A high serum interleukin-12p40 level prior to Kasai surgery predict a favourable outcome in children with biliary atresia

Liver Int. 2012 Nov;32(10):1557-63. doi: 10.1111/liv.12001. Epub 2012 Sep 7.

Abstract

Background: Biliary atresia (BA) is a paediatric cholestatic disease characterized by a progressive fibro-inflammation of the biliary tree. Current treatment of choice is to establish good bile flow via the Kasai operation.

Aims: We aimed to identify outcome-predictive serum biomarkers in BA infant.

Methods: Thirty-three BA children recruited from 1986 to 2007 served as the baseline-study group. An additional 11 children recruited from 2008 to 2011 served as the validation group. Serum samples were collected immediately before and 6 months after the Kasai operation for the assessment of serum cytokines, including tumour necrosis factor-α (TNF-α), transforming growth factor-β (TGF-β), interferon-γ (IFN-γ), interleukin-2 (IL-2), IL-10, IL-12p40 and IL-12p70 as the candidate biomarkers.

Results: Increased serum TGF-β levels indicated a lower Knodell hepatitis activity index at Kasai operation. The serum TGF-β levels declined after the operation. Serum IL-12p40 levels before the Kasai operation were higher in the subjects with a 3-month jaundice-free status than in others (P = 0.001). A serum pre-operative IL-12p40 level of 33 pg/ml was predictive of a 3-month jaundice-free status after surgery (positive predictive value=81.0%; negative predictive value=83.3%). This biomarker was also predictive of a better outcome, in terms of 3-year survival with native liver (risk ratio [RR = 4.00]; P < 0.001), and 3-year jaundice-free survival with native liver (RR = 12.00; P < 0.001). We confirmed the predictive power of a high pre-operative IL-12p40 level on 3-month jaundice-free status in the validation group.

Conclusions: The pre-operative IL-12p40 level was a good predictive biomarker of clinical outcome in children with BA undergoing the Kasai operation.

Publication types

  • Evaluation Study
  • Research Support, Non-U.S. Gov't
  • Validation Study

MeSH terms

  • Biliary Atresia / blood*
  • Biliary Atresia / surgery*
  • Biomarkers / blood*
  • Female
  • Humans
  • Infant
  • Interleukin-12 Subunit p40 / blood*
  • Jaundice, Obstructive / pathology*
  • Jaundice, Obstructive / prevention & control
  • Male
  • Odds Ratio
  • Portoenterostomy, Hepatic / methods*
  • Predictive Value of Tests
  • Prognosis
  • ROC Curve

Substances

  • Biomarkers
  • Interleukin-12 Subunit p40