Serial circulating markers of inflammation in biliary atresia—Evolution of the post-operative inflammatory process

Abstract

Biliary atresia (BA) may be characterized as an occlusive cholangiopathy affecting both intra- and extra-hepatic parts of the biliary tree, together with a pronounced inflammatory response consisting of hepatic infiltration of (predominantly) CD4+ lymphocytes and macrophages. Soluble cellular adhesion molecules are also known to be raised at the time of portoenterostomy, presumably reflecting intrahepatic disease. We investigated this measurable inflammatory component longitudinally by studying a panel of cellular adhesion molecules (soluble intercellular adhesion molecule-1 [sICAM-1], soluble vascular cell adhesion molecule-1 [sVCAM-1]) and soluble proinflammatory mediators (T helper 1 [interleukin [IL]-2 and interferongamma] and T helper 2 [IL-4 and IL-10]) cytokines and macrophage markers (tumor necrosis factor [TNF] alpha and IL-18) in 21 consecutive infants with BA post-Kasai portoenterostomy (KP). The levels of all adhesion molecules and cytokines (except IL-10) increased progressively by 6 months post-portoenterostomy. The response was non-polarized but with 100-fold increases in IL-2, TNFalpha and IL-18 particularly but only modest elevations in IL-10. When proinflammatory profiles were related to outcome, we found poor discrimination if assessed as clearance of jaundice but markedly higher values for IL-2, interferongamma, IL-4, IL-10, TNFalpha and sICAM-1 for those who would be transplanted by 1 year. Using ROC curve analysis for sICAM-1 levels at 1 month post-KP, a cutoff level of 1,779 ng/ml was determined to predict the need for transplantation at 1 year with 92% specificity and 87% sensitivity. The early circulating inflammatory process in BA is persistent, progressive and involves a non-polarized T cell, macrophage and cell adhesion molecule response only partially ameliorated by KP.