The Liver in Alpha-1 Antitrypsin Deficiency
Alpha-1 Antitrypsin Deficiency (Alpha-1) can cause liver problems in infants, children or adults – as well as the better-known adult lung disease. In people with Alpha-1 (Alphas), large amounts of abnormal alpha-1 antitrypsin protein (AAT) are made in the liver; nearly 85 percent of this protein gets stuck in the liver. If the liver cannot break down the abnormal protein, the liver gradually gets damaged and scarred.
Currently, there is no way to prevent the abnormal AAT from getting stuck in the liver. Since not everyone with Alpha-1 gets liver disease, there must be other things that contribute to liver disease. Researchers are studying these “other things,” hoping to find new treatments. The lack of AAT in the blood allows the lungs to get damaged by cigarette smoke and air pollution, which can show up as lung disease in adults with Alpha-1.
The signs and symptoms of Alpha-1 liver disease
In babies, some common symptoms of Alpha-1 are jaundice (eyes and skin turning yellow) swelling of the abdomen, and poor growth.
Most jaundiced infants do not have Alpha-1 or other liver problems; their jaundice usually lasts just a few days and is harmless. Blood tests can tell if the jaundice is due to a liver problem or the common harmless type.
Babies with Alpha-1 liver disease may also have diarrhea and lack of normal weight gain. Sometimes a doctor examining a child finds an enlarged liver or spleen, or a parent bathing the child notices a swollen belly. This can be caused by scarring of the liver caused by Alpha-1 and a number of other liver problems. Liver scarring can also lead to ascites (swelling of the abdomen caused by fluid buildup), and intestinal bleeding. Older children and adults with Alpha-1 liver disease may also have these symptoms, and may report feeling weak and tired.
Keep in mind that most children and adults with Alpha-1 have no symptoms of liver disease at all!
Alpha-1 is inherited
Alpha-1 is a genetic condition – passed on from parents to their children through genes. Genes are codes that are found on chromosomes, the genetic material in every cell in our bodies.
The alpha-1 genes are codes that tell the liver how to make the alpha-1 antitrypsin protein, which the liver sends into the blood so it can protect the lungs and other parts of the body. If someone has two abnormal alpha-1 genes, then the liver makes an abnormal form of the alpha-1 protein, or AAT. The abnormal protein becomes trapped in the liver rather than being released into the blood; the blood doesn’t get as much of the protein as it needs to help other parts of the body. This makes the lungs more sensitive to damage from cigarette smoke and other air pollutants. The buildup of the AAT protein in the liver can damage the liver, which may then develop scar tissue.
An Alpha-1 carrier is a person who has one normal (M) alpha-1 gene and one changed alpha-1 gene (usually Z or S). Most Alpha-1 “carriers” are called either MS or MZ. Being an Alpha-1 carrier is very common. About 19 million people in the United States are carriers. Alpha-1 carriers have less AAT protein in their blood than other people, but they seldom have liver or lung problems. The parents of children with Alpha-1 are usually carriers and often have no symptoms at all related to Alpha-1.
What happens to the liver in Alpha-1?
The liver is in the upper right part of your abdomen, just below the right lung. One of the largest organs in the body, it is very important to your health because it has so many functions: it cleans your blood, helps digest food, manufactures chemicals your body needs, and helps fight infections. The liver stores vitamins, sugars, fats and other nutrients from the foods you eat. It also breaks down alcohol, drugs and other toxic substances that can hurt your body. A normal liver also removes a yellow substance called bilirubin that builds up in the blood in many liver diseases.
Of all babies who are born with two abnormal alpha-1 genes (ZZ or SZ), about 1 in 20 will get liver disease, sometimes severe, in the first year of life. These infants usually have jaundice, the distinctive yellow color of the skin and the eyes, and a swollen liver and belly. Usually they do not gain weight well. They may develop serious scarring of the liver.
Most Alpha-1 babies stay healthy
Of all infants born with ZZ or SZ genes, about 1 in 4 will have blood tests showing that the liver is being injured – and yet, the infants look and feel fine. In most children with abnormal blood tests, the liver disease improves by itself by the time these children reach their teens, and they remain healthy. Adults with Alpha-1 can also get liver disease, usually involving cirrhosis, which is scarring of the liver. This is especially true for those over age 50. People with Alpha-1 have up to a 30-40 percent chance of developing a liver problem during their lifetime. These problems include cirrhosis (scarring of the liver) and liver cancer.
