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Alpha-1 antitrypsin deficiency is a common hereditary disorder characterized by reduced levels of alpha-1 antitrypsin. Alpha-1 antitrypsin is a blood protein that is produced in the liver; its main function is to protect the lungs so they can work normally.
After the liver releases it into the bloodstream, alpha-1 diffuses into tissues and protects the tissues from being digested by enzymes released from inflammatory cells, such as white blood cells. The body's white blood cells help protect from infection; they also release an enzyme called neutrophil elastase. Neutrophil elastase serves a useful purpose in lung tissue: it digests damaged or aging cells and bacteria. This promotes healing, or the growth of newer, heartier cells. However, neutrophil elastase does not know when to stop digesting; left on its own it will soon move on to attack healthy tissue. In normal lungs, alpha-1 antitrypsin protects lung tissue by trapping and destroying neutrophil elastase before it has a chance to outlive its usefulness and cause damage.
Certain gene mutations can cause an abnormal form of alpha-1 antitrypsin that gets hung up in the liver and cannot enter the blood stream. The actual amount of alpha-1 produced may be close to normal, but the liver does not secrete enough into the bloodstream. In addition, the abnormal alpha-1 is often defective, so that the small amount released cannot effectively "trap" the neutrophil elastase in time. Different mutations cause different varieties of this disorder, some more severe than others.
When the lungs do not have enough alpha-1 antitrypsin, neutrophil elastase is free to destroy tissue. Lung tissue is particularly vulnerable, since the lungs are continuously exposed to toxins in the environment. This leads to lung disease (most commonly emphysema), and occasionally liver disease.
The pathophysiology (functional changes associated with or resulting from disease or injury) of liver disease in alpha-1 antitrypsin deficiency is less understood than that of the associated lung disease.
It is generally thought that the liver disease associated with alpha-1 antitrypsin deficiency is not caused by the alpha-1 deficiency in the bloodstream, but by excessive amounts of alpha-1 stuck in the liver cells.
Liver damage occurs in about 10% of infants born with the severe form of alpha-1 antitrypsin deficiency. Some alpha-1 antitrypsin deficiency patients have cirrhosis of the liver. This affects very young alpha-1 antitrypsin deficiency children, as well as 12% – 15% of adult alpha-1 antitrypsin deficiency patients.
Children with alpha-1 antitrypsin deficiency that affects their livers may experience some or all of these symptoms:
The diagnosis of alpha-1 antitrypsin deficiency liver disease can be established with the results of a simple blood test. If a patient's symptoms suggest more advanced liver dysfunction, a liver biopsy may be recommended.
There is no specific treatment for liver disease associated with alpha-1 antitrypsin deficiency; clinical care primarily treats symptoms as they occur and aims to prevent potential complications. Avoidance of substances known to be capable of causing liver damage, as well as appropriate nutritional management, is an essential part of treatment.
For those who suffer severe progressive liver damage, a liver transplant is currently the only option available for survival. Fortunately, studies indicate that only about 10% of people with alpha-1 antitrypsin deficiency have liver damage so severe that it requires liver transplantation. Usually, liver transplants are done in children with the type of infantile hepatitis associated with severe alpha-1 antitrypsin deficiency. In these patients, a transplant completely replaces the liver cells that produce mutated alpha-1, thereby correcting the protein abnormality.
Living-related liver transplantation is becoming more popular as medical knowledge and techniques improve. The usual donor is a parent; however, a consenting sibling 18 years of age or older, or a grandparent or other family member may be considered.
To preserve lung function, intravenous replacement of human alpha-1 derived from human blood (Prolastin®) is administered once every one or two weeks. Inhaled Alpha-1 is currently being tested.
Gene therapy is also currently being studied. With gene therapy, the normal gene for alpha-1 is put into a non-infectious virus. When the virus is administered to the patient (by inhalation or other means), it infects the tissue cells, causing production of normal alpha-1 by the normal gene it contains. So far, only minimal success has been achieved by this method, but it is extremely promising. However, this therapy would only be beneficial in the treatment of alpha-1 antitrypsin deficiency related pulmonary disease, since liver disease associated with alpha-1 antitrypsin deficiency is not related to the diminished level of circulating alpha-1.
Learn about other Liver Disease States.
Children's Hospital's main campus is located in the Lawrenceville neighborhood. Our main hospital address is:
Children’s Hospital of Pittsburgh of UPMC
One Children’s Hospital Way
4401 Penn Ave.
Pittsburgh, PA 15224
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