Skip to main content

Advertisement

SpringerLink
Log in

Early and Peri-operative Prognostic Indicators in Infants Undergoing Hepatic Portoenterostomy for Biliary Atresia: a Review

  • Pediatric Gastroenterology (S Orenstein, Section Editor)
  • Published:
Current Gastroenterology Reports Aims and scope Submit manuscript

Abstract

Purpose of Review

Biliary atresia is the most common indication for liver transplantation among children. In recent years, prospective, multi-centre collaboration has been underway with the aim of providing high-quality data on the natural history of the condition, prior to and following hepatic portoenterostomy.

Recent Findings

There is increasing evidence that specific histological findings, and age, at the time of portoenterostomy have relevance as prognostic indicators. Recent data suggest that the sub-type of biliary atresia, its co-existence with other anomalies and concurrent infection may also be important variables.

Summary

This review provides a comprehensive summary of the histological predictors of outcome following portoenterostomy. Later age at portoenterostomy, advanced degree of hepatic fibrosis and co-existence with other congenital anomalies are strongly correlated with poor outcomes following portoenterostomy. There is increasing evidence to suggest that common serological indices and the presence or absence of cytomegalovirus (CMV) co-infection may have utility as early prognostic indicators.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

Papers of particular interest, published recently, have been highlighted as: • Of importance

  1. Hartley JL, Davenport M, Kelly DA. Biliary atresia. Lancet. 2009;374:1704–13.

    Article  PubMed  Google Scholar 

  2. • Jimenez-Rivera C, Jolin-Dahel KS, Fortinsky KJ, Gozdyra P, Benchimol EI. International incidence and outcomes of biliary atresia. J Pediatr Gastroenterol Nutr. 2013;56(4):344–54. Provides global epidemiological data on the course and outcomes in infants with biliary atresia.

    Article  PubMed  Google Scholar 

  3. Kasai M, Sawaguchi S, Akiyama H. A proposal of new classification of extrahepatic biliary atresia. J Jpn Soc Pediatr Surg. 1976;12:327–31.

    Google Scholar 

  4. • Superina R, Magee JC, Brandt ML, Healey PJ, Tiao G, Ryckman F, 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;254(4):577–85. A multi-centre, prospective study with large numbers which showed that the sub-type of biliary atresia and association with other congenital anomalies were important prognostic variables.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Nightingale S, Stormon MO, O’Loughlin EV, Shun A, Thomas G, Benchimol EI, et al. Early Post-Hepatoportoenterostomy Predictors of Native Liver Survival in Biliary Atresia. J Pediatr Gastroenterol Nutr. 2016.

  6. Miyano T, Suruga K, Tsuchiya H, Suda K. A histopathological study of the remnant of extrahepatic bile duct in so-called uncorrectable biliary atresia. J Pediatr Surg. 1977;12(1):19–25.

    Article  CAS  PubMed  Google Scholar 

  7. Kasai M, Suzuki SA. A new operation for "non-correctable" biliary atresia—portoenterostomy. Shijitsu. 1959;13:733–9.

    Google Scholar 

  8. Kasai M. Treatment of biliary atresia with special reference to hepatic portoenterostomy and its modification. Baltimore: University Park Press; 1974.

    Google Scholar 

  9. Chandra RS, Altman RP. Ductal remnants in extrahepatic biliary atresia: a histopathologic study with clinical correlation. J Pediatr. 1978;93(2):196–200.

    Article  CAS  PubMed  Google Scholar 

  10. Ohi R, Shikes RH, Stellin GP, Lilly JR. In biliary atresia duct histology correlates with bile flow. J Pediatr Surg. 1984;19(4):467–70.

    Article  CAS  PubMed  Google Scholar 

  11. Lilly JR, Karrer FM, Hall RJ, Stellin GP, Vasquez-Estevez JJ, Greenholz SK, et al. The surgery of biliary atresia. Ann Surg. 1989;210(3):289–96.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Mirza Q, Kvist N, Petersen BL. Histologic features of the portal plate in extrahepatic biliary atresia and their impact on prognosis—a Danish study. J Pediatr Surg. 2009;44:1344–8.

    Article  PubMed  Google Scholar 

  13. Lawrence D, Howard ER, Tzannatos C, Mowat AP. Hepatic portoenterostomy for biliary atresia. A comparative study of histology and prognosis after surgery. Arch Dis Child. 1981;56:460–3.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Tan CEL, 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;29(11):1459–64.

