Increased Circulating VAP-1 Levels Are Associated with Liver Fibrosis in Chronic Hepatitis C Infection

Abstract

Vascular adhesion protein-1 (VAP-1) is a multifunction protein. While membrane-bound VAP-1 is an adhesion protein, soluble VAP-1 catalyzes the deamination of primary amines through its semicarbazide-sensitive amino oxidase (SSAO) activity. VAP-1 supports the transmigration of leukocytes and increases oxidative stress. In chronic liver diseases, it plays a role in leukocyte infiltration and fibrogenesis. Here, we measured VAP-1 plasma concentration and its SSAO activity in 322 patients with chronic hepatitis C infection and evaluated the association of VAP-1 with fibrosis stages. VAP-1 concentration strongly correlated with liver stiffness and was the second strongest influencing variable after gamma-glutamytransferase (GGT) for liver stiffness in regression analysis. The VAP-1 concentration increased with advancing fibrosis stages and the highest concentrations were found in patients with cirrhosis. According to the receiver operating characteristic (ROC) analysis, a VAP-1 cut-off value of 541 ng/mL predicted histologically confirmed cirrhosis (sensitivity 74%; specificity 72%). SSAO activity correlated only moderately with liver stiffness, showing a relatively small increase in advanced fibrosis. To our knowledge, this is the first study on VAP-1 in chronic hepatitis C infection showing its association with progressive fibrosis. In conclusion, VAP-1 plasma concentration, rather than its SSAO activity, may represent a non-invasive biomarker for monitoring fibrogenesis in patients with chronic hepatitis C infection.