What Is Alagille Syndrome?

Alagille syndrome is a rare, multisystem disease that largely affects the liver. It can also affect 
other major parts of the body, including the heart, face, eyes, kidneys, and spine.

Liver
Heart
Face
Eyes
Kidneys
Spine

How does Alagille syndrome affect the liver?


Bile acid buildup

In the liver, there is a network of tubes called bile ducts. For people with Alagille syndrome, these tubes are smaller than normal or malformed. This prevents bile from flowing out of the liver.

When bile is not able to flow out of the liver, bile acids—a part of bile—build up in the liver and the blood.

BILE ACID 101

Bile is a fluid that is created in the liver and then released into the intestines. Bile has many purposes, including:

Aiding in the digestion of fats

Helping with the absorption of fat and certain types of vitamins (vitamins A, D, E, and K)

What are the effects of bile acid buildup?


When bile acids build up in the liver, they spill over into the bloodstream. This can cause an increase in bile acids throughout the entire body.

These high levels of bile acids are an underlying cause of cholestatic pruritus (itch) in Alagille syndrome. The itch affects up to 88% of people with Alagille syndrome, and is considered the most burdensome symptom.

Over time, the buildup of bile acids in the liver can lead to long-term problems, including:

Inflammation
Damage to the liver that worsens over time
Scar tissue in the liver (fibrosis)
Bile acid buildup causes immediate problems (the itch) and has long-term impacts (liver problems).

Cholestatic pruritus (itch) is more than just scratching


Itch is often a very challenging symptom for people with Alagille syndrome.

Beyond the scratching, the itch can affect a person’s emotional, mental, and physical well-being. Signs and symptoms related to the itch can look different during the day and/or night, vary among patients, or even change with age.

A COMMON AND CHALLENGING SYMPTOM

The itch affects up to 88% of people with Alagille syndrome. It is considered the most burdensome symptom.

The itch in Alagille syndrome is frequently first seen in infancy or early childhood. Early signs of itching may often look like hunger or tired cues, such as wiggling, rubbing of the eyes and ears, and/or irritability.

Wiggling
Wiggling
Rubbing eyes and ears
Rubbing eyes and ears
Irritability (fussiness)
Irritability (fussiness)

Over time, children may start to show their discomfort in different ways. They may experience various symptoms because of the itch, including active scratching, red marks and scarring, sleep troubles, and/or difficulty focusing.

Active scratching
Active scratching
Red marks and scarring
Red marks and scarring
Sleep disturbances
Sleep disturbances
Restlessness
Restlessness
Irritability
Irritability
Unable to focus
Unable to focus

Teenagers and young adults are navigating changes and emotions. Those who struggle with the itch may deal with physical discomfort, mental and emotional health effects, scarring, and/or difficulty sleeping.

Sleep disturbances
Sleep disturbances
Unable to focus
Unable to focus
Irritability
Irritability
Physical discomfort
Physical discomfort
Scarring
Scarring
Normalizing or downplaying the itch
Normalizing or downplaying the itch

CAN YOU RECOGNIZE THE SIGNS OF ITCH?

Download the Pruritus Finder
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What else should you know about cholestatic pruritus (itch) in Alagille syndrome?


Symptoms start early.

Symptoms start early.

Signs and symptoms of Alagille syndrome often appear in infancy or early childhood.

Only scratching the surface.

Only scratching the surface.

In the past, there were limited treatment options for cholestatic pruritus (itch) in Alagille syndrome. As a result, burdensome symptoms like the itch and the damage caused by bile acid buildup often led to surgery or liver transplant being used as treatment.

The talk about transplant.

The talk about transplant.

In Alagille syndrome, the unmanageable itch was a reason for 49% to 82% of liver transplants.

For people with Alagille syndrome, there's a need for effective treatment options that lower bile acid buildup, rapidly relieve the itch, and improve long-term liver outcomes.

LIVMARLI is the only FDA-approved treatment for the itch in patients with Alagille syndrome who are 3 months of age and older.

LIVMARLI logo

Understanding LIVMARLI

What it is. Who it’s for. How it works.

Learn About LIVMARLI
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Indication

LIVMARLI is a prescription medicine used to treat cholestatic pruritus (itch) in patients who are 3 months of age and older with Alagille syndrome.

It is not known if LIVMARLI is safe and effective in children with Alagille syndrome who are under 3 months of age. It is not known if LIVMARLI is safe and effective in adults who are 65 years of age and older.

Important Safety Information

What are the possible side effects 
of LIVMARLI?

  • Liver injury. Changes in certain liver tests are common in patients but may worsen during treatment with LIVMARLI. These changes may be a sign of liver injury and can be serious. Your health care provider should do blood tests and physical exams before starting and during treatment to check your liver function. Tell your health care provider right away if you get any signs or symptoms of liver problems, including:
    • nausea or vomiting
    • your skin or the white part of your eye turns yellow
    • dark or brown urine
    • pain on the right side of your stomach (abdomen)
    • fullness, bloating, or fluid in your stomach area (ascites)
    • loss of appetite
    • bleeding or bruising more easily than normal, including vomiting blood
  • Stomach and intestinal (gastrointestinal) problems. LIVMARLI can cause stomach and intestinal problems, including diarrhea and stomach pain during treatment. Diarrhea can also cause the loss of too much body fluid (severe dehydration). Your health care provider may advise you to monitor for new or worsening stomach problems, including stomach pain, diarrhea, blood in your stool, or vomiting. Tell your health care provider right away if you have any new or worsening signs or symptoms of stomach and intestinal problems, including:
    • diarrhea
    • more frequent bowel movements than usual
    • stools that are black, tarry, or sticky, or have blood or mucous
    • severe stomach-area pain or tenderness
    • vomiting
    • urinating less often than usual
    • dizziness
    • headache
  • A condition called Fat-Soluble Vitamin (FSV) Deficiency caused by low levels of certain vitamins (vitamin A, D, E, and K) stored in body fat. FSV deficiency is common in patients with Alagille syndrome but may worsen during treatment. Your health care provider should do blood tests before starting and during treatment, and may monitor for bone fractures and bleeding, which are common side effects.

Tell your health care provider about all medicines that you take, as LIVMARLI may interact with other medicines. If you take a medicine that lowers cholesterol by binding bile acids, such as cholestyramine, colesevelam, or colestipol, take it at least 4 hours before or 4 hours after you take LIVMARLI.
Your health care provider may change your dose, or temporarily or permanently stop treatment if you have certain side effects.

LIVMARLI is taken by mouth, 1 time each day, 30 minutes before a meal in the morning. Be sure to use the provided oral dosing dispenser to accurately measure the dose of medicine.

These are not all of the possible side effects of LIVMARLI. For more information, ask your health care provider or pharmacist. Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.