History

Regardless of etiology, the clinical presentation of neonatal cholestasis is remarkably similar in most infants. Typical symptoms include variable degrees of jaundice, dark urine, and light stools.^[14]

In the case of biliary atresia, most infants are full-term, although a higher incidence of low birthweight may be observed.

In most cases, acholic stools are not noted at birth but develop over the first few weeks of life. Appetite, growth, and weight gain may be normal.

Physical Examination

Physical findings do not identify all cases of biliary atresia. No findings are pathognomonic for the disorder. Infants with biliary atresia are typically full term and may manifest normal growth and weight gain during the first few weeks of life.

Hepatomegaly may be present early, and the liver is often firm or hard to palpation. Splenomegaly is common, and an enlarging spleen suggests progressive cirrhosis with portal hypertension.

Direct hyperbilirubinemia is always an abnormal finding and it is typically present from birth in the fetal/embryonic form. Consider biliary atresia in all neonates with direct hyperbilirubinemia.

In the more common postnatal form, physiologic jaundice frequently merges into conjugated hyperbilirubinemia. The clinician must be aware that physiologic unconjugated hyperbilirubinemia rarely persists beyond 2 weeks. Infants with prolonged physiologic jaundice must be evaluated for other causes.

Harpavat et al reported that screening newborns with direct or conjugated bilirubin measurements detected all known cases of biliary atresia in their study population of 124,385 infants. In addition, after screening was instituted, the mean age at which infants underwent Kasai portoenterostomy was significantly younger (36 days vs 56 days before routine screening).^[15]

In patients with the fetal/neonatal form (polysplenia/asplenia syndrome), a midline liver may be palpated in the epigastrium. The presence of cardiac murmurs suggests associated cardiac anomalies.

A high index of suspicion is key to making a diagnosis because surgical treatment by age 2 months has clearly been shown to improve the likelihood of establishing bile flow and to prevent the development of irreversible biliary cirrhosis.

Differential Diagnoses

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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. 1998 Jul. 27(1):57-64. [QxMD MEDLINE Link].
Chang MH, Huang HH, Huang ES, et al. Polymerase chain reaction to detect human cytomegalovirus in livers of infants with neonatal hepatitis. Gastroenterology. 1992 Sep. 103(3):1022-5. [QxMD MEDLINE Link].
Wilson GA, Morrison LA, Fields BN. Association of the reovirus S1 gene with serotype 3-induced biliary atresia in mice. J Virol. 1994 Oct. 68(10):6458-65. [QxMD MEDLINE Link]. [Full Text].
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. 1995 Mar. 21(3):697-702. [QxMD MEDLINE Link].
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. 2011 Jun 22. EPub ahead of print. [QxMD MEDLINE Link]. [Full Text].
Uemura M, Ozawa A, Nagata T, et al. Sox17 haploinsufficiency results in perinatal biliary atresia and hepatitis in C57BL/6 background mice. Development. 2013 Feb. 140(3):639-48. [QxMD MEDLINE Link].
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. 2011 Oct. 254(4):577-585. [QxMD MEDLINE Link].
[Guideline] Murray KF, Carithers RL Jr. AASLD practice guidelines: Evaluation of the patient for liver transplantation. Hepatology. 2005 Jun. 41(6):1407-32. [QxMD MEDLINE Link].
Tessier ME, Harpavat S, Shepherd RW, Hiremath GS, Brandt ML, Fisher A, et al. Beyond the Pediatric end-stage liver disease system: solutions for infants with biliary atresia requiring liver transplant. World J Gastroenterol. 2014 Aug 28. 20(32):11062-8. [QxMD MEDLINE Link]. [Full Text].
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Harpavat S, Garcia-Prats JA, Anaya C, et al. Diagnostic yield of newborn screening for biliary atresia using direct or conjugated bilirubin measurements. JAMA. 2020 Mar 24. 323 (12):1141-50. [QxMD MEDLINE Link].
Ye W, Rosenthal P, Magee JC, Whitington PF, Childhood Liver Disease Research and Education Network. Factors Determining δ-Bilirubin Levels in Infants With Biliary Atresia. J Pediatr Gastroenterol Nutr. 2015 May. 60 (5):659-63. [QxMD MEDLINE Link].
Shneider BL, Magee JC, Karpen SJ, et al. Total Serum Bilirubin within 3 Months of Hepatoportoenterostomy Predicts Short-Term Outcomes in Biliary Atresia. J Pediatr. 2016 Mar. 170:211-217.e2. [QxMD MEDLINE Link].
Zhou L, Shan Q, Tian W, Wang Z, Liang J, Xie X. Ultrasound for the Diagnosis of Biliary Atresia: A Meta-Analysis. AJR Am J Roentgenol. 2016 May. 206 (5):W73-82. [QxMD MEDLINE Link].
Shteyer E, Wengrower D, Benuri-Silbiger I, Gozal D, Wilschanski M, Goldin E. Endoscopic retrograde cholangiopancreatography in neonatal cholestasis. J Pediatr Gastroenterol Nutr. 2012 Aug. 55(2):142-5. [QxMD MEDLINE Link].
Ng VL, Haber BH, Magee JC, Miethke A, Murray KF, Michail S, et al. Medical status of 219 children with biliary atresia surviving long-term with their native livers: results from a North American multicenter consortium. J Pediatr. 2014 Sep. 165 (3):539-546.e2. [QxMD MEDLINE Link].
Bezerra JA, Spino C, Magee JC, Shneider BL, Rosenthal P, Wang KS, et al. Use of corticosteroids after hepatoportoenterostomy for bile drainage in infants with biliary atresia: the START randomized clinical trial. JAMA. 2014 May 7. 311 (17):1750-9. [QxMD MEDLINE Link].
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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. 2008 Dec. 122(6):e1236-41. [QxMD MEDLINE Link].
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Chin LT, D'Alessandro AM, Knechtle SJ, et al. Liver transplantation for biliary atresia: 19-year, single-center experience. Exp Clin Transplant. 2004 Jun. 2(1):178-82. [QxMD MEDLINE Link].
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Media Gallery

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.

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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 Association for Physician Leadership, New York Academy of Medicine, Gastroenterology Research Group, American Gastroenterological Association, American Pediatric Society, North American Society for Pediatric Gastroenterology, Hepatology and Nutrition, Society for Pediatric Research

Disclosure: Nothing to disclose.

Specialty Editor Board

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, AGAF Founder and Director Emeritus, Celiac Disease Center, University of Chicago; Former Chief, Section of Pediatric Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, University of Chicago Medicine; Professor Emeritus, The University of Chicago Pritzker School of Medicine

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

Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: Imaware.health.

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, Royal College of Physicians and Surgeons of Canada

Disclosure: Received honoraria from Prometheus Laboratories for speaking and teaching; Received honoraria from Abbott Nutritionals for speaking and teaching. for: Abbott Nutritional, Abbvie, speakers' bureau.

Additional Contributors

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, Latin American Society of Pediatric Gastroenterology, Hepatology & Nutrition, American Society for Gastrointestinal Endoscopy, American Society for Parenteral and Enteral Nutrition, North American Society for Pediatric Gastroenterology, Hepatology and Nutrition

Disclosure: Nothing to disclose.

Pediatric Biliary Atresia Clinical Presentation

History

Physical Examination

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