What is Biliary Atresia?
Biliary atresia is a condition where the bile ducts, which are tubes that carry bile from the liver, are blocked. It’s not clear why this happens. This condition can affect ducts inside and outside the liver. Symptoms usually appear in newborns and include constant yellow skin (jaundice), light-colored poop, and a large liver. If biliary atresia is not treated, it can be deadly. Less than 10% of children with this condition will live to see their third birthday if they don’t receive treatment.
This condition was first identified in 1817 by Dr. John Burns, who dubbed it a condition that could not be cured. The first successful surgery was done by Dr. William Ladds in 1920, but the outlook for most patients remained poor until the 1950s. This changed when Dr. Morio Kasai introduced a new surgery. In this procedure, called the Kasai porto-enterostomy, the blocked section of the bile duct is removed, and a loop of intestine is connected to the liver. Nowadays, this operation is the standard treatment for all children who have the condition.
As medical knowledge and technology have improved, liver transplantation has also become a treatment option for children with biliary atresia. This treatment is used for children whose initial Kasai surgery wasn’t successful in restoring the flow of bile or who have developed advanced liver cirrhosis, which is severe scarring of the liver.
What Causes Biliary Atresia?
The exact cause of a medical condition called biliary atresia is not known. Researchers suggest it could be a combination of both genetic factors and things that happen after a child is born, or acquired factors.
Some children with biliary atresia also have another related syndrome or abnormality from birth. The disease is also more common in certain geographic regions, suggesting that genes might play a role in causing the disease. Although, no single cause has been found yet. It’s also worth noting that only a few families have more than one child with this condition, and it doesn’t seem to be more common in twins.
The development of bile ducts, which are tubes that deliver bile from the liver to the small intestine, starts early during the development of a fetus. The part of the liver where these bile ducts meet is very important for the development of a healthy, functional biliary system. Non-syndromic, or unrelated, biliary atresia might be caused by issues during fetal development at this area of the liver. This theory is strengthened by similarities found in certain protein patterns in biliary atresia patients and fetal bile ducts. It suggests biliary atresia could occur due to the bile ducts not developing properly.
Other theories suggest that biliary atresia could be caused by something that happens after birth, like inflammation or infection. Certain viruses are of particular interest because they have caused biliary atresia in animal models. However, these findings have not been consistently seen in human studies.
Some studies have shown immune-related damage in the bile ducts of biliary atresia patients, suggesting the body’s immune response might play a role in causing the disease. Other findings suggest that this condition could be related to certain environmental factors, like the season of the year, or previous illnesses in the children.
Biliary atresia is not a single disease caused by a specific factor. Instead, it appears as a symptom resulting from different causes. It is divided into two broad categories; syndromic, which is related to other medical conditions, and non-syndromic, which appears by itself. There are also several specific types of biliary atresia based on their defining characteristics.
One is called Biliary Atresia Splenic Malformation Syndrome (BASM) which includes multiple organ abnormalities. Another is Cystic Biliary Atresia, characterized by a blockage of the biliary system with dilated, or expanded, cysts. A third type is associated with certain virus antibodies and is usually seen in non-white children and carries the worst prognosis. The majority of biliary atresia cases don’t fit into these specific groups and are known as Isolated Biliary Atresia, with an unknown cause.
Furthermore, biliary atresia can be classified based on the location and nature of the blockage. This includes four types: Type I is a blockage of the common bile duct. Type IIa is a blockage of the common hepatic duct, which is a part of the bile duct system. Type IIb is a blockage that also includes the cystic duct, but the gall bladder is normal. Type III is the most common type and involves blockages that include the common bile, hepatic, and cystic ducts.
Risk Factors and Frequency for Biliary Atresia
Biliary atresia, a severe liver disorder, exhibits significant regional differences. There are higher rates in places like Taiwan and Japan, with approximately 1 to 5 cases in every 1,000 live births. On the other hand, places such as England and Wales report lower rates, with about 1 to 5 cases in every 20,000 live births. Some studies also reveal that these cases might vary with different seasons and may also be slightly more common in females.
The rate can also vary based on the specific type of Biliary Atresia. For instance, the BASM type is reported in approximately 10% of cases in European studies, but is less commonly seen in Asia. In fact, most of the biliary atresia cases related to CMV IgM positivity are reported from China.
- Biliary Atresia cases are more common in Taiwan and Japan, approximately, ranging from 1 to 5 in every 1,000 live births.
- In England and Wales, the cases are fewer, about 1 to 5 in every 20,000 live births.
- Some studies suggest that the occurrence of Biliary Atresia may change with the seasons.
- The condition might also be slightly more common in females.
- There are different types of Biliary Atresia with some showing variations in geographical occurrence. One such type, BASM, is seen in about 10% of cases in Europe but its incidence in Asia is relatively less.
- Most Biliary Atresia cases related to CMV IgM positivity are found in China.
