Bile Acid Profiles in Intrahepatic Cholestasis of Pregnancy: Is This the Solution to the Enigma of Intrahepatic Cholestasis of Pregnancy?

Sinakos, Emmanouil; Lindor, Keith D.

doi:10.1038/ajg.2009.639

Cited by 16 publications

(8 citation statements)

References 30 publications

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“…However, their data lack confirmation. Here we present comprehensive bile acid profiles that were measured using state-of-the-art technology [28], [29].…”

Section: Discussionmentioning

confidence: 99%

The Reversed Feto-Maternal Bile Acid Gradient in Intrahepatic Cholestasis of Pregnancy Is Corrected by Ursodeoxycholic Acid

et al. 2014

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Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy-specific liver disorder associated with an increased risk of adverse fetal outcomes. It is characterised by raised maternal serum bile acids, which are believed to cause the adverse outcomes. ICP is commonly treated with ursodeoxycholic acid (UDCA). This study aimed to determine the fetal and maternal bile acid profiles in normal and ICP pregnancies, and to examine the effect of UDCA treatment. Matched maternal and umbilical cord serum samples were collected from untreated ICP (n = 18), UDCA-treated ICP (n = 46) and uncomplicated pregnancy (n = 15) cases at the time of delivery. Nineteen individual bile acids were measured using HPLC-MS/MS. Maternal and fetal serum bile acids are significantly raised in ICP compared with normal pregnancy (p = <0.0001 and <0.05, respectively), predominantly due to increased levels of conjugated cholic and chenodeoxycholic acid. There are no differences between the umbilical cord artery and cord vein levels of the major bile acid species. The feto-maternal gradient of bile acids is reversed in ICP. Treatment with UDCA significantly reduces serum bile acids in the maternal compartment (p = <0.0001), thereby reducing the feto-maternal transplacental gradient. UDCA-treatment does not cause a clinically important increase in lithocholic acid (LCA) concentrations. ICP is associated with significant quantitative and qualitative changes in the maternal and fetal bile acid pools. Treatment with UDCA reduces the level of bile acids in both compartments and reverses the qualitative changes. We have not found evidence to support the suggestion that UDCA treatment increases fetal LCA concentrations to deleterious levels.

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“…However, their data lack confirmation. Here we present comprehensive bile acid profiles that were measured using state-of-the-art technology [28], [29].…”

Section: Discussionmentioning

confidence: 99%

The Reversed Feto-Maternal Bile Acid Gradient in Intrahepatic Cholestasis of Pregnancy Is Corrected by Ursodeoxycholic Acid

et al. 2014

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“…Intrahepatic cholestasis of pregnancy (ICP) is a liver disease characterised by pruritus and abnormal liver function that affects approximately 0.7% of pregnancies. Increased serum bile acid (BA) concentrations are diagnostic, with cholic acid (CA) and chenodeoxycholic acid (CDCA) being the main BA species to rise in maternal serum. Liver enzymes are also often elevated …”

Section: Introductionmentioning

confidence: 99%

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

Manna

Ovadia

Lövgren‐Sandblom

et al. 2019

BJOG

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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.

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“…20 In addition, some studies showed that CA significantly increased in the third trimester when compared with the first, 21,22 whereas other work showed no difference. 23 Raised SBA in the absence of symptoms of cholestasis have been reported, and labelled as asymptomatic hypercholoanaemia (AHP), 24 reportedly affecting up to 10% of the pregnant population. 8,14 Bile acid abnormalities have demonstrated a geographic and ethnic variation, with countries such as Finland and Chile showing an increased incidence of OC.…”

Section: Discussionmentioning

confidence: 99%

Reference standard for serum bile acids in pregnancy

Egan

Bartels

Khashan

et al. 2012

BJOG

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Objective Obstetric cholestasis (OC) is a liver disorder characterised by pruritus and elevated serum bile acids (SBA) that affects one in 200 pregnant women. It is associated with adverse perinatal outcomes such as premature delivery and stillbirth. Mild OC is defined as SBA levels of 10-39 lmol/l, and severe OC is defined by levels >40 lmol/l. SBA levels in normal pregnancy have not been investigated. We aimed to establish reference values for SBA in healthy pregnant women across different trimesters of pregnancy.Design Cross-sectional analysis of SBA levels.Setting A large tertiary referral university teaching maternity hospital.Population Healthy pregnant women with a singleton pregnancy and a body mass index (BMI) < 40, excluding women with significant alcohol intake, history of liver disease, prior cholecystectomy and OC.Methods Cross-sectional analysis of SBA levels at 12, 20, 28 and 36 weeks of gestation, and on days 1-3 postpartum.Main outcome measures SBA levels in lmol/l.Results A total of 219 women attending for antenatal care were recruited, and SBA levels were assayed at 12, 20, 28 and 36 weeks of gestation, and up to 72 hours postpartum (n = 44-49 cases at each stage). The majority were white European women, with a median age of 30 years (range 17-46 years) and median BMI of 25 (range 18-38). Values of SBA ranged from 0.3 to 9.8 lmol/l in 216 women, with only three measurements outside this range. There were no significant changes throughout pregnancy.Conclusions SBA values in uncomplicated pregnancies are consistent, regardless of gestation, and are not elevated in pregnancy. The current reference values for the diagnosis of OC appear to be appropriate.

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Bile Acid Profiles in Intrahepatic Cholestasis of Pregnancy: Is This the Solution to the Enigma of Intrahepatic Cholestasis of Pregnancy?

Cited by 16 publications

References 30 publications

The Reversed Feto-Maternal Bile Acid Gradient in Intrahepatic Cholestasis of Pregnancy Is Corrected by Ursodeoxycholic Acid

The Reversed Feto-Maternal Bile Acid Gradient in Intrahepatic Cholestasis of Pregnancy Is Corrected by Ursodeoxycholic Acid

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

Reference standard for serum bile acids in pregnancy

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