with irregular appearing areas. Ultrasound may also screen for hepatocellular carcinoma, portal hypertension and Budd-Chiari syndrome (by assessing flow in the hepatic vein).

A new type of device, the FibroScan (transient elastography), uses elastic waves to determine liver stiffness which theoretically can be converted into a liver score based on the METAVIR scale. The FibroScan produces an ultrasound image of the liver (from 20–80 mm) along with a pressure reading (in kPa.) The test is much faster than a biopsy (usually last 2.5–5 minutes) and is completely painless. It shows reasonable correlation with the severity of cirrhosis.^[11]

Other tests performed in particular circumstances include abdominal CT and liver/bile duct MRI (MRCP).

Endoscopy

Gastroscopy (endoscopic examination of the esophagus, stomach and duodenum) is performed in patients with established cirrhosis to exclude the possibility of esophageal varices. If these are found, prophylactic local therapy may be applied (sclerotherapy or banding) and beta blocker treatment may be commenced.

Rarely diseases of the bile ducts, such as primary sclerosing cholangitis, can be causes of cirrhosis. Imaging of the bile ducts, such as ERCP or MRCP (MRI of biliary tract and pancreas) can show abnormalities in these patients, and may aid in the diagnosis.

Pathology

Cirrhosis leading to hepatocellular carcinoma (autopsy specimen).

Macroscopically, the liver may be initially enlarged, but with progression of the disease, it becomes smaller. Its surface is irregular, the consistency is firm and the color is often yellow (if associates steatosis). Depending on the size of the nodules there are three macroscopic types: micronodular, macronodular and mixed cirrhosis. In micronodular form (Laennec's cirrhosis or portal cirrhosis) regenerating nodules are under 3 mm. In macronodular cirrhosis (post-necrotic cirrhosis), the nodules are larger than 3 mm. The mixed cirrhosis consists in a variety of nodules with different sizes.

However, cirrhosis is defined by its pathological features on microscopy: (1) the presence of regenerating nodules of hepatocytes and (2) the presence of fibrosis, or the deposition of connective tissue between these nodules. The pattern of fibrosis seen can depend upon the underlying insult that led to cirrhosis; fibrosis can also proliferate even if the underlying process that caused it has resolved or ceased. The fibrosis in cirrhosis can lead to destruction of other normal tissues in the liver: including the sinusoids, the space of Disse, and other vascular structures, which leads to altered resistance to blood flow in the liver and portal hypertension.^[12]

As cirrhosis can be caused by many different entities which injure the liver in different ways, different cause-specific patterns of cirrhosis, and other cause-specific abnormalities can be seen in cirrhosis. For example, in chronic hepatitis B, there is infiltration of the liver parenchyma with lymphocytes;^[12] in cardiac cirrhosis there are erythrocytes and a greater amount of fibrosis in the tissue surrounding the hepatic veins;^[13] in primary biliary cirrhosis, there is fibrosis around the bile duct, the presence of granulomas and pooling of bile;^[14] and in alcoholic cirrhosis, there is infiltration of the liver with neutrophils.^[12]

Grading

The severity of cirrhosis is commonly classified with the Child-Pugh score. This score uses bilirubin, albumin, INR, presence and severity of ascites and encephalopathy to classify patients in class A, B or C; class A has a favourable prognosis, while class C is at high risk of death. It was devised in 1964 by Child and Turcotte and modified in 1973 by Pugh et al..^[15]

More modern scores, used in the allocation of liver transplants but also in other contexts, are the Model for End-Stage Liver Disease (MELD) score and its pediatric counterpart, the Pediatric End-Stage Liver Disease (PELD) score.

The hepatic venous pressure gradient, i.e. the difference in venous pressure between afferent and efferent blood to the liver, also determines severity of cirrhosis, although hard to measure. A value of 16 mm or more means a greatly increased risk of dying.^[16]

Management

Generally, liver damage from cirrhosis cannot be reversed, but treatment could stop or delay further progression and reduce complications. A healthy diet is encouraged, as cirrhosis may be an energy-consuming process. Close follow-up is often necessary. Antibiotics will be prescribed for infections, and various medications can help with itching. Laxatives, such as lactulose, decrease risk of constipation; their role in preventing encephalopathy is limited.

