Fibrosis and liver inflammation are key regulators of α1-acid glycoprotein fucosylation

Background and AimsThere is an urgent need for new high-quality markers in the early detection of hepatocellular carcinoma (HCC). [A]strom et al. suggested that S2-bound 1-acid glycoprotein (AGP) might be a promising marker. Consequently, we evaluated S2-bound AGP for a predictive advantage in the early detection of HCC. MethodsIn a retrospective case-control study of patients chronically infected with hepatitis C virus (HCV) and treated with direct-acting antiviral agents (n=93), we measured S2-bound AGP using the HepaCheC(R) ELISA kit (Glycobond AB, Linkoping, SE) at treatment start, end of treatment and follow-up (maximum: 78 months). Patients were retrospectively propensity score matched (1:2). 31 patients chronically infected with HCV developed HCC after sustained virological response while 62 did not. In addition, samples of HBV, MASLD and HCC from different etiologies patients were measured. ResultsS2-bound AGP elevation in HCC patients was confirmed. However, we did not observe a predictive advantage of S2-bound AGP in early detection of HCC during treatment and follow-up. Interestingly, S2-bound AGP levels correlated with aspartate aminotransferase ({rho}=0.56, p=9.5x10-15) and liver elastography ({rho}=0.67, p=2.2x10-16). Of note, S2-bound AGP decreased in patients chronically infected with HCV after treatment-induced clearance of HCV. ConclusionFibrosis and liver inflammation are key regulators in the fucosylation of AGP. The potential role of S2-bound AGP as a novel tumor marker requires further investigation. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=139 SRC="FIGDIR/small/23298443v1_ufig1.gif" ALT="Figure 1"> View larger version (56K): org.highwire.dtl.DTLVardef@5440c2org.highwire.dtl.DTLVardef@167a9c1org.highwire.dtl.DTLVardef@b9e494org.highwire.dtl.DTLVardef@4db1f1_HPS_FORMAT_FIGEXP M_FIG C_FIG