Soluble adhesion molecule profiling in preoperative infants with biliary atresia

Abstract

Objective: Intercellular adhesion molecule (ICAM) expression in liver and bile duct remnant is a feature of the inflammatory component of biliary atresia (BA). Circulating levels of such soluble adhesion molecules (SAM) should reflect intrahepatic disease and would prove a useful adjunct in the evaluation of BA.

Study design: Serum ICAM-1 (sICAM-1), serum vascular cell adhesion molecule (sVCAM-1), and serum E selectin (sE-selectin) were measured by enzyme-linked immunosorbent assay in infants with BA at the time of portoenterostomy and stratified by outcome. Results are quoted as medians (range). Binary logistic regression analysis and actuarial survival curves were used to investigate the relationship of SAM profile to outcome. Significance was assumed at P values of < or = .05.

Results: Sixty-one infants with BA were treated between 1996 and 2002 and at follow-up; 39 of these were alive and jaundice-free (good outcome, n = 39); 21 had been transplanted, and 1 died (poor outcome, n = 22). Preoperative values for sICAM-1 were 1233 (400-2000) ng/mL; sVCAM-1, 1204 (517-1921) ng/mL; and sE-selectin, 71 (26-192) ng/mL. sVCAM-1 (P < .0001) and sICAM-1 (P < .0001) significantly increased compared with normal control infants, although sE-selectin did not (P = .17). There was a significant correlation of age at surgery with sICAM-1 (r = 0.33, P = .01) but not with sVCAM-1 (r = 0.16, P = .23) or sE-selectin (r = 0.05, P = .70). Binary logistic regression analysis showed that the variables, sICAM-1, sE-selectin, or age at surgery, were not significant predictors of outcome, although sVCAM-1 approached significance (P = .069). A cutoff value for sVCAM-1 of 1380 ng/mL was defined by receiver operating characteristic curve analysis, and the cohort of patients with sVCAM-1 (> 1380 ng/mL) showed a significantly worse actuarial survival (P = .05).

Conclusion: Levels of sICAM-1 and sVCAM-1 are grossly elevated in BA, whereas sE-selectin levels are normal. Only sVCAM-1 levels have prognostic significance. SAM profiling has the potential to monitor the inflammatory process of BA and may guide more novel forms of pharmacological intervention or immunomodulation.