    Article  CAS  PubMed  Google Scholar 

  15. Vasquez-Estevez J, Stewart B, Shikes RH, Hall RJ, Lilly JR. Biliary atresia: early determination of prognosis. J Pediatr Surg. 1989;24(1):48–51.

    Article  Google Scholar 

  16. Hossain M, Murahashi O, Ando H, Iio K, Kaneko K, Ito T. Immunohistochemical study of proliferating cell nuclear antigen in hepatocytes of biliary atresia: a parameter to predict clinical outcome. J Pediatr Surg. 1995;30(9):1297–301.

    Article  CAS  PubMed  Google Scholar 

  17. Webb NL, Jiwane A, Ooi CY, Nightingale S, Adams SE, Krishnan U. Clinical significance of liver histology on outcomes in biliary atresia. J Paediatr Child Health. 2016. doi:10.1111/jpc.13371

  18. Weerasooriya VS, White FV, Shepherd RW. Hepatic fibrosis and survival in biliary atresia. J Pediatr. 2004;144(1):123–5.

    Article  PubMed  Google Scholar 

  19. Santos JL, Kieling CO, Meurer L, Vieira S, Ferreira CT, Lorentz A, et al. The extent of biliary proliferation in liver biopsies from patients with biliary atresia at portoenterostomy is associated with the postoperative prognosis☆. J Pediatr Surg. 2009;44:695–701.

    Article  PubMed  Google Scholar 

  20. Shteyer E, Ramm GA, Xu C, White FV, Shepherd RW. Outcome after portoenterostomy in biliary atresia: pivotal role of degree of liver fibrosis and intensity of stellate cell activation. J Pediatr Gastroenterol Nutr. 2006;42:93–9.

    Article  PubMed  Google Scholar 

  21. Roy P, Chatterjee U, Ganguli M, Banerjee S, Chatterjee SK, Basu AK. A histopathological study of liver and biliary remnants with clinical outcome in cases of extrahepatic biliary atresia. Indian J Pathol Microbiol. 2010;53(1):101–5.

    Article  PubMed  Google Scholar 

  22. Muthukanagarajan SJ, Karnan I, Srinivasan P, Sadagopan P, Manickam S. Diagnostic and prognostic significance of various histopathological features in extrahepatic biliary atresia. J Clin Diagn Res. 2016;10(6):EC23–EC7.

    PubMed  PubMed Central  Google Scholar 

  23. Gupta L, Gupta SD, Bhatnagar V. Extrahepatic biliary atresia: correlation of histopathology and liver function tests with surgical outcomes. J Indian Assoc Pediatr Surg. 2012;17(4):147–52.

    Article  PubMed  PubMed Central  Google Scholar 

  24. Salzedas-Netto AA, Chinen E, de Oliveira DF, Pasquetti AF, Azevedo RA, da Silva Patricio FF, et al. Grade IV fibrosis interferes in biliary drainage after Kasai procedure. Transplant Proc. 2014;46(6):1781–3.

    Article  CAS  PubMed  Google Scholar 

  25. Kang N, Davenport M, Driver M, Howard ER. Hepatic histology and the development of esophageal varices in biliary atresia. J Pediatr Surg. 1993;28(1):63–6.

    Article  CAS  PubMed  Google Scholar 

  26. Segawa O, Miyano T, Fujimoto T, Watanabe S, Hirose M, Fujiwara T. Actin and myosin deposition around bile canaliculi: a predictor of clinical outcome in biliary atresia. J Pediatr Surg. 1993;28(6):851–6.

    Article  CAS  PubMed  Google Scholar 

  27. Suominen JS, Lampela H, Heikkila P, Lohi J, Jalanko H, Pakarinen MP. Myofibroblastic cell activation and neovascularization predict native liver survival and development of esophageal varices in biliary atresia. World J Gastroenterol. 2014;20(12):3312–9.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Davenport M, Howard ER. Macroscopic appearance at portoenterostomy—a prognostic variable in biliary atresia. J Pediatr Surg. 1996;31(10):1387–90.

    Article  CAS  PubMed  Google Scholar 

  29. Wadhwani SI, Turmelle YP, Nagy R, Lowell J, Dillon P, Shepherd RW. Prolonged neonatal jaundice and the diagnosis of biliary atresia: a single-center analysis of trends in age at diagnosis and outcomes. Pediatrics. 2008;121(5):e1438–40.