Treating underlying causes

Alcoholic cirrhosis caused by alcohol abuse is treated by abstaining from alcohol. Treatment for hepatitis-related cirrhosis involves medications used to treat the different types of hepatitis, such as interferon for viral hepatitis and corticosteroids for autoimmune hepatitis. Cirrhosis caused by Wilson's disease, in which copper builds up in organs, is treated with chelation therapy (e.g. penicillamine) to remove the copper.

Preventing further liver damage

Regardless of underlying cause of cirrhosis, alcohol and paracetamol, as well as other potentially damaging substances, are discouraged. Vaccination of susceptible patients should be considered for Hepatitis A and Hepatitis B.

Preventing complications

Ascites

Main article: Ascites

Salt restriction is often necessary, as cirrhosis leads to accumulation of salt (sodium retention). Diuretics may be necessary to suppress ascites.

Esophageal variceal bleeding

Main article: Esophageal varices

For portal hypertension, propranolol is a commonly used agent to lower blood pressure over the portal system. In severe complications from portal hypertension, transjugular intrahepatic portosystemic shunting is occasionally indicated to relieve pressure on the portal vein. As this can worsen encephalopathy, it is reserved for those at low risk of encephalopathy, and is generally regarded only as a bridge to liver transplantation or as a palliative measure.

Hepatic encephalopathy

Main article: Hepatic encephalopathy

High-protein food increases the nitrogen balance, and would theoretically increase encephalopathy; in the past, this was therefore eliminated as much as possible from the diet. Recent studies show that this assumption was incorrect, and high-protein foods are even encouraged to maintain adequate nutrition.

Hepatorenal syndrome

Main article: Hepatorenal syndrome

The hepatorenal syndrome is defined as a urine sodium less than 10 mmol/L and a serum creatinine > 1.5 mg/dl (or 24 hour creatinine clearance less than 40 ml/min) after a trial of volume expansion without diuretics.^[17]

Spontaneous bacterial peritonitis

Main article: Spontaneous bacterial peritonitis

Cirrhotic patients with ascites are at risk of spontaneous bacterial peritonitis.

Transplantation

Main article: Liver transplantation

If complications cannot be controlled or when the liver ceases functioning, liver transplantation is necessary. Survival from liver transplantation has been improving over the 1990s, and the five-year survival rate is now around 80%, depending largely on the severity of disease and other medical problems in the recipient.^[18] In the United States, the MELD score (online calculator)^[19] is used to prioritize patients for transplantation. Transplantation necessitates the use of immune suppressants (cyclosporine or tacrolimus).

Decompensated cirrhosis

In patients with previously stable cirrhosis, decompensation may occur due to various causes, such as constipation, infection (of any source), increased alcohol intake, medication, bleeding from esophageal varices or dehydration. It may take the form of any of the complications of cirrhosis listed above.

Patients with decompensated cirrhosis generally require admission to hospital, with close monitoring of the fluid balance, mental status, and emphasis on adequate nutrition and medical treatment - often with diuretics, antibiotics, laxatives and/or enemas, thiamine and occasionally steroids, acetylcysteine and pentoxifylline. Administration of saline is generally avoided as it would add to the already high total body sodium content that typically occurs in cirrhosis.

Epidemiology

Disability-adjusted life year for cirrhosis of the liver per 100,000 inhabitants in 2004.^[20]

     no data      less than 50      50-100      100-200      200-300      300-400      400-500      500-600      600-700      700-800      800-900      900-1000      more than 1000

Cirrhosis and chronic liver disease were the 10th leading cause of death for men and the 12th for women in the United States in 2001, killing about 27,000 people each year.^[21] Also, the cost of cirrhosis in terms of human suffering, hospital costs, and lost productivity is high.

