Biliary atresia

Overview

Biliary atresia is a rare liver condition that affects newborns and infants. It occurs when the bile ducts become inflamed and blocked or fail to form correctly. Bile ducts are slender tubes that carry the digestive fluid bile from the liver to the small intestine. When bile cannot flow out of the liver, it builds up and causes liver damage, scarring and, eventually, progressive and severe scarring known as cirrhosis.

Biliary atresia appears in about 1 in every 10,000 to 20,000 live births, making it the leading cause of liver transplants in children. Babies with biliary atresia usually appear healthy at birth. The first sign of illness is often yellowing of the eyes and skin, called jaundice, and pale stools that last beyond two weeks.

Babies with biliary atresia should undergo a surgery called Kasai surgery. It also is called hepatoportoenterostomy. This procedure helps relieve bile buildup and slow liver damage, but it does not cure the condition. The surgery works best when done early in life, ideally within the first 60 days. The earlier it is performed, the better the outcome.

Although many children eventually require a liver transplant, a successful Kasai surgery can delay this need for many years. Some individuals may reach adulthood without ever needing a liver transplant.

Types

Healthcare professionals sometimes describe biliary atresia as either syndromic or nonsyndromic, depending on whether other birth defects are present.

• Syndromic biliary atresia. In some babies, biliary atresia occurs along with other structural problems, such as heart defects, spleen problems or differences in how the intestines are arranged. These babies may need extra tests and specialized care for those conditions.
• Nonsyndromic biliary atresia. In most cases, biliary atresia occurs without other malformations.

Healthcare professionals classify biliary atresia using the Kasai classification, which describes where the bile ducts are blocked:

• Type 1. The main bile duct, also called the common bile duct, is blocked. But the ducts inside the liver are still open.
• Type 2. The blockage is higher up, where the right and left bile ducts come together. But the smaller ducts inside the liver are still open.
• Type 3. Blockage is at the duct where bile leaves the liver, called the porta hepatis, with complete blockage of the extrahepatic biliary tree. This is the most common and severe form.

Understanding the type of biliary atresia helps healthcare professionals decide what approach may offer the best outcome.

Causes

Scientists don't yet know exactly what causes biliary atresia, but research shows it likely begins before the baby is born. There is no evidence that biliary atresia is inherited or caused by anything a parent did or didn't do during pregnancy. It also isn't something a child with biliary atresia will pass on to their own children.

Researchers believe biliary atresia may be triggered by a mix of factors. These include problems with how the bile ducts form during pregnancy, certain genes, and possibly infections or toxins that affect the baby in the womb. The more-common type appears in healthy-looking babies during the first few weeks of life. A less common type happens alongside other birth defects, such as heart or spleen problems. This less common type is called embryonic biliary atresia. It's also known as syndromic biliary atresia.

Diagnosis

In most cases, biliary atresia cannot be detected before birth. Routine prenatal ultrasounds usually look healthy. On rare occasions, a small or missing gallbladder may be seen, but this is not enough to confirm a diagnosis.

Diagnosing biliary atresia in a newborn involves a combination of lab tests and imaging studies. It is usually confirmed through a liver biopsy or a special imaging test done during surgery under anesthesia, called intraoperative cholangiography. The process usually begins when a baby's jaundice lasts longer than two weeks. While jaundice is common in newborns, persistent yellowing of the skin and eyes can be a sign that bile is not flowing properly out of the liver. Healthcare professionals use several tools to figure out whether biliary atresia is the cause.

Blood tests

One of the first steps is checking the baby's bilirubin levels through a blood test. Bilirubin is a yellow substance made when the body breaks down old red blood cells. The liver usually turns it into a water-soluble form, called direct or conjugated bilirubin. This bilirubin is released into bile and leaves the body through the intestines.

In babies with biliary atresia, the bile ducts are blocked, so direct bilirubin builds up in the blood. This can lead to symptoms such as jaundice, dark urine and pale stools due to the lack of bile reaching the intestines.

Healthcare professionals are especially concerned when direct bilirubin is over 1.0 milligrams per deciliter (mg/dL) after two weeks of age in babies. Other lab values that may not be within standard range include:

• Gamma-glutamyl transpeptidase (GGT), which is often very high in biliary atresia.
• Mildly elevated aspartate aminotransferase (AST) and alanine aminotransferase (ALT), which are liver enzymes.

Matrix metalloproteinase-7 testing

Healthcare professionals also may use a newer blood test called matrix metalloproteinase-7 (MMP7) to help support the diagnosis. MMP7 is a protein that is often much higher in babies with biliary atresia than in those with other liver conditions. While promising, this test is still being studied and is not yet used on its own to make a final diagnosis.

