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

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-alpha (TNF-alpha), transforming growth factor-beta (TGF-beta), interferon-beta (IFN-beta), interleukin-2 (IL-2), IL-10, IL-12p40 and IL-12p70 as the candidate biomarkers. Results Increased serum TGF-beta levels indicated a lower Knodell hepatitis activity index at Kasai operation. The serum TGF-beta 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