Alpha 1 antitrypsin deficiency
related liver disease
What is Alpha-1 Deficiency Disease?
• Alpha-1 deficiency disease (or AATD) is an inherited condition
• Alpha-1 deficiency leads to very low levels of circulating Alpha-1 antitrypsin enzyme inhibitor. This enzyme inhibitor is needed to neutralise toxins in the lung to protect from damage
• In AATD, the liver and lungs are both affected, but in slightly different ways
What are the genetics of AATD?
• One gene is inherited from each parent
• The normal M gene results in normal levels of the AAT enzyme.
• The abnormal gene could be Z gene or the S gene, and this leads to lower than normal levels of AAT enzyme
• If you get one abnormal gene from one parent and one normal gene from the other parent you could become a carrier (MZ or MS)
• If you get abnormal genes from each parent, you could have very low levels of AAT enzyme (such as ZZ)
How does AATD affect the lungs?
• AATD leads to a lack of protective enzymes and this may cause emphysema or chronic obstructive pulmonary disease (COPD), which is associated with breathing problems
How does AATD affect the liver?
• The mechanism of liver injury in AATD is different to the lungs, it is believed that AAT proteins have difficulty leaving the liver causing build-up of the protein in the liver leading to liver injury
What kind of liver damage can happen in AATD?
• Liver fibrosis- Early liver injury, can be reversible if cause identified and treated
• Liver cirrhosis- Extensive liver scarring, may not be reversible
• Liver injury can be made worse by excessive alcohol intake (more than the recommended limits), being overweight or obese, or having diabetes
What kind of symptoms can I get?
• Liver disease in AATD is generally asymptomatic unless advanced
• Fatigue
• Jaundice (yellowing of skin or eyes)
• Abdominal swelling (due to build-up of fluid)
• Pale or dark stools
How is AATD diagnosed?
• Blood tests, including gene testing and liver function tests, levels of alpha 1 antitrypsin enzyme
• Liver scans to assess for liver fibrosis and cirrhosis (ultrasound and fibroscan)
• Liver biopsy which would involve taking out a small amount of tissue from the liver under local anaesthetic
How is AATD treated?
• There is no specific treatment for AATD related liver disease at present, but clinical trials are ongoing
• Monitor liver for fibrosis and scarring
• Identify and address compounding factors that may lead to liver scarring/ cirrhosis, like excessive alcohol intake, or being overweight/obese
Useful links:
https://www2.hse.ie/conditions/alpha-1-antitrypsin-deficiency/