Predictive Value of Serum Cholic Acid and Lithocholic Acid for the Diagnosis in an Intrahepatic Cholestasis of Pregnancy Population with High Levels of Total Bile Acids and the Correlation with Placental Hypoxia-Inducible Factor-1α

Abstract

Objective This study aimed to investigate the ability of serum cholic acid (CA) and lithocholic acid (LCA) in the diagnosis and perinatal prognosis assessment of intrahepatic cholestasis of pregnancy (ICP), and the relationship between both indicators and hypoxia-inducible factor-1α (HIF-1α). Methods Between March 2020 and March 2021, pregnant women with high levels of total bile acid (TBA) in the late pregnancy with TBA ≥10 μmol/L and TBA <10 μmol/L (control group) were included for the retrospective study. Those with TBA ≥10 μmol/L were divided into the ICP group and the asymptomatic hypercholanaemia of pregnancy (AHP) group based on ICP symptoms. The comparison of the bile acid profiles, the receiver operating characteristic (ROC) curve analysis, and Pearson correlation analysis were conducted successively. Results Nine types of bile acids were significantly higher in ICP and AHP than in the control group, while CA and LCA serum levels in the AHP group were significantly lower than those in the ICP group ( P < 0.05). The ROC curve analysis showed that LCA, CA, and LCA+CA were all diagnostic indicators for ICP, and LCA+CA displayed the greatest diagnostic value (area under the curve (AUC), 0.923). Subgroup analysis using the LCA+CA cut-off point (3.28 μmol/L) as the subgroup indicator proved that the incidence of adverse perinatal outcomes and the placental HIF-1α positivity were significantly higher in the high LCA+CA group than in the low LCA+CA group ( P < 0.05). Pearson correlation analysis revealed significant positive correlations of HIF-1α expression levels to LCA, CA and LCA+CA (r = 0.473, 0.537, 0.619, respectively. P < 0.05 in all). Conclusion This study confirmed that CA and LCA have a predictive diagnostic value for ICP in pregnant women, and the combined evaluation is associated with adverse perinatal outcomes, and LCA+CA positively correlates to placental HIF-1α expression levels.

Cholic acid exposure during late pregnancy causes placental dysfunction and fetal growth restriction by reactive oxygen species‐mediated activation of placental GCN2/eIF2α pathway

“…Cholic acid (CA), a major primary bile acid, is the principal toxic bile acid species. Serum TBA profiles showed that elevated serum TBA was dominated by CA in patients with gestational cholestasis 9 . Studies of both animals and humans demonstrated that ursodeoxycholic acid (UDCA) treatment rescued ICP‐induced adverse pregnancy events via decreasing serum CA levels 10 .…”

“…Serum TBA profiles showed that elevated serum TBA was dominated by CA in patients with gestational cholestasis. 9 Studies of both animals and humans demonstrated that ursodeoxycholic acid (UDCA) treatment rescued ICP-induced adverse pregnancy events via decreasing serum CA levels. 10 Indeed, CA-induced cholestasis as animal models for ICP has been well established in rodents.…”

Serum placental growth factor, total cholesterol, and triglycerides for prediction of intrahepatic cholestasis of pregnancy

“…Remarkably, a substantial proportion of pregnant women with TBA levels equal to or exceeding 10 μmol/L may exhibit no clinical indications of ICP during their medical evaluations. [ 10 ] Consequently, the identification of potential predictors capable of diagnosing ICP before clinical symptoms manifest is of paramount importance.…”