Alpha-1 antitrypsin deficiency (AATD) is an inherited genetic disorder. It can occur in anyone but is more common in people with ancestry in North and Central Europe.

People with AATD experience altered production of a protein called alpha-1 antitrypsin (AAT). The function of AAT is to protect your body from an enzyme called elastase. Neutrophils, a type of infection-fighting white blood cell, make elastase.

AATD can cause a variety of health complications. These include lung damage, liver disease, and a painful skin condition called panniculitis.

Below, we’ll discuss the different aspects of liver disease due to AATD, including its causes, symptoms, diagnosis, and treatment. Continue reading to learn more.

AATD happens when you inherit two copies of an atypical version of the SERPINA1 gene. You receive one copy from each parent. SERPINA1 is the gene that codes for the AAT protein.

While there are many variations of SERPINA1, the most common ones are:

  • M: M leads to regular production of AAT. Most people within the general population have two copies of M.
  • S: S causes moderately lower production of AAT.
  • Z: Z results in very low production of AAT. People with two copies of Z are at a higher risk of having liver disease or lung damage due to AATD.

Your genes typically make AAT in your liver. Your liver then releases it into the bloodstream, where it can help protect you from the potentially harmful effects of elastase.

However, in AATD, abnormal AAT proteins get stuck in the liver instead of entering the bloodstream. Accumulation of these abnormal proteins within the liver can go on to cause liver damage and scarring.

The symptoms of AATD liver disease are consistent with liver disease from other causes, such as:

AATD liver disease can show up at any point in a person’s lifetime. Further, how it presents can also be highly variable.

For example, in children, AATD may not cause any liver-related signs or symptoms. Others might have elevated liver enzymes. It’s also possible for some children with AATD to have cholestasis or even cirrhosis or liver failure.

In adults who did not receive an AATD diagnosis in childhood, liver disease can often go undetected for many years until they have symptoms of cirrhosis or liver cancer.

Overall, AATD is an underdiagnosed and underreported condition. According to a 2020 research review, about 80% to 90% of people with AATD don’t know they have it because of factors like a lack of symptoms or misdiagnosis.

Doctors often suspect AATD in situations where a person has:

  • a close relative with AATD or a known family history of AATD
  • liver disease or emphysema that runs in their family
  • liver problems that cannot be explained by other health conditions
  • emphysema at a younger age or without a history of smoking
  • panniculitis

The diagnostic process starts with a doctor performing a physical exam and taking your medical history. They may ask about your symptoms, when they started, and whether anyone in your family has an AATD diagnosis.

Doctors use the following tests to diagnose AATD, specifically AATD liver disease:

  • Blood tests: A blood test can help determine the levels of AAT in your blood and whether they’re low. Your doctor may also do liver function tests to check how well your liver is working.
  • Isoelectric focusing: Isoelectric focusing looks at how AAT proteins migrate through a special gel. Because we know that the various versions of SERPINA1 can make slightly different proteins, doctors can use this technique to see what types of the protein your body is making.
  • Genetic tests: Genetic tests are done on a blood sample to look for atypical versions of the SERPINA1 gene.
  • Biopsy: A liver biopsy isn’t required to diagnose AATD liver disease. But doctors may use it in difficult diagnostic situations or to help estimate your outlook.

There’s currently no specific treatment available for AATD liver disease. But clinical trials are underway for treatments that can correct the abnormal protein so that it can safely enter your bloodstream rather than build up in your liver.

Until such treatments are approved, supportive measures mainly manage AATD liver disease. These measures don’t directly treat your condition. Instead, they focus on alleviating symptoms and improving your quality of life.

Additionally, your doctor will suggest that you make lifestyle changes that promote liver health. These can include:

If you have AATD liver disease, your doctor will also want to periodically monitor your condition in case it progresses. They’ll likely want to check in with you at least once per year. Any follow-up may involve:

According to a 2021 research review, many children and adults with AATD liver disease remain stable and live generally unaffected lives for many years.

For example, one 2019 study involved 1,595 adults with severe AATD. (This means they have two copies of the Z variation of the SERPINA1 gene.) Over an average follow-up period of 12 years, researchers found that:

  • 10% developed liver disease of any kind
  • 7% developed cirrhosis
  • 2% developed liver cancer

The average age of onset of liver disease in study participants was 61 years. Some risk factors associated with developing AATD liver disease in adulthood included:

However, it’s still important to note that the progression of AATD and AATD liver disease can still be unpredictable. AATD liver disease is associated with a variety of complications, including:

  • cirrhosis, which is widespread scarring of the liver
  • portal hypertension, which is high blood pressure in the liver’s portal vein
  • bleeding problems from impaired blood clotting
  • liver cancer
  • liver failure

Overall, liver transplantation is the only cure for AATD liver disease. But doctors typically only recommend this for people with very severe or end-stage liver disease.

Since AATD is an inherited genetic disorder, you can’t prevent it.

But if you’ve received an AATD diagnosis, be sure to visit your doctor for regular health check-ins that include assessments of your liver function. This can help identify any signs of liver disease early.

You can also follow certain lifestyle strategies that protect your liver health, such as:

  • abstaining from alcohol
  • eating a nutritious, balanced diet
  • staying up to date on hepatitis vaccinations

If AATD runs in your family, you may also consider genetic testing to find out whether you’re carrying a copy of the Z variation of SERPINA1. This can help you determine the chances of any future children having the condition.

AATD is an inherited genetic disorder. People with AATD can experience liver disease, lung damage, and skin problems.

How AATD affects the liver differs from person to person. Many people will be relatively unaffected. Others will develop liver disease that can eventually progress to cirrhosis or liver failure.

There’s currently no specific treatment for AATD liver disease. Instead, management focuses on supportive care and lifestyle strategies.

If you have AATD or AATD liver disease, be sure to visit your doctor for regular checkups. Doing so helps to better monitor your condition and catch any signs of progression early.