Close
New

Medscape is available in 5 Language Editions – Choose your Edition here.

 

Pediatric Biliary Atresia Workup

  • Author: Steven M Schwarz, MD, FAAP, FACN, AGAF; Chief Editor: Carmen Cuffari, MD  more...
 
Updated: Jun 28, 2016
 

Laboratory Studies

See the list below:

  • Serum bilirubin (total and direct): Conjugated hyperbilirubinemia, defined as any level exceeding either 2 mg/dL or 20% of total bilirubin, is always abnormal. Interestingly, infants with biliary atresia typically show only moderate elevations in total bilirubin, which is commonly 6-12 mg/dL, with the direct (conjugated) fraction comprising 50-60% of total serum bilirubin.
    • A study by Shneider et al found that infants whose total bilirubin does not fall below 2.0 mg/dL within 3 months of hepatoportoenterostomy were at high risk for early disease progression, suggesting they should be considered for liver transplantation in a timely fashion. The study also added that interventions increasing the likelihood of achieving total bilirubin <2.0 mg/dL within 3 months of hepatoportoenterostomy may enhance early outcomes.[10]
  • Alkaline phosphatase (AP), 5' nucleotidase, gamma-glutamyl transpeptidase (GGTP), serum aminotransferases, serum bile acids
    • These candidate tests have been proposed as a means to increase both sensitivity and specificity of routine laboratory evaluation. Unfortunately, no single biochemical determination accurately discriminates between biliary atresia and the other causes of neonatal cholestasis.
    • In addition to direct hyperbilirubinemia (a universal finding in neonatal cholestasis), enzyme abnormalities include elevated AP levels. In some cases, skeletal sources of AP can be differentiated from hepatic sources by measuring the liver-specific AP fraction, 5' nucleotidase.
    • GGTP is an integral membrane protein of the bile canaliculus and is elevated in cholestatic conditions. GGTP levels closely correlate with AP findings and are increased in all biliary obstructive conditions. However, GGTP levels may be within the reference range in some forms of cholestasis of hepatocellular origin.
    • Aminotransferase levels are not particularly helpful in establishing a diagnosis, although a markedly elevated alanine aminotransferase level (>800 IU/L) indicates significant hepatocellular injury and is more consistent with the neonatal hepatitis syndromes.
  • Serum alpha1-antitrypsin with Pi typing: Alpha1-antitrypsin deficiency is the most common inherited liver disease that presents with neonatal cholestasis. The abnormal PiZZ phenotype, as determined by electrophoresis, is associated with neonatal cholestasis in approximately 10% of subjects.
  • Sweat chloride (Cl): Biliary tract involvement is a well-recognized complication of cystic fibrosis (CF), and an association between meconium ileus in the newborn and cholestasis has been described. A diagnosis of CF should be strongly considered in any infant with direct hyperbilirubinemia, particularly if other associated signs or symptoms (ie, respiratory, GI) are present. Sweat Cl iontophoresis remains the criterion standard for diagnosing CF.
Next

Imaging Studies

See the list below:

  • Ultrasonography
    • In neonatal cholestasis syndromes, ultrasonography can exclude specific anomalies of the extrahepatic biliary system, particularly choledochal cysts. Today, a diagnosis of choledochal cyst should be made in utero using fetal ultrasonography.
    • In biliary atresia, ultrasonography may demonstrate absence of the gallbladder and no dilatation of the biliary tree.[11] Unfortunately, the sensitivity and specificity of these findings, even in the most experienced centers, probably do not exceed 80%. For this reason, ultrasonography has been found unreliable in the evaluation of biliary atresia.
  • Hepatobiliary scintiscanning
    • Hepatobiliary imaging, using technetium-labeled diisopropyl iminodiacetic acid (DISIDA) nuclear scintiscan, is useful in evaluating infants with suspected biliary atresia. Unequivocal evidence of intestinal excretion of radiolabel confirms patency of the extrahepatic biliary system.
    • Two cautionary notes are required. First, reliability of the scintiscan is diminished at very high conjugated bilirubin levels (>20 mg/dL). Second, the test has been associated with a 10% rate of false-positive or false-negative diagnostic errors.
Previous
Next

Other Tests

Duodenal intubation and duodenal string test

These studies are performed in some centers to evaluate duodenal bile excretion; however, in the author's experience, these studies are cumbersome, time-consuming, and unreliable.

Endoscopic retrograde cholangiopancreatography (ERCP)

This diagnostic procedure has previously been unavailable for use during infancy because of technical considerations. However, endoscope manufacturers are now producing side-viewing instruments that may be successfully used in neonates.

