AAT deficiency may be associated with a range of liver and/or lung complications.
- Fibrosis, or the initial formation of scar tissue in the liver
- Cirrhosis, or widespread scarring of the liver
- Hepatocellular carcinoma (HCC), the most common type of primary liver cancer
- Chronic obstructive pulmonary disease (COPD)
- Bronchiectasis, or thickening of the walls of the bronchi from inflammation or infection
Who is at risk for AAT deficiency-associated liver disease?
Researchers estimate that more than 250,000 people around the world have the pair of gene variants called “ZZ.” This is the specific pair that most commonly leads to AATLD. Although most individuals with this pair will not develop liver disease, some will.
AAT deficiency occurs most frequently among people of Northern European descent
How is AAT deficiency diagnosed?
If a healthcare provider suspects that an individual may have AAT deficiency based on their health history and other factors, he or she may order a genotype test to help diagnose AAT deficiency. This is a test that determines whether a person has the variant gene combination associated with increased risk of AAT deficiency. The provider can also check levels of AAT in the blood, as well as order specific tests to assess liver or lung function, depending on an individual’s specific symptoms.
For assessing liver function, the provider can order bloodwork to measure liver enzyme levels or can examine the liver via ultrasound or other imaging techniques such as computed tomography (CT) scanning. In some cases, a physician may order a biopsy to understand the extent and severity of liver disease.
Who should be tested?
Current guidelines recommend that anyone with COPD or unexplained liver disease should be tested for AAT deficiency. Family members of individuals known to have an abnormal gene for AAT should also be tested and provided with genetic counseling.
How is AAT deficiency-associated liver disease treated?
There are no available therapies specifically designed to treat AATLD. Several treatments are currently availble for individuals with AAT deficiency that affects the lungs. Healthcare providers generally offer supportive care to help patients manage their liver disease symptoms.
Some individuals with AATLD will require a liver transplant, after which AAT protein levels typically return to normal. Transplantation is currently the only effective therapeutic approach for AATLD. However, at present, liver transplantation fails to meet the needs of many individuals with this condition.
- Liver transplant surgery carries a risk of significant complications
- Individuals who undergo transplantation must take drugs to suppress their immune system for the rest of their lives, which can cause a number of side effects and increase risk of infection
- Individuals may not be eligible for transplantation if they are not healthy enough to undergo the surgery or tolerate the required lifelong medications
- The number of individuals in need of a liver transplant greatly exceeds the number of donor livers available for transplant
What is the Impact of AAT Deficiency?
Many patients with AAT deficiency require extended medical monitoring and treatment. Individuals with the “ZZ” gene combination may have a shortened lifespan due to serious complications of the disease, such as COPD (especially if they smoke) or liver failure.
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