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.
Highlights
Vascular adhesion protein-1 (VAP-1) is a 170 kDa sialoglycoprotein
We investigated the levels of VAP-1 and sensitive amino oxidase (SSAO) activity in different fibrosis stages, which were assessed by transient elastography (Fibroscan®) as liver stiffness and liver biopsy in some cases
In our study on 322 chronic HCV infection patients, we show that the VAP-1 concentration, as well as the SSAO activity, were significantly elevated in patients with moderate or severe fibrosis especially in the presence of cirrhosis
Summary
Vascular adhesion protein-1 (VAP-1) is a 170 kDa sialoglycoprotein. It exists in soluble and membrane-bound forms [1]. VAP-1 has an enzymatic domain that is responsible for its primary amine oxidase activity, referred to as the semicarbazide-sensitive amino oxidase (SSAO) activity [2]. It is involved in the conversion of exogenous and endogenous amines, for example benzylamine and methylamine, into aldehydes by oxidative deamination, thereby releasing cytotoxic products such as hydrogen peroxide and ammonia. In the soluble form, VAP-1 is present in the human blood [1]
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