Signs and Symptoms of Biliary Atresia
Neonatal children sometimes show persistent symptoms such as ongoing yellowing of the skin and whites of the eyes (jaundice), light-colored poop (clay-colored stools), and an enlarged liver (hepatomegaly). It’s critical to not dismiss any case of jaundice that lasts more than 14 days as normal. Such cases should be examined further. A considerable number of children with a condition known as biliary atresia initially excrete normal-colored poop, but this gradually becomes pale or colorless. As the disease progresses, they can also show signs of liver cirrhosis and failure, recognizable by an enlarged liver or spleen, fluid accumulation in the abdomen (ascites), symptoms of increased blood pressure in the liver (portal hypertension), and failure to grow properly.
- Persistent yellowing of the skin and eyes (jaundice)
- Light-colored poop (clay-colored stools)
- Enlarged liver (hepatomegaly)
- Normal colored poop turning pale or colorless
- Enlarged spleen (splenomegaly)
- Fluid accumulation in the abdomen (ascites)
- Symptoms of increased blood pressure in the liver (portal hypertension)
- Failure to grow properly (failure to thrive)
Testing for Biliary Atresia
To diagnose biliary atresia, which is a condition in the liver’s bile ducts, there isn’t just one specific test that can do it completely. Instead, children undergo a combination of blood tests, imaging tests, and an examination of the tissues to reach a diagnosis.
Biliary atresia causes high levels of both direct and indirect bilirubin in the blood, with the conjugated (or direct) part being more elevated. Because children naturally have high levels of a substance called alkaline phosphatase due to their bones growing, a specific type of it (5′ nucleotidase) should be measured. Another substance, gamma-glutamyl transpeptidase (GGTP), is found in the bile membrane in the liver and it is increased in cases of blockages in the bile ducts. Its presence can help diagnose biliary atresia with an accuracy between 50% to 60%. The levels of enzymes known as serum transaminases are also slightly increased in biliary atresia.
Imaging tests like an ultrasound are non-invasive, easily available, and can provide valuable information about the texture of the liver, the flow of blood through the liver, and any fluid buildup in the abdomen. In addition, an ultrasound can rule out other causes of jaundice such as a cyst in the bile duct. For biliary atresia, an ultrasound might show a small or missing gallbladder. Even though an ultrasound is widely available and easy, it can only accurately diagnose biliary atresia about 78% of the time.
Hepatobiliary scintigraphy is another test that uses a technetium-labeled compound to show whether this compound reaches the intestine, which would rule out biliary atresia. However, this test is less reliable when the levels of conjugated bilirubin are high and has a 10% chance of producing a false-positive or false-negative result.
Some other tests include endoscopic retrograde cholangiopancreatography (ERCP), duodenal intubation, and magnetic resonance imaging (MRI). ERCP isn’t widely used because few places have the necessary equipment. Duodenal intubation isn’t often done either due to it being invasive and unreliable. MRIs, while offering better accuracy, are not frequently done due to high costs and the need for sedation.
A liver biopsy, or taking a small sample of liver tissue for examination, can also help to accurately differentiate biliary atresia from other causes of jaundice. The biopsy might show features like increased bile ducts, bile plugging, the presence of cells with many nuclei, partially dead tissue, formation of blood cells outside the bone marrow, and immune cell infiltration. Of all these, the increase in bile ducts is seen as the most sensitive and specific feature for diagnosing biliary atresia.
Treatment Options for Biliary Atresia
Surgical examination is the most reliable way to diagnose and treat biliary atresia, a condition where the normal openings in the liver’s bile ducts are blocked or absent.
During the operation, a test called a peri-operative cholangiogram is conducted. This involves injecting a dye that can be visualized using X-rays into the bile ducts. If the dye fails to pass into the bile ducts within the liver and leading from the liver, then biliary atresia is confirmed.
The standard treatment for biliary atresia involves a surgical procedure known as the Kasai technique, or the Roux-en-Y hepatic porto-enterostomy. Here, surgeons remove the damaged bile ducts and create a loop, known as a Roux-en-Y loop, from a portion of the intestines. This loop is then connected to the liver to recreate a pathway for bile, a digestive fluid, to travel from the liver to the intestines.
In rare instances, where the gallbladder and the common bile duct are unblocked, a surgical procedure known as a porto-cholecystostomy may be considered. However, this procedure is not as adaptable as the standard Kasai technique and has been linked with a higher risk of repeated blockages and less favorable long-term outcomes. In some cases, another surgical procedure called a hepaticojejunostomy is used, but the outcomes are not as good as the standard Kasai procedure.
Following the operation, certain drugs are often prescribed to aid with bile drainage. The two most commonly used drugs are steroids and ursodeoxycholic acid. Steroids are given as they can reduce inflammation and promote the clearing of bile. However, high doses of steroids have been shown in studies to not improve bile clearance and can have earlier onset of side effects. Meanwhile, ursodeoxycholic acid, a substance naturally present in small amounts in the body, is well known in helping to promote the clearance of bile.