Established cirrhosis has a 10-year mortality of 34-66%, largely dependent on the cause of the cirrhosis; alcoholic cirrhosis has a worse prognosis than primary biliary cirrhosis and cirrhosis due to hepatitis. The risk of death due to all causes is increased twelvefold; if one excludes the direct consequences of the liver disease, there is still a fivefold increased risk of death in all disease categories.^[22]

Little is known on modulators of cirrhosis risk, apart from other diseases that cause liver injury (such as the combination of alcoholic liver disease and chronic viral hepatitis, which may act synergistically in leading to cirrhosis). Studies have recently suggested that coffee consumption may protect against cirrhosis, especially alcoholic cirrhosis.^[23]

References

1. ^ "Cirrhosis – MayoClinic.com". http://www.mayoclinic.com/print/cirrhosis/DS00373/DSECTION=all&METHOD=print. 
2. ^ "Liver Cirrhosis". Review of Pathology of the Liver. http://www.meddean.luc.edu/lumen/MedEd/orfpath/cirhosis.htm. 
3. ^ "Pathology Education: Gastrointestinal". http://www.pathology.vcu.edu/education/gi/lab3.h.html. 
4. ^ Roguin A (2006). "Rene Theophile Hyacinthe Laënnec (1781-1826): the man behind the stethoscope". Clinical medicine & research 4 (3): 230–5. PMID 17048358. 
5. ^ Li CP, Lee FY, Hwang SJ, et al. (1999). "Spider angiomas in patients with liver cirrhosis: role of alcoholism and impaired liver function". Scand. J. Gastroenterol. 34 (5): 520–3. doi:10.1080/003655299750026272. PMID 10423070. 
6. ^ ^{a b} Rodríguez-Roisin R, Krowka MJ, Hervé P, Fallon MB (2004). "Pulmonary-Hepatic vascular Disorders (PHD)". Eur. Respir. J. 24 (5): 861–80. doi:10.1183/09031936.04.00010904. PMID 15516683. 
7. ^ Alcohol-Induced Liver Disease; http://www.liverfoundation.org/education/info/alcohol/
8. ^ Iredale JP (2003). "Cirrhosis: new research provides a basis for rational and targeted treatments". BMJ 327 (7407): 143–7. doi:10.1136/bmj.327.7407.143. PMID 12869458. PMC 1126509. http://bmj.bmjjournals.com/cgi/content/full/327/7407/143. 
9. ^ Grant, A; Neuberger J (1999). "Guidelines on the use of liver biopsy in clinical practice". Gut 45 (Suppl 4): 1–11. doi:10.1136/gut.45.2008.iv1. PMID 10485854. http://gut.bmj.com/cgi/content/full/45/suppl_4/IV1. "The main cause of mortality after percutaneous liver biopsy is intraperitoneal haemorrhage as shown in a retrospective Italian study of 68,000 percutaneous liver biopsies in which all six patients who died did so from intraperitoneal haemorrhage. Three of these patients had had a laparotomy, and all had either cirrhosis or malignant disease, both of which are risk factors for bleeding.". 
10. ^ Halfon P, Munteanu M, Poynard T (2008). "FibroTest-ActiTest as a non-invasive marker of liver fibrosis". Gastroenterol Clin Biol 32 (6): 22-39. PMID 18973844. 
