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NORD is very grateful to Jorge A. Bezerra, MD, William and Rebecca Balistreri Chair of Pediatric Hepatology, Professor of Pediatrics; Director, Digestive Health Center, Cincinnati Children's Hospital Medical Center, Division of Gastroenterology, Hepatology and Nutrition, for assistance in the preparation of this report.
Extrahepatic biliary atresia is a rare gastrointestinal disorder characterized by destruction or absence of all or a portion of the bile duct that lies outside the liver (extrahepatic bile duct). The bile duct is a tube that allows the passage of bile from the liver into the gall bladder and, eventually, the small intestine. Bile is a liquid secreted by the liver that plays an essential role in carrying waste products from the liver and promoting absorption of fats and vitamins by the intestines. In extrahepatic biliary atresia, absence or destruction of the bile ducts results in the abnormal accumulation of bile in the liver. Affected infants have yellowing of the skin and whites of the eyes (jaundice) and scarring of the liver (fibrosis). In some cases, additional abnormalities may be present, including heart defects and intestinal, spleen and kidney malformations. The exact cause of extrahepatic biliary atresia is unknown.
The symptoms of extrahepatic biliary atresia usually appear by the age of two to six weeks and include a yellowish coloration of the skin and whites of the eyes (jaundice), abnormally pale stools, and dark urine. Infants may also have swollen (distended) stomach and/or abnormal enlargement of the liver (hepatomegaly). By the age of six to 10 weeks, additional symptoms may also develop including poor weight gain, irritability and/or an increase in blood pressure within the veins that carry blood from the intestine to the liver (portal hypertension). Bile ducts inside the liver (intrahepatic bile ducts) are also involved. If left untreated, biliary atresia may result in permanent scarring of the liver (cirrhosis) and, eventually, liver (hepatic) failure.
In some cases, children with biliary atresia may have additional congenital abnormalities including malformations of the heart (e.g., situs inversus, levocardia, and ventricular septal defects) and/or kidneys. Situs inversus is a condition in which the internal organs are on the opposite side of the body from normal. Levocardia is a condition in which the heart is malpositioned. (For more information on ventricular septal defects see the Related Disorders section below.)
Additional features may be associated with some cases of extrahepatic biliary atresia including absence of the spleen (asplenia), the presence of more than one spleen (polysplenia), and/or other anatomical abnormalities.
The exact cause of extrahepatic biliary atresia is unknown. Several factors may contribute to the development of the disorder, including immunologic, infectious, genetic, environmental, and/or other factors. In most cases of extrahepatic biliary atresia, the bile ducts are normal at birth, but something causes them to be damaged (independently or with the help of an activated immune system) and replaced with fibrous tissue (sclerosis). Several viruses, including cytomegalovirus, reovirus type 3 and rotavirus infections are being studied as possible causative agents.
A minority of cases may be caused by defects during the development (morphogenesis) of the liver and biliary tree during pregnancy. Some of these cases may be diagnosed during gestation by a prenatal ultrasound that shows a cyst in the biliary system. Biliar atresia is not an inheritable disease, and no specific genetic predisposition for the disorder has been validated.
Extrahepatic biliary atresia is a rare disorder with a slight increased frequency in females. It occurs in approximately 1 in 10,000 to 15,000 births in the United States. Approximately 400-600 new cases of biliary atresia are encountered in the United States each year. According to one estimate, the prevalence of biliary atresia in Europe is approximately 1 in 12,000 births. Biliary atresia is the most common cause of end-stage liver disease and liver transplantation in children.
Symptoms of the following disorders can be similar to those of extrahepatic biliary atresia. Comparisons may be useful for a differential diagnosis:
Neonatal hepatitis (sometimes referred to as neonatal cholestasis) is a term used to describe a group of disorders that present with jaundice due to inflammation of the liver and/or injury of the bile duct structure within the liver (intrahepatic). Despite the name "hepatitis," most of these disorders are not caused by infections. Some of the more common disorders are the Alagille syndrome, deficiency of alpha-1-antitrypsin protein, cystic fibrosis, progressive familial intrahepatic cholestasis, and defects in synthesis of bile acids. The cause for neonatal hepatitis in some infants remains unknown. In these infants, some studies suggest an association with an infectious or viral disease. Symptoms of neonatal hepatitis typically appear during the first few weeks of life and may include a yellow discoloration of the skin and whites of the eyes (jaundice), an abnormally enlarged liver (hepatomegaly), poor feeding, slow growth, itchy skin, abdominal discomfort, lightly colored stools, and/or dark urine. (For more information on this disorder, choose "Neonatal Hepatitis" as your search term in the Rare Disease Database.)
