In normal infants bile drains from the liver to the duodenum (the first portion of the small intestine) through a series of ducts. Ducts are like pieces of hollow tubing. Thousands of very small ducts in the liver become two large ducts that join to form a single hepatic duct that drains into the intestine. The gallbladder is a reservoir for bile that empties into the hepatic duct halfway between the liver and the duodenum. After the gallbladder joins the main duct draining the liver, the duct is called the common bile duct. Biliary atresia is a disorder occurring in infants in which the bile ducts disappear or scar closed, preventing the passage of bile out of the liver.
The incidence of biliary atresia is approximately 1 in 15,000 live births. Biliary atresia is slightly more common in girls (female-to-male ratio of 1.7). Approximately 10% of infants have an associated congenital heart defect.
Cause of Biliary Atresia
The cause of biliary atresia is not known and there may be more than one cause. There is evidence that some viruses (including reovirus, human papillomavirus, rotavirus and cytomegalovirus) are associated with biliary atresia but it has not been proven if or how they cause the bile ducts to close off. Another possible cause may involve a loss of blood flow to the developing bile ducts in the fetus. The fact that some infants clearly have bile in their stool at birth shows that the bile ducts were open in at least one point in time. Infants can then progress to biliary obstruction. This suggests that biliary atresia is not a single fetal event, but rather a progressive inflammatory process that begins either just before or shortly after birth.
Inflammatory cells surround the bile ducts of nearly all infants with biliary atresia and presumably begin to accumulate in fetal life. Inflammation narrows and may block off the opening (lumen) of small ducts inside the liver and the large duct outside the liver. Inflammation leads to scar formation in the liver around the bile ducts and then between ducts. This scar formation is called cirrhosis.
Whatever the cause of biliary atresia, cirrhosis makes it difficult for blood to flow through the liver. This leads to backflow of blood in the main blood vessel to the liver called the portal vein. The portal vein carries blood from the intestines to the liver. This blood carries many of the nutrients we absorb from our food and the liver processes these nutrients into forms our bodies can use. The high pressure in the portal vein eventually results in bleeding from the esophagus and accumulation of fluid in the abdomen, called ascites. Most infants who do not undergo an operation to address biliary atresia die before 20 months of age.
Jaundice is common in newborns due to diminished activity of an enzyme in the liver that converts bilirubin to a form, called direct bilirubin, that can dissolve in bile and be removed from the body. In these cases, the undissolved bilirubin, called indirect bilirubin, is elevated in the blood. This type of jaundice is common in the first few weeks of life and usually goes away. Jaundice that persists for more than two weeks after birth is considered abnormal. Jaundice that is due to obstruction of bile flow, as in biliary atresia, as opposed to a problem of converting indirect bilirubin to its dissolvable form can be identified by elevation of direct bilirubin in the blood. Prompt evaluation of suspected obstructive jaundice should be done during the first month of life.
A wide range of disorders may cause persistent jaundice. Infants in whom more than 20% of the bilirubin is direct bilirubin have what is called “cholestasis.” Cholestasis means the bile is not flowing in the ducts very well. Cholestasis may be due either to slow bile flow or an actual obstruction to bile flow. Disorders which fall into this category with an elevated direct bilirubin include infections, slow bile flow in babies who do not eat, and biliary atresia. It is important to figure out whether the elevated direct bilirubin is due to a cause that needs surgery to correct, such as biliary atresia or if it is due to a problem that can be cared for without surgery. A series of observations and measurements including the presence of bile in the intestine, green or brown stool, positive tests for cystic fibrosis, assessment of certain enzyme levels such as alpha-1-antitrypsin, and cultures or other tests that reveal infection identify most causes of cholestasis. Most of these causes do not need surgery. If these studies are negative, in other words do not come up with a diagnosis, the diagnostic choice lies between biliary atresia and neonatal hepatitis. The causes of neonatal jaundice that do not require an operation can usually be excluded before the age of four weeks.
The stools of infants with biliary atresia are acholic, meaning that they are gray or clay-colored. The urine may appear dark. The liver becomes large and firm by four weeks. Spleen enlargement may develop by six weeks. Ascites (abdominal fluid) with large abdominal wall veins is evidence of advanced liver disease but usually does not occur until after six months.
If the tests mentioned above do not reveal the diagnosis, than another series of tests will be done to help determine if the infant has biliary atresia. Abdominal ultrasound may reveal a very small gallbladder or the gallbladder may be completely absent. This is typical in biliary atresia while for many of the other diagnoses being considered the gallbladder may look normal. The bile ducts within the liver rarely become dilated (enlarged) and most likely cannot even be seen on ultrasound in infants with biliary atresia.
A HIDA scan uses a contrast dye that is injected into a vein and is concentrated in the liver. In the normal situation the contrast dye is then passed out of the liver into the bile ducts and into the intestine. This is detected on the pictures taken by the scanner. In cases of biliary atresia no contrast dye leaves the liver because there are no bile ducts present and there is no way for the contrast dye to leave the liver and enter the intestine. There are also other illnesses that can cause this same situation where no contrast leaves the liver. Because of this, the HIDA scan cannot prove that a child has biliary atresia. If however, contrast does leave the liver and get into the intestine, the scan can prove that biliary atresia is not the problem.
Obtaining a piece of liver tissue may be useful to help determine the diagnosis and some hospitals and doctors use a needle biopsy of the liver as a routine part of the work up for biliary atresia. The infant is sedated or anesthetized and the biopsy is taken with a needle passed through the skin into the liver. There are certain findings under the microscope that may be able to distinguish biliary atresia from other conditions causing jaundice. Some doctors prefer not to use this method as there may some overlap in the findings seen with biliary atresia and neonatal hepatitis.