Although not yet widely used, reports have demonstrated the use of ERCP in diagnosing biliary atresia; one recent study reported a diagnosis of biliary atresia in 5 infants undergoing ERCP for neonatal cholestasis. With continued refinement and wider use of this diagnostic modality, ERCP may become part of the management algorithm in assessing neonatal direct hyperbilirubinemia, for which other studies have failed to confirm a diagnosis.[12]

Previous
Next

Procedures

See the list below:

  • Percutaneous liver biopsy
    • Percutaneous liver biopsy is widely regarded as the most valuable study for evaluating neonatal cholestasis. Morbidity is low in patients without coagulopathy. When examined by an experienced pathologist, an adequate biopsy specimen can differentiate between obstructive and hepatocellular causes of cholestasis, with 90% sensitivity and specificity for biliary atresia. See the image below.
      Bile ductular proliferation in liver biopsy specim 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.
    • Several cholestatic conditions, including biliary atresia, may demonstrate an evolving histopathological pattern. Accordingly, biopsies are not usually diagnostic in those younger than 2 weeks, and serial samples, usually at 2-week intervals, may be required to reach a definitive diagnosis.
  • Intraoperative cholangiography: This procedure definitively demonstrates anatomy and patency of the extrahepatic biliary tract. Perform intraoperative cholangiography when liver biopsy findings suggest an obstructive etiology. The study is also indicated when biopsy results are equivocal or scintiscan fails to demonstrate clear evidence of duodenal bile excretion.
Previous
Next

Histologic Findings

See the list below:

  • Despite the fact that several variants of extrahepatic biliary atresia have been described, suggesting a role for both ontogenic and acquired causes, no discernible qualitative differences in histopathological characteristics are evident.
  • Surgical specimens demonstrate a spectrum of abnormalities, including active inflammation with bile duct degeneration, a chronic inflammatory reaction with proliferation of both ductular and glandular elements, and fibrosis. The progressive nature of the disorder is confirmed by its evolving histological picture.
  • Ultimately, evidence of biliary tract obstructive disease confirmed by liver biopsy findings determines which infants require exploratory laparotomy and intraoperative cholangiography. Portal bile ductular proliferation, bile plugging, portal-portal fibrosis, and an acute inflammatory reaction are characteristic findings in infants with neonatal cholestasis of an obstructive etiology.
  • Periodic acid-Schiff (PAS) staining of biopsy tissue can also be used to confirm a diagnosis of alpha1-antitrypsin deficiency by finding intracellular PAS-positive granules resistant to digestion by diastase.
Previous
 
 
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 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 Founder and Medical 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, North American Society for Pediatric Gastroenterology, Hepatology and Nutrition, European Society for Paediatric Gastroenterology, Hepatology & Nutrition, North American Society for the Study of Celiac Disease

Disclosure: Received consulting fee from AbbVie for consulting.

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.

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.

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

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

  3. Mogul D, Zhou M, Intihar P, Schwarz K, Frick K. Cost-Effective Analysis of Screening for Biliary Atresia With The Stool Color Card. J Pediatr Gastroenterol Nutr. 2014 Sep 11. [Medline].

  4. 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. [Medline].

  5. 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. [Medline].

  6. 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. [Medline]. [Full Text].

  7. 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. [Medline].

  8. 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. [Medline]. [Full Text].

  9. 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. [Medline].

  10. 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. [Medline].

  11. 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. [Medline].

  12. 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. [Medline].

  13. 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. [Medline].

  14. 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. [Medline].

  15. Lindor KD, Kowdley KV, Luketic VA, et al. High-dose ursodeoxycholic acid for the treatment of primary sclerosing cholangitis. Hepatology. 2009 Sep. 50(3):808-14. [Medline]. [Full Text].

  16. 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. [Medline].

  17. Chen Y, Nah SA, Chiang L, Krishnaswamy G, Low Y. Postoperative steroid therapy for biliary atresia: Systematic review and meta-analysis. J Pediatr Surg. 2015 Jun 5. [Medline].

  18. 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. [Medline].

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

  20. 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. [Medline]. [Full Text].

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

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

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

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

  25. 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. [Medline].

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

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

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

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

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

  31. 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. 1998 Jun. 8(3):142-5. [Medline].

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

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

  34. 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. 1997 Jan. 181(1):235-44. [Medline].

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

  36. 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. 1994 Jul. 20(1 Pt 2):41S-48S. [Medline].

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

  38. 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. 1994 Nov. 29(11):1459-64. [Medline].

  39. 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. 1998 Nov. 30(7):3326-7. [Medline].

  40. [Guideline] 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. 2005 Aug. 147(2):180-5. [Medline].

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

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

  43. Yoon PW, Bresee JS, Olney RS, et al. Epidemiology of biliary atresia: a population-based study. Pediatrics. 1997 Mar. 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 © 1994-2016 by WebMD LLC. This website also contains material copyrighted by 3rd parties.