11. ^ Foucher J, Chanteloup E, Vergniol J, et al. (2006). "Diagnosis of cirrhosis by transient elastography (FibroScan): a prospective study". Gut 55 (3): 403–8. doi:10.1136/gut.2005.069153. PMID 16020491. 
12. ^ ^{a b c} Brenner, David; Richard A. Rippe (2003). "Pathogenesis of Hepatic Fibrosis". in Tadataka Yamada. Textbook of Gastroenterology. 2 (4th ed.). Lippincott Williams & Wilkins. ISBN 978-0781728614. 
13. ^ Giallourakis CC, Rosenberg PM, Friedman LS (November 2002). "The liver in heart failure". Clin Liver Dis 6 (4): 947–67, viii–ix. doi:10.1016/S1089-3261(02)00056-9. PMID 12516201. 
14. ^ Heathcote EJ (November 2003). "Primary biliary cirrhosis: historical perspective". Clin Liver Dis 7 (4): 735–40. doi:10.1016/S1089-3261(03)00098-9. PMID 14594128. 
15. ^ Pugh RN, Murray-Lyon IM, Dawson JL, Pietroni MC, Williams R (1973). "Transection of the oesophagus for bleeding oesophageal varices". Br J Surg 60 (8): 646–9. doi:10.1002/bjs.1800600817. PMID 4541913. 
16. ^ Patch D, Armonis A, Sabin C, et al. (1999). "Single portal pressure measurement predicts survival in cirrhotic patients with recent bleeding". Gut 44 (2): 264–9. PMID 9895388. PMC 1727391. http://gut.bmj.com/cgi/content/abstract/44/2/264. 
17. ^ Ginés P, Arroyo V, Quintero E, et al. (1987). "Comparison of paracentesis and diuretics in the treatment of cirrhotics with tense ascites. Results of a randomized study". Gastroenterology 93 (2): 234–41. PMID 3297907. 
18. ^ "E-medicine liver transplant outlook and survival rates". Emedicinehealth.com. 2009-06-09. http://www.emedicinehealth.com/liver_transplant/page11_em.htm. Retrieved 2009-09-06. 
19. ^ Cosby RL, Yee B, Schrier RW (1989). "New classification with prognostic value in cirrhotic patients". Mineral and electrolyte metabolism 15 (5): 261–6. PMID 2682175. 
20. ^ "WHO Disease and injury country estimates". World Health Organization. 2009. http://www.who.int/healthinfo/global_burden_disease/estimates_country/en/index.html. Retrieved Nov. 11, 2009. 
21. ^ Anderson RN, Smith BL (2003). "Deaths: leading causes for 2001". National vital statistics reports: from the Centers for Disease Control and Prevention, National Center for Health Statistics, National Vital Statistics System 52 (9): 1–85. PMID 14626726. 
22. ^ Sørensen HT, Thulstrup AM, Mellemkjar L, et al. (2003). "Long-term survival and cause-specific mortality in patients with cirrhosis of the liver: a nationwide cohort study in Denmark". Journal of clinical epidemiology 56 (1): 88–93. doi:10.1016/S0895-4356(02)00531-0. PMID 12589875. 
23. ^ Klatsky AL, Morton C, Udaltsova N, Friedman GD (2006). "Coffee, cirrhosis, and transaminase enzymes". Arch. Intern. Med. 166 (11): 1190–5. doi:10.1001/archinte.166.11.1190. PMID 16772246. 

