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Last updated:
July 19, 2019
Years published: 1986, 1990, 1994, 2003, 2007, 2009, 2012, 2016, 2019
NORD gratefully acknowledges 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.
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 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 biliary atresia is unknown.
The symptoms of 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.
Some 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 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 biliary atresia is unknown, but several factors contribute to the development of the disorder, including immunologic, infectious/toxic, and genetic factors. Although the bile ducts may be normal at birth, one or more of these factors initiate epithelial damage (independently or with the help of an activated immune system) and trigger rapid production of fibrous tissue (sclerosis) causing an obstruction of bile ducts. 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. Biliary atresia is not an inherited disease; rare genetic variants are being reported in children who also have non-liver defects (see above).
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.
The diagnosis of 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 bile ducts and into the small intestine. The physician/surgeon 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, gamma-glutamyl transpeptidase, and bilirubin and detect viral agents; high blood levels of matrix metalloproteinase-7 has been discovered to be highly specific for biliary atresia. Ultrasound of the liver may show absence of the gall bladder.
Treatment
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 (also known as “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 to allow for bile drainage. The exact surgical procedure may vary according to the location and nature of the obstruction. In the majority of cases, bile drainage can be established with this surgical procedure. 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 biliary atresia and their families. Other treatment is symptomatic and supportive.
In 2002, the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) created 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 Network (ChiLDReN) and publications from this consortium are available here:
https://childrennetwork.org/publications.aspx.
Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov
All studies receiving U.S. government funding, and some supported by private industry, are posted on this government web site.
For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:
Tollfree: (800) 411-1222
TTY: (866) 411-1010
Email: prpl@cc.nih.gov
Some current clinical trials also are posted on the following page on the NORD website:
https://rarediseases.org/living-with-a-rare-disease/find-clinical-trials/
For information about clinical trials sponsored by private sources, contact:
www.centerwatch.com
For information about clinical trials conducted in Europe, contact:
https://www.clinicaltrialsregister.eu/
TEXTBOOKS
Fauci AS, et al., eds. Harrison’s Principles of Internal Medicine, 14th Ed. New York, NY: McGraw-Hill, Inc; 1998:1733.
Yamada T, et al., eds. Textbook of Gastroenterology. 2nd ed. Philadelphia, PA: J.B. Lippincott Company; 1995:2184-5.
Sleisenger MH, et. al. Gastrointestinal Disease. 4th ed. Philadelphia, PA: W. B. Saunders Co; 1989:1639-40.
JOURNAL ARTICLES
Yang L, et al. Diagnostic accuracy of serum matrix metalloproteinase‐7 for biliary atresia. Hepatology 2018;68:2069-77.
Lertudomphowanit C, et al. Large-scale proteomics identifies MMP-7 as a sentinel of epithelial injury and of biliary atresia. Sci Transl Med. 2017 Nov 22;9(417).
Sokol RJ, Mack C. Etiopathogenesis of biliary atresia. Semin Liver Dis. 2001;21:517-24.
Stoll C, et al. Extrahepatic biliary atresia with laterality sequence anomalies. Genet Couns. 2001;12:157-61.
SaggiomoG, et al. Biliary atresia syndrome and splenic malformation. Minerva Pediatr. 2001;53:355-7.
Ohi R. Surgery for biliary atresia. Liver. 2001;21:175-82.
Bates MD, et al. Biliary atresia: pathogenesis and treatment. Semin Liver Dis. 1998;18:281-93.
Lefkowitch JH. Biliary atresia. Mayo Clin Proc. 1998;73:90-5.
Ando K, et al. Sibling occurrence of biliary atresia and biliary dilatation. J Pediatr Surg. 1996;31:1302-4.
Betz BW, et al. MR imaging of biliary cysts in children with biliary atresia: clinical associations and pathologic correlation. Am J Roentgenol. 1994;162:167-71.
Westra SJ, et al. Imaging in the pediatric liver transplantation. Radiographics. 1993;13:1081-9.
Davenport M, et al. Biliary atresia splenic malformation syndrome: an etiologic and prognostic subgroup. Surgery. 1993;113:662-8.
Carmi R, et al. Extrahepatic biliary atresia and associated anomalies: etiologic heterogeneity suggested by distinctive patterns of associations. An J Med Genet. 1993;45:683-93.
Linn JN, et al. The efficacy of kasai operation for biliary atresia: a single institutional experience. J Pediatr Surg. 1992;27:704-6.
Gunasekaran TS, et al. Recurrence of extrahepatic biliary atresia in two half sibs. Am J Med Genet. 1992;43:592-4.
Smith BM, et al. Familial biliary atresia in three siblings including twins. J Pediatr Surg. 1991;26:1331-3.
Hart MH, et al. Neonatal hepatitis and extrahepatic biliary atresia associated with cytomegalovirus infection in twins. Am J Dis Child. 1991;145:302-5.
Knisely AS. Biliary atresia and its complications. Ann Clin Lab Sci. 1990;29:540-2.
Howard ER, et al. Biliary atresia. Br J Hosp Med. 1989;41:123-4, 128-30.
Lachaux A, et al. Familial extrahepatic biliary atresia. J Pediatr Gastroenterol Nutr. 1988;7:280-3.
INTERNET
Online Mendelian Inheritance in Man (OMIM). The Johns Hopkins University. Biliary Atresia, Extrahepatic; EHBA. Entry No: 210500. Last Update 09/06/2013. Available at: https://omim.org/entry/210500 Accessed May 28, 2019.
NORD strives to open new assistance programs as funding allows. If we don’t have a program for you now, please continue to check back with us.
NORD and MedicAlert Foundation have teamed up on a new program to provide protection to rare disease patients in emergency situations.
Learn more https://rarediseases.org/patient-assistance-programs/medicalert-assistance-program/Ensuring that patients and caregivers are armed with the tools they need to live their best lives while managing their rare condition is a vital part of NORD’s mission.
Learn more https://rarediseases.org/patient-assistance-programs/rare-disease-educational-support/This first-of-its-kind assistance program is designed for caregivers of a child or adult diagnosed with a rare disorder.
Learn more https://rarediseases.org/patient-assistance-programs/caregiver-respite/