(See also Overview of Congenital Gastrointestinal Anomalies Overview of Congenital Gastrointestinal Anomalies Most congenital gastrointestinal (GI) anomalies result in some type of intestinal obstruction, frequently manifesting with feeding difficulties, distention, and emesis at birth or within 1 or... read more .)
The incidence of biliary atresia in the US is about 1/8,000 to 1/18,000 live births (1 General reference Biliary atresia is obstruction of the biliary tree due to progressive sclerosis of the extrahepatic bile duct. Diagnosis is by blood tests, ultrasonography, liver biopsy, and hepatobiliary scan... read more ).
In most cases, biliary atresia manifests several weeks to months after birth, probably after inflammation and scarring of the extrahepatic (and sometimes intrahepatic) bile ducts. It is rarely present in premature infants or in neonates at birth (or is unrecognized in neonates). The cause of the inflammatory response is unknown. Several infectious organisms have been implicated, including reovirus type 3 and cytomegalovirus, but no definitive association has been noted. In addition, there may be a genetic component with defects in one of several genes (CFC1, FOXA2).
Cirrhosis Cirrhosis Cirrhosis is a late stage of hepatic fibrosis that has resulted in widespread distortion of normal hepatic architecture. Cirrhosis is characterized by regenerative nodules surrounded by dense... read more , with progressive, irreversible scarring of the liver, can be present by 2 months of age if the defect is not treated.
About 15 to 25% of infants have other congenital defects, including polysplenia/asplenia, intestinal atresia, situs inversus, and cardiac anomalies Overview of Congenital Cardiovascular Anomalies Congenital heart disease is the most common congenital anomaly, occurring in almost 1% of live births (1). Among birth defects, congenital heart disease is the leading cause of infant mortality... read more or renal anomalies Overview of Congenital Genitourinary Anomalies Congenital anatomic anomalies of the genitourinary tract are more common than those of any other organ system. Urinary tract anomalies predispose patients to many complications, including urinary... read more .
1. Harpavat S, Garcia-Prats JA, Anaya C, et al: Diagnostic yield of newborn screening for biliary atresia using direct or conjugated bilirubin measurements. JAMA 323(12):1141–1150, 2020. doi: 10.1001/jama.2020.0837
Infants with biliary atresia are jaundiced Neonatal Hyperbilirubinemia Jaundice is a yellow discoloration of the skin and eyes caused by hyperbilirubinemia (elevated serum bilirubin concentration). The serum bilirubin level required to cause jaundice varies with... read more and often have dark urine (containing conjugated bilirubin), acholic stools, and hepatosplenomegaly.
By 2 to 3 months of age, infants may have poor growth with malnutrition, pruritus, irritability, and splenomegaly.
Untreated, hepatic fibrosis progresses to cirrhosis Cirrhosis Cirrhosis is a late stage of hepatic fibrosis that has resulted in widespread distortion of normal hepatic architecture. Cirrhosis is characterized by regenerative nodules surrounded by dense... read more resulting in portal hypertension Portal Hypertension Portal hypertension is elevated pressure in the portal vein. It is caused most often by cirrhosis (in developed countries), schistosomiasis (in endemic areas), or hepatic vascular abnormalities... read more , abdominal distention resulting from ascites Ascites Ascites is free fluid in the peritoneal cavity. The most common cause is portal hypertension. Symptoms usually result from abdominal distention. Diagnosis is based on physical examination and... read more , dilated abdominal veins, and upper gastrointestinal bleeding resulting from esophageal varices Varices Varices are dilated veins in the distal esophagus or proximal stomach caused by elevated pressure in the portal venous system, typically from cirrhosis. They may bleed massively but cause no... read more .