If the liver does get damaged, there are treatments to prevent or slow down problems that can be caused by the liver damage. Healthy living is important. This includes avoiding alcoholic drinks, maintaining a healthy weight, getting vaccinated against infections (like hepatitis) that can damage the liver, and eating a healthy diet. If the liver damage becomes severe or life-threatening, then liver transplantation is an option.
Alpha-1 carriers almost never develop liver problems related to Alpha-1. When they do, this is probably caused by something else that damaged the liver, like viruses, drinking too much alcohol or being severely overweight.
How is Alpha-1 liver disease found and diagnosed?
Alpha-1 liver disease is found by a doctor’s physical exam and by blood tests. The physical exam may show an enlarged, firm liver or spleen. The blood tests include measuring how much of the AAT protein is in the blood and how well the liver works. In addition, ultrasound of the liver may be ordered. Ultrasound is a painless procedure using sound waves through the skin to make a picture of the liver.
The specific diagnosis of Alpha-1 is made by a blood test called the phenotype test. This test shows the type (M, Z, or S) of AAT protein in a person’s body. Doctors can also test a person’s genes (called a genotype test) for AAT.
A liver biopsy is usually not needed to diagnose Alpha-1. Usually, a liver biopsy is a procedure performed by a doctor, after a patient has received local anesthesia to numb the skin and prevent pain. The doctor pushes a needle through the skin into the liver and removes a small piece of liver in the needle. Liver biopsies are sometimes used to see how bad the liver disease is, and to look for other reasons for liver damage.
How is Alpha-1 liver disease treated?
When doctors treat someone with Alpha-1 liver disease, they focus on treating symptoms – keeping patients as healthy as they can be and preventing health problems. Treatments are available for intestinal bleeding, ascites (fluid in the abdomen), nutrition and other problems from scarring of the liver.
There is no cure for Alpha-1, but there are ways to prevent or reduce health problems related to Alpha-1.
People with Alpha-1 should do the following important things:
- get hepatitis A and B vaccinations
- get regular exams by a doctor
- get regular medical tests as suggested by their doctors, such as blood tests and liver ultrasound or X-ray tests – for example, liver CT (CAT) scans
- stay away from tobacco smoke and heavy air pollution
- avoid drinking alcohol
- eat a balanced diet and maintain a healthy weight
- speak to your doctor before using any herbal, vitamin or other therapies
Severe liver damage and scarring is called cirrhosis. In some people with severe cirrhosis caused by Alpha-1, a liver transplant may be necessary. A liver transplant is surgery to remove a sick liver and replace it with a healthy one from another person.
Some adults with lung damage are treated with augmentation therapy — AAT protein given intravenously to raise the level of AAT in the blood and lungs. However, augmentation therapy is not helpful in reducing or preventing damage to the liver.
What is the outlook for someone with Alpha-1?
There is a wide variation in how sick people get from Alpha-1. Some patients have severe disease, while others have little or none. Some infants may have quick scarring of the liver that leads to the need for a liver transplantation in the first few years of life. However, this is rare; most children affected with Alpha-1 liver disease do well and reach adulthood without major liver problems.
Lung problems from Alpha-1 do not usually occur in childhood, but it is very important for children with Alpha-1 to avoid all exposure to cigarette smoke or heavy air pollution to protect their lungs. Sometimes children with Alpha-1 can have severe asthma. It is best to talk with your doctor to figure out how your Alpha-1, or your child’s, might turn out and what can be done to protect the lungs and liver.
How to learn more
How can you learn more about liver disease in people with Alpha-1? Ask your healthcare provider, or see the links on this page.
The Alpha-1 Foundation acknowledges the generous help of the Cholestatic Liver Disease Consortium (CLiC), part of ChiLDREN, the Childhood Liver Disease Research and Education Network, with the preparation of this information on the liver and Alpha-1.
- The new ChiLDREN website and information on CLiC
- Complete list of children’s liver research centers in CLiC, with contact information
Jeffrey H. Teckman, MD, answers your questions on Alpha-1 Liver Disease. You can read those answers here, on our Alpha-1 Liver Disease Q&A Page.
More information on the liver
- American Association for the Study of Liver Disease
- American Liver Foundation
- Canadian Liver Foundation
- Children’s Liver Association for Support Services
- Children’s Liver Disease Foundation
Support Group Websites
- American Society of Transplantation
- LifeGift Organ Donation Center
- Transplant Living
- Transplant Buddies