Effects of ursodeoxycholic acid on conjugated bile acids and progesterone metabolites in serum and urine of patients with intrahepatic cholestasis of pregnancy

Meng, Ling; Reyes, Humberto; J, Palma; Hernández, Ismael; Ribalta, J; Sjövall, Jan

doi:10.1016/s0168-8278(97)80147-x

Cited by 95 publications

(67 citation statements)

References 45 publications

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“…1 Ursodeoxycholic acid normalises the ratio of 3a to 3h hydroxysteroid in women with obstetric cholestasis and decreases the accumulation of bile acids in the fetus. 2,3 S-Adenosyl-L-methionine is implicated in methylation reactions, and in animal experiments, it protects against hormone-induced cholestasis by facilitating the transsulphuration of bile salts into excretory forms. 4 Anecdotal evidence suggests that improvement in serum biochemical abnormalities may also result in improved pruritus and perinatal outcome.…”

Section: Introductionmentioning

confidence: 99%

A randomised controlled trial of ursodeoxycholic acid and S‐adenosyl‐l‐methionine in the treatment of gestational cholestasis

Roncaglia

Locatelli

Arreghini

et al. 2003

BJOG

108

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Objective To compare the efficacy of S-adenosyl-L-methionine and ursodeoxycholic acid in improving serum biochemical abnormalities in gestational cholestasis. Design Randomised clinical trial.Setting University hospital.Population All women at <36 weeks of gestation with severe gestational cholestasis during June 1996 to December 2001. Methods Enrolled women were randomly assigned oral S-adenosyl-L-methionine 500 mg twice daily or oral ursodeoxycholic acid 300 mg twice daily until delivery. Main outcome measures Reduction in the concentration of serum bile acids. Other variables considered included obstetric and neonatal outcome, clinical symptoms and other laboratory measurements (serum levels of transaminases and bilirubin). The two groups were compared using Student's t test, Wilcoxon's signed rank sum test and Fisher's exact test, with a two-tailed P < 0.05 being considered significant. Results Of the 46 women enrolled, 24 received ursodeoxycholic acid and 22 S-adenosyl-L-methionine. At enrolment, gestational age, duration of therapy, rate of nulliparity, pruritus score and biochemical characteristics were similar between the groups. Both therapies significantly and equally improved pruritus. Women receiving ursodeoxycholic acid had a significantly greater improvement in the concentration of serum bile acids ( P ¼ 0.001), aspartate aminotransferase ( P ¼ 0.01), alanine aminotransferase (<0.001) and bilirubin ( P ¼ 0.002) compared with those receiving S-adenosyl-L-methionine. Duration of therapy was significantly greater in women receiving ursodeoxycholic acid compared with S-adenosyl-Lmethionine ( P ¼ 0.04), whereas gestational age at delivery and rate of prematurity were similar in the two groups. Conclusions In women with intrahepatic cholestasis of pregnancy, ursodeoxycholic acid is more effective than S-adenosyl-L-methionine at improving the concentration of serum bile acids and other tests of liver function, whereas both therapies are equally effective at improving pruritus.

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Section: Introductionmentioning

confidence: 99%

A randomised controlled trial of ursodeoxycholic acid and S‐adenosyl‐l‐methionine in the treatment of gestational cholestasis

Roncaglia

Locatelli

Arreghini

et al. 2003

BJOG

108

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“…In fact, the existence of subclinical cholestasis during pregnancy may also make difficult the diagnosis of the disease. Moreover, pruritus in pregnancy is a common symptom in ICP but this evidence is not sufficient to discriminate women with ICP from those with benign condition of pruritus gravidarum (Meng et al, 1997, Castaño et al, 2006.…”

Section: Diagnosis and Treatmentmentioning

confidence: 99%

“…With regard to this point, serum bile acid profile has proved to be more informative than the determination of TSBA (Baqc et al;1995, Meng et al, 1997Castaño et al, 2006;Lucangioli et al, 2009). Although many authors agree on the benefits of evaluating serum bile acids individually, there is no consensus in assigning a particular bile acid determination as the www.intechopen.com Cholestasis 6 most useful indication in order to diagnose ICP or in establishing adequate bile acids ratios to solve how to recognize the disease.…”