Biliary atresia is identified by an elevation in both total and direct bilirubin. The serum alpha-1 antitrypsin levels should be determined because alpha-1 antitrypsin deficiency Alpha-1 Antitrypsin Deficiency Alpha-1 antitrypsin deficiency is congenital lack of a primary lung antiprotease, alpha-1 antitrypsin, which leads to increased protease-mediated tissue destruction and emphysema in adults.... read more is another relatively common cause of cholestasis. Tests that are needed to evaluate the liver include albumin, liver enzymes, prothrombin time/partial thromboplastin time (PT/PTT), and ammonia level. The sweat chloride concentration should also be determined to rule out cystic fibrosis Sweat testing Cystic fibrosis is an inherited disease of the exocrine glands affecting primarily the gastrointestinal and respiratory systems. It leads to chronic lung disease, exocrine pancreatic insufficiency... read more . Frequently, additional testing is needed to evaluate for other metabolic, infectious, genetic, and endocrine causes of neonatal cholestasis Diagnosis Cholestasis is failure of bilirubin secretion, resulting in conjugated hyperbilirubinemia and jaundice. There are numerous causes, which are identified by laboratory testing, hepatobiliary scan... read more . Elevated serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) levels, and gamma-glutamyl transferase (GGT) support the diagnosis of biliary atresia and exclude other rare causes of cholestasis (eg, progressive familial intrahepatic cholestasis type 2 [PFIC2]) that cause low GGT.
Abdominal ultrasonography is noninvasive and can assess liver size and certain abnormalities of the gallbladder and common bile duct. Infants with biliary atresia often have a small contracted gallbladder or one that cannot be seen. However, these findings are nonspecific. A hepatobiliary scan using hydroxy iminodiacetic acid (HIDA scan) should also be done; excretion of contrast into the intestine rules out biliary atresia, but lack of excretion can occur with biliary atresia, severe neonatal hepatitis, and other causes of cholestasis.
A definitive diagnosis of biliary atresia is made with a liver biopsy and intraoperative cholangiography. The classic histologic findings are enlarged portal tracks with fibrosis and bile duct proliferation. Bile plugs may also be noted in the bile ducts. Intraoperative cholangiography reveals the lack of a patent extrahepatic bile duct.
Infants with presumed biliary atresia require surgical exploration with an intraoperative cholangiogram. If biliary atresia is confirmed, a portoenterostomy (Kasai procedure) should be done. Ideally, this procedure should be done in the first month of life. After this period, the prognosis significantly worsens. Postoperatively, many patients have significant chronic problems, including persistent cholestasis, recurrent ascending cholangitis, and failure to thrive. If cholestasis persists for ≥ 3 months postoperatively, referral to a transplant center should be considered. Prophylactic antibiotics (eg, trimethoprim/sulfamethoxazole or neomycin) are frequently prescribed for a year postoperatively in an attempt to prevent ascending cholangitis. Drugs that increase bile production (choleretic agents), such as ursodiol about 10 mg/kg orally 3 times a day, are frequently used postoperatively. Nutritional therapy including supplemental fat-soluble vitamins is very important to ensure adequate intake to support growth (1 Treatment reference Biliary atresia is obstruction of the biliary tree due to progressive sclerosis of the extrahepatic bile duct. Diagnosis is by blood tests, ultrasonography, liver biopsy, and hepatobiliary scan... read more ). Even with optimal therapy, about 50% of infants will develop cirrhosis and require liver transplantation.
Infants who cannot undergo portoenterostomy frequently require liver transplantation by 1 year of age.
1. Mouzaki M, Bronsky J, Gupte G, et al: Nutrition support of children with chronic liver diseases: A joint position paper of the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition and the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition. J Pediatr Gastroenterol Nutr 69(4):498–511, 2019. doi: 10.1097/MPG.0000000000002443
In most cases, biliary atresia manifests several weeks after birth, probably after inflammation and scarring of the extrahepatic (and sometimes intrahepatic) bile ducts.
Infants are jaundiced and often have dark urine (containing conjugated bilirubin), acholic stools, and hepatosplenomegaly.
By age 2 to 3 months, infants may have poor growth with malnutrition, pruritus, irritability, and splenomegaly.
Diagnose using blood test results, ultrasonography, hepatobiliary scan, liver biopsy, and intraoperative cholangiography.
Treatment is with portoenterostomy (Kasai procedure).
Often, liver transplantation is subsequently required.