Pediatric Biliary Atresia 

  • Author: Steven M Schwarz, MD, FAAP, FACN, AGAF; Chief Editor: Carmen Cuffari, MD   more...
 
Updated: Oct 6, 2011
 

Background

Biliary atresia is characterized by obliteration or discontinuity of the extrahepatic biliary system, resulting in obstruction to bile flow.[1] The disorder represents the most common surgically treatable cause of cholestasis encountered during the newborn period. If not surgically corrected, secondary biliary cirrhosis invariably results. Patients with biliary atresia can be subdivided into 2 distinct groups: those with isolated biliary atresia (postnatal form), which accounts for 65-90% of cases, and patients with associated situs inversus or polysplenia/asplenia with or without other congenital anomalies (fetal/embryonic form), comprising 10-35% of cases.

Biliary atresia. Biliary atresia.

The pathology of the extrahepatic biliary system widely varies in these patients, and the following classification is based on the predominant site of atresia:

  • Type I involves obliteration of the common duct; the proximal ducts are patent
  • Type II is characterized by atresia of the hepatic duct, with cystic structures found in the porta hepatis
  • Type III (>90% of patients) involves atresia of the right and left hepatic ducts to the level of the porta hepatis. These variants should not be confused with intrahepatic biliary hypoplasia, which comprises a group of distinct and surgically noncorrectable disorders.
Next

Pathophysiology

Although histopathologic features of biliary atresia have been extensively studied in surgical specimens from excised extrahepatic biliary systems of infants undergoing portoenterostomy, the pathogenesis of this disorder remains poorly understood. Early studies postulated a congenital malformation of the biliary ductular system. Problems of hepatobiliary ontogenesis are suggested by the fetal/embryonic form of atresia that is associated with other congenital anomalies. However, the more common neonatal type is characterized by a progressive inflammatory lesion, which suggests a role for infectious and/or toxic agents causing bile duct obliteration.

In type III, the most prevalent histopathological variant, the fibrous remnant demonstrates complete obliteration of at least a portion of the extrahepatic biliary system. Ducts within the liver, extending to the porta hepatis, are initially patent during the first few weeks of life but may progressively be destroyed. The same agent or agents that damaged the extrahepatic ducts may be causative, and the effects of retained toxins in bile are contributing factors.

Identification of active and progressive inflammation and destruction of the biliary system suggests that extrahepatic biliary atresia likely represents an acquired lesion. However, no single etiologic factor has been identified. Infectious agents seem to be the most plausible candidates, particularly in the isolated (neonatal) form of atresia. Several studies have identified elevated antibody titers to reovirus type 3 in patients with biliary atresia when compared with controls. Other viruses, including rotavirus and cytomegalovirus (CMV), have also been implicated.

Previous
Next

Epidemiology

Frequency

United States

Individual studies suggest an overall incidence in the United States of 1 per 10,000-15,000 live births.

International

The incidence of biliary atresia is highest in Asian populations, and it may be more common in Chinese infants compared with Japanese infants.

Mortality/Morbidity

Prior to the development of liver transplantation as a therapeutic option for children with end-stage liver disease, the long-term survival rate for infants with biliary atresia following portoenterostomy was 47-60% at 5 years and 25-35% at 10 years. In one third of all patients, bile flow is inadequate following surgery, and these children succumb to complications of biliary cirrhosis in the first few years of life unless liver transplantation is performed. Following portoenterostomy, complications include cholangitis (50%) and portal hypertension (>60%).

Hepatocellular carcinoma may be a risk for patients with cirrhosis and no clinical evidence of portal hypertension. Progressive fibrosis and biliary cirrhosis develop in children who do not drain bile. Thus, as discussed below (see Prognosis), liver transplantation may be the only option for long-term survival in most patients.[2]

Race

Incidence of biliary atresia is highest in Asian populations. The disorder also occurs in black infants, with an incidence approximately 2 times higher than that observed among white infants.

Sex

Extrahepatic biliary atresia is more common in females than in males.

Age

Biliary atresia is a disorder unique to the neonatal period. Two presentations are described in this chapter (see Background). The fetal/perinatal form is evident within the first 2 weeks of life; the postnatal type presents in infants aged 2-8 weeks.

Previous
Proceed to Clinical Presentation
 
 
Contributor Information and Disclosures
Author

Steven M Schwarz, MD, FAAP, FACN, AGAF  Professor of Pediatrics, Children's Hospital at Downstate, State University of New York Downstate Medical Center

Steven M Schwarz, MD, FAAP, FACN, AGAF is a member of the following medical societies: American Academy of Pediatrics, American College of Nutrition, American College of Physician Executives, American Gastroenterological Association, American Pediatric Society, Gastroenterology Research Group, New York Academy of Medicine, North American Society for Pediatric Gastroenterology and Nutrition, and Society for Pediatric Research

Disclosure: Curemark, LLC Consulting fee Board membership; Centocor, Inc. Grant/research funds Independent contractor; Johnson & Johnson, Inc. Grant/research funds Independent contractor

Specialty Editor Board

Jorge H Vargas, MD  Professor of Pediatrics and Clinical Professor of Pediatric Gastroenterology, University of California, Los Angeles, David Geffen School of Medicine; Consulting Physician, Department of Pediatrics, University of California at Los Angeles Health System

Jorge H Vargas, MD is a member of the following medical societies: American Liver Foundation, American Society for Gastrointestinal Endoscopy, American Society for Parenteral and Enteral Nutrition, Latin American Society of Pediatric Gastroenterology, Hepatology & Nutrition, and North American Society for Pediatric Gastroenterology and Nutrition

Disclosure: Nothing to disclose.