    Article  PubMed  Google Scholar 

  30. Subramaniam R, Doig CM, Bowen J, Bruce J. Initial response to portoenterostomy determines long-term outcome in patients with biliary atresia. J Pediatr Surg. 2000;35:593–7.

    Article  CAS  PubMed  Google Scholar 

  31. • Qiao G, Li L, Cheng W, Zhang Z, Ge J, Wang C. Conditional probability of survival in patients with biliary atresia after Kasai portoenterostomy: a Chinese population-based study. J Pediatr Surg. 2015;50(8):1310–5. A study with large numbers which showed that age at Kasai portoenterostomy of greater than 90 days was associated with poor native liver survival.

    Article  PubMed  Google Scholar 

  32. Rhu J, Jung SM, Choe YH, Seo JM, Lee SK. PELD score and age as a prognostic index of biliary atresia patients undergoing Kasai portoenterostomy. Pediatr Surg Int. 2012;28(4):385–91.

    Article  PubMed  Google Scholar 

  33. de Vries W, de Langen ZJ, Groen H, Scheenstra R, Peeters PM, Hulscher JB, et al. Biliary atresia in the Netherlands: outcome of patients diagnosed between 1987 and 2008. J Pediatr. 2012;160(4):638–44 e2.

    Article  PubMed  Google Scholar 

  34. Chen G, Zheng S, Sun S, Xiao X, Ma Y, Shen W, et al. Early surgical outcomes and pathological scoring values of older infants (>/= 90 d old) with biliary atresia. J Pediatr Surg. 2012;47(12):2184–8.

    Article  PubMed  Google Scholar 

  35. Nio M, Sasaki H, Wada M, Kazama T, Nishi K, Tanaka H. Impact of age at Kasai operation on short- and long-term outcomes of type III biliary atresia at a single institution. J Pediatr Surg. 2010;45(12):2361–3.

    Article  PubMed  Google Scholar 

  36. Zani A, Quaglia A, Hadzic N, Zuckerman M, Davenport M. Cytomegalovirus-associated biliary atresia: an aetiological and prognostic subgroup. J Pediatr Surg. 2015;50(10):1739–45.

    Article  PubMed  Google Scholar 

  37. Davenport M, Puricelli V, Farrant P, Hadzic N, Mieli-Vergani G, Portmann B, et al. The outcome of the older (≥100 days) infant with biliary atresia. J Pediatr Surg. 2004;39(4):575–81.

    Article  CAS  PubMed  Google Scholar 

  38. van Heurn LW, Saing H, Tam PKH. Portoenterostomy for biliary atresia: long-term survival and prognosis after esophageal variceal bleeding. J Pediatr Surg. 2004;39:6–9.

    Article  PubMed  Google Scholar 

  39. Chung PH, Wong KK, Tam PK. Predictors for failure after Kasai operation. J Pediatr Surg. 2015;50(2):293–6.

    Article  PubMed  Google Scholar 

  40. Yang L, Fu J, Peng XF, Pang SY, Gao KK, Chen ZR, et al. Validation of aspartate aminotransferase to platelet ratio for diagnosis of liver fibrosis and prediction of postoperative prognosis in infants with biliary atresia. World J Gastroenterol. 2015;21(19):5893–900.

    CAS  PubMed  PubMed Central  Google Scholar 

  41. Suominen JS, Lampela H, Heikkila P, Lohi J, Jalanko H, Pakarinen MP. APRi predicts native liver survival by reflecting portal fibrogenesis and hepatic neovascularization at the time of portoenterostomy in biliary atresia. J Pediatr Surg. 2015;50(9):1528–31.

    Article  PubMed  Google Scholar 

  42. Grieve A, Makin E, Davenport M. Aspartate aminotransferase-to-platelet ratio index (apri) in infants with biliary atresia: prognostic value at presentation. J Pediatr Surg. 2013;48(4):789–95.

    Article  PubMed  Google Scholar 

  43. Wai CT, Greenson JK, Fontana RJ, Kalbfleisch JD, Marrero JA, Conjeevaram HS, et al. A simple noninvasive index can predict both significant fibrosis and cirrhosis in patients with chronic hepatitis C. Hepatology. 2003;38(2):518–26.

    Article  PubMed  Google Scholar 

  44. Lind RC, Verkade HJ, Porte RJ, Hulscher JB. Aspartate transaminase-to-platelet ratio index is not correlated with severity of fibrosis or survival in children with biliary atresia. J Pediatr Gastroenterol Nutr. 2012;54(5):698.