Imaging tests

Once blood tests raise concern for biliary atresia, health professionals use imaging to take a closer look at the liver, gallbladder and bile ducts to help confirm the diagnosis.

• Ultrasound. If the lab results suggest bile flow blockage, the next step is usually an abdominal ultrasound. This test uses sound waves to create images of the liver and bile ducts. On ultrasound, signs of biliary atresia may include:

  • A very small or missing gallbladder.
  • A bright, cone-shaped area called the triangular cord sign near the liver, which suggests scarring where the bile duct should be.

  A newer ultrasound technique looks for a short bile duct just outside the liver, called the duct at the hilum. If this duct isn't seen, it may point to biliary atresia. The test can be done while the baby is feeding and takes only a few minutes. In one study, this approach accurately identified all infants with biliary atresia and most without the disease. Results from this study suggest that this approach may reduce the need for more-invasive tests such as liver biopsy or intraoperative cholangiogram.

• Hepatobiliary iminodiacetic acid (HIDA) scan. This imaging test shows how well bile moves from the liver into the small intestine. A small, safe amount of radioactive tracer is given through an IV, and a special camera tracks how the liver and bile ducts handle it.

  If the tracer doesn't reach the intestine, it suggests that bile isn't flowing as it should. But that can happen in several liver conditions, not just biliary atresia. Likewise, some babies with biliary atresia may have a typical HIDA scan. Because of this, the HIDA scan is used together with blood tests, ultrasound and sometimes a liver biopsy to help medical professionals understand the cause of a baby's jaundice.

Liver biopsy

If imaging and lab results suggest biliary atresia, healthcare professionals may recommend a liver biopsy under anesthesia. This involves taking a very small sample of liver tissue to examine under a microscope. In biliary atresia, the biopsy often shows:

• Extra growth of small bile ducts, called bile duct proliferation.
• Thick bile trapped in the ducts, known as bile plugs.
• Early scarring of the liver, called fibrosis.

These findings suggest bile duct blockage, most commonly biliary atresia. But they also can be seen in other conditions.

Intraoperative cholangiogram

If imaging and biopsy suggest biliary atresia but the diagnosis is still uncertain, healthcare professionals may recommend a minor surgery. During this procedure, surgeons perform an intraoperative cholangiogram. This involves injecting dye directly into the bile ducts and taking X-rays. If the dye does not flow into the intestines, this confirms the diagnosis.

In the same surgery, healthcare professionals may go ahead with treatment by performing Kasai surgery to help drain bile from the liver.

Other conditions that may look like biliary atresia

Several other conditions can cause jaundice or pale stools in infants, so it's important for medical professionals to rule them out:

• Neonatal hepatitis. This is liver inflammation caused by infection or other factors. It can cause jaundice and dark urine but usually doesn't block the bile ducts. Most infants with this condition do not need surgery and may improve over time or with specific treatment.
• Alagille syndrome. This is a genetic condition that causes the liver to form too few bile ducts. It can look similar to biliary atresia but usually includes other signs such as heart defects, butterfly-shaped spine bones and a distinct facial appearance. Alagille syndrome is managed differently and doesn't respond to bile duct surgery.
• Choledochal cyst. This condition occurs when part of the bile duct is widened or forms a cyst. It can block the normal flow of bile and cause jaundice. Unlike biliary atresia, the bile ducts are still present, and surgery can correct the blockage.
• Alpha-1 antitrypsin deficiency. This is a genetic condition that affects how the liver processes a certain protein. When this protein builds up in the liver, it can cause inflammation and jaundice in infants.
• Progressive familial intrahepatic cholestasis (PFIC). PFIC is a rare inherited condition that prevents bile from flowing out of the liver as it should. Babies with PFIC may have jaundice, poor growth and itching as the disease progresses.

Coping and support

Learning that your baby has biliary atresia can be overwhelming. You may feel worried, sad or uncertain about what comes next. With time, many parents find ways to cope and feel more confident in caring for their child. These ideas may help:

• Learn about your baby's condition. Ask your baby's care team to explain what biliary atresia means, what tests and treatments are planned, and what to expect during recovery. Understanding the condition can help you feel more prepared and involved in your child's care.
• Lean on your support network. Family and friends can be an important source of strength. Accept offers of help, such as meals, child care or someone to talk to. Sharing your worries and small victories can make a big difference.
• Connect with others who understand. Many parents find comfort in talking with others who have gone through something similar. Ask your healthcare team about support groups for families affected by liver disease or organ transplant. National organizations such as the American Liver Foundation and Children's Liver Disease Foundation also offer online communities and information.
• Take care of yourself. Caring for a baby with a serious condition is stressful. Try to rest when you can, eat regularly and make time for breaks. You'll be better able to care for your child when you care for yourself too.