Inverse association between serum concentrations of actin-free vitamin D-binding protein and the histopathological extent of fibrogenic liver disease or hepatocellular carcinoma

Background and Aim Next to its role as a carrier protein for vitamin D and its plasma metabolites, the primary function of vitamin D-binding protein (DBP; Gc-globulin) is to serve and to bind and neutralize extracellular monomeric actin (G-actin) released from necrotic cells, which in its long filamentous form (F-actin) triggers coagulation. We, therefore, investigated the kinetics of serum concentrations of actin-free DBP during the pathogenetic sequence from liver fibrosis to hepatocellular carcinoma (HCC) to initiate a discussion on a hypothetical association of serum concentrations of actin-free DBP and, thus, altered actin clearance in the circulation, and an increased risk of thrombosis in patients with functional liver insufficiency. Results Our data show that serum levels of actin-free DBP are decreased in patients with liver fibrosis (n=288) and HCC (n = 1 02) compared with healthy controls (n = 1 20 and n=63 ) and nonliver disease sick (n=312) and that the level of decrease correlates with the severity of disease as determined according to the score by the French METAVIR Cooperative Study Group staging system for hepatic fibrosis or the Edmondson-Steiner's grading system for the assessment of HCC. Conclusion Although further, in particular, longitudinal studies are still necessary to back up our data, the presented findings suggest that decreasing levels of the actin-scavenger DBP could potentially contribute to the thrombophilic predisposition frequently observed in patients with chronic fibrogenic liver disease and HCC.