Increased syndecan-1 and glypican-3 predict poor perinatal outcome and treatment resistance in intrahepatic cholestasis

Background:Intrahepatic cholestasis of pregnancy(ICP)increases the risk of adverse pregnancy outcomes.This study aimed to explore the association between serum syndecan-1 and glypican-3 levels and the adverse perinatal outcome as well as the responses to the treatment of ursodeoxycholic acid(UDCA).Methods:This prospective,case control study included 88 pregnant women(44 women with ICP and 44 healthy controls).The primary end points were the perinatal outcome and the response to UDCA therapy.A logistic regression model was used to identify the independent risk factors of adverse pregnancy outcomes and reduced response to UDCA therapy.Results:Women with ICP had significantly higher serum syndecan-1(1.27±0.36 ng/m L vs.0.98±0.50 ng/m L;P=0.003),glypican-3(1.78±0.13 ng/m L vs.1.69±0.16 ng/m L;P=0.004),AST(128.59±1.44 vs.13.29±1.32 U/L;P<0.001),and ALT(129.84±1.53 vs.8.00±3.67 U/L;P<0.001)levels compared with the controls.The increased levels of syndecan-1(OR=4.715,95%CI:1.554–14.310;P=0.006),glypican-3(OR=8.465,95%CI:3.372–21.248;P=0.007),ALT(OR=1.382,95%CI:1.131–1.690;P=0.002),and postprandial bile acid(PBA)(OR=3.392,95%CI:1.003–12.869;P=0.026)were correlated to ICP.The adverse neonatal outcome was related to increased glypican-3(OR=4.275,95%CI:2.726–5.635;P=0.039),and PBA(OR=3.026,95%CI:1.069–13.569;P=0.037).Increases of syndecan-1(OR=7.464,95%CI:2.130–26.153,P=0.017)and glypican-3(OR=6.194,95%CI:2.951–13.002;P=0.025)were the risk factors of decreased response to UDCA treatment.Conclusion:Syndecan-1 and glypican-3 might be powerful determinants in predicting adverse perinatal outcome in patients with ICP,and they can be used to predict the response to the UDCA treatment.