Mary L Windle, PharmD  Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

Stefano Guandalini, MD  Director, Celiac Disease Center, Chief, Section of Pediatric Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, University of Chicago Medical Center; Professor, Department of Pediatrics, Section of Gastroenterology, Hepatology and Nutrition, University of Chicago Division of the Biological Sciences, The Pritzker School of Medicine

Stefano Guandalini, MD is a member of the following medical societies: American Gastroenterological Association, European Society for Paediatric Gastroenterology, Hepatology & Nutrition, and North American Society for Pediatric Gastroenterology and Nutrition

Disclosure: Nothing to disclose.

David Pallares, MD  Clinical Assistant Professor, Department of Pediatrics, Division of Allergy and Immunology, University of Louisville School of Medicine

David Pallares, MD is a member of the following medical societies: American Academy of Allergy Asthma and Immunology

Disclosure: Nothing to disclose.

Chief Editor

Carmen Cuffari, MD  Associate Professor, Department of Pediatrics, Division of Gastroenterology/Nutrition, Johns Hopkins University School of Medicine

Carmen Cuffari, MD is a member of the following medical societies: American College of Gastroenterology, American Gastroenterological Association, North American Society for Pediatric Gastroenterology, Hepatology and Nutrition, and Royal College of Physicians and Surgeons of Canada

Disclosure: Nothing to disclose.

References

  1. Haber BA, Erlichman J, Loomes KM. Recent advances in biliary atresia: prospects for novel therapies. Expert Opin Investig Drugs. Dec 2008;17(12):1911-24. [Medline].

  2. Bassett MD, Murray KF. Biliary atresia: recent progress. J Clin Gastroenterol. Jul 2008;42(6):720-9. [Medline].

  3. Fischler B, Ehrnst A, Forsgren M, et al. The viral association of neonatal cholestasis in Sweden: a possible link between cytomegalovirus infection and extrahepatic biliary atresia. J Pediatr Gastroenterol Nutr. Jul 1998;27(1):57-64. [Medline].

  4. Chang MH, Huang HH, Huang ES, et al. Polymerase chain reaction to detect human cytomegalovirus in livers of infants with neonatal hepatitis. Gastroenterology. Sep 1992;103(3):1022-5. [Medline].

  5. Wilson GA, Morrison LA, Fields BN. Association of the reovirus S1 gene with serotype 3-induced biliary atresia in mice. J Virol. Oct 1994;68(10):6458-65. [Medline]. [Full Text].

  6. Steele MI, Marshall CM, Lloyd RE, Randolph VE. Reovirus 3 not detected by reverse transcriptase-mediated polymerase chain reaction analysis of preserved tissue from infants with cholestatic liver disease. Hepatology. Mar 1995;21(3):697-702. [Medline].

  7. Wang W, Donnelly B, Bondoc A, Mohanty SK, McNeal M, Ward R, et al. The rhesus rotavirus gene encoding VP4 is a major determinant in the pathogenesis of biliary atresia in newborn mice. J Virol. Jun 22 2011;EPub ahead of print. [Medline]. [Full Text].

  8. Willot S, Uhlen S, Michaud L, Briand G, Bonnevalle M, Sfeir R, et al. Effect of ursodeoxycholic acid on liver function in children after successful surgery for biliary atresia. Pediatrics. Dec 2008;122(6):e1236-41. [Medline].

  9. Superina R, Magee JC, Brandt ML, et al. The Anatomic Pattern of Biliary Atresia Identified at Time of Kasai Hepatoportoenterostomy and Early Postoperative Clearance of Jaundice Are Significant Predictors of Transplant-Free Survival. Ann Surg. Oct 2011;254(4):577-585. [Medline].

  10. Murray KF, Carithers RL Jr. AASLD practice guidelines: Evaluation of the patient for liver transplantation. Hepatology. Jun 2005;41(6):1407-32. [Medline].

  11. Balistreri WF, Grand R, Hoofnagle JH, et al. Biliary atresia: current concepts and research directions. Summary of a symposium. Hepatology. Jun 1996;23(6):1682-92. [Medline].

  12. Barshes NR, Lee TC, Balkrishnan R, et al. Orthotopic liver transplantation for biliary atresia: the U.S. experience. Liver Transpl. Oct 2005;11(10):1193-200. [Medline].

  13. Bates MD, Bucuvalas JC, Alonso MH, Ryckman FC. Biliary atresia: pathogenesis and treatment. Semin Liver Dis. 1998;18(3):281-93. [Medline].