Most physicians believe that the surgery to treat biliary atresia is best done by eight weeks of age. The testing to determine the cause of neonatal jaundice should be completed by eight weeks of age to minimize the bad effects of untreated biliary atresia. There are cases, however where the diagnosis was made even later than eight weeks of age and the babies did well with surgical treatment, but in general it is best to make the earlier the diagnosis earlier than eight weeks if possible. If the diagnosis of biliary atresia is suspected and all of the other tests cannot find some other definite cause for the jaundice, the final step is an operation to examine the liver, gallbladder and bile ducts. A dye study called a cholangiogram is done and a wedge biopsy of the liver is obtained. If the dye study shows no bile ducts or if there is no gallbladder, then the diagnosis of biliary atresia is made. This dye study provides a sharper image of the bile ducts than does the HIDA scan mentioned before, but one has to do an operation to perform the cholangiogram. This is why the HIDA scan is done first to see if the diagnosis can be made without an operation. If biliary atresia is found a Kasai operation is performed during that same operation. This operation is also called a portoenterostomy.
Operative management of suspected biliary atresia should be performed soon after the diagnosis is suspected. As already mentioned making the diagnosis and performing the surgery to try and correct it before 8 weeks of age is preferable. The prognosis for many babies worsens after this time. Older infants without advanced liver disease may still benefit from the Kasai operation. If the liver disease has become advanced however, primary liver transplantation rather than a Kasai operation may best serve those patients.
The operation that is performed in most cases of biliary atresia is the Kasai portoenterostomy. This operation was first developed in 1959 in Japan. In most cases of biliary atresia there are no normal bile ducts either inside the liver (intrahepatic) or outside of the liver (extrahepatic). The extrahepatic bile ducts have most often become scarred cords of tissue. The objective of the operation is to remove the scarred extrahepatic bile ducts and replace them with a piece of intestine. This piece of intestine is sewn to the liver in the place where the bile ducts should have been when they exited the liver. The hope is that any tiny microscopic bile ducts left to drain the liver will drain into this piece of intestine. (Fig. 64-2). If the remaining bile ducts are large enough and the liver is not irreversibly damaged, bile will flow into the intestine and jaundice will be relieved.
After the operation antibiotics are usually given to prevent infection of the bile ducts (cholangitis). Patients receive supplemental vitamins, in particular those vitamins that require fats for absorption (Vitamins A,D,E,K). Babies need these vitamins because bile helps with fat absorption and if there is not enough bile, these vitamins are not well absorbed. One of several medicines may be used to help stimulate bile flow. Because inflammation around the remaining small bile ducts may continue despite a technically successful Kasai operation, some physicians use steroid therapy for a period of time after surgery. This inflammation may contribute to the disease getting worse despite surgery.
Postoperative complications include cholangitis (infection of the remaining bile ducts), progressive cirrhosis (scarring of the liver) and eventually liver failure. Cholangitis causes a decrease in bile flow, fever and recurrence of jaundice. It is often a clinical diagnosis meaning it may be difficult to diagnose definitively with a specific test. Blood cultures may be useful to make the diagnosis. Babies with cholangitis may have in addition to fever, what are called acholic stools. After a successful Kasai the stool becomes colored, either green or brown. When cholangitis is present, bile flow decreases and the stool looses color again. Lose of stool color after a Kasai operation is an important finding and should be reported to the doctor. Cholangitis is usually treated when it is suspected. Cholangitis is treated with antibiotics and possibly other medicines to stimulate bile flow and decrease inflammation.
Results of Treatment
A successful outcome after the Kasai operation depends on many factors including precise performance of the procedure, age of the patient, severity of liver damage at the time of operation, the size of the ducts at the edge of the liver, whether bile flow adequate to reduce jaundice is achieved after the operation and the occurrence of postoperative cholangitis. Within four weeks of the operation the prognosis can usually be determined. Infants who produce bile and clear their jaundice have a good chance of long-term survival and maintenance of near-normal liver function with their own liver. In infants who remain jaundiced but with stabilization of the progression of liver disease, extended survival can be expected. Such patients are likely to require a liver transplant within a few years, however. The Kasai operation has failed if bile does not flow and the liver disease continues to progress. Most surgeons agree that if bile flow is not present after a technically correct Kasai operation re-operation is not successful and should be avoided. Patients in this category become candidates for transplantation during the first 12 to 16 months of life. Patients who are diagnosed with biliary atresia very late and show signs of impending or established liver failure are most likely to require transplantation rather than a Kasai as the first form of surgery.
The age of the patient at the time of the Kasai operation is a crucial variable. The younger the patient at the time of operation, the better the overall prognosis. Eight weeks is the important threshold; the likelihood for survival with a functioning native liver begins to fall in patients older than eight weeks of age. Some surgeons question whether the Kasai operation should be attempted at all in patients older than three months of age, reasoning that the liver disease has progressed beyond the point where the operation would be of benefit and that early transplantation is the best option. However, reports of infants greater than three months of age who have undergone a successful Kasai operation and the scarcity of infant donor livers has led many centers to proceed with the Kasai operation in older patients.
About one third of patients operated on by eight weeks of age have a successful outcome and may never require transplantation. An additional third of infants are improved after Kasai operation and have an extended survival. In this group transplantation may not be required until the child is much older and of an age and size when the donor pool is larger and it is easier to get a donor organ. Transplantation is a life-saving procedure for the remaining third of infants who present late in the course of disease or fail to improve after the Kasai operation. These infants will usually be transplanted within the first year of life.
All infants treated for biliary atresia need long term follow in the doctors office to check on liver function and nutritional status in addition to the usually childhood checkups.
Article and graphics adapted from O'Neill: Principles of Pediatric Surgery.© 2003, Elsevier.