Therapeutic Advances in Gastroenterology (Mar 2009)
sPECAM-1 and sVCAM-1: role in pathogenesis and diagnosis of chronic hepatitis C and association with response to antiviral therapy
Abstract
Aim: To analyze the relationship between pretreatment clinical or histological features and the levels of soluble platelet-endothelial cell adhesion molecule-1 (sPECAM-1) and soluble vascular cell adhesion molecule-1 (sVCAM-1), to determine their serum concentration in responders and nonresponders, to evaluate the behavior under antiviral therapy, to explain their relationship in response to therapy and to assess the association between these two molecules in chronic hepatitis C (CHC). Methods: The study analyzed 65 CHC patients, including 50 patients (Group 1) with marked fibrosis treated with peginterferon plus ribavirin, 15 patients without fibrosis (Group 2) and 13 healthy volunteers (the control group, Group 3). sPECAM-1 and sVCAM-1 levels were assessed by an immunoenzymatic method (ELISA) before and after therapy. Results: sVCAM-1 and sPECAM-1 serum concentrations increased significantly in CHC patients (p<0.001). sPECAM-1 levels corresponded to inflammatory grade (p = 0.03) and fibrosis stage (p = 0.01). sVCAM-1 increased only in advanced fibrosis. After therapy, sPECAM-1 levels decreased significantly (p<0.001) with no difference between responders and nonresponders. sPECAM-1 correlated positively with inflammatory activity (p = 0.02), fibrosis stage (p<0.001), sVCAM-1 (r = 0.56, p<0.001) and alanine aminotransferase activity (r = 0.30, p = 0.05). Receiver operating characteristic curve analysis showed a good discriminant power of serum sPECAM-1 concentrations for detection of liver fibrosis — stage 0 versus stage 1—3, AUC 0.81; cut-off 221.0 ng/ml and a fair discriminant power for distinguishing bridging fibrosis, AUC 0.78; cut-off 237.1 ng/ml. Conclusions: Hepatitis C virus (HCV) infection results in upregulation of sPECAM-1 and sVCAM-1. sPECAM-1 levels are related to necroinflammatory activity and may also identify patients with advanced fibrosis. The sPECAM-1 value was decreased by therapy but its measurement cannot predict therapy outcome and confirm HCV persistence. sPECAM-1 may influence VCAM-1 expression.