Alpha-1 Liver Disease

What is Alpha-1 Liver Disease?

Alpha-1 Antitrypsin deficiency (often called “Alpha-1”) is a genetic condition. Most often, this condition leads to lung disease, but can also cause liver disease in some people.

To develop Alpha-1 liver disease, a person needs to inherit one abnormal (or “Z mutation”) Alpha-1 antitrypsin gene (DNA material) from each parent. People with two Alpha-1 Z genes are at greatest risk of Alpha-1 liver disease, although other rarer Alpha-1 genes may also increase the risk of liver disease. 1 out of 4 people with ZZ Alpha-1 will develop liver disease at some point in their lifetime.

The risk of liver disease in Alpha-1 increases if the person suffers additional liver injury such as from:

• Viral infections (hepatitis A, B or C, or HIV infection)
• Alcohol abuse
• Fat deposition in the liver (fatty liver)
• Occupational exposures to liver-toxic chemicals  
• Association with other genetic diseases (e.g., hemochromatosis)

The liver disease can be present at birth, and up to 5 percent of infants develop severe liver disease during the first year of life. After the first year of life, children are most commonly tested for Alpha-1 disease when they develop jaundice or have elevation of their liver blood tests during other acute childhood illnesses. In adults, anyone with unexplained liver abnormalities such as elevated liver enzymes should be tested for Alpha-1.

Signs and Symptoms

Many people with Alpha-1 liver disease have no symptoms until late stages of the disease. When the liver damage reaches the most severe form, liver cirrhosis can occur. Cirrhosis is when the hepatocytes are replaced with scar tissue.

People with cirrhosis often experience:

• loss of appetite
• weakness, fatigue
• nausea
• abdominal pain
• weight loss
• skin discoloration (jaundice or yellowing of the skin)
• fluid accumulation under the skin (edema) or within the abdomen (ascites)
• Bruising easily and abnormal bleeding, like nose or gastrointestinal bleeding.

Other symptoms of severe liver disease can include:

• Sensitivity to certain medications cleared from the system via the liver
• Changes in personality and sleep habits
• Increased risk for infections
• Liver cancer

Diagnosis

To diagnose Alpha-1 liver disease, your doctor may perform genetic testing or various tests of liver health and function.

H3 Genetic Tests

The easiest way to determine if you have Alpha-1 mutations involves testing the protein made from the alpha-1 antitrypsin gene in the body or the genes themselves. The phenotype, or Pi-type (a name for the structure of the protein made by the Alpha-1 gene) of the alpha-1 antitrypsin protein in a person is determined by identifying how the protein moves on an electrified gel.

A normal protein is referred to as an M protein. A person with normal alpha-1 antitrypsin proteins is referred to as Pi MM. Testing the Alpha-1 DNA, a process called genotyping, also can indicate if there are mutations that make a person more likely to develop Alpha-1.

The most common abnormal proteins are S, Z and F. Sometimes a gene will make no protein; this a “null” gene. When you have two Z genes, you are known as Pi ZZ and are most likely to get Alpha-1 lung and/or liver disease.

Imaging Tests

Ultrasound or CT of the liver: Ultrasound or CT imaging of the liver allows your doctor to measure liver size and blood flow within the liver as well as scar and fat accumulation in the liver to help determine if cirrhosis has occurred.

Lab Tests

Biopsy or elastography: These tests can determine how much scarring has occurred compared to healthy liver tissue

Blood tests: These tests can include a liver panel, blood clotting tests, blood cell counts, kidney function, and markers for tumors, and help monitor liver function.

MELD Score: This is a specialized blood test for determining the severity of liver disease. 

People with only the Z gene and no current liver disease may be able get a liver panel and liver ultrasound less often. Testing frequency should be discussed with your doctor.

Treatment

The liver scarring associated with adult Alpha-1 liver disease should be treated the same way as other sources of scarring. This includes: 

• Treatments for elevated blood pressure in the liver
• Monitoring and treatment of abnormal veins in the esophagus
• Adjustment of medication doses to allow the liver to still process them properly
• Other measures as determined by your doctor

Children and adults diagnosed with one or two abnormal Z genes should avoid alcohol, medications or herbal products that are toxic to the liver. They should be vaccinated against hepatitis A and B as well.

Family members of people with one or two abnormal Z genes should receive genetic counseling because the condition runs in families. An early diagnosis of Alpha-1 liver disease has a significant effect on the outcome of the condition.

If the liver disease continues to worsen in spite of treatments, liver transplantation is the only potential cure.

Therapies for Cirrhosis

People with cirrhosis caused by Alpha-1 liver disease may receive treatment with:

• vitamin supplements to help with clotting disorders and blood cell count
• diuretics to help with fluid retention
• antibiotics to prevent infections
• propranolol for blood pressure
• bands, clips or sclerosis (treatments for abnormal esophagus veins using a scope)
• TIPS (transhepatic intraportal shunt, a surgical procedure) to help decrease the blood flow from the liver to abnormal esophagus veins.

Procedures

Liver Transplantation: Severe infant liver failure in Alpha-1 is always treated with liver transplantation. This cures the disease by replacing the failing liver with a healthy donor liver that has normal Alpha-1 genes. A successful liver transplant leads to normal blood and lung levels of normal alpha-1 antitrypsin protein. Liver transplant, in general, is a very successful procedure, but the demand for donor livers is much higher than the supply. Sadly, some people who need a transplant may not be able to get one in time.

Clinical Trials

Clinical trials help determine new treatment options for diseases and conditions. Patients with Alpha-1 have access to clinical trials and should speak with their doctor to determine what trials may work best for them.