Primary sclerosing cholangitis is a rare progressive disorder characterized by inflammation, thickening, and abnormal formation of fibrous tissue (fibrosis) within the passages that carry bile from the liver (bile ducts). This often results in the decrease of bile flow from the liver (cholestasis). This disorder is more common in older children and adults. The neonatal form of sclerosing cholangitis is rare and may share features with biliary atresia and neonatal hepatitis. The cause is not known, but most cases are associated with defects in the immunologic or hematologic systems. Symptoms associated with sclerosing cholangitis include fatigue and itching (pruritis), followed by yellowing of the skin, mucous membranes, and whites of the eyes (jaundice). In addition, affected individuals may have dark urine, light-colored stools, abdominal pain, and/or nausea. The exact cause of primary sclerosing cholangitis is not known. (For more information on this disorder, choose ìprimary sclerosing cholangitisî as your search term in the Rare Disease Database.)
The following disorders may be associated with extrahepatic biliary atresia as secondary characteristics. They are not necessary for a differential diagnosis:
Ventricular septal defects (VSDs) are heart defects that are present at birth (congenital). The normal heart has four chambers. The two upper chambers, known as atria, are separated from each other by a fibrous partition known as the atrial septum. The two lower chambers are known as ventricles and are separated from each other by the ventricular septum. Valves connect the atria (left and right) to their respective ventricles. The aorta, the main vessel of arterial circulation, carries blood from the left ventricle and away from the heart. VSDs can occur in any portion of the ventricular septum. The size and location of the defect determine the severity of the symptoms. Small ventricular septal defects can close on their own (spontaneously) or become less significant as the child matures and grows. Moderately-sized defects can cause congestive heart failure, which is characterized by an abnormally rapid rate of breathing (tachypnea), wheezing, unusually fast heartbeat (tachycardia), enlarged liver (hepatomegaly), and/or failure to thrive. (For more information on this disorder, choose "ventricular septal defects" as your search term in the Rare Disease Database.)
The diagnosis of extrahepatic biliary atresia requires a direct examination of the bile ducts by abdominal surgery (laparotomy) and the microscopic examination of tissue from the liver (liver biopsy). During the surgery special contrast dye is injected into the gallbladder and x-ray films are taken to outline how the dye fills the major bile ducts (intraoperative cholangiogram). These films show the movement (or lack of movement) of the dye through the liver, bile ducts, and small intestine. The physician is then able to evaluate the structure of the bile ducts and to determine the site of the blockage (proximal or distal). Blood tests may demonstrate elevated levels of liver enzymes and bilirubin and detect viral or bacterial agents. Ultrasound of the liver may show absence of the gall bladder.
No cure exists for biliary atresia, but the timely diagnosis and surgical intervention improves short- and long-term outcomes in most patients. Special attention to the nutritional needs and diet are essential for children with this disorder. Special supplements, formulas, and dietary restrictions may be necessary for affected infants.
Surgery must be performed to remove the obstruction and allow bile to flow into the bile ducts and small intestine (Kasai hepatoportoenterostomy). In this procedure, the extrahepatic bile ducts are removed and replaced with a portion of the affected infant's small intestine thereby forming a conduit for improved bile flow. The exact surgical procedure may vary according to the location and nature of the obstruction. In the majority of cases, bile flow can be established with these surgical procedures. However, some children may experience variable degrees of liver dysfunction even after successful surgery. The Kasai procedure may also be used as an early intermediate procedure to support the child's growth. Despite the Kasai procedure, liver transplantation may ultimately become necessary in many cases. Antibiotics may be used to treat infections of the bile ducts (cholangitis).
Genetic counseling may be of benefit for people with extrahepatic biliary atresia and their families. Other treatment is symptomatic and supportive.
In October of 2002, the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) created the a national consortium comprised of several pediatric liver centers to collect and maintain a database of clinical information as well as serum and tissue samples from children with biliary atresia and other causes of neonatal cholestasis in order to encourage and perform clinical, epidemiological and therapeutic research. The consortium is named Childhood Liver Disease Research and Education Network (ChiLDREN) and is currently investigating the efficacy of corticosteroids to improve bile flow and long-term outcome following surgical treatment for biliary atresia.
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Report last updated: 2012/03/07 00:00:00 GMT+0