Enzymatic quantification of total serum bile acids as a monitoring strategy for women with intrahepatic cholestasis of pregnancy receiving ursodeoxycholic acid treatment: a cohort study

Abstract

Objective To evaluate enzymatic total serum bile acid quantification as a monitoring strategy for women with intrahepatic cholestasis of pregnancy (ICP) treated with ursodeoxycholic acid (UDCA). Design Cohort.Setting One UK university hospital.Population 29 ICP cases treated with UDCA.Methods Serial samples were collected prospectively throughout gestation. Total serum bile acids were measured enzymatically and individual bile acids by high-performance liquid chromatographytandem mass spectrometry. Data were log-transformed and analysed with random effects generalised least square regression.Main outcome measures The relationship between enzymatic total bile acid measurements and individual bile acid concentrations after UDCA treatment. ResultsIn untreated women, cholic acid was the principal bile acid (51%) and UDCA concentrations were <0.5%, whereas UDCA constituted 60% (IQR 43-69) of serum bile acids following treatment and cholic acid fell to <20%. Changes in the total bile acid measurement reflected similar alterations in the concentrations of the pathologically elevated bile acids, e.g. a twofold increase in enzymatic total bile acids is accompanied by approximately a two-fold increase in cholic acid and chenodeoxycholic acid at most UDCA doses (P < 0.001). Most of the effects of UDCA on cholic acid occur in the first week of treatment (60% relative reduction, P = 0.025, 95% CI 0.2-0.9, from 10 micromol/l (4.7-17.6) to 3.5 micromol/l (1.4-7.5).Conclusion Ursodeoxycholic acid becomes the main component of the bile acid measurement after treatment. Enzymatic total bile acid assays are good predictors of both cholic acid and chenodeoxycholic acid, the primary bile acids that are raised prior to treatment.Keywords Bile acid assay, cholestasis, pregnancy, ursodeoxycholic acid.Tweetable abstract Ursodeoxycholic acid constitutes approximately 60% of the bile acid measurement and reduces pathological cholic acid in treated women.Please cite this paper as: Manna LB, Ovadia C, L€ ovgren-Sandblom A, Chambers J, Begum S, Seed P, Walker I, Chappell LC, Marschall H-U, Williamson C. Enzymatic quantification of total serum bile acids as a monitoring strategy for women with intrahepatic cholestasis of pregnancy receiving ursodeoxycholic acid treatment: a cohort study.

Ursodeoxycholic acid enriches intestinal bile salt hydrolase-expressing Bacteroidetes in cholestatic pregnancy

“…Lower C4 concentrations were consistent with increased negative feedback on de novo hepatic bile acid synthesis through fibroblast growth factor receptor 4/ beta-klotho hepatic signalling. This finding is consistent with reports of reduced serum concentrations of the endogenous primary bile acids in UDCA-treated women 15 .…”

“…We confirmed that an increase in the CDCA:CA ratio occurs in the serum of women with ICP during UDCA treatment 15,21 . We conclude that hepatic bile acid synthesis via the classical pathway to produce CA is more affected by UDCA treatment than intra-and extra-hepatic synthesis of CDCA via the alternative pathway, secondary to the hepatic action of FGF19.…”

“…We have previously demonstrated the effect of UDCA treatment on individual serum bile acids 15 , with UDCA comprising approximately 60% (42.8-69.0%, median (IQR)) of the bile acid pool in treated, and 0.3% (0.0-0.9%) in untreated women. To determine the relative effect on classical and alternative pathways of bile acid synthesis, we used this dataset to compare the ratio of CA to chenodeoxycholic acid (CDCA) following treatment ( Supplementary Fig.…”

“…Ursodeoxycholic acid may reduce the non-UDCA total serum bile acids for women with ICP 8,9,15 . This mechanism of action has been attributed to increased hepatic bile acid secretion, with enhanced choleresis secondary to vesicular exocytosis (reviewed by Beuers et al) 16 .…”

Effect of ursodeoxycholic acid therapy due to pregnant intrahepatic cholestasis on chemerin and irisin levels

“…Analysis of the biochemical indicators determined in the blood serum of pregnant women with ICP indicates an increased concentration of bile acids as well as hepatic transaminases (Glantz, Marschall, & Mattsson, 2004). An increased, uncontrollable secretion of bile acids has a negative effect on the fetus (Manna et al, 2019).…”