External links

• Cirrhosis of the Liver at the National Digestive Diseases Information Clearinghouse (NDDIC). NIH Publication No. 04-1134, December 2003.
• [1] at the National Library of Medicine and the National Institutes of Health. Medline Plus: Cirrhosis – also called: Hepatic fibrosis

v • d • e Digestive system · Digestive disease · Gastroenterology (primarily K20–K93, 530–579) Upper GI tract Esophagus Esophagitis (Candidal) · rupture (Boerhaave syndrome, Mallory-Weiss syndrome) · UES (Zenker's diverticulum) · LES (Barrett's esophagus) · Esophageal motility disorder (Nutcracker esophagus, Achalasia, Diffuse esophageal spasm, GERD) · Esophageal stricture · Megaesophagus Stomach Gastritis (Atrophic, Ménétrier's disease, Gastroenteritis) · Peptic (gastric) ulcer (Cushing ulcer, Dieulafoy's lesion) · Dyspepsia · Pyloric stenosis · Achlorhydria · Gastroparesis · Gastroptosis · Portal hypertensive gastropathy · Gastric antral vascular ectasia · Gastric dumping syndrome · Gastric volvulus Lower GI tract: Intestinal/ enteropathy Small intestine/ (duodenum/jejunum/ileum) Enteritis (Duodenitis, Jejunitis, Ileitis) — Peptic (duodenal) ulcer (Curling's ulcer) — Malabsorption: Coeliac · Tropical sprue · Blind loop syndrome · Whipple's · Short bowel syndrome · Steatorrhea · Milroy disease Large intestine (appendix/colon) Appendicitis · Colitis (Pseudomembranous, Ulcerative, Ischemic, Microscopic, Collagenous, Lymphocytic) · Functional colonic disease (IBS, Intestinal pseudoobstruction/Ogilvie syndrome) — Megacolon/Toxic megacolon · Diverticulitis/Diverticulosis Large and/or small Enterocolitis (Necrotizing) · IBD (Crohn's disease) — vascular: Abdominal angina · Mesenteric ischemia · Angiodysplasia — Bowel obstruction: Ileus · Intussusception · Volvulus · Fecal impaction — Constipation · Diarrhea (Infectious) Rectum Proctitis (Radiation proctitis) · Proctalgia fugax · Rectal prolapse Anus Anal fissure/Anal fistula · Anal abscess  · Anal dysplasia  · Pruritus ani GI bleeding/BIS Upper (Hematemesis, Melena) · Lower (Hematochezia) Accessory Liver Hepatitis (Viral hepatitis, Autoimmune hepatitis, Alcoholic hepatitis) · Cirrhosis (PBC) · Fatty liver (NASH) · vascular (Hepatic veno-occlusive disease, Portal hypertension, Nutmeg liver) · Alcoholic liver disease · Liver failure (Hepatic encephalopathy, Acute liver failure) · Liver abscess (Pyogenic, Amoebic) · Hepatorenal syndrome · Peliosis hepatis Gallbladder Cholecystitis · Gallstones/Cholecystolithiasis · Cholesterolosis · Rokitansky-Aschoff sinuses · Postcholecystectomy syndrome · Porcelain gallbladder Bile duct/ other biliary tree Cholangitis (PSC, Secondary sclerosing cholangitis, Ascending) · Cholestasis/Mirizzi's syndrome · Biliary fistula · Haemobilia · Gallstones/Cholelithiasis common bile duct (Choledocholithiasis, Biliary dyskinesia) · Sphincter of Oddi dysfunction Pancreatic Pancreatitis (Acute, Chronic, Hereditary) · Pancreatic pseudocyst · Exocrine pancreatic insufficiency · Pancreatic fistula Abdominopelvic Hernia Diaphragmatic: Congenital diaphragmatic · Hiatus — Abdominal hernia: Inguinal (Indirect, Direct) · Umbilical · Incisional · Femoral — Obturator hernia · Spigelian hernia · Internal hernia Peritoneal Peritonitis (Spontaneous bacterial peritonitis) · Hemoperitoneum · Pneumoperitoneum digestive system navs: anat of tract,glands,perit,diaphragm/physio/dev, noncongen/congen/congen of d+w/neoplasia, symptoms+signs/eponymous, proc

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Dansk (Danish)
n. - cirrose, skrumpning

Nederlands (Dutch)
leverziekte (cirrose)

Français (French)
n. - cirrhose

Deutsch (German)
n. - (Med.) Zirrhose, Schrumpfung

Ελληνική (Greek)
n. - (παθολ.) κίρρωση (του ήπατος)

Italiano (Italian)
cirrosi

Português (Portuguese)
n. - cirrose (f) (Med.)

Русский (Russian)
цирроз

Español (Spanish)
n. - cirrosis

Svenska (Swedish)
n. - cirrhos (med.)

中文（简体）(Chinese (Simplified))
硬化

中文（繁體）(Chinese (Traditional))
n. - 硬化

한국어 (Korean)
n. - 간장 등의 경화

日本語 (Japanese)
n. - 硬変

العربيه (Arabic)
‏(الاسم) مرض تليف أو تشمع الكبد‏

עברית (Hebrew)
n. - ‮שחמת (מחלה), צמקת‬

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