Variations in human liver fucosyltransferase activities in hepatobiliary diseases

The hyperfucosylation of a number of glycoconjugates observed in liver diseases involves the action of several specific fucosyltransferases (F.T.) notably responsible for synthesizing histo-blood group antigens. We determined the activities of alpha 3, alpha 2 and alpha 3/4 F.T. in 35 liver biopsy samples from patients with fatty liver, alcoholic or post-hepatic liver cirrhosis, primary or secondary biliary cirrhosis, acute hepatitis or a normal liver. F.T. activities were measured by transfer of GDP [14C] fucose to asialotransferrin for alpha 3 F.T., to phenyl beta-D-galactoside for alpha 2 F.T. and to 2' fucosyllactose for alpha 3/4 F.T. The diseased liver extracts showed an early increase in non-Le gene-associated alpha 3 F.T. activity (p = 0.001), which was related to the number of steatosic hepatocytes and the degree of intralobular inflammatory infiltration. Overexpression of this alpha 3 F.T. provides an explanation for the strong expression of 3-fucosyl lactosamine structures described in several hepatobiliary diseases. alpha 2 F.T. levels were significantly elevated in the two groups of liver cirrhosis and acute hepatitis (p = 0.05), but not enough to consider alpha 2 F.T. as a sensitive feature of mesenchymal cell injury. All Lewis-positive biopsies displaying biliary alterations showed increased Le gene-encoded alpha 3/4 F.T. activity (p = 0.001), which was related to the intensity of neoductular proliferation. Elevated levels of alpha 3/4 F.T. may be a very early sign of biliary regeneration.