Alpha-1 Liver Disease: Causes, Symptoms, Diagnosis and Treatment

Alpha-1 Antitrypsin Deficiency (Alpha-1) is best known for its effects on the lungs, but it is also a significant cause of liver disease in both children and adults. Liver disease is the second most common health complication associated with Alpha-1, and like lung disease, it can develop slowly and remain undetected for many years.

Understanding how Alpha-1 affects the liver can help individuals and families seek appropriate testing, monitoring and support.

What Is the Role of the Liver?

The liver is one of the body’s most important organs. It filters the blood, stores nutrients including sugars, fats and vitamins, and breaks down alcohol, medications and toxic substances that could otherwise cause harm.

Liver disease occurs when the liver is unable to perform these functions properly, often as a result of damage, scarring or inflammation over time.

How Does Alpha-1 Cause Liver Disease?

Alpha-1 Antitrypsin (AAT) is a protein produced primarily by the liver. Under normal circumstances, AAT is released into the bloodstream where it circulates throughout the body to protect organs — particularly the lungs — from damage.

In people with Alpha-1, a genetic mutation causes the AAT protein to become misfolded, changing its shape so that it becomes trapped inside the liver cells rather than being released into the bloodstream.

When AAT becomes stuck in the liver, it forms clumps known as polymers. The liver cannot break these polymers down, and the resulting build-up can cause progressive liver damage, including:

• Fibrosis — the development of scar tissue in the liver
• Cirrhosis — severe scarring that impairs liver function
• Liver cancer — which can develop in some people with advanced liver damage

Of the more than 150 known Alpha-1 gene mutations, the ZZ genotype is most commonly associated with liver disease. The Z gene produces a misfolded protein that is particularly prone to becoming trapped in the liver.

Scientists do not yet fully understand why some people with Alpha-1 develop liver disease while others do not. There is currently no treatment to prevent AAT from accumulating in the liver, however clinical trials are underway and research into potential therapies is actively progressing.

Who Is at Risk of Alpha-1 Liver Disease?

Alpha-1 liver disease can affect people at any stage of life, from newborns through to older adults.

Children

Most children with the ZZ genotype will show abnormal liver function test results at some point, though these often return to normal during childhood. However:

• Some infants with Alpha-1 experience prolonged jaundice, which may indicate that AAT is becoming trapped in the liver
• Approximately 10% of children with the ZZ genotype will experience significant liver problems
• Around 2% of affected children will develop liver failure and require a liver transplant within the first two years of life

Adults

Liver disease in adults with Alpha-1 tends to develop gradually and may not become apparent until later in life.

• Approximately 30% of adults with the ZZ genotype will develop liver disease
• Older adults are more likely to have liver scarring, though liver function test results may remain relatively normal until after the age of 60
• Adults with the MZ genotype are also at some risk of liver disease, particularly if they have pre-existing liver damage from other causes such as alcohol use or viral hepatitis

Symptoms of Alpha-1 Liver Disease

Symptoms of liver disease in people with Alpha-1 can vary significantly between individuals and may develop gradually. Common symptoms include:

• Yellowing of the eyes or skin (jaundice)
• Swelling of the abdomen (ascites) or legs
• Vomiting blood or passing blood in the stool
• Abnormal or persistent itching (pruritus)
• Fatigue and reduced energy levels

Many people with Alpha-1 liver disease do not experience obvious symptoms in the early stages, which is why regular monitoring is important for those who have been diagnosed with Alpha-1.

How Is Alpha-1 Liver Disease Diagnosed?

Several tests may be used to assess liver health in people with Alpha-1:

• Liver function blood tests — to check how well the liver is working
• Ultrasound scan — to assess the structure of the liver
• Fibroscan — a non-invasive scan that measures the stiffness of the liver, which can indicate the degree of scarring
• CT scan — recommended periodically for people over 50 with worsening cirrhosis, due to the increased risk of liver cancer
• Liver biopsy — rarely required but may be used in severe or complex cases to assist with diagnosis

Regular liver testing — ideally on an annual basis — is recommended for people with Alpha-1, even in the absence of symptoms.

Treatment Options for Alpha-1 Liver Disease

There is currently no specific treatment to prevent or reverse Alpha-1 liver disease. Medical management focuses on supportive care and addressing the health complications that arise as the condition progresses.

It is important to note that augmentation therapy, which is used to treat Alpha-1 lung disease, does not help with liver disease however some research indicates augmentation therapy may reduce liver inflammation. The two conditions (lung and liver disease) require different management approaches.

In severe cases where the liver is significantly damaged, liver transplantation may be considered. A transplanted liver will produce normal AAT, effectively resolving the Alpha-1 deficiency in the liver and changing Alpha-1 status if the donor did not have Alpha-1.

How to Support Your Liver Health

People with Alpha-1 can take several steps to help protect their liver and reduce the risk of disease progression:

• Limit or avoid alcohol — alcohol is a direct liver toxin and can accelerate damage
• Get vaccinated against hepatitis A and hepatitis B
• Eat a balanced diet and avoid excessive carbohydrates and sugar, which can contribute to fatty liver disease
• Exercise regularly to support overall liver and metabolic health
• Avoid unnecessary medications or supplements that may place additional strain on the liver
• Attend regular liver function testing as recommended by your healthcare team
• Who Should Be Tested for Alpha-1 Liver Disease?

Testing for Alpha-1 is recommended for:

• Anyone with unexplained liver disease, including newborns, children and adults
• Relatives of people already diagnosed with Alpha-1
• People with a family history of liver disease or Alpha-1
• Individuals diagnosed with unexplained lung conditions including COPD, chronic bronchitis or early onset emphysema

A simple blood test can confirm an Alpha-1 diagnosis. Early identification allows for regular monitoring and lifestyle adjustments that may help protect liver health over time.