    Article  CAS  PubMed  Google Scholar 

  45. Dhawan A, Trivedi P, Cheeseman P, Baker AJ, Howard ER, Mieli-Vergani G. Serum hyaluronic acid as an early prognostic marker in biliary atresia. J Pediatr Surg. 2001;36(3):443–6.

    Article  CAS  PubMed  Google Scholar 

  46. Trivedi P, Dhawan A, Ristelli J, Ristelli L, Mirza M, Cheeseman P, et al. Prognostic value of serum hyaluronic acid and type I and II procollagen peptides in extrahepatic biliary atresia. Pediatr Res. 1995;38(4):568–73.

    Article  CAS  PubMed  Google Scholar 

  47. Trivedi P, Cheeseman P, Portmann B, Mowat AP. Serum type III procollagen peptide as a non-invasive marker of liver damage during infancy and childhood in extrahepatic biliary atresia, idiopathic hepatitis of infancy and α1 antitrypsin deficiency. Clin Chim Acta. 1986;161:137–46.

    Article  CAS  PubMed  Google Scholar 

  48. Fujimoto T, Ohya T, Miyano T. A new clinical prognostic predictor for patients with biliary atresia. J Pediatr Surg. 1994;29(6):757–60.

    Article  CAS  PubMed  Google Scholar 

  49. Caponcelli E, Knisely AS, Davenport M. Cystic biliary atresia: an etiologic and prognostic subgroup. J Pediatr Surg. 2008;43:1619–24.

    Article  PubMed  Google Scholar 

  50. Nio M, Wada M, Sasaki H, Tanaka H. Does hepatic hilum morphology influence long-term prognosis in type I/I cyst biliary atresia? Pediatr Surg Int. 2015;31(10):931–6.

    Article  PubMed  Google Scholar 

  51. Landing BH. Considerations of the pathogenesis of neonatal hepatitis, biliary atresia and choledochal cyst--the concept of infantile obstructive cholangiopathy. Prog Pediatr Surg. 1974;6:113–39.

    CAS  PubMed  Google Scholar 

  52. Brindley SM, Lanham AM, Karrer FM, Tucker RM, Fontenot AP, Mack CL. Cytomegalovirus-specific T-cell reactivity in biliary atresia at the time of diagnosis is associated with deficits in regulatory T cells. Hepatology. 2012;55(4):1130–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Xu Y, Yu J, Zhang R, Yin Y, Ye J, Tan L, et al. The perinatal infection of cytomegalovirus is an important etiology for biliary atresia in China. Clin Pediatr (Phila). 2012;51(2):109–13.

    Article  Google Scholar 

  54. Moore SW, Zabiegaj-Zwick C, Nel E. Problems related to CMV infection and biliary atresia. S Afr Med J. 2012;102(11 Pt 2):890–2.

    Article  PubMed  Google Scholar 

  55. Shah I, Bhatnagar S. Biliary atresia and cytomegalovirus and response to valganciclovir. Indian Pediatr. 2012;49:484–6.

    Article  PubMed  Google Scholar 

  56. Schukfeh N, Al-Gamrah A, Petersen C, Kuebler JF. Detection of hepatotropic viruses has no impact on the prognosis after Kasai procedure. J Pediatr Surg. 2012;47(10):1828–32.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Gastroenterology, Sydney Children’s Hospital, High Street, Randwick, Sydney, NSW 2031, Australia

    Robert N. Lopez, Chee Y. Ooi & Usha Krishnan

  2. Discipline of Paediatrics, School of Women’s and Children’s Health, Medicine, University of New South Wales, South Wales, Australia

    Chee Y. Ooi & Usha Krishnan

Authors
  1. Robert N. Lopez
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Chee Y. Ooi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Usha Krishnan
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Robert N. Lopez.

Ethics declarations

Conflict of Interest

The authors declare that they have no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

Additional information

This article is part of the Topical Collection on Pediatric Gastroenterology

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Lopez, R.N., Ooi, C.Y. & Krishnan, U. Early and Peri-operative Prognostic Indicators in Infants Undergoing Hepatic Portoenterostomy for Biliary Atresia: a Review. Curr Gastroenterol Rep 19, 16 (2017). https://doi.org/10.1007/s11894-017-0555-z

Download citation

  • Published:

  • DOI: https://doi.org/10.1007/s11894-017-0555-z

Keywords

Search

Navigation