Longitudinal Profiles of 15 Serum Bile Acids in Patients With Intrahepatic Cholestasis of Pregnancy

Tribe, Rachel M.; Dann, A T; Kenyon, A; Seed, Paul; Shennan, Andrew; Mallet, Anthony I.

doi:10.1038/ajg.2009.633

Cited by 75 publications

(66 citation statements)

References 30 publications

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“…Real-time quantitative polymerase chain reaction (qRT-PCR) was used to measure liver expressions of bile acid metabolism enzymes, transporters, and nuclear receptors. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 7 7-dehydrocholic acid (7-DHCA), isodeoxycholic acid (isoDCA), apocholic acid (apoCA), 6-ketolithocholic acid (6-KLCA), 7-ketolithocholic acid (7-KLCA), 12 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 9 µL water (with 0.1% formic acid). After centrifugation, 5 µL supernatant was injected for measurement.…”

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confidence: 99%

Distinct Plasma Bile Acid Profiles of Biliary Atresia and Neonatal Hepatitis Syndrome

et al. 2015

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Biliary atresia (BA) is a severe chronic cholestasis disorder of infants that leads to death if not treated on time. Neonatal hepatitis syndrome (NHS) is another leading cause of neonatal cholestasis confounding the diagnosis of BA. Recent studies indicate that altered bile acid metabolism is closely associated with liver injury and cholestasis. In this study, we systematically measured the bile acid metabolome in plasma of BA, NHS, and healthy controls. Liver bile acids were also measured using biopsy samples from 48 BA and 16 NHS infants undergoing operative cholangiography as well as 5 normal adjacent nontumor liver tissues taken from hepatoblastoma patients as controls. Both BA and NHS samples had significantly elevated bile acid levels in plasma compared to normal controls. BA patients showed a distinct bile acid profile characterized by the higher taurochenodeoxycholic acid (TCDCA) level and lower chenodeoxycholic acid (CDCA) level than those in NHS patients. The ratio of TCDCA to CDCA in plasma was significantly higher in BA compared to healthy infants (p < 0.001) or NHS (p < 0.001). The area under receiver operating characteristic curve for TCDCA/CDCA to differentiate BA from NHS was 0.923 (95% CI: 0.862-0.984). These findings were supported by significantly altered expression levels of bile acid transporters and nuclear receptors in liver including farnesoid X receptor (FXR), small heterodimer partner (SHP), bile salt export pump (BSEP), and multidrug resistant protein 3 (MDR3) in BA compared to NHS. Taken together, the plasma bile acid profiles are distinct in BA, NHS, and normal infants, as characterized by the ratio of TCDCA/CDCA differentially distributed among the three groups of infants.

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Distinct Plasma Bile Acid Profiles of Biliary Atresia and Neonatal Hepatitis Syndrome

et al. 2015

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“…The present study (1) identified three sulfated progesterone metabolites, 5a-pregnan-3a,-20a-diol-3,20-disulfate, 5b-pregnan-3a-20a-diol-3-sulfate, and 5b-pregnan-3a-20a-diol-3,20-disulfate, that were present in ICP patients in serum samples obtained even at [9][10][11][12][13][14][15] Abbreviations: ICP, intrahepatic cholestasis of pregnancy; PG, pruritus gravidarum.…”

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confidence: 99%

“…Patients with these characteristics have been identified in several studies, being usually labeled as having pruritus gravidarum (PG), an enigmatic entity that does not carry the fetal risks of a genuine ICP. (5,(9)(10)(11) Table 1 summarizes clinical and biochemical data previously reported in patients with ICP and in normal pregnancies, (7) comparing them with a concurrent unreported cohort of patients with PG in whom pruritus appeared at the same gestational age but was slightly less severe than in patients with ICP. In three of these patients with PG, pruritus diminished spontaneously 1 week prior to delivery; and in another patient, pruritus disappeared in the final week of pregnancy, a phenomenon that was not observed in patients with a genuine ICP.…”

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confidence: 99%

Sulfated progesterone metabolites in the pathogenesis of intrahepatic cholestasis of pregnancy: Another loop in the ascending spiral of medical knowledge