Section: Diagnosis and Treatmentmentioning

confidence: 99%

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Intrahepatic Cholestasis of Pregnancy: The Usefulness of Serum Bile Acid Profile for Diagnosis and Treatment

Lucangioli¹,

Tripodi²

2012

Cholestasis

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“…Some studies have reported that UDCA administration also reduces maternal plasma concentrations of some PMS [9,10], and this has been related to the improved maternal hepatobiliary function [11]. During intra-uterine life, the placenta is essential for this function in the foetus.…”

Section: Introductionmentioning

confidence: 99%

Effect of ursodeoxycholic acid treatment on the altered progesterone and bile acid homeostasis in the mother‐placenta‐foetus trio during cholestasis of pregnancy

Estiú¹,

Monte

Rivas

et al. 2015

Brit J Clinical Pharma

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AIMIntrahepatic cholestasis of pregnancy (ICP) is characterized by pruritus and elevated bile acid concentrations in maternal serum. This is accompanied by an enhanced risk of intra-uterine and perinatal complications. High concentrations of sulphated progesterone metabolites (PMS) have been suggested to be involved in the multifactorial aetiopathogenesis of ICP. The aim of this study was to investigate further the mechanism accounting for the beneficial effect of oral administration of ursodeoxycholic acid (UDCA), which is the standard treatment, regarding bile acid and PMS homeostasis in the mother-placenta-foetus trio. METHODUsing HPLC-MS/MS bile acids and PMS were determined in maternal and foetal serum and placenta. The expression of ABC proteins in placenta was determined by real time quantitative PCR (RT-QPCR) and immunofluorescence. RESULTSIn ICP, markedly increased concentrations of bile acids (tauroconjugates > glycoconjugates >> unconjugated), progesterone and PMS in placenta and maternal serum were accompanied by enhanced concentrations in foetal serum of bile acids, but not of PMS. UDCA treatment reduced bile acid accumulation in the mother-placenta-foetus trio, but had no significant effect on progesterone and PMS concentrations. ABCG2 mRNA abundance was increased in placentas from ICP patients vs. controls and remained stable following UDCA treatment, despite an apparent further increase in ABCG2. CONCLUSIONUDCA administration partially reduces ICP-induced bile acid accumulation in mothers and foetuses despite the lack of effect on concentrations of progesterone and PMS in maternal serum. Up-regulation of placental ABCG2 may play an important role in protecting the foetus from high concentrations of bile acids and PMS during ICP. WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT• Intrahepatic cholestasis of pregnancy (ICP) is characterized by an increase in maternal serum concentrations of bile acids and sulphated progesterone metabolites. WHAT THIS STUDY ADDS• The accumulation of sulphated progesterone metabolites in the serum of ICP patients is associated with enhanced concentrations of progesterone. Although these compounds may be involved in the aetiopathogenesis of ICP, the magnitude of this accumulation does not correlate with the degree of hypercholanaemia in ICP patients.• The beneficial effect of ursodeoxycholic acid (UDCA) treatment includes a reduction of maternal hypercholanaemia, which is not dependent on the correction of progesterone metabolites accumulation.• In spite of marked increases in maternal serum concentrations of sulphated progesterone metabolites and bile acids in ICP patients, the concentrations of these compounds in foetal serum remain normal or are only moderately elevated, respectively. The latter can be corrected by treatment with UDCA.• The ABCG2 export pump located at the apical membrane of trophoblast cells plays an important role in the placental barrier for sulphated progesterone metabolites and bile acids. ABCG2 up-regulation during ICP, and further by UDCA treatment, ...

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Effects of ursodeoxycholic acid on conjugated bile acids and progesterone metabolites in serum and urine of patients with intrahepatic cholestasis of pregnancy

Cited by 95 publications

References 45 publications

A randomised controlled trial of ursodeoxycholic acid and S‐adenosyl‐l‐methionine in the treatment of gestational cholestasis

A randomised controlled trial of ursodeoxycholic acid and S‐adenosyl‐l‐methionine in the treatment of gestational cholestasis

Intrahepatic Cholestasis of Pregnancy: The Usefulness of Serum Bile Acid Profile for Diagnosis and Treatment

Effect of ursodeoxycholic acid treatment on the altered progesterone and bile acid homeostasis in the mother‐placenta‐foetus trio during cholestasis of pregnancy

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