Outcomes of biliary atresia in the Nordic countries – a multicenter study of 158 patients during 2005–2016,☆☆

https://doi.org/10.1016/j.jpedsurg.2017.08.048Get rights and content

Abstract

Background/purpose

Biliary atresia is the most common reason for newborn cholestasis and pediatric liver transplantation. Even after normalization of serum bilirubin after portoenterostomy, most patients require liver transplantation by adulthood due to expanding fibrosis. We addressed contemporary outcomes of biliary atresia in the Nordic countries.

Methods

Data on center and patients characteristics, diagnostic practices, surgical treatment, adjuvant medical therapy after portoenterostomy, follow-up and outcomes were collected from all the Nordic centers involved with biliary atresia care during 2005–2016.

Results

Of the 154 patients, 148 underwent portoenterostomy mostly by assigned surgical teams at median age of 64 (interquartile range 37–79) days, and 95 patients (64%) normalized their serum bilirubin concentration while living with native liver. Postoperative adjuvant medical therapy, including steroids, ursodeoxycholic acid and antibiotics was given to 137 (93%) patients. Clearance of jaundice associated with young age at surgery and favorable anatomic type of biliary atresia, whereas annual center caseload > 3 patients and diagnostic protocol without routine liver biopsy predicted early performance of portoenterostomy. The cumulative 5-year native liver and overall survival estimate was 53% (95% CI 45–62) and 88% (95% CI 83–94), respectively. Portoenterostomy age < 65 days and annual center caseload > 3 patients were predictive for long-term native liver survival, while normalization of serum bilirubin after portoenterostomy was the major predictor of both native liver and overall 5-year survival.

Conclusions

The outcomes of biliary atresia in the Nordic countries compared well with previous European studies. Further improvement should be pursued by active measures to reduce patient age at portoenterostomy.

Retrospective prognosis study

Level II.

Section snippets

Study design and data collection

This was an international multicenter retrospective observational survey. All children with confirmed BA born in the Nordic countries during 1.1.2005–30.6.2016 and followed-up at least for 4 months were included. Data were collected locally by pediatric surgeons, pediatric hepatologists and pediatricians in all Nordic centers involved with the treatment of BA according to a collectively approved questionnaire and data extraction sheet. The participating centers included one from Denmark

Center characteristics

The median number of patients treated in the participating six centers annually ranged from 0.7 to 3.7, while only two centers managed over three patients annually (Supplementary Table 1). Cholescintigraphy, operative cholangiography and ultrasound were uniformly used diagnostic investigations, whereas preoperative diagnostic liver biopsy, MRI, PTC and ERC were less commonly employed. In five centers one surgeon or surgical team operated all BA patients and none used laparoscopic surgical

Discussion

The results of this study show that the clearance of jaundice rate, the 5-year native liver survival after PE and overall survival in the Nordic countries compared well with previous European studies (Table 5). Following PE, serum bilirubin concentration normalized in 64%, and 55% of the Nordic patients were alive with their native livers at 5 years. Their median serum bilirubin and blood platelet levels were in the normal range, reflecting well-preserved native liver function. The diagnostic

References (37)

  • A. Asai et al.

    Pathogenesis of biliary atresia: defining biology to understand clinical phenotypes

    Nat Rev Gastroenterol Hepatol

    (2015)
  • W. de Vries et al.

    Biliary atresia in the Netherlands: outcome of patients diagnosed between 1987 and 2008

    J Pediatr

    (2012)
  • R. Superina 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)
  • S.S. Sundaram et al.

    Biliary atresia: indications and timing of liver transplantation and optimization of pretransplant care

    Liver Transpl

    (2017)
  • R. Arnon et al.

    Liver transplantation for biliary atresia: is there a difference in outcome for infants?

    J Pediatr Gastroenterol Nutr

    (2016)
  • J.S. Neto et al.

    Impact of Kasai portoenterostomy on liver transplantation outcomes: a retrospective cohort study of 347 children with biliary atresia

    Liver Transpl

    (2015)
  • S. Malenicka et al.

    Impaired intention-to-treat survival after listing for liver transplantation in children with biliary atresia compared to other chronic liver diseases: 20 years' experience from the Nordic countries

    Pediatr Transplant

    (2017)
  • P. Russo et al.

    Key histopathologic features of liver biopsies that distinguish biliary atresia from other causes of infantile cholestasis and their correlation with outcome: a multicenter study

    Am J Surg Pathol

    (2016)
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    No conflicts of interest to declare.

    ☆☆

    Financial support: MPP was supported by grants from the Finnish Pediatric Research Foundation, the Sigrid Juselius Foundation and the Helsinki University Central Hospital research funds. JFS and MA were supported by grants from the Crown Princess Lovisa Foundation and Sällskapet Barnavård.

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