Reyes

2016

Hepatology

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P rogress in medical knowledge can be represented by an ascending spiral in which every loop stands over previous data, adds new findings that deepen our understanding of a disease, and helps to design further research and therapeutic strategies. New loops are frequently inspired by novel approaches to accepted hypotheses and usually supported by the use of more advanced technologies, as seems to be the case in the article by Abu-Hayyeh et al. (1) Intrahepatic cholestasis of pregnancy (ICP), a frequent liver disorder of pregnancy, implies an unpredictable risk of fetal distress, with premature deliveries and stillbirths. Its pathogenesis has been linked to effects of sex hormones during pregnancy, and in recent decades successive reports have revealed a role for progesterone derivatives.In this regard, the spiral started in 1970 when Sj€ ovall and Sj€ ovall reported increased sulfated metabolites of progesterone in serum and urine of Swedish patients with ICP, in contrast to normal pregnancies.(2) Furthermore, this biochemical peculiarity was identified in two patients during an early stage of pregnancy, before the onset of pruritus and abnormalities in serum liver tests, suggesting that it could have predicted the development of ICP.In 1979, Giusti et al. reported that an increase in sulfated progesterone metabolites in plasma from Italian patients with ICP did not occur in patients with viral hepatitis in pregnancy, giving further support to its specificity in ICP. In the 1990s, a series of reports centered in Sj€ ovall's laboratory, in Stockholm, Sweden, using now more sophisticated and precise techniques applied to serum and urine from Chilean patients with ICP and their controls, clarified that a distinctive biochemical feature in ICP was the switch of progesterone metabolism toward a four-fold to 10-fold increase in serum and urine concentration of sulfated metabolites, with an increased ratio of 3a-hydroxysteroid sulfates to 3b-hydroxysteroid sulfates, changes that were reversed after treatment with ursodeoxycholic acid. (4) Among other important steps in this research line, Glantz et al., in Sweden, reported similar changes in the pattern of progesterone metabolites in urine of ICP patients, with a reversal after ursodeoxycholic acid administration, correlating with an improvement in maternal pruritus (5) ; and Abu-Hayyeh et al. also reported increased levels of progesterone sulfates in ICP patients studied in the United Kingdom. (6) Therefore, this metabolic pattern has been detected in ICP patients from different geographic locations and ethnic origins.The present study (1) identified three sulfated progesterone metabolites, 5a-pregnan-3a,-20a-diol-3,20-disulfate, 5b-pregnan-3a-20a-diol-3-sulfate, and 5b-pregnan-3a-20a-diol-3,20-disulfate, that were present in ICP patients in serum samples obtained even at 9-15 Abbreviations: ICP, intrahepatic cholestasis of pregnancy; PG, pruritus gravidarum.

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“…Tribe et al (1) in their study published in this issue of the Journal evaluated prospectively the serum bile acid composition during 16 weeks of gestation and 4 weeks postpartum in a cohort of women with ICP ( n = 63), pruritus gravidarum ( n = 43), and normal pregnancy ( n = 26). Samples were analyzed using an HPLC-MS protocol with an electrospray interface (ESI-MS) allowing simultaneous measurement of the fi ve bile acids (CA, CDCA, LCA, deoxycholic acid, UDCA) and their taurine and glycine conjugates.…”

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confidence: 99%

“…(1) reported the results regarding longitudinal profi les of 15 serum bile acids in women with intrahepatic cholestasis of pregnancy (ICP) using a novel method of measurement. Th e bile acid values were compared with those of women with pruritus gravidarum and normal pregnancy.…”

mentioning

confidence: 99%

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

Sinakos

Lindor

2010

American Journal of Gastroenterology

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Longitudinal Profiles of 15 Serum Bile Acids in Patients With Intrahepatic Cholestasis of Pregnancy

Cited by 75 publications

References 30 publications

Distinct Plasma Bile Acid Profiles of Biliary Atresia and Neonatal Hepatitis Syndrome

Distinct Plasma Bile Acid Profiles of Biliary Atresia and Neonatal Hepatitis Syndrome

Sulfated progesterone metabolites in the pathogenesis of intrahepatic cholestasis of pregnancy: Another loop in the ascending spiral of medical knowledge

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

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