If the cirrhosis, scarring of the liver, is very advanced, or if the Kasai procedure hasn’t been successful, a liver transplant may be considered. It involves removing the damaged liver and replacing it with a donor’s healthy liver.
What else can Biliary Atresia be?
There are several conditions that can affect the liver and digestive system in children. Some of these include:
- Alagille syndrome
- Alpha 1 antitrypsin deficiency
- TORCH (conditions caused by certain infections during pregnancy, including toxoplasmosis, others, rubella, cytomegalovirus, herpes simplex virus)
- Caroli disease
- Choledochal cyst
- Idiopathic neonatal hepatitis (a liver inflammation in newborns for which the cause is unknown)
- Lipid metabolism disorders (problems with how the body processes fats)
- Total parenteral nutrition-associated hepatitis (a condition related to a special type of nutrition given through a vein)
What to expect with Biliary Atresia
The success of a Portoenterostomy surgery, which is a procedure that connects the liver to the intestines, depends on a number of factors.
The age of the patient when they have the initial operation is one of the factors. However, the relationship between the age when the surgery is performed and the outcome is not straightforward. One study found that for the first 90 days of life, the result of the operation can’t be predicted by age alone in the case of a specific type of liver disease known as biliary atresia.
Another factor is whether the patient has a syndromic type of biliary atresia, which means that the disease is part of a syndrome that includes a range of symptoms. Infants with this type of biliary atresia may not respond as well to the surgery and may have poorer outcomes, with a higher risk of death.
The disease can also be associated with a viral infection known as cytomegalovirus (CMV), and infants who test positive for an antibody known as CMV IgM tend to have poorer outcomes and a higher risk of death.
Post-operative bile flow is crucial. Patients who have satisfactory bile flow and good bile clearance after the surgery tend to have better survival rates. Some reports highlight that patients who had normal to moderately elevated liver function test results more than 20 years post-surgery.
Also, the size of the tiny bile ducts in the part of the bile duct that’s removed during surgery can affect the outcome. Some studies have suggested this has significance, although others have disputed this finding.
Possible Complications When Diagnosed with Biliary Atresia
After surgery, some individuals may experience various complications such as cholangitis (inflammation of the bile duct), anastomotic leak (a break in the intestinal sutures), intestinal obstruction, portal hypertension (high blood pressure in the vein leading to the liver), and hepatopulmonary syndrome (a liver condition causing lung issues).
Cholangitis, the condition where the bile duct connected to the liver is inflamed, is not yet fully understood. What is known is that it often develops after surgery where a bilio-intestinal flow is restored, which can lead to bacterial growth and a subsequent infection. This condition happens in up to 50% of the cases, and various past attempts to lower the risk during surgery have not proved successful. If a child has cholangitis, they may have a fever, worsening jaundice, and high liver enzymes. In such cases, it’s important to treat them quickly with special antibiotics.
Portal hypertension, or high blood pressure in the liver’s vein, is common in infants with a liver condition called biliary atresia. A bad sign, this condition often leads to further health complications like variceal bleeding, portal hypertension, and stage liver failure.
Variceal bleeding is another potential side effect where the esophagus starts to bleed. Around 60% of kids that went through a specific bile duct surgery develop this condition within two to three years, and a third are susceptible to bleeding. It is recommended for these children to undergo medical surveillance.
Another potential complication is ascites, where fluid accumulates in the stomach. This can happen due to portal hypertension, low albumin (a type of protein), and low sodium levels. Doctors usually prescribe a medication called spironolactone to deal with it.
Some people may develop “biliary lakes” or cysts within the liver, which can trigger repeated cholangitis episodes. People suffering from this condition are generally advised to keep taking a wide range of antibiotics for a long time. If needed, they may have to undergo a liver transplantation.
The hepatopulmonary syndrome is a condition that includes symptoms like bluish skin and shortness of breath due to liver disease. It’s thought that compounds from the gut that widen blood vessels bypass degradation in the liver and could be to blame. To halt the process, patients often need a liver transplant.
Finally, there have been rare reports of cancers developing in severely damaged livers after surgery, including hepatocellular carcinoma or cholangiocarcinoma.
Preventing Biliary Atresia
Parents should know that a certain surgical procedure called Kasai porto-enterostomy, used to restore bile flow, has an initial success rate of about 60%. The likelihood of needing a liver transplant is reduced if this surgery is done within the first 10 weeks of a child’s life. The earlier the diagnosis, the better the chances of the child living with their own liver.
When a child has symptoms like jaundice (a condition that causes yellow skin and eyes), clay-colored stools, and dark urine, it might indicate a condition called biliary atresia. If these symptoms are present, they should be checked for this condition, and be referred to a specialty medical center if necessary.
Tools like stool color charts and a mobile app that monitors stool color are available. They were designed to help increase awareness of biliary atresia and to encourage people to seek medical referral sooner.
