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Cirrhosis

Description

An in-depth report on the causes, diagnosis, treatment, and prevention of cirrhosis

Causes

Several processes can lead to cirrhosis.

Alcoholism

Alcoholism particularly endangers the liver. Alcoholic cirrhosis (also sometimes referred to as portal, Laennec's, nutritional, or micronodular cirrhosis) is the primary cause of cirrhosis in the U.S. It is estimated to be responsible for 44% of deaths from cirrhosis in North America. Some experts believe this estimate is low. One Canadian study found alcohol to be the major contributor to 80% of all cirrhosis deaths.

The relationship between alcohol and cirrhosis is generally as follows:

• Alcohol is absorbed from the small intestine, and the blood carries it directly into the liver, where it becomes the preferred energy source.
• In the liver, alcohol converts to toxic chemicals, such as acetaldehyde (AcH), which trigger the production of powerful immune factors called cytokines. These molecules in large amounts can cause inflammation and tissue injury and are proving to be major culprits in the destructive process in the liver. AcH is particularly being researched because it plays a role in most actions of alcohol, including damaging effects on the liver that may lead to cirrhosis.
• The injured liver eventually is unable to breakdown fatty acids, compounds that make up fat. Over time, then, fat accumulates, further impairing the liver's ability to absorb oxygen and increasing its susceptibility to injury. During the initial phase, the fat-laden liver becomes greatly enlarged, but it eventually shrinks as cirrhosis develops.

Chronic Hepatitis

Chronic hepatitis, either hepatitis B or hepatitis C, is the second leading cause of cirrhosis. Chronic hepatitis C is the more dangerous form and accounts for one-third of all cirrhosis cases. About 5 - 20% of patients with chronic hepatitis C, and 5 – 10% of patients with chronic hepatitis B, eventually develop cirrhosis over the course of several decades. The longer a patient has had chronic hepatitis, the greater the risk for eventually developing cirrhosis. A 2005 study indicated that cirrhosis develops in 70% of patients who have had hepatitis C for more than 60 years.

The hepatitis virus can produce inflammation in liver cells, resulting in their injury or destruction. If the condition is severe enough, the cell damage becomes progressive, builidng a layer of scar tissue over the liver. In advanced cases, as with alcoholic cirrhosis, the liver shrivels in size, a condition called postnecrotic or posthepatic cirrhosis.

Autoimmune Liver Disease

Autoimmune liver diseases include autoimmune hepatitis and primary biliary cirrhosis . Like other autoimmune disorders, these conditions most likely develop because a genetically defective immune system attacks the body's own cells and organs. People who have one of these liver diseases also often have other autoimmune conditions, including systemic lupus erythematosus, rheumatoid arthritis, Sjögren's syndrome, scleroderma, inflammatory bowel disease, glomerulonephritis, and hemolytic anemia.

Autoimmune Hepatitis. Autoimmune chronic hepatitis occurs when an abnormal immune response causes an attack on the liver cells. It accounts for about 20% of all chronic hepatitis cases. Autoimmune chronic hepatitis typically occurs in women between the ages of 20 and 40 who have other autoimmune diseases. Some research indicates that the postmenopausal period may be another peak in incidence of AIH among women. About 30% of patients are men, however, and in both genders there is often no relationship to another autoimmune disease. In general, no major risk factors have been discovered for this condition.

Suspects for triggering this hepatitis include the measles virus, a hepatitis virus, or the Epstein-Barr virus, which causes mononucleosis. It is also possible that a reaction to a drug or other toxin that affects the liver also triggers an autoimmune response in susceptible individuals.

Primary Biliary Cirrhosis. Up to 95% of primary biliary cirrhosis (PBC) cases occur in women, usually around age 50. In the case of PBC, the immune system attacks and destroys cells in the liver’s bile ducts. Like many autoimmune disorders, the causes of PBC are unknown. Recent research indicates the following risk factors:

• Family history of PBC
• Family history of Sjögren's syndrome (another autoimmune disorder)
• Individual history of urinary tract infections (UTIs)
• History of smoking
• History of nail polish use
• Hormone replacement therapy
• Exposure to toxins from hazardous waste sites

This research suggests that environmental factors (chemicals, cigarette smoke) or infectious organisms (bacteria that causes UTIs) may trigger PBC in patients who are genetically susceptible to the disease. Women who have never been pregnant appear less likely to develop PBC.

Nonalcoholic Fatty Liver Disease

Nonalcoholic fatty liver disease (NAFLD) resembles alcoholic liver disease, but it occurs in people who do not consume significant amounts of alcohol. Obesity and type 2 diabetes are the two main causes of a fatty liver. Some evidence suggests that insulin resistance (the primary problem in type 2 diabetes) is a major factor in development of a fatty liver. A diet high in fatty foods may also be a risk factor, as dietary fat accumulates in the liver. Due to the recent rise in childhood obesity, NAFLD is increasingly occurring in children. In fact, NAFLD is now the most common liver disease in American children.

NAFLD can lead to nonalcoholic steatohepatitis (NASH). Liver inflammation and injury, as well as a fatty liver, characterize NASH. NASH occurs in about half of people with diabetes and up to 75% of obese people.

NAFLD is usually benign and very slowly progressive. But, in certain patients it can lead to cirrhosis, liver failure, or liver cancer. About 20% of people with NASH go on to develop cirrhosis. A 2006 study indicated that NASH-related cirrhosis causes fewer deaths than cirrhosis that is caused by chronic hepatitis C. However, many patients with NASH have coronary artery disease and heart failure and have a high risk of dying from heart disease.

Weight reduction and diabetes and cholesterol management are the primary approaches to controlling NAFLD and NASH.

Hemochromatosis and Iron Overload

Hemochromatosis is a disorder of iron metabolism that is characterized by excess iron deposits throughout the body, including the liver, where they can cause cirrhosis. Once believed to be rare, hereditary hemochromatosis is now considered to be one the most common genetic diseases among Caucasians. Between 2 - 4% of people of European ancestry are believed to carry the gene, and the disease itself is estimated to occur in 2 - 3 Causacions per 1,000. Early symptoms of hemochromatosis include:

• Fatigue
• Joint pain (arthralgia)
• Impotence in men
• Arthritis

A 2000 study further suggested that both hemochromatosis patients and their relatives who carry the trait are at higher risk for cirrhosis. Elevated iron levels, even in the absence of this disease, have been associated with liver scarring, particularly when accompanied by other risk factors for cirrhosis, including hepatitis, NASH, and, alcoholism.

Other Causes of Cirrhosis

Inherited Diseases. Cirrhosis can be caused by several inherited diseases, including:

• Cystic fibrosis
• Alpha-1 antitrypsin deficiency
• Galactosemia
• Glycogen storage diseases
• Wilson's disease

Other Rare Causes. Rare causes of cirrhosis include:

• Schistosomiasis, caused by a parasite found in the Far East, Africa, and South America.
• Small intestine bypass surgery (rarely, if ever, performed anymore).
• Long-term or high level exposure to certain chemicals and drugs can cause cirrhosis, including arsenic, methotrexate, and toxic doses of vitamin A.

Changes That Resemble Cirrhosis

Cancers that have metastasized to the liver, blood clots in the hepatic or portal vein, or obstructions in the bile duct can cause changes that resemble cirrhosis.

• Review Date: 8/18/2006
• Reviewed By: Harvey Simon, M.D., Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital.

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