  14. Bittmann S. Surgical experience in children with biliary atresia treated with portoenterostomy. Curr Surg. Jul-Aug 2005;62(4):439-43. [Medline].

  15. Chin LT, D'Alessandro AM, Knechtle SJ, et al. Liver transplantation for biliary atresia: 19-year, single-center experience. Exp Clin Transplant. Jun 2004;2(1):178-82. [Medline].

  16. el-Youssef M, Whitington PF. Diagnostic approach to the child with hepatobiliary disease. Semin Liver Dis. 1998;18(3):195-202. [Medline].

  17. Karrer FM, Price MR, Bensard DD, et al. Long-term results with the Kasai operation for biliary atresia. Arch Surg. May 1996;131(5):493-6. [Medline].

  18. Kasai M. Treatment of biliary atresia with special reference to hepatic porto- enterostomy and its modifications. Prog Pediatr Surg. 1974;6:5-52. [Medline].

  19. Lai MW, Chang MH, Hsu SC, et al. Differential diagnosis of extrahepatic biliary atresia from neonatal hepatitis: a prospective study. J Pediatr Gastroenterol Nutr. Feb 1994;18(2):121-7. [Medline].

  20. Mack CL, Sokol RJ. Unraveling the pathogenesis and etiology of biliary atresia. Pediatr Res. May 2005;57(5 Pt 2):87R-94R. [Medline]. [Full Text].

  21. Matsuo S, Suita S, Kubota M, Shono K. Long-term results and clinical problems after portoenterostomy in patients with biliary atresia. Eur J Pediatr Surg. Jun 1998;8(3):142-5. [Medline].

  22. Mowat AP. Biliary atresia into the 21st century: a historical perspective. Hepatology. Jun 1996;23(6):1693-5. [Medline].

  23. Muraji T, Higashimoto Y. The improved outlook for biliary atresia with corticosteroid therapy. J Pediatr Surg. Jul 1997;32(7):1103-6; discussion 1106-7. [Medline].

  24. Nio M, Ohi R, Shimaoka S, et al. The outcome of surgery for biliary atresia and the current status of long-term survivors. Tohoku J Exp Med. Jan 1997;181(1):235-44. [Medline].

  25. Okazaki T, Kobayashi H, Yamataka A, et al. Long-term postsurgical outcome of biliary atresia. J Pediatr Surg. Feb 1999;34(2):312-5. [Medline].

  26. Otte JB, de Ville de Goyet J, Reding R, et al. Sequential treatment of biliary atresia with Kasai portoenterostomy and liver transplantation: a review. Hepatology. Jul 1994;20(1 Pt 2):41S-48S. [Medline].

  27. Ryckman FC, Alonso MH, Bucuvalas JC, Balistreri WF. Biliary atresia--surgical management and treatment options as they relate to outcome. Liver Transpl Surg. Sep 1998;4(5 Suppl 1):S24-33. [Medline].

  28. Tan CE, Davenport M, Driver M, Howard ER. Does the morphology of the extrahepatic biliary remnants in biliary atresia influence survival? A review of 205 cases. J Pediatr Surg. Nov 1994;29(11):1459-64. [Medline].

  29. Tanaka H, Kita Y, Kawarasaki H, et al. Beneficial effect of ursodeoxycholic acid on serum gamma-GTP in patients with biliary atresia following living related liver transplantation. Transplant Proc. Nov 1998;30(7):3326-7. [Medline].

  30. Utterson EC, Shepherd RW, Sokol RJ, et al. Biliary atresia: clinical profiles, risk factors, and outcomes of 755 patients listed for liver transplantation. J Pediatr. Aug 2005;147(2):180-5. [Medline].

  31. Valayer J. Conventional treatment of biliary atresia: long-term results. J Pediatr Surg. Nov 1996;31(11):1546-51. [Medline].

  32. Visser BC, Suh I, Hirose S, et al. The influence of portoenterostomy on transplantation for biliary atresia. Liver Transpl. Oct 2004;10(10):1279-86. [Medline].

  33. Yoon PW, Bresee JS, Olney RS, et al. Epidemiology of biliary atresia: a population-based study. Pediatrics. Mar 1997;99(3):376-82. [Medline]. [Full Text].

 
Previous
Next
 
Biliary atresia.
Bile ductular proliferation in liver biopsy specimen (hematoxylin and eosin stain) from patient with biliary atresia. Also note hepatocellular bile staining as a consequence of cholestasis.
 
 
 
All material on this website is protected by copyright, Copyright © 1994-2012 by WebMD LLC.
This website also contains material copyrighted by 3rd parties.

DISCLAIMER: The content of this Website is not influenced by sponsors. The site is designed primarily for use by qualified physicians and other medical professionals. The information contained herein should NOT be used as a substitute for the advice of an appropriately qualified and licensed physician or other health care provider. The information provided here is for educational and informational purposes only. In no way should it be considered as offering medical advice. Please check with a physician if you suspect you are ill.