Variations in human liver fucosyltransferase activities in hepatobiliary diseases

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Abstract
— 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 α3, α2 and α3/4 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 α3 F.T, to phenyl β-D-galactoside for α2 F.T. and to 2′ fucosyllactose for α3/4 F.T. The diseased liver extracts showed an early increase in non-Le gene-associated α3 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 α3 F.T. provides an explanation for the strong expression of 3-fucosyl lactosamine structures described in several hepatobiliary diseases. α2 F.T. levels were significantly elevated in the two groups of liver cirrhosis and acute hepatitis (p = 0.05), but not enough to consider α2 F.T. as a sensitive feature of mesenchymal cell injury. All Lewis-positive biopsies displaying biliary alterations showed increased Le gene-encoded α3/4 F.T. activity (p = 0.001), which was related to the intensity of neoductular proliferation. Elevated levels of α3/4 F.T may be a very early sign of